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Full text of "A treatise on therapeutics, comprising materia medica and toxicology, with especial reference to the application of the physiological action of drugs to clinical medicine"

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TREATISE ON THERAPEUTICS, 



COMPRISING 



MATERIA MEDICA AND TOXICOLOGY, 



^fiTn. 



ESPECIAL REFERENCE TO THE APPLICATION OF THE 

PHYSIOLOGICAL ACTION OF DRUGS TO 

CLINICAL MEDICINE. 



BY 



H. C. WOOD, M.D., LL.D, 



I'ROPKSSOR OP MATERIA MRDICA AXD THKRAPBUTICS, AKD CLIXICAL PROPK880R OF 
DISEASES OP THE NERVOUS SYSTEM IN THE UNIVERSITT OP PENNSYLVANIA; 
PBYSICIAN TO THE PHILADELPniA HOSPITAL, MEMBER 
NATIONAL ACADEMY OF SCIENCE, ETC. 



FIFTH EDITION, REVISED AND ENLARGE. 




pn I L adelphia: 

J. B. LIPPINCOTT & CO. 

1883. 



••• •••• •• •••• 

Entered, aooording to Act of CongreM, in the year 1875, by 

J. B, UPPINCdTT Jk CO., 
In tbe OAoe of the Librariui of Congreee, M Wnehingtoa. 



Copyright, 1879, by J. B. Lippiroott A Co. 



Copyright, 1882, by J. B. Lippivoott k Co. 



Copyright, 188S, by J..B. Lippihcott k Co. 



\ee3 



TO 

DR GEORGE B. WOOD, LL.D, 

THIS BOOK 

IS DEDICATED BY TUB ACTIIOR, HIS NBPHEW. 

AS A TOKEN OF RESPECT AND AFFECTION. 



PREFACE TO THE FIRST EDITION. 



At tbe preeeot time, when the ahelTes of priTate and public libraries &re 
aiD^ benejitb their ever-increiising loadfi, when a thousand presses in every 
ity scud forth day and night their printed messages until the earth is filled 
with ihem, it seeais almost preguniptuous for any one to offer new Yolumea to • 

^the world. Indeed, art is so long, life is so short, that every student has the I 
right to demand of an author by what authority he doeth these things, and * 
to challenge every memoir for its raison d'etre. This being so, it assuredly 
wiU not appear egotistical for the author to state that his voluntary task waa 
fir&t suggested by bis own wantii, and that to lt£ perloi-manee be has brought 

|the training, labor, and ej^perience of years spent in tbe laboratoiy, the study^ 
the cIas8-room, and the hospital ward. 

There are a number of excellent treatises upon materia medica and thera- 
peutics ; yet in various attempts at original rtisearch, as well as in the ward 
and the lecture*room of the hospital, i have keenly fblt tbe want of something 
more. There arc many points of view from whicih a subject can be looked at; 
there are many patlis by which it may be approachud ; and to me, other points 
of view, other modes of approach^ have been far more enticing tlian those 
adopted in our standard treatises. 

Tbe old and tried method in therapeutics is that of empiricism, or, if the 

Etcrm sound harsh, of clinical experience. As stated by one of its most ardent 
iUpportcTS, tbe best possible development of this plan of investigation is to bo 
fotmd in a close and careful analysis of cases before and a^r the administra- 
tioD of a remedy, and, if the results bo favorable, tlie continued use of the 

Idrug in similar cases. It is evident that this is not a new putbT but a highway < 
Ircady worn with the eager but weary feet of the prt»fession for two thousand ( 



That very much hjis been thus accomplished it were folly to deny. 
Leaving out of sight the growth of the la^st two decades, almost ail of the 
currunt therapeutic knowledge has been gained in this way. 

Thcnipeutics developed in this manner cannot, however, rest upon a secure 
(buudation. WTiut to-day is believed is to-morrow to be cast aside, certainly 
has been the law of advancement, and seemingly must continue to bo so. 
Wh:it has clinical therapeutics established pernianeutly and indisputably? 
Scarcely anything beyond tiic primary facts that *|uinia will arrest an inter- 
]iiitt4?nt, that salts will purge, and that opium will fiuict paiu and lull to sleep. 

To <Mtablif^fi tberufHjutic facts the profci^siou clings as with the heart 

y 



vi PREFACE TO THE FIRST EDITION. 

and hand of one man, — clings with a desperation and unanimity whose inten- 
sity is the measure of the unsatisfied desire for something fixed. Yet with 
what a Babel of discordant voices does it celebrate its two thousand years of 
experience I 

This is so well known that it seems superfluous to dte examples of the 
therapeutic discord ; and one only shall be mentioned, namely, rheumatism. 
In this disease, bleeding, nitrate of potassium, quinine, mercurials, flying blis- 
ters, purgation, opium, the bromides, veratria, and a host of other remedies, 
ill have their advocates clamorous for a hearing ; and above all the tumult 
tre to be heard the trumpet-tones of a Chambers, '* Wrap your patients in 
blankets and let them alone.'* 

Experience is said to be the mother of wisdom. Yerily she has been in 
medicine rather a blind leader of the blind ; and the histoiy of medical progress 
is a history of men*groping in the darkness, finding seeming gems of truth 
one after another, only in a few minutes to cast each back to the vast heap of 
forgotten baubles that in their day had also been mistaken for verities. In 
the past, there is scarcely a conceivable absurdity that men have not tested 
by experience and for a time found to be the thing desired ; in the present, 
homoeopathy and other similar delusions are eagerly embraced and honestly 
believed in by men who rest their faith upon experience. 

Narrowing our gaze to the regular profession and to a few decades, what 
do we see? Experience teaching that not to bleed a man suffering from 
pneumonia is to consign him to an unopened grave, and experience teaching 
that to bleed a man suffering from pneumonia is to consign him to a grave 
never opened by nature. Looking at the revolutions and contradictions of 
the past, — ^listening to the therapeutic Babel of the present, — is it a wonder 
that men should take refuge in nihilism, and, like the lotos-caters, dream that 
all alike is folly, — that rest and quiet and calm are the only human fruition? 

Since the profession has toiled so long and (bund so little, if fuither pragresa 
is to be made we must question the old methods and search out new ones, 
which haply may lead to more fruitful fields. In the ordinary afi'airs and 
business of life, when anything is to be accomplished, the efi'oit always is to 
discover what is to be done, and then what are the means at command. A 
primary knowledge of the end to be accomplished, and a secondary aequaintr- 
ance with the instruments, are a necessity for successful human efibrt ; and 
until the sway of this law is acknowledged by physicians, medicine can never 
rise from the position of an empirical art to the dignity of applied science. 
Until within a comparatively recent period, it has been impossible to comply 
with this law. But, through the advances made by the pathologists and 
by the students of the natural history of disease, we are fast learning the 
methods in which nature brings the body back to health. When this b 
done, — wlien disease is thoroughly understood, — we shall have wrought out 
the fii'st olcnient of the problem, shall have complied with the first requirement 
of the law. 



I 



PREFACE TO THE FIRST EDITION, vii 

It is s<»roely within the province of tbe therapeutist, and certainly is not 
pcmble within the scope and limitA of this work, to discuss at length the 
mnra] history of disease; hut it is allowable to point out evident indications 
finr relief; and this I have done to a greater or less extent throughout th^ 

lKK)k, 

The work of the thernpeutist is cliiefly with the second portion of the law. 
Evidently, it is his especijil province to find out what are the means at coin- 

md, wlmt the individual drugs in use do when put into a human system, 

>k lecminfrly self-evident that the physiological action of a remedy can 
} be made out by a study of \iB use in disease. Under all circumstances, 
tte prohk-m is one of the most connjlex with wliich the human mind has to 
^grapple ; and to introduce into this prohlera the new and ever-varying fuctora 
the effect of disease and its natural vibrations on the system is to put thfl 
Baalter beyond human prescience* 

lo spile, then, of Dr, Niemoyer's assertion^ that erperiroents made with 
nedieamentij upon the lower animals or upon healthy human beings have, as 
been of no direct service to our means of treating disease, and that a 

Dtinuation of such experiments gives no prospect of such service, it is 
dertain that in these* experiments is the only rational acieiitific ground wurk 
for the traitment of disease. We must discover wliat influence a drug exerts 
when put into the body of a patient before we can use it rationally; and we 
can gain this coveted knowledge only in the method indicated. 

It has been strenuously objected, especially to experiments upon animals^ 
that drugs do not act upon the lower creatures in the sumo manner as they 
do upon man. Wlien I first commenced the studies whose outcome is the 
present vohime, I was profoundly impressed with the truth of tliis ofl^re- 
pelted aasertion and with the difficulties which it put in the way. To-day 
I do not believe that, stated in its broad sense, it is true. Indeed, more 
irtrong^Vj I assert that it is not true ; that, in the vast mnjonty of cases, the 
actions of dnigs upon man and upon the lower animals are, though seem- 
ingly different^ in reality similar ; that tlie more knowledge we acquire, the 
fewer exceptions remain unexphnned ; and that the whole matter is in all 
probability subject to laws whose development will greatly aid in our expla- 
Diiticiti of various obscure clinical phenomena. 

The general proofs of these a-^j-ertions arc suflSciently obvious, I tliink, in 
the folio wir»g pages to render it unnecessary for me \o dwell upon them at 
length here : moreover, if they be not so obnous to others as to myself, 
ipaoe ia here wanting for a full discussion of the subject I can only make 
general remarks, and point out some of what I believe to be the 
ring laws, 

In the first place, degree and quality are distinct things, and should not be 
confounded. Yet they frequently arc ; and because it requires as much mor- 
ptik to kill a pigeon of a pound weight as to destroy a man, we are told that 
medicines act differently upon man and the lower animals. Evidently the 



viii PREFACE TO THE FIRST EDITION, 

conclusion is a non-sequitur, and difference of susceptibility is no proof of dif 
ference in the mode of impression. A teaspoonful of Epsom salt may purge 
one man, whilst it may require ounces to affect another. Evidently there is 
a difference of susceptibility; but when the impression is once made it is of 
the same character in each case. As with man and man, so with man and 
the pigeon. — susceptibility is no measure or gauge of the character of the 
impression. 

A large number of drugs — indeed, it may be said, the larger number of 
important drugs — exert in the system antagonistic actions. Thus, atropia 
stimulates the spinal cord, but destroys the conducting power of the nerve- 
trunks. It is evident that as one or the other of these influences predomi- 
nates, will there be convulsions or paralysis. Now, if for any reason one 
animal be exceedingly sensitive to the spinal action of atropia, that animal 
will in belladonna-poisoning suffer from convulsions, whilst its fellow, which 
is affected chiefly by the nerve-action of the drug, will, under like circum- 
stances, have paralysis. Here the mere clinician, with his superiicial knowl- 
edge, seeing the paralyzed and the convulsed Ijring side by side, says. What 
a hopeless muddle I Poor fools, these vivisectors ! they will never come to 
any good I In truth, the differences in symptoms ii» these and in many 
other cases simply depend upon differences in susceptibility ; and the only 
lesson that the circumstance teaches is the importance of discovering the laws 
which govern these susceptibilities. 

A law which governs the susceptibility to the action of drugs is, that the 
more highly specialized any system is, the more readily affected is it by a 
medicine. Thus, the cerebrum of a man is far more highly organized than 
that of any other animal, and consequently he is far more sensitive to the 
action of drugs which affect the cerebrum than are the lower forms. Again, 
in the frog the spinal system is especially developed, — probably, in proportion to 
the cerebrum, more so than in any other of the animals commonly experimented 
with : consequently the batrachian is excessively sensitive to remedies which, 
like strychnia, affect the spinal cord. In obedience to this law, we have 
resulting the action of opium, — an action which has been considered the 
strongest proof of the hopelessness of any attempt to explain the effects of 
drugs upon a man by experiments upon the lower animals. In man, opium 
causes deep stupor and general relaxation ; in the frog, it causes tetanic con- 
vulsions. The explanation of these seeming inconsistencies is, however, very 
evident when the whole subject is looked at Opium in all animals has a 
double action, one upon the cerebrum and one upon the spinal centres. In 
the frog, the latter being the more highly organized, the spinal action over- 
comes the cerebral ; in man, the cerebrum being the more sensitive, stupor 
replaces the convulsions: yet in man convulsions sometimes occur in opium- 
poisoning, and in the frog the dose can be so managed as to cause stupor. 

A second law which seems to hold sway over the action of drugs upon 
different animals is that great differences of function in a system affect it? 



PREFACE TO THE FIRST EDITION. 



fdatioQ to drugs : thus, in a kerbivorous animal die alimentary canal \b very 
different from what it is in the ctirnivora, whuse digest! vo orj^aiia la turn 
differ irom those of man, — the omnivoro. Medicines which act upon the 
dimeDtiiry canal are apt to vary in their effects upon different orders of animals. 

Convert to the above law is that which renders systcma which are little 
spocimluBed similarly acted upon by drugs in different ebsses of aiiimak. 

Thus, the general structure and the functions of the circulatory system are 
very uniform among vertebrates^ as is also the action of those drugs which 
affect chiefly the ciix'ulation : thus, aconite, or digitalis, or potash, influences 
in the one way the heart of the frog, of the rabbit, and of n»an, 

Tliere are a very few apparent exceptions to the uniformity of the action 

idrugs upon all auimuk, which Boemingly contravene the laws that have 
mentioned. These exceptiouH are so few, h^wevcr^ that wit bout doubt ad- 
vaociug knowledge will hy-atid-by explain them all and s1h»w wlnit are the laws 
which for the time being hold tn abeyance or overcome tliose already stated* 

An adaerted fact, which haa recently been brought forward as revealing 
the worthlessncss of annual experimeututioii, is that some monkeys are not 
loaoeptible to the action of strychnia^ whibt othera are. Graiiiing the truth 
of the asserted fact^ it certainly is explainable. It is at Icat^t conceivable 
that a given species of anliuid may, by the gradmilly-aef|uired habit of teed- 
bg upon a substance containing a narcotic poisiiin, acN^|uire an insusceptibility 
to the iufiuenee of that poison, which shall, as it were, belong to its speciiie 
type, or, in other words, be an actjuired specifie churacter. The nervous 
of the opium-eater becomes accustomed to the stimulant, and it is not 
ibie thiit a measure of the habit should be transmitted. If the Bar- 
winiao law of the gradual evolution by the sur\'ival of the fittest have any 
force, these curious apparent freiiks of medicines in regard to their physio- 
logical action may be the result of this law^ espc»cially since it is species which 
ire afiiected It is not all monkeys that are proof against strychnia, but, as 
we are distinctly told, only one s[MX'i«3s of monkey ; and, so far as I know, it 
ia not all deer tliat are said to thrive when fed u|>on tobacco, but only the 
Yirgiaia deer. Whether this conception bo or be not a mere fancy, this much 
ii to my mind very clear, that the few scattered cxc*eptiuns ought not to out- 
weigh the immense majis of evidence upon the other side, and tliat it is ineon- 
oeivable that drugs, in their relations to animal organisms, differ fi-um all other 
created things in not being subject to law. 

Id the early fjortion of this preface I stated that the work had grown out 
of a oetHl felt by myself: that need was for a W>ok into which should he 
giithered the many scattered facts in regard to the physiologicid action of 
medicine, — a book in which ao attempt should be made to sill the true from 
the false, to reconcile seeming differences, to point out what we know and 
what we do not know, and to give a platform from which investigators might 
itart forward without the necessity of being, as is so oflen the csise, ignoniiil 
of what was already achieved, or of spending a great deal of time in a wild 




^ 



X PREFACE TO THE FIRST EDITION. 

hunt through the almost boundlcts, but often scattered and inacceflsibley 
ranges of Continental literature. 

The plan of the present work has been to make the physiological action <^ 
remedies the principal point in discussion. A thoroughly scientific treatise 
would in eadi article simply show what the drug docs when put into a healthy 
man, and afterwards point out to what diseases or morbid processes such action 
is able to afford relief. Unfortunately, in the great majority of cases our 
knowledge is not complete enough for this, and the clinical method has to be 
used to supplement the scientific plan. 

I have added to the book a consideration of toxicology, so far as it is of 
interest to the physician. This has been done for several reasons. First, it 
was necessary to study the action of poisonous drugs upon man, in order to 
make out their physiological action ; secondly, physicians are constantly re- 
quired to diagnose and to treat oases of poisoning ; thirdly, it is ofUm of the 
greatest importance for a medical man in a court of bw to be able to statu 
what arc the symptoms and post-mortem appearances produced by a given 
poison, whut diseases they simulate, and how far and in what they differ from 
the phenomena of these diseosos. That part of the science of toxiook)gy 
which treats of the recognition of poisons in the cadaver, or in food and 
drink, belungs to the domain of the chemist, and I have avoided it altogether. 
For a situilar reason, in the sections on materia medica, the chemical relations 
of muicral substances have not been discussed at all 

Preface to the Fifth Edition. — The exhaustion of the fourth edition 
of this book in about six months has not only been a personal gratification 
to its author, but has stimulated him to render the volume, as far as lay in 
his power, worthy of the kind judgment and continued favor of his co- 
laborers. Attention has been paid not only to recent but also to past litera- 
ture, and it is believed that the book represents more thoroughly than ever 
before the best therapeutic thoughts of the day. 



TABLE OF CONTKNTS. 



_ IitTaaDUCTioK.— Pharmacy— Tlierapeutica — Materia Medico — PbarmaoofKeift 

— Preparulioiw— Effect* of Medici noa— Classification. 

PART I -DRUGS. 

DIVISION I.-- SYSTEMIC REMEDIES. 

SUBDIVISION I.— GENERAL RPIMEDIES. 

BTRiKOKKTfl. — VegeiahU Aatrin^ent^, — Timnic Acrd — Galllo Acid — GaiU— 
Catechu— KLno—Hasmatoxy Ion — Rhatany— Oak Barks— HoBeB—Oerunium 
— SuTnacb. 

Mineral A$tringcnU. — Alum — Sulphate of Aluminium^Lead and ita 
Reparations — Bismuth and iu Froparationfi — Oxalate of Ceriuto — Zino 
od ita Preparations — Cudnuum and its Preparationa— Copper and ita 
Preparations — Silver and it* Preparations. 
ToHics. — SimpU ^i««r#.— QuttiKsm— Si mar uba ^ Gentian — Nectandra — Bar- 
berry — Columbo—Boneiet— Chi ret ta— Dogwood* 

Peculiar Biitera, — Wild Cherry Burk — Cinchona — Sulphate of Quinine 
— Tannate of Quinine^ — Sulphwte of Cinchonine — Sulphate of Quinidine — 
Dextro-Qui nine— Sulphate of Cinchonidino — Chinoidine— Picric Acid-^ 
Carbazotate of Ammonium. 

AromoHe BitUrs. — Chamomile — Virginia Snakeroot — Cascarilla — An- 
gUBiura. 

True Aromaiict. — Cinnamon — Cloves — Nutmeg — A lUpice^ — Cardamom 
— Ginger — Black Pepper — Red Pepper— Oil of Cajeput^— Eucalyptus, etc. 

Mineral Thnies.—lTnn and itA Proparntions— Rulphurie Acid — Muriatic 
Acid— Nitric Acid — Nitromunatic Acid— Lactic Acid— Phosphorus. 

Cardiac Stimulants.— Ammonia and tt« Salts— Alcohol— Brandy— Whisky 
— Wine — Turpentine^ — Di|^italis — Convallaria Majalis. 

CARi>tAC Sedatives.- Antimony and its Preparations— Veratr urn Viride— 
Teratrum Album — Arnica — Sabadilla — Veratria— Aconite Leaves and 
Root — Prusiic Acid^ — Cyanide of Potassium — Vegetnblo Acids. 

AjrTiarA5^MOD[a».—Kusk—43asior ^Valerian —Valerianic Acid— AssHfetida— 
Camphor^Oil of Camphor — Braminatcd Cumpbor^Carbokted Camphor 
— ^Arulier — Oil of Amber — Holfman's Anodyne — Hops — Lactuearium^ 
Black Snakeroot— Coffee, Tea, Mat4, Caffein. 

xi 



xii TABLE OF CONTENTS. 

Analgesics. — Opium — Morphia — Narcein — Codeia — Narcotina — Thebaia — 
Papaverina — Laudania — Porphyroxia — Cryptopia — Meconia — Hydrocotar- 
nia — Pseudomorphia — Opiania — Meconic Acil — Indian Hemp — American 
Hemp. 

Mydriatics. — Belladonna — Atropia — Hyoscyamus — Stramonium. 

An^sthktics.— Nitrous Oxide — Ether— Chloroform— Bichloride of Methyl — 
Bromide of Ethyl. 

ExciTO-MoTORS.— Strychnia and Drugs containing it. 

Depresso- Motors. — Calabar Bean — Bromide of Potassium — Bromide of So- 
dium — Bromide of Ammonium — Bromide of Lithium — Bromal Hydrate 
— Chloral — Metachloral — Chloral Camphor — Butyl Chloral — Nitrite of 
Amyl — Nitrite of Potassium — Nitro-Glycerine — Valerianate of Amyl — 
Lobelia — Oelsemium — Tobacco — Conium. 

Alteratives. — Arsenic and its Preparations — Mercury and its Preparations — 
Iodine and its Preparations — Iodoform — Cod-Liver Oil— Phosphoric Acid 
and the Phosphates — Colchicum — Sarsaparilla — Guaiac — Mezereum — Sas- 
Kafra:i — Dandelion. 

SUBDIVISION II.— LOCAL REMEDIES. 

Emetics. — Vegetable Emetics, — Ipecacuanha — Blood root — Apomorphia — Gille- 
nia — Mustard — Squill. 

Mineral Emetics, — Antimony — Sulphate of Zinc — Sulphate of Copper — 
Alum. 

C ATHARTics. — Loxatives. — Foods — Tamarinds — Cassia Fistula — Magnesia — 
.Sulphur — Potassii Sulphuretum — Sulphide of Calcium. 

Purges. — Castor Oil — Mercury — Rhubarb — Goa Powder — Chrysophanic 
Acid — Butternut — Aloes — Senna — Euonymus — Saline Purgatives. 

Drastics. — Scammony — Colocynth — Compound Cathartic Pills — Podo- 
phyllum — Elaterium — Gamboge — Croton Oil — Black Hellebore. 
Diuretics. — Hydragogue Diuretics, — Squill — Digitalis — Broom — Sweet Spirit 
of Nitre. 

Refrigerant Diuretics. — Potash and its Preparations — Lithium Salts — 
Anthydropin. 

Stimulating Diuretics. — Buchu — Pareira — Uva Ursi — Pipsissewa — Juni- 
per — Carota— Erigeron — Turpentine — Copaiba — Cubeb— Matico— Cantha- 
rides. 
Dlaphoretics. — Nauseating Diaphoretics. — Refrigerant Diaphoretics. — Simple 
Diaphoretics. — Jaborandi — Spirit of Mindererus — Sweet Spirit of Nitre — 
Alcohol — Warburg's Tincture. 
ExpECTO rants. — A tomization . 

Nauseating Expectorants. — Lobelia — Ipecacuanha — Tartar Emetic. 

Stimulating Expectorants. — Chloride of Ammonium — Senega — Ammo- 
niac — Benzoin — Benzoic Acid — Balsams of Tolu and Peru — Garlic — Squill 
—Tar. 
Emmenaqooues. — Tonic Emmenagogues. — Purgative Emmenagogues. — Stimu^ 
lating Emmenagogues, — Savine — Rue — Parsley — Apiol — Cantharides— 
Guaiac — Tansy. 



TABLE OF CONTENTS. xiii 

Oxytocics. — Ergot — Cotton Root — Smut of Indian Corn. 

SiALAOOOUES. — Pellitory. 

Ebrhinss. 

Epispastics. — Counter-irritation — Cantharides. 

Rubefacients. — Mustard — Spices — Turpentine — Burgundy and Canada Pitch. 

EsCHAROTics. — Potash — Vienna Paste — Arsenic — Chloride of Zinc — Canquoin's 
Paste — Corrosive Sublimate — Acid Nitrate of Mercury — Chromic Acid — 
Bromine, etc. 

Dkmulcents. — Gum Arabic — ^Tragacanth — Slippery Elm — Iceland Moss — 
Irish Moss — Liquorice Root — Sassafras — Tapioca — Arrowroot — Sago- 
Barley. 

Emollients. — Glycerine — Poultices. 

Diluents. 

Protectives — Collodium — Solution of Gutta-Percha. 

DIVISION IL— NONSYSTEMIC REMEDIES. 

Antacids. — Sodium and its Preparations — Lime. 

Anthelmintics. — Pinkroot — Wormseed — Koosso— Santonin — Male Pern — 

Pumpkin-Seed, Pomegranate, Cowhage, Kameela, etc. 
Diqestants. — Pepsin. 
Absorbents. — Charcoal. 

Disinfectants. — Oxidizing IHsinfeciants. — Permanganate of Potassium — 
Chlorine and its Preparations— Iodine — Bromine. 

DeaulphuraHfiff Disinfectants. — Metallic Salts — Lime. 

AnHzymotics — Borax — Sulphurous Acid — Carbolic Acid — Salicylic Acid 

— Salicin— Thymol. 

Absorbing Disinfectants. 



PART II.— FORCES. 



Caloric. — Heat: its Use in Shock, Collapse, etc. — Cold: its Local Use; it? 
Use as a Tonic ; its Use in Pyrexia. 

nLEOTRiciTT- — General Considerations ; Diagnostic Use ; Use in Palsies ; Use 
in Neuralgias ; Application to Motor Apparatus ; Application to Sensory 
Apparatus ; Application to Nerve-Centres ; Use as a Tonic. 



appendix. 



The Art of Prescribing Medicines. 
Tables. 



A TREATISE 



OH 



THERAPEUTICS. 



IKOLUDIiro 



MATERIA MEDICA AND TOXICOLOGY. 



INTRODUCTION, 



AliTHauaii PoAHif ACT, or the adenoe of preparing medicmes^ is entirely 
&tiiiet from Trerapeuticb, or the eciencc of the application of medicinee to 
like essti of disease, it is evident that some aequaintanoe with the former ia 
Movaaary ta the correct appreeitition of the latter.. Further, as the basiB of 
boUi these stadies, mu^ first oome a knowledge of Materia Medica, or the 
filfaMaiiMi wed as tnedktQfia. Pbaruaooi^oot is the general term cm- 
ploj^ U> emhrace Uiese thoee divi^ona* 

In every civilised eonntrj there is some recognised officia] list of dmgs and 
ikmr prepmitionay known aa the Pharmacopotia, In most places, this, heing 
(fvpftred with the sanction of the government, partakes of the nature of a 
Jpirt hot in the United States conform it j to it depends upon the voluntary 
of the professions of Medicine and Pharmacy, by a repre^ntative con- 
of which it was ori<;^nally prepared and is decennially revised. 
The United States Pfuirmacopma is divided into three portions : & primary 
and a Mectmdaty matena medtca li$t^ and a chap»ter on prtparationn^ with 
dbeetio&s for their manufacture. The primary list contains medicines whose 
repotation is believed to be assured ; the secondary list, those still on trial, 
or thoee which ejcperienee \\m islmwn to he not altogether valuoleKs, but yet 
of iittl# importance. It is evident that a knowledge of the officinal or reco^- 
wmi preparations, of their general mode of manufacture, and of their strength, 
b omisial to the therapeutist. The United States Pbarmacopo&ia rocogniisea 
r«iity-nine classes of them, as ibtlows : 

DlXX>CTA. — Decoctions are made by boiling erode drugs for a greater or 
in water. It is evident that this methixl of preparirjg is ineligible 
2 IT 



18 INTRODUCTION. 

when the actiye principle is volatile or is easily decomposed by heat, or when 
the drag contains much starch, whose extraction would make the prepai&tion 
very thick and predispose it to rapid decomposition. The method is especially 
adapted to woody, hard substances, and to those containing much albumen 
which is coagulated by the boiling water and left in the drug. 

Infusa. — Infugiom are made with water, either cold or hot, without boil- 
ing. They are prepared by maceration, or by displacement. 

LiQUORES. — Solutions are preparations in which an active, non-vokude 
principle is dissolved in water. 

AQUiE. — Waters are solutions of volatile principles in water. 

MiBTURiE. — Mixtures are preparations in which one or more medicinal 
substances are held in suspension in water. Of such nature arc emulsions, in 
which some oily material is suspended by a gummy or an albuminous body. 

MuciLAQiNES. — Mucilages are solutions of gummy substances in water. 

Strupi. — Si/rups are sugary liquids, the menstruum or basb of which is 
water, with, in some cases, vin^ar or alcohol. 

Mellita. — Honeys are preparations whose basis is honey. 

AcETA. — Vinegars are those preparations in which vinegar, or dilute acetic 
acid, is used as the menstruum. 

TiNCTURiE. — Tinctures are alcoholic solutions prepared by maceration or 
displacement from the crude drug, or by dissolving non-volatile principles. In 
some of them strong, in others dilute, alcohol is used. 

Spiritus. — Spirits are alcoholic solutions of volatile principles, made by 
direct solution or by distillation from the crude drugs. 

Vina. — Wines are preparations whose menstruum is wine. 

Glycerita. — Glycerites are preparations in which glycerine is the solvent 

Olea Destillata. — Volatile Oils are activa principles of such natore, 
prepared by distillation. 

OLEORESiNiE. — Oleoresins are concentrated preparations, composed gen 
erally of a volatile oil and a resin. They are really ethereal extracts, made by 
the action of ether upon the crude drugs ; in the case of ginger, a mixture of 
alcohol and ether is used. 

Succi. — Fresh Juices are obtained by expression of the green plant, enough 
alcohol being added to preserve them. 

ExTRACTA. — Solid extracts are of two kinds ; one being prepared by the 
evaporation of the fresh juice, the other being made in various ways from 
the crude drugs. 

ExTRAOTA Fluida. — Fluid extracts are very concentrated fluid prepara- 
tions, generally so made that one minim represents one grain of the crude 
drug. 

Resins. — Resins are purgative resinous principles, obtained by the pre- 
cipitation of saturated tinctures with water. 

CoNFECTiONES. — Confections arc medicinal substances beaten up with 
sugar into a pasty mass. 



INTRODVCTION. 



19 



Trochtsci. — Trochtn^ or lozert^es^ are gummy pelleta or diska, so made w* 
► diasolve slowly in the moutlx. 

ScTPOSlTORlA. — Supptmtorirs are conical bodies, prepared for mtrodue- 
41 mto the rectum, where they melt with the heat of the body. Their 

I m geaemlly cacao butter, 
Unguenta and CeraTA,^ — Omfments and OrraUsvLX^ fatty solid prepara- 
llrtid ibr external use. The cerates containing war (cerd) are the firmer of 
lie two. 

Emplastra. — Piasters are solid substances spread by the aid of hem uiH>n 
l^t^lin, skin, or other similar material, and of such nature d« to be adhesive 
the temperature of the body. 

Charts. — Papers are medicated leaves or sheets of paper for external ubc. 
The only officinal are those of mustard and of cantharides. 

LlxniEMTA, — Liniments are lifjuid preparations, generally soapy or oily» 
and always intended to be applied externally by rubbing. 

The names of PlLirL.« {PlUs) and Pulvkres {Powders) sufficiently indi- 
cate lije character of the preparations. 

The British Pharmacopoeia is not divided as that of the United States, but 
the dm^ and their preparations are arranged alphabetically. 

In wlmt way medicines produce changes in the life-actions of various jvATtH 
is, and probably mo^ ever reniaitj, uiiknowu, precisely as it is beyond th«» 
lit of the human intellect to know why the nerve-<?ell or the spemmtos&oon 
^rfanns the prodigies of which it m capable. The fact that various sub- 
do pCMBeaB a selective tendency, so to speak, do act more forcibly on 
ome form of tissue than on another^ is, however, indisputable. 

The cffdcts of medicine arc commonly divided into the primari/ and second' 

fy or the immediate and the remote. An example will probably nhow the 

ftsrenoe between these in the briefest and most forcible manner. Thus, the 

aiddiate effect of a diuretic m increased urination : the secondary effect 

ay be nmiaval of serous effmiion in some part of the body. It is evident 

. the ktter ia brouj;ht about not by the medicine itself, but by the changes 

imiueea ; the incrtmsed excretion musing a diminution of the amount of 

be fluid in the blood-vessels, which in turn predisposes to ahfiorption. 

The term or expression tntlicotifm for a given remedy, being in constant 

«j out^ht to be distinctly underwtond; by it is meant the pointings of 

lure, or, in otliex word^, the evident needs of the «Hystem. Thns^ bard fjiDces 

^llected in the colon are an indication for a purgative of such character as 

produw wat£iy discbat^cs to sf>ftcn them. Relaxation in a part indi- 

a rcmetly of .nuch pmpcrttes that it will awake into new life the natural 

wiinictiUty of the part. Agziin, the snppn»Hsion of secretion from over- 

3lt4iiuctitt or from irritation, is an indication for some drug which will allay 

whiLst the same suppression, when dependent upon t^^rpor or loss 

iviiy, will call fur an excil^int, — on irritant. The childish absurdity 

treating symptoma by any such bw as '^ similia gtmillbus curantur/' or 



20 INTRODUCTION. 

*' dissimilia difiBimilibus curantur," is at once apparent Symptoms are merely 
the snrfacc-play of disease ; and the rational therapeutist always seeks out 
their hidden meaning. 

By far the greater number of remedies are absorbed into the blood, and 
thus find access to the part upon which they act. It is necessary, thereftnrei 
for them to be so placed that they can be taken into the blood-vessels. 

There are five paths of entrance for medicines into the circulation, — the 
stomach, the cellular tissue, the rectum, the skin, the lungs. By far the moFt 
frequently employed of these is the first-named. It is evident that, in order 
to pass rapidly and readily into the absorbents, medicmes must be in solution. 
When administered by the stomach, however, it is equally plain that solu- 
bility in an ordinary menstruum, snch as water, is not a tine qua nan, since 
the varying acidities, alkalinities, and organic contents of the alimentary 
juices give to them a solvent power far above that of less complex and vary- 
ing fluids. Thus, a medicine insoluble in water may be dissolved by the acids 
of the gastric juice, while another drug may owe its activity to its solution 
by the alkalies or by the fatty matters of the intestinal fluids. 

The dissolving power of the rectal fluids is very slight : hence, in order to 
act efiiciently, medicines when given by the rectum must be in solution or 
readily soluble. Absorption, moreover, does not occur so rapidly from the 
rectum as from the stomach, and greater time is therefore needed to impress 
the system in this way. In the great majority of cases medicines are thus 
exhibited to obtain peculiar effects more or less local in character. Thus, an 
opium suppository is given in dysentery, or to quiet irritation of the genito 
urinary organs, or to check vomiting. 

The subcutaneous tissue affords the most rapid route to the central organs. 
The substance must, however, always be in perfect solution, and not too irri- 
tating. It is thrown under the skin by means of a small syringe with a sharp 
hollow needle for its nozzle. Great care should be taken to avoid throwing a 
medicine into a vein, and so producing a sudden overwhelming effect. The 
point of the syringe-needle should not be thrust deeply into the tissues, but 
be kept just beneath the skin, and be withdrawn a little, after having been 
pushed along under the skin farther than necessary. The objections to the 
method are the danger of injecting into a vein, the slight pain of the opera- 
tion, and the skill required for the latter, so that the administration cannot 
be left to the nurse, together with the local irritation and, it may be, inflam- 
mation, to which many drugs so used give rise. Tlie pain may be to a great 
extent avoided by slightly freezing the skin by means of a spray-producer, 
yet, for the other reasons mentioned, the hypodemiic method should not be 
employed except under certain circumstances. When, as in severe suffering, 
an immediate decided action is required, it is beyond all value, — the system 
coming under the influence of the remedy as if by magic. The dose sliould 
always be smaller than that by the mouth. 

There are several ways in which medicinal principles are introduced through 



INTRODUCTION, 



21 



tWflkin, although the only one in common use is the application of nicdieatecl 
fkuy preparations^ either with or without friction. Absorption tnkes pWo, 
of euiirs>ej iiiasl rapidly in those pusitions at which thf! skin is thinnost, — 
tbe imide of the thighs, the eurface of the abdonien, and especially the arm- 
pita. Almost the only remcily which is introduecMl into the system in (his 
way Is mercury. Absorption will take place through the skin frum buths, but 
m slowly that advaDtage m never taken of it in the ooustltutional treatment 
of disease, — unless the sulphur baths, Bometimes employed in rheuinutisin, 
impress the general system by abst>rptian, which seems to nie doubtful. 
Formerly, medicines wero sometimes exhibited by placing them on blistered 
suHacess beneath the raised cuticle ; but^ except iu the instance of morphia, 
BO used in gastric disturbanoe, at present the endermic method is very rarely 
employed. 

To inBuence the general system, the lungs are only used for the introduo- 
tioD of the vapors of the ansesthetica. 

For foc^l purposes medicines are applied to various parts, — ^to the skin^ to 
the ear, narra, &ucee, stomach, larynx, lungs, rectum, va^a, urethra, etc. 
For the last three, Uquid preparations known as injectiom^ or solid ones 
known as wppoakories^ or, io case of the uretlira, as boupeSj are employed* 

For the puqx>se of making local applications to the respiratory organs, 
iMtOMtzafion is very commtmly practiced. Very many forms of apparatus are 
io use, but the principle in all of them is the same. A rapid current of air, 
Of of st/CAm, is forcibly ejected frrim a horizontal pipe, through a capillary 
orifice, directly across a similar opening in a vertical tube. The ru^li of the 
vapor over this second orifice forms a vacuum ] the fluid into which the base 
of the vertical tube ts set, rushing up to fill this, is sucked or drawn out 
thr<.ni«;h the orifice, and as it emerges is broken into a tine spray, and is car- 
ried along by the current of air or steam int<i a niuuth-piece, at which sit^ the 

I patient. It cannot be gainsaid that in this way we are able to cairy medieinal 
IOCS not merely into the larynx, hut into the lungs themselves. Yoh- 
Bcines vaporized by heat are als4:> sometimes employed in the treatment 

' of lung affections. 

There are various classes of agencies which so modify the action of drugs 
sfl to uccsessitate their oonsideration. Such are disease, climate, habit, tern- 
penuoent, idiosyncrasies, sex^ age, time of administration, imd emotions. 

DiMeiise often furtifies the system against the action of remedies, so that the 
dose has to be greatly increased to obtain perceptible effects. Thus, pain or 
^Uriunt tremens will interfere greatly with the production of narcotism by 
opitun ; or spinal disease with purgation. Disease may altogather prevent the 

I mdmm of a remedy. In all these eases two rules should never be lost sight 
rf : fiT«t> never give the medicine in such doses as would in health clause 
dcaili ; second, always be sure, before giving large amount**, that the Remedy 
wQl not make matters worse (as a drastic in Intussusception). 

Ctimnie^ by giving physical Imbita or tendencies ti> the patient, often greatly 



22 INTRODUCTION. 

influences the proper selection and dose of remedies. It is only necessary 
to allude to the great consumption of quinine in malarial regions as an ex- 
ample. 

Uahit — including mode of life — seems to alter, as it were, the very consti- 
tution of man. Not only does it give type to disease, by producing habitual 
plethora, or its opposite, but it also fortifies against the action of single reme- 
dies, or whole classes of them. Thus, in the opium-eater, a dose sufficiently 
large to kill an ordinary man serves only to gratify the cravings of appetite. 
Again, a man accustomed to one narcotic, as alcohol or opium, loses, to a 
greater or less degree, his susceptibility to all narcotic influence ; and the 
patient whose bowels require daily to be moved by a cathartic finds himself 
react more and more slowly to medicines of that class. Again, a nervous 
system blunted by exposure and toil in the open air is far less susceptible to 
the action of remedies, and requires larger doses to influence it, than the deli- 
cate organization of a woman weakened by indolence and luxury. 

Temperaments are peculiarities of organization characterizing classes of 
individuals ; idiospicrcLsies, peculiarities belonging to single individuals. This 
is scarcely the place to discuss the subject of temperaments, but it is allowable 
to state that while the phlegmatic person is no more easily moved by medicinal 
than by other agencies, the nervous individual answers as quickly to the one 
as to the other. Idiosyncrasies seem at present to be beyond law. They are 
often very remarkable, and a knowledge of them is most important for the 
practitioner. Thus, a relative of the author's is thrown into the most alarm- 
ing fainting-fits by eating even so much butter as would be ordinarily used 
as a dressmg for vegetables at dinner. Some persons are poisoned by the 
slightest touch of turpentine, others are frightfully salivated by a mere par- 
ticle of a mercurial. These idiosyncrasies are numerous, cannot be foreseen, 
and are often very important : hence the necessity, in prescribing for an un- 
familiar patient, of always asking as to his or her peculiarities. 

Sex, of course, modifies all diseases connected with the organs or the pro- 
cess of generation, but it does more. Woman is more impressible, less robust, 
with less power of resisting external agencies, than is man. Consequently, 
the dose for her should, as a rule, be less than that for him. It is needless 
to remark here at length on the necessity for abstinence from strongly per- 
turbing remedies during pregnancy or at the menstrual periods. 

Age, of course, modifies materially the dose. The rule of Dr. Young, the 
one which seems to me the most practical and generally useful, is to add 
twelve to the age and divide the age by the result. Thus, a child one year 
old would require one-thirteenth, one three years old three-fifteenths, of the 
amount necessary for an adult. Other rules have been invented, but the 
only one which seems to me practical is the following, proposed by Dr. R. O. 
Cowling (^American Practitioner^ vol. i.) : 

" The proportionate dose for any age under adult life is represented by the 
number of the following birthday divided by twenty-four :" i.e., for one year 



IODVCTIOKT 



■ 



ifl ^ ^=^ ^ ; for two jre^TB, /^ = I ; for tlirce yeara, ^ = J ; fof five jctini, 
^^ = i ; for eleveo years, ^} == J , etc, 

Ph>C Clarke (Boston Me<L atui Sur^. Journal^ 1872) has propoaed a rule, 
which, although probably more accurat43 than cither of those given, seems too 
cumbetsome for ordinary purposes. It is based upon relative weights : 

** Aasuming the average weight of an adult to be one hundred and fifty 
pounds^ for whom an appropriate dose L^ 1^ or one drachm, the dose of moBi 
medioines must be increnaed or diminished in the proportion of the weight of 
the patient to that ntimber of pounds. This proportion is represented by a 
Iraciioii whose numerator is the patient's weight, and whose denominator is 
150, If a child at birth weighs six piunds, the appropriate dose for it would 
be -j-f^, or ^ ; if it weighs tj^n pounds, ^^, or ^. A ehild two years old, 
weigliing twenty pounds, would require ^^, or about ^ of an adult dt^e ; or, 
more precisely, X. A person whose weight is two hundred pounds :sliould 
have ^J, or IJ of an average adult dose/' 

It must never be lost sight of that cliildren bear narcoties very badly, and 
that the doses of such remedies for them should always be proportionally 
imaller than for the adult 

Ttme of Admitmtration, — Absorption takes place most rapidly in an empty 
stomach, and consequently, when rapidity of action is desired, the medicine 
should be given under such circumstances. Thus, a purgative acts soonest 
wheQ given before breakfast* Substances which are irritating to the stomach 
fiboidd always be administered not only proi>erly diluted, but also when the 
Tiscus is filled by a mass of food, which may serve still further to lessen their 
eonoentmtion. Hence, such remedies as iodine and arsenic are preferably 
exhibited after me»ds. Again, some drugs, such as iron, are best dissolved 
by the acid gtistric juice, and it is a matter of some importance to place them 
in the stomach ailer eating, when the proc^css of digestion is most vigorous. 

Mental Emotion. — Space is wanting to discuss at any length the influence 
of the imagination up<m the action of remedies ; and the reader must be 
referred to the delightiiil hook of Dr, Tukc for illustration. Suffice it to 
slate that a pi^ksitive announcement that a remedy will have a certain effect 
hon ciften a most remarkable influence in producing that effect, especially on 
pcrwns of nervous organization and of not too great culture to have faith. 
I have given a hypodermic injection of a grain of morphia to a man, inducing 
a degree of hypnotism, and the next day, doubling the si^e of the injectioD 
ili withdrawing aU morphia, have caused a much more intetise effect 



It is ervident that every treatise upon pharmacology must have some plan 
in acoordance with which the various subsUmoes treated of arc arranged.* 

At preseat^ all that, in my opinion, can be reasonably demanded of any 
^alem ia that it be a convenient row of pegs upon which to hang otir ideas 
nnd facta, so that they may be ea^ly retained, and be easily accessible when 



■ For A diBeuflsioQ of eWslilcatiui], see the firit edition of this work. 



24 INTRODUCTION. 

wanted. Under these circiimstanoes I venture to offer, as the basis of the 
present treatise, without further comment, the following chnioo-physiological 
classification, founded upon, but very different from, that of Prof. Qeoige B. 
Wood. 

CLASSIFICATION. 

PART I.— DRUGS. 

1. SUBSTANOIS WHICH AOT ON THE SOLIDS AND FLUIDS OY THS BODT. 

a. General Remedies. 
Class I. — Astringents. 
« II.— Tonics. 

" HL — Cardiac Stimulants. 
" IV. — Cardiac Sedatives. 
" V. — ^Antispasmodics. 

" VI. — ^Analgesics. 
" VII.— Mydriatics. 
« Vin.— Anaesthetics. 
" IX. — Excito-motors. 
" X. — ^Depresso-motors. 

" XI. — ^Alteratives. 

b. Local Remediu. 
Class L — ^Emetics. 

" n.— Cathartics. 

** HL— Diuretics. 

« IV.— Diaphoretics. 

** V. — Expectorante. 

" VI. — ^EmmenagogutiS. 

« VIL— Oxytocics. 

*' VTIL — Sialagogues. 

" IX.— Errhines. 

" X. — Epispastics. 

« XL— Rubefaciente. 

" XIL— Escharotics. 

" XIII.— Demulcents. 

« XIV.— EmoUients. 

" XV.— Diluents. 

" XVI.— Protectives. 

2. Substances which act externally to the Body. 

Class I. — Antacids. 
" n. — Anthelmintics. 

" m.— Digestants. 

" IV.— Absorbents. 
" V. — ^Dismfectants. 

PART II.— REMBDIBS WHICH ARE NOT DRUGS 



DRUGS. 



'DIVISION L-SYSTEMIO REMEDIES. 

Subdivision I.— General Remedies. 
CLASS L-ASTRINGENTS. 

Abtrinoents aro tbo^e drugs whicli catiBe ooQtractioa of living tifisuea. 
Tbat thej do not act, as baa been supposed, either bj coagulutin^ aJbumen or 
bj calling into actioQ the nms<;ular function^ is demonstrated by tbe transit 
tonocss of their effects, and by the fact that they influenoe tisaues oontaiDiDg 
BO muicolar fibre. Every livin^^ sofl tissue appears to poasess a normal degree 
of coodeDsatioD, which may be departed fi%>m on either hand ; when this hap- 
peoSi the part is tsaid to be relaxed In tbe one casej in the other to have itfl 

Dicitj Increased, or to be aetringcd. The action of astringents is alwaya 
thc*il OfUi — i.d., produced not through the intervention of the nervous sys- 
tem, but by direct contact with the part affected. A pure astringent should be 
capable of doing nothing beyond Lududng contraction ; but in reality there is 
acaroely such a drag. All astringents are, when applied too freely, irritants; 
indeed r it \& doubtful whether their therapeutical property of astringency is 
oat due to the exercise of a mild form of irritation* 

Our knowledge of the actbn of astringents upon blood-vessels is still very 
Bmited, The only published experiments are those of M. Rosenstein (RoU' 
tfiMeh*t PliannayAog. Untermchutigm^ Bd. ii. p. 80). He placed solutions 
of nitrate of silver, of acetate of lead, of sesquiobloride of iron, and of tan- 
nic, gallic, and pyro-gallio acids upon the exposed mesenteric vessels of a 
caramcd frog. The first three solutions contracted arterioles, venules, and 
enptlUncii, nitrate of silver being much the most powerful and the iron salt 
the weakest ; the effect on the capillaries was the most permanent. The 
adds instead of contracting enlarged the vessels* This dilatation was not 
reflex, us it occurred after destructiun of all of the nerre-centres. It was 
probably due to the irritant action of the acid. 

The indications for the use of an astringent are very evident. 

In the firi^t rank among such indications is the exhtence of relaxation, 
al relaxation is almost always the result of previous over-excitement. 
Thus, a throat is relaxed after over-use, or after inflammation. 

Astringents are more efficient as local than as general remedies, but in 

of inflammfltion care must be taken to use them in such way that they 

alul] not net as Irritants. Applied too soon or too vigorously, they may do 

hanu. These remarks are scarcely applicable to some of the mineral astriu 

25 




26 SYSTEMIC REMEDIES, 

gents, such as lead and nitrate of silver, which really appear to have sedative 
properties, and may with care be used advantageously in all stages of inflam- 
mation, whenever there is distention and relaxation of the blood-vessels, 
although the general action of the part be above par. 

Closely allied to relaxation is over -secretion^ and astringents arc constantly 
u/»ed to check morbid discharges. Indeed, these discharges are often simply 
the result of relaxation. Thus, Asp has experimentally proven that division 
of the intestinal nerves and consequent paralysis and relaxation of the vessels 
are followed by free watery secretion. In such cases the indication for astrin- 
gents is very plain. But when a morbid discharge really represents a high 
d(^ee of inflammation, the same care must be practiced in the use of astrin- 
gents as in treating other local inflammations. Especially is this true since 
free secretion is often nature's method of relieving local inflammation. Thus, 
when abnormal alvine discharges are dependent upon intestinal relaxation, the 
astringents are most valuable, but when they are dependent upon enteritis or 
colitis, astringents do harm. 

If the morbid discharge by its profuseness endanger life, as in serous diar- 
rhoea, astringents are urgently demanded. Very rarely, if ever, are these 
discharges other than paralytic in their origin ; even, however, if they be due 
to over-action, an astringent may be necessary to check their excessiveness. 

Another indication for the use of astringents is to check hemorrhage^ and 
the same general reasoning is applicable to this as to the other indications. 
Hemorrhage dependent upon over-action demands other treatment than by 
astringents. Sometimes in these cases it is necessary, however, to check the 
hemorrhage at all hazards, and then astringents may be used in conjimction 
with other measures, although they may be to some extent contra-indicated. 
Various astringents are employed locally to check hemorrhage due to trau- 
matic or other ruptures of vessels. In such cases the astringents are employed 
as styptics J and do not act so much by their astringency as by coagulating the 
albumen of the blood, and thus forming a clot and mechanically arresting 
the flow. 

Under certain circumstances there seems to be a general relaxation or loss 
of tone throughout the whole system, which may be best met by a oonsentar 
neous use of tonics and astringents. ^ 

VEGETABLE ASTRINGENTS. 

The active principle of the vegetable astringents is tannic acid, and, as it 
is almost their sole therapeutic principle and represents them very closely, it 
seems proper flrst to consider it, and afterwards to point out any especial 
therapeutic virtues the crude drugs of the class may possess. 

AOIDUM TANiriOUM-TAinsriO AOID. U.S. 
There are two kinds of tannic acid, the ffallo- and the kino-fannic ; of these 
the former yields, upon exposure to the air in a moist state, gaUtc acid^ the 



VEGETABLE ASTRINGENTS, 



CT 



a ^fJaiinous^ in^rt subi^tance* They arc further Jlstin^iLshed hy the 
Dior of tJbe precipitates which they yield witli tlic pc^rsults of mm ; gullf>- 
tannic acid producing a blae-blaek, kluotannie a grt^in-black color. 

The officinal tannic acid — the g?illo*tiintiie acid — Is obtained by trcatinfif 
powdered galls with woished ether, which on statiding separates into two stnita, 
the upp^ of which is ethereal, and contains chiefly the color ing-matter uiid 
€Hher imparities. The lower watery stratum contains the tanuie acid, which 
is reooverod by evaporation. 

Cotiimercial totinio acid is a light, feathery, noft-eryatalluie powder, of a 
yellow fsh*whi to color, a fiiint odor, and an astringent, somewhat bitter taste. 
WTjen absolutely pure, it is colorless and free feoui odor or taste other thiin 
that of agttrlugency. It^ reactlou is Btron;xly acid, and it unites fredy with 
oth urj;anio and inorganic buses. It is very freely soluble in water, even 
tore 84* uj glycerinCj somewhat so in dilate alcohol, scarcely at all in absolute 
alc<jhol, and not at all in ether free from water. By a heat of from 180^ C. 
215° C* it is changed into pi/ro-gaUic acid^ which crystallizes in white, 
ining pktaa, of a bitter ta^te and neutral reaction. With salts of the alka- 
loids it produces a wliitiah precipitate, very soluble in acetic acid ; with per* 
fidtfl of iron, a black (bluish or greenish) prccipitat<? ; with lime-water, a 
|»ieeipiLat€ which is at first whitish, then gray, dingy greenish, and finally 
owuitih ; with gelatine or albumen, a whitish coa^lum. All of these sco- 
adxiry products are tannates. Tannic acid also dissolves in concentrat-ed 
BuJphurie acid, with the production of a black color. By prolonged exposure 
in solutioQ to the air, or by the action of dilute sulphuric acid, it is converttsd 
into gallic acid. 

Phtsiologicai* Action. — When applied locally to a part tannic acid 
is a very powerful astringent^ causing contraction, and in the case of a 
Bmoous membrane, great drynej^a. Sometimes, when it is used very freely, 
tti! irritiint inBucnce see ma to (>vercome its astringent action, and I hav« 
seen diarrhoea result from its administration. Several experimenters (Ro- 
seost^nn, Untersuck. Fhirmakolog, In»titni Wurzbur^^ 1875 ; Fikentscher, 
luiiay, DUserf.^ Erlangen, 1877) have denied that it caui^cs contraction of 
the blood- vc*s.-«eU, because when they applied it to the exposed mesentery 
of A •* Cobnheim Irog," stasis of the blood with dilatation of the vessels, 
pot preced<;d by contraction, occurred. Daniels, however (^Inaug, J)isseH,^ 
Ronn, 18»>4), uffing rabbits, obtained different resuhs, and Lewin has 
bhown that the method of experimentation is faulty. Clinical experience 
bundantly proves that tannic acid applied to relaxed raucous membranes 
ETeetj; their whole substance. 

Tannic acid coagulates albumen with mj much avidity that it has been 
pupposed incapable of absorption, but the very elaborate investigation of 
Dr* L<rwiu cast much doubt upon the older views on thia subject ( Vifchow** 
Irchiv, Ixxxi. 74j. Thrown nipid!}^ into the blood it undoubtedly causes 
nl lUnjtuhohih ; but Lewin asserts that when it is injected slowly and in 



28 SYSTEMIC REMEDIES. 

moderate quantities the resulting tannate of albumen is held in solution by 
the alkaline carbonates of the blood. He has also discovered that whilst 
tannin, in five per cent, solution, precipitates peptones out of watery solu- 
tion, it is powerless in the presence of muriatic acid. Assuming the correct- 
ness of the investigation of Dr. Lewin, it is plain that tannic acid, when put 
in the stomach in small doses, muAt to some extent be absorbed unchanged. 
Dr. Lewin also asserts that it is, at least in part, eliminated unaltered, as 
he has frequently recovered it from the urine. At the same time it seems 
very probable that most of the tannic acid is converted into gallic acid, 
either in the stomach before absorption, or subsequently in the system, 
since in the viscera of a rabbit poboned with it, Schroff (/>te Pflantenstoffe^ 
Drs. Husemann, p. 1005) found only gallic acid ; and according to Clams 
(^Ibid.) the greater part of ingested tannic acid can be recovered from the 
stools as tannate of albumen or as gallic acid. Wohler and Frerichs have 
also found gallic acid with pyro-gallic acid in the urine afler the exhibition 
of tannic acid. Whether it acts chiefly as tannic or as gallic acid, it seems 
after absorption to exert marked astringent powers. Lewin has shown that 
in frogs poboned with it the muscles are shortened and narrowed, and when 
loaded stretch less and recover their original length more nearly than do 
normal muscles. Kiichenmeister {Arch. Physiolog. Heilk., 1851, 493) and 
Hennig (Arch. Pharmak.j Febr. 1853) found that in poisoned cats the 
spleen is notably diminished in size and increased in firmness ; and Lewin 
has found in rabbits that it causes primary arrest of the urinary secretion, 
followed by a marked increase of the flow. 

Therapeutics. — As tannic acid undergoes in the system conversion 
into gallic acid, the latter is to be preferred to it when the part to be acted 
on can only be reached through the circulation. As a local application, 
tannic acid is much more powerful than gallic acid. Locally applied, it 
may be used to overcome relaxation^ as in »pongy gumSy mercurial sore 
mouth, hemorrhoids^ chronic sore throat. To clieck hemorrhage it may be 
used whenever the source of the flow can be reached directly, as in epis- 
taxis^ hmmaiemetisy hemorrhage from, the bowels, etc. To arrest excessive 
secretion it may be employed locally in leucorrhaea, diarrhoea, old abscesses^ 
chronic ulcers, excessive perspiration, osmidrosis, and various diseases of the 
skin. It is also often very useful for the purpose of hardening parts exposed 
to friction, as in cases of sore nipples and tender feet. 

ToxiGOLOQY. — Tannic acid can scarcely be called poisonous; although 
Rollett reports the case of a young girl in whom a very large quantity of it 
induced severe gastric and abdominal pains, with obstinate vomiting and con- 
stipation, fever and general malaise. Both Schroff and Judell assert that 
eighty grains of it produce no symptoms of importance in the rabbit. 

As an antidote it is useful in tartar emetic poisoning, forming an insoluble 
tannate of antimony. It is also the best chemical antidote for tho poisonous 
alkaloids ; but, as the compounds it makes with them are slowly dissolved by 



VEQETABLB ASTRINGENTS, 



29 



the fluids of the alimentary canul^ it mtiat alwujs be followed by emotica ajid 
ealliiirtics. 

Administration.^ — When given to act on tlic stotnach, na in hacmatcnw^ 
sia, tannic acid should be in powder (ten to twenty gniins). Wlien the 
bowel is to be influenced, as in diiunliaoai the drug sliould be administered 
in pill (three to five grains), m that, if possible^ It may piias the pylorus u«- 
dissulved^ For lucal use a Mjliition in glycerin may be eujpluycd, or the 
officinal Ointment {UnffuentHm Audi Tttnmci^ U. S*, 1 to 9), or the troche 
( TrochUci Acidi Tannici^ U. S., 1 grain each). 

AOroiTM GALLIOUM-GALLIO AOID. U.S. 

Gallic acid is a white, powdery substance, in fine aci«ndar pritttos, soluble 
in one hundred piirtj of cold water, in three parts of boiling water, and freely 
soluble in alcohol and etlier. IXb taste is ucidulouH and itstringeiit. 

According to the officinal method, gallic acid In prq>arod by the exposure 
of moistened powdered nut-gall^ in a warm place for n month. A .H|»ccies of 
fcrmenttition, with the development of a peculiar fungiw, is jimid to occui, 
daring which oxygen is absorbed, carbonic acid evolved, and ghicose and 
gallic acid are produced. M. Saoc (^Chemical NewSy July 24, 1871} has 
recently denied this, aflBrming that the change is simply one of hydration, 
tjiDriic acid being an anhydride of gallic acid. Tannic acid also maj bo 
rapidly converted into gallic acid by the action of dilute sulphuric acid. 

Gallic acid produces with salts of the alkaloids whitiiih precipitates, with 
pGTsaltB of iron a bluish precipitate, with lime-water a whitish precipitat*'', 
changing to blue, and then to violet or purplish, — all of these precipitates 
doing gallatea. It does not coaffulnte gelatine or album en ^ and dissolves in 
concentrated sulphuric acid, with production of a deep-red color. It has the 
power of n;duciDg silver from its solution slowly in the cold, instanUmeously 
if wanned. As an astringent it is similar to, but much less powerful than, 
lAnnic acid. It escapes from the body through the kidneys, 

TnEaAPEUTlc Action. — Gallic acid is not nearly so efficient as tautiic 
when applied locally, but, because it docs not coagulate albumen, should 
always be preferred when the part is to be reached through the medium of 
the circulation. It is useful as an astringent in hminoptt/nU^ hiFjnnturin^ 
eoUiquatit€ wweatM^ etc. It has been recoumiendcd in bronchtrrrhma and in 
tht? profuije expectoraticm ot chronic phthish. In my hands, however, it hai 
Dplotely fidled in the latter affections. In certain forms of Bright' a dus- 
e, when there was an abnonually lai^e secretion of highly albuminous 
vrtike, I have found it to lessen very materially the excretion of albumen. 

Administration. — Gallic acid may be given in powder, or sometimes in 
pm funti. Tha dose of it ts from ten to thirty grains, repeated as oilen as 
piy U.' necessary* An oifUment (^Unguentum Acuii GfiUidy 1 to 9 J is 



30 SYSTEMIC REMEDIES. 

0ALLA-0ALL8. U.S. 

Grails are v^ctable excrescences, which are produced by the deposition of 
the ova of insects. They occur on almost all kinds of plants, even on fungi, 
but the officinal gall is developed on the Quercus infectoria by the act of the 
fly Cynxps {Diplolepis) tinctoria. There are in commerce two varieties of 
galls, derived chiefly from the Levant. The hlue or green galls are globular, 
solid bodies, from the size of a pea to that of a hickory-nut, externally smooth, 
or more commonly marked with large tubercles. They are the young galls 
which have been gathered before the ova of the fly have hatched, or before 
the caterpillar has eaten out the interior of its birthplace. The white gaBs 
are large, light, hollow bodies, with a hole, through which the Cynips has 
escaped after having fed upon the interior during its whole larval life. They 
contain but little tannic acid, and are of comparatively little value. 

Therapeutics. — The sole value of galls is as the source of tannic acid. 
As galls, they should not be used in medicine ; but the United States Phar- 
macopoeia recognizes a tinctfire ( Tinctura GcUlx, 1 to 5), and an ointment 
{Unguentum GaUx, 1 to 9). 

OATEOHU-OATEOHU. U.S. 

An extract of the wood of an East Indian tree, — ^the Acacia Catechu. It 
occurs in masses of various shapes, or in small fragments, of a dull reddish- 
brown color, and having a bitterish, astringent, and, after a time, sweetish 
taste. It contains kino-tannic and catechuic acid. Pale catechu^ or gnmlnr^ 
which is officinal in the British but not in the United States Pharmacopoeia, 
occurs in small cubes, about an inch in diameter, lighter than water, pale- 
yellowish within, deep-yellowish or reddish-brown externally. Catechu is a 
powerful astringent, which may be used externally, or for diarrhoea, in the 
dose of twenty to thirty grains. 

Tlie U. S. Pharmacopoeia recognizes a compound tincture ( Tinctura 
Catechu Compotita, Catechu 12, Cinnamon 8, to 100), of which thedow 
is one to three fluidrachms, and a troche (^Trochisci Catechu^ 1 grain 
each). 

KiHO-inro. U.S. 

The inspissated juice of Pterocarpus marsupium and of other plants. It 
occurs in small, int^ular, angular, shining, reddish, brittle fragments, of a 
bittorish, highly astringent, and, after a time, sweetish taste. There are four 
viiriotii^ — the EaM, India, West India, Botany Bay, and African. Of these, 
the first is common, the second rare, and the last two are never seen in our 
nmrkot. Kino contains kino-tannic acid, and in its therapeutic powers is 
almost identical with catechu. The dose is twenty to thirty grains. A 
tincture (^Tinctura Kino, 1 to 10) is offieinal. Dose, one fluidrachm. 



VEGETABLE ASrmi\'OENTS. 



m 



HJUTATOXYLON-HJEMATOXYLON. U,S. 
The heart-wood of Hsematoxylot] Campechiairaiii, or logwood-tice, a native 
of C<*ntriiJ America, A dense, liQuvy wood, of a deep reddisli-brown color, 
ot>iitAiniDg^ Viesides kiDo*tannic acid, a crystalline principle, I/stmatm or 
Uxmafoxyiin^ which when pure is yellow, but readily yields retl or purjde 
dyes, Ilaeniatoxylon is a mild efficient astring-ent^ valued on account of ilA 
Bweetish taate. It is readily taken by children, hut is sometimes objected 

^ to on account of the staining of the diapers by tlie blood-red stools which it 
produces. Tlie following furjjiula offers an efficient and elegant reiuedy for 

i iiiarrhiriu of relaxation ; the proportions may be varied to suit individual 
cafies: B Ext. haematoxyli^ 5»i'i Acid, sulph. aromat,, fjiiii Tinct, opii 
cainph., fji^i Syrupi sdngiberia, q. s. ad f3vi. M,^ — Dose, a tahlogpoonful, 
pft)|M£fly diluted. The extract (Extnwtum Hmmatox^li) is officinal, dose, 
ten to thirty grains. 

rEAMERIA-KHATAinr* tJ.S. 
The root of Krameria tnandra, a native shrub of Pom. This woody root, 
a0 it occurs in our markets, varies from one-iburth inch to one inch in diam- 
eter, and from half a foot to three feet in length. The readily fM7>anible bark 
19 of a doep-rcddish color. The internal woody portion is of a lighter hue, 
although decidedly reddish. Tlie bark contains a much larger perci^ntage of 
ihe active principle, kinr^tannic acid, than the wood. Bhatany is a powerful 
■Olringent, nmilar in virtue to kino and catechu, but is never admin istered in 
I pfiwdcr. The United States Phannacopoeia recognizes an extract f Extractvm 
ICmmaim), dose, grs. v-x ; a (inc'ture ( Thictura Krameria^ 1 gr. to 1 
CLc ; and a Jlaid extract (^Exlraclum Kramerlm Flaidum)^ dose, twenty 



QuEECua ALBA, U. 8., and Qckrcus tinctoria are the inner barks of 
|Im» treed whose names they bear, — the white and the black oak respectively. 
The latter is a rough, yellowbh-brown bark, which is used in dyeing, under 
tbe n&me of quercitron. On acconnt of its imparting readily its color, it is 
nreljt if ever, employed in medicine. White-oak bark also stain.^, but not 
nearly m deeply as does black-oak bark, and, containing largely of gallo- 
taniiio add, is used aa a means of making cheap astringent infusions for 
botha, vagintd washes, etc., also in powder for poultices. 

Roi^a Qaluoa, U.S., Is the dried petals of the half opened flowers of 
tW hundred" leaved rose. They are of a deep-red color, of a pleasant scarcely 
astringent taste, and contain a small percentage of gallo-tannic acid, red color- 
mg-cuattcr, and a trace of volatile oil. Sulphuric acid ehan^j^es their infusions 
or tinctures to a bright-red color. Tliey are almost destitute of therapeutic 
TtrttMa, but their preparations, except the fluid extract, are used as elegant 
Ytliicks. The D. S. Pharmacopceia recognizes a Jluid extract (^Extractum 



32 SYSTEMIC REMEDIES. 

RosBi Flnidum), a honey (Mel Rosx, 1 to 12.6), a confection (Con/ectw 
RoBat)^ and a syrup (Syrupus Rosa^ fluid extract, 1 to 10). 

Rosa Centifolia, IT. S., or Pale Rose, contains no tannic acid, but a 
Tolatile oil, and is used simply on account of its pleasant odor ; out of it are 
prepared rose tocUer (Aqua Rosse, U. S.) and the yery elegant, bland emol- 
lient ointment, cold cream ( Unyttentum Aqum Rosee, U. S.). 

The rhizome of Geranium maculatum Linn., an herbal plant, which grows 
abundantly in open woods in the middle United States, and may be recognized 
by its light-purplish petals, slender pointed sepals, and five-parted leaves, is 
officinal under the name of Geranium, It occurs in pieces from one to three 
inches long, one^uartcr to one-half inch in thickness, wrinkled, contorted, 
tuberculated, often fibrillated, brownish externally, grayish internally. The 
taste is a nearly pure astringent one. It contains largely of gallic and tannic 
acids, and is a somewhat popular astringent, although rarely used by prao- 
titioners. It may be boiled in milk for children needing a mild astringent. 
Dose, grs. xx-xxx. 

Rhus Glabra. U. S. — The fruit or berries of the sumach contain a very 
large percentage of tannic and malic acids. They are not used internally, 
but their fluid extract (Extractum Rhois Glahrx Fluidum, U. S.) aflbrds 
a very superior gargle in anginose affections. It may be diluted with from 
two to four parts of water, and chlorate of potash added to saturation. 

MINERAL ASTRINGENTS. 

ALUMEN-ALUM. U.S. 
Formerly the double salt of alumina and potash constituted the ordinary 
alum as well as the officinal drug. Ammonia as a seoondaiy product in the 
manufacture of coal gas has become so cheap, however, that it is now used 
very largely instead of potash, although the potash alum is alone recognised 
in our officinal standard. The two salts are identical in physical and medical 
qualities, but when the ammonia alum is triturated with lime the odor of 
ammonia is at once evolved. Alum occurs in octahedral colorless crystals, 
which are often aggregated into large masses. Its taste is astringent, acid- 
ulous, and sweetish. It is soluble in about fifteen times its weight of cold 
and in about three-fourths its weight of boiling water. It is slightly efflo- 
rescent, and when heated a little beyond 112® Fahr. parts with its water of 
crystallization, and is converted into a white powder, which is officinal as 
Alumen Exstccatum, or Dried Alum, The alkalies and their carbonates, 
^ lime, magnesia and its carbonate, tartrate of potadsium, and acetate of lead 
are incompatible with alum. 

Physiological Action. — As alum, even m very dilute solutions, co- 
agulates albumen, it would appear as though it could not be absorbed. Since, 
however, both I>r8. G^eo. B. Wood and A. Stills assert, on what authority I 



MINERAL ASTRINGENTS, 33 

do not know, that alumina can be detected in the urine of persons taking 
it, it or its derivatiyes must find a way into the blood. What changes it 
undergoes in the alimentary canal, or in what form it enters the blood, is not 
known. 

Applied to a tissue, it acts as a very powerful astringent and irritant. Or- 
fik found that in dogs one or two ounces of it simply induce violent vomiting 
and purging, whilst in Mitscherlich's experiments two drachms of it produced 
in rabbits fatal gastritis, evidently on account of their inability to vomit. 

In man, large doses mtemally produce symptoms of violent gastric irritation. 
One ounce and five drachms of the burnt alum caused death in a man in eight 
hours. (^L' Union Midicale^ No. 64, 1873.) 

Therapeutics. — Alum may be used locally to serve all the purposes of a 
very active astringent. It has been employed very frequently with success 
as a styptic to arrest hemorrhage ; and, applied by the atomization of its satu- 
rated solution, I have found it of signal service in hsemoptysis and in hron^ 
chorrhota. It also frequently enters into the composition of gargles for sore 
throat ; but this practice is to be reprobated, since alum acts very destruc- 
tively on the teeth. In coUlquative sweats^ sponging at bedtime with alum- 
water, or, still better, the taking of an alum-water bath, will often materially 
aid in restoring the lost tone to the skin. In chronic ulcers with exuberant 
spongy granulations, and in certain conditions of conjunctivitis ^ alum curd is 
often applied with benefit. When it is desired to exert an astringent action 
upon the internal organs, alum is not nearly so useful a^ other members of 
the class. 

Owing to its irritant properties, alum when given in sufficient amount acts 
as a mechanical emetic, and may be used as an adjuvant to the sulphate of 
rinc or of copper in narcotic poisoning. Originally introduced by Dr. C. D. 
Meigs, it is believed to be of service in membranous croup not only by its 
emetic action, but also by modifying the mucous membranes with which it 
comes in contact in its passage down and up. 

So long ago as the last century. Dr. Grashius, of Holland, commended alum 
in cf^ica pictonum, and although for a long time its value was not recognized, 
abundant confirmative testimony has recently been brought forward. Since 
it is a soluble sulphate, it is of course a chemical antidote to any lead salt 
which may be in the alimentary canal. It is, however, of service when there 
is no lead in the primas vise, and must act in some way as yet unknown. It 
has, indeed, been used with asserted success in other neuroses of the ali 
mentary canal, — in gastralgia and in intestinal neuralgia. Dr. Aldredge 
even commends it in habitiud constipation. Burnt alum is used as a very 
mild escharotic for exuberant granulations in ulcers. 

Administration. — As an astringent, the dose of alum is from ten to 
twenty grains ; as an emetic, a teaspoon ful of the powder for a child, a tablc- 
scpoonful for an adult, in syrup, repeated in fifteen minutes ; in colica pictonum^ 
twenty to forty grains every three or four hours, combined with morphia. 

3 



34 SYSTEMIC REMEDIES. 

Alum curd may be made by dissolving two drachms in a pint of milk, and 
straining, or by rubbing the alum with white of egg. 

Aluminii Sulphas — Sulphate op Aluminium (A1,0,3S0,+ 18H0 
— 3S0^,A1, + 18H0), U.S. — This salt, which occurs as a white powder, or 
in lamellated cakes, or in a crystalline cake, is used externally as a powerftd 
astringent and antiseptic. Its solution has also been employed by injection 
for the preservation of cadavers. 

PLUMBUM-LEAD. (Pb.) U.S. 

When a soluble salt of lead is applied to a part in not too concentrated 
solution, it acts as an astringent and sedative. Owing to the*contraction of 
the vessels which is induced, the tissue becomes blanched, and any inflam- 
matory action which may be present is remarkably affected. When in con- 
centrated solution, the mildest preparations of lead are capable of acting aa 
irritants, increasing or even originating inflammation. When the salts of 
lead are taken internally in therapeutic doses, no decided symptoms are gen- 
erally induced, except a diminution of the secretions, e^ecially of those of 
the alimentary canal. Sometimes, when full therapeutic doses are exhibited, 
a slight lowering of the frequency and force of the pulse (see Laidlaw's Obser- 
vations, quoted by Stills, T/ierapeuticSj second edition, p. 177, vol. i.) is said 
to result, but I have never witnessed this. The insoluble preparations of lead 
act similarly but less decidedly than the soluble ; yet it is doubtful whether 
they can under any circumstances become irritant. 

Toxicology. — The salt of lead with which intentional or accidental acute 
poisoning is most frequently induced is the acetate."*" The first result of a 
toxic dose of this is in most cases a persistent sweet, somewhat metallic taste ; 
this in a few minutes is followed by vomiting, which may or may not be pre 
ceded by nausea. The matters vomited are often milky-white, from the 
presence of chloride of lead. A severe burning persistent pain in the abdo- 
men now comes on, and is accompanied with a craving for drink. There may 
be obstinate constipation, or diarrhoea may ensue ; in either case the stools 
are generally black from the sulphuret of lead. In certain cases a state of col- 
lapse is developed ; the pulse falls to forty or fifty per minute, the voice is lost, 
the face is deadly pale, the lips are livid, and syncope seems imminent. In 
other instances the nervous symptoms may predominate, or they may accom- 
pany those of disordered circulation : cramps in the calves of the legs, severe 
neuralgic pains in the extremities, paralysis and ana&sthesia, vertigo, stupor, 
may any or all of them be present. In fatal cases, coma, with or without 
convulsions, finally develops. A distinctive mark of lead-poisoning, which 
sometimes is present very early, is the blue line upon the gums. After 
death inflammation of the alimentary mucous membrane is sometimes, but 
not always, found. 

•According to Husemann {ffnndhiteh der Toxicoloyfe), the Poadre de Succession, so 
famous during the reign of Louis XIV., was coinpo:$cd chiefly of acetat« of lead. 



MINBUAL ASTJi/XGENTS, 



35 



t fatal dose of sugar of lead is between um* and twu ounces ; tlie stib- 
I of lead b even more poisonous^ and the aknit^ acts as a violent irri- 
tAOf-, The carljonate appears to be incnpablo of cuusin«^ acute p)oi»nning. 

The treatment of aatte Ifud-poiMontn^ consists iti the evueuution nf tlie 
«itotDach, if neceasaiy, the exhibition of the snlphat« of sodium or of ftiag- 
tiesium, and the meeting of th*- iudicsitions as they arise. The Epsom and 
(Itauber's salt^ act ru* chemical antidotes, by precipitating the insoluble sul- 
phate of leaii, and also, if in excc^, empty the bowel of the compound 
fanned. To alluy the gas trn- intestinal ii'ritation^ albuminous drinks should 
be given and npium freely exhibited. 

Of all fonns of poisoning, chronic lead-poisoning is the most common. It 
Is almost always accidental, mid occurs most fretjucntly among those whose 
occupation exposes Ihem to daily contact with some c<>mponud of the m^^tal, 
fuiinufaeturcn of white lead» painters, glaziers, and y^imilar artisana furninbing 
the greater niimboT of victims. It is seen, however, in pei'sons of all curidi 
tlons of life, for although neither fmnl nor drink is ofUm purposely adulterated 
with it, yet it is frcfjuently introduced into the f^ystem accidcntidly along with 
tlio^ neee^itics. Lead pipes are habit uallj' uftcd for the conveyance of water, 
and when that water contains salts of lime, even in minute proportion^ no evil 
reealts, because through the dccomjiosition which endues insoluble coatings 
are deposited on the inside of the pi^^cs.* When the water is pure, no such 
reactions occurring, the lead is slowly di.ssolved in the form of a carborjat<j, 
and poisoning may result. Poisoning has also fref|nently resulted from the 
ctae of eosraetics and hair-dyes, from cooking bread with painted wood (Le 
Pr^r^ Metlj 1S77, 349), from imperfectly burnt pottery (Schmitlt'n Jahr- 
bUeher, Bd. cxiiv. p. 279; Fhiia. Med. lunes, vol. iv. pp. 241, 483), and 
in other ourioas ways, 

Tlie most ordinary form of chronic lead-poisoning is that in which colic is 
Iho fimit docidcd sympUim. After some days of malaise and wretchedness, 
0r sometimes very suddenly, the victim is taken with alKlominal colicky 
paoofl, which increase in intensity until they become very severe. They are 
COBSlBDt^ with (jpccaaional exacerbations, are sometimes dull, sometimes sharp, 
arQ gimcnlly dcscrilnHl as twisiting, and seem to centre around the umbilicus. 
Thifftf is very often repeated relching and vomitings The walls of the abdo* 
men are retructed, rigid, knotted j the bowels are obstin«tely costive ; the 
ton§n)^ is contracted and whitish ; the appetite gone; and the tliirst some- 
liiDcs cxceffiivc. Neuralgic pains in the thorax and in the oxtremiMcs are 
Iff fVequout occurrence^ In some cases the conjunctiva is distinctly ictcrode, 

T iiiptoms umiiJly abate after a time, but are very apt to recur with 

itii -I' verity, especially simong those who are habitUiiUy cxp*)8«.*d to the 

*3kU^. In one of these rei)eated attacks severe cerebral synjpt/ims nuiy come 



* Tot ftji elaboml« Article on tho ohomiGat retatioo of water to kn,ilf a«e St.'hmidt*9 J*thr* 
McA«r« Bi. cxUr. p. 270. 



36 SYSTEMIC REMEDIES. 

on suddenly, or aft^r some days of lieadache ; delirium, either mild or mani- 
acal, or stupor, is in some such cases the chief manifestation, but epileptiform 
convulsions are more common. These convulsions are oflen very severe, and 
end in coma, in which death may take place. The more ordinary nervous 
symptoms of lead-poisoning may be developed after the first attack of colic, 
or they may occur without being preceded by any marked abdominal dis- 
turbance. The most common of all of them is the local paralysis known as 
*^ drop wrist." This is a complete paralysis of the extensor muscles of the 
fore-arm, which allows the hand to drop forward. It is often associated with 
complete or partial ansBsthesia of the part aflfectcd, or, in some cases, of the 
still unparalyzed shoulders. Strabismus is sometimes present in lead-palsy, 
due to the paralysis of the external recti. 

Among the rarer forms of nervous disturbance induced by lead may be 
mentioned — amaurosis from atrophy of the optic nerve, the atrophy being 
probably the result of an optic neuritis (see Phila, Med, Times, iv. 241 ) — 
hemiplegia and hemiansesthesia — and violent and intractable chorea.* I 
have seen one case in which the symptoms exactly resembled those of an 
acute poliomyeliUs, with rapid wasting of all the muscles of the arms and 
shoulders, the legs also being affected. Even the bladder and rectum 
were paralyzed, but the patient, long at the point of death, finally recovered. 

In some cases of lead-poisoning the kidneys are fatally involved, although 
temporary albuminuria may occur without serious implication of the kidneys. 
On the other hand, fatal nephritis may exist when there is no albumen in 
the urine. (Dr. Lanceraux, Trans, Internat, Med, Congress, 1881, ii. 191.) 
A persistent low specific gravity of the urine in a saturnine patient is of 
very serious import. Geppert {Ztschr, Klin, Med., v. p. 161) confirms the 
observation, previously made by Olivier, that in temporary plumbic albumi- 
nuria many isolated kidney epithelial cells may oft^n bo found in the urinary 
sediment, and it is evident that a persistence of this condition must end in 
chronic renal disease. Aft«r death, which may be induced by uraemia, the 
kidneys are found contracted, granular, with excessive development of the 
fibrous tissue (followed by contraction) and great thickening of the walls 
of the blood-vessels : these changes are identical with those of contracted 
kidney produced by gouty and other irritant poisons. According to Lan- 
c^raux, the resemblance to gout in plumbism is sometimes complete, the 
joints as well as the kidneys, during life and aft<jr death, presenting appear- 
ancea precisely like those of gout; but it may be doubted whether in such 
instances the plumbism has not been simply a c(»mplication of gout. 

According to Dr. E. Levy {Schmidt's Jahrhiicher, Bd. clii. p. 250), acute 
asthma is rarely produced by the inhalation of the dust of white leail, and 

• For discufflion of details of these peculiar conditions, ace Beau, Arch, G/u., 1S4S; 
Manouvricz, Arch, ih Phytiolfuj, Normal et Patholog., 1870, 411; 1876, p. 702; A. De 
Cours, I)e VHcmianirHthetia taturniney Paris, 1875; Prou<«t, Proyrh Med., 1879, vii, 5J0; 
Debove, Ibid., 99, 117. 



MINERAL ASTRrNOENTS. 



37 



elirouic saturnioe astbraa is sometiraca seen in feeble, narrow-obested people. 
The epileptiform convulsions produced by lead ure in some cases secondary to 
chrouic nepbritls, but in other instances are due directly to the action of the 
lead (see paper of Dr. Rosenatein, Virchow's Archiufiir pathoh^. Anatomies 
BJ- rxxix., 18G7, p. 4). Upon pregnant women the influence of the poison 
IB Tery deleterious, and Dr. Constuntlue Paul {Archives Oen^rales^ 5th serii^s, 
to!. XV., 1860, p. 5 13 J has shown that it very couimunly produces the eiu'ly 
death of the fcetua. 

As any of these obscure m an ifca Nations of lead'fK>isuniug may exist, 
mud even prove fatal, without a distinct history of other nmre cbaructen«tic 
phenomena, great care is sometimes necessary to avoid beitig misled, and 
not rarely the true nature of saturnine epile|>8y or of saturnine albuminuria 
is overlooked. Hence the import;ince of the Une line upon the (junu where 
ihrg Join the tccth^ which probably exists in a greater or less degree in all 
persons suffering from lead-poisoning who have teeth, although very great 
deanJiuess may lessen it. It is gaid to be the r^utt of a formation in the 
wsUs of the capillaries of the sulphide of lead* 

I have seen in painteri^ a paralysis of one arm and one-sided wrist-drop, 
apparently the result of a loeal action of the poison ; Dr. Manouvriez (^e- 
cAerche* cliniqu^'it $ur t Intoxication nalnrnine locale et dirccte^ Paris, 1874) 
ba£t recorded similar observations. (See also La France Med.^ 1882, i. 892.) 

In those cases of lead-poisoning which pursue a slow course to death, the 
paralysis involves after a time the extensors of the lower as well as of the 
upper extremities, epileptic paroxysms occur at intervals, racking pains shoot 
through the limbs, points of cutaneous anaesthtssia appear, and often albumi^ 
onm aids in produciug the fatal issue. Gradually the patient becomes more 
sod more cachectic, general oodema, with the whit'eued skin, betrays the 
inofeasiiig ami^mia, the paralysis e^cteuds from muscle to muscle, locomotion 
omcfl im|/f)8ft*ible, and, if a convulsion or otlier accident do not close the 

cue, death at last takes place from loss of power in the respiratory muscles. 
Mahi!<sez hui? found that in the atu'euiiu uf lead-poisoning tbe n^d ghtbulcs 
ore not only diminished in nuniber but also increased in size ( Archiv*'» de> 
Physiok*gic, 1874, p. 50). 

After death lead has been fret^uently found in the tissues. Heubel found 
most of it in the bones, and less in the muscular than in the nervous system 
)Vlrrhow tftni flerjth'x JahrbUch^r^ 1871, vol. i. p. 316), Prof. Chatin 
f Compter- Re hdvs Soc. Biolotf.^ T. iv., 1862, p. 84) obtained from the deep- 
gmj upper cervical cord three milligrammoB of the sulphuret of lead in one 
liotidr^d and fifty grammes of nerve- tissue. 

This elect ri>- muscular contnictility is affected very early in lead-poison- 
tsg, and may be lost before the voluntary movements. It is stated by 
M. Raymond that the short extensor of the thumb preserves its function 
when all the other ext^jnsor muscles are paralyzed. The pnndys&ed muscles 

\ finally exceedingly wasted, and their structure may be so totally destroyed 



38 SYSTEMIC REMEDIES. 

that scarcely a single striated fibre can be found. The nerve- trunks are 
lessened in size, iu many of their tubules the medulla has been replaced by 
fatty <rranules, and in some cases every trace of the tubules has disappeared 
and the nerve been reduced to a fibrous cord. According to the researches 
of M. Degerine i^CompL-Rend, Soc, Blolog., 1880), the first appearance of 
change in a nerve-truuk consists in the myeline becoming broken up into 
blocks, and the nature of the change is a commingling of a parenchymatous 
and interstitial neuritb, which both Degerine and M. Yulpian have traced 
upwards as far as the anterior spinal roots. Lanc^raux (^Gaz. Med, de 
Fan's, 1862, 1871), Wcstphal (Arch. . Fsi/cL, Bd. iv. 776), Friedlander 
( Virchows Arch., Ixxv. 24), and others may be cited as having found very 
distinct peripheral lesions in lead-poisoning. Whether these lesions begin in 
the nerve or in the muscles cannot be considered as determined. Gourbault 
(Z/c Progrhs Med., 1880) describes primary alterations in the nerves, similar 
to those seen after section, as occurring in poisoned guinea-pigs, whilst MM. 
Debove and Roaut {Le Progrhs Med,, 1876, 151) describe the first changes 
as resembling those of subacute myositis, and Fricdliinder emphatically asserts 
that lessening in the size of the muscular fibres and multiplication of the mus- 
cular nuclei precede the nerve-degeneration. Moreover, it is still a question 
whether the primary lesion of lead-poisoning is peripheral or centric. Many 
recent investigators believe it to be a dii^seminatcd neuritis, which in their 
view may be bilateral, and in its symptoms exactly simulate poliomyelitis. 
D<^g6rine denies, however, the existence of such an ascending disseminated 
neuritis, and has found poliomyelitis after lead-paralysis. 

Lead undoubtedly escapes with the urine, but cannot be always detected 
in the secretion of those suffering from chronic poisoning. The elimina- 
tion seems to be capricious, and much affected by iodide of potassium 
(Melsens, Ann, Phys, ct Cheni., xxvi. ; Pouchet, Arch, de Physiol., xii. p. 
74) and by other influences.* 

The treatment of chronic lead-poisoning evidently arranges itself under 
three indications: 1st, to prevent the ingestion of more of the poison ; 2d, 
to aid in the elimination of that in the system ; 3d, to relieve symptoms and 
restore lost functions. In lead-colic both of the last two indications are met 
by purgatives, to which opium should be added to relieve pain. It is often 
necessary to use the most powerful drastics, such as croton oil ; but senna, 
salts, and other of the milder cathartics should always be tried first. Alum 
acts in some unknown way as a specific in lead-colic, and from twenty to sixty 
grains of it may be given four or five times a day. In the more chronic forms 
of lead-poisoning, to fulfil the second indication baths of sulphuret of potas- 
sium should be employed, and iodide of potassium be administered inter- 

* Lead has been found in the urine of man or animals by Orfila, Lewald {Auwcheidnng 
der Arzneimittelf Brcslau, 1861), GuBserow ( Vtrckoio'g Archiv, Bd. xxi.), Annu9chat {Arch, 
Experim. Pathol, und Pharm.y x. 260), and Oottingcr ( Wiener Wochentchri/t, 1858); also 
in my clinical service at the University Hospital. 



MINERAL ASTRINOESTS. 



39 



lly. The bath sliould be gircn (Dr. A* Kulenbiirg» Dettfschesf Archin 
■r KUn, Med., Bd. ill, p. 506) in a wooden tub, two or tliree tinier a week, 
and ©hould contain six or BCTen (ounces of the giilt. The patient, during the 
hatf-hour of his continuance in it, should be from time to time well rubbed 
wilK a ooarse toweL On coming out ho w tx> be thoroughly washed with 
wurta soap-suds. The dose of the iodide should be from fifteen tx> twenty 
^smtOA, sdniiniatered after meals, in dilute solution. A caae is reported in 
the Tjondon Lancet^ 1876, ii. 53, in whieh galvanic baths were used success- 
ftilljf, the patient being placed in the bath and the positive pole of a twenty- 
ingbt-eell battery applied to nape of neck, the negative to the feet. When 
•cTcre cerebral symptoms arise, treatment is of little avail, and should be 
Urgiely exfiectaot. 

The local use of electricity is exceedingly important to restore the k^st 
fiitiction of ncr^*c and muscle. Wliew the laradidc current elicits a response it 
sbould always be employed; but in some cases (Me^er'i Electricih/^ Ne^ 
YoTk, 1SC9, p. 284) the continued turrent retains its power after the induced 
has loet all its influence?, The rule is always to apply that current which ciiuscs 
conimction ; if both fail^ the continued current should be used, the poles being 
r m rerae d at intervals of four or five seconds. The electrical si^anoes should he 
tri^weekly, each Listing about fifteen minutes, and they should be persevered 
In for mnntha. I have seen great improvement in a case which for the first 
foor months yielded no results ; indeed, long after voluntary movement hud 
in great measure returned, no form of elect ricit}" would ciiuse contraction of 
tlie afiected muscles. 

PursioLOOlCAL Action^ — The symptoms of acute lead- poisoning are 
chiefly due to lU local irritant action^ but those of chronic poisoning are of 
vuler Bignifioanoe. How the lead is absorbed to produce them is unoortain, 
pfobabJj as an albuminate. All of the compounds of lead and albumen as 
yet diaoovered by the chembt are, however, precipitated by alkaline curbon- 
ttles^ and cannot therefore exist in the blood. 

'Jlie syiuptouia of dironic lead-in loxication to be accounted for are the 
colic, the anaemia and wasting, the palsies, the rare cases of cerebral symp- 
tom**, or of kidney degeneration. In explaining them we are chiefly indebted 
to the researches of Dr. Ernest IJurnack (Archtv JUr Exprrim. Fathoh^ie, 
1878), who cmj)loyed the compound of lead and ethyl, first discovered by 
lioewig. When this is injected into animals in large qunntitieB it causes a 
rapidly fital train of symptoms, evidently due to the action of the compound 
itfidt When, however, the introduction into the system has been slow, a 
chronic poisoning is produced by the lead set free in the blood and tissues. 

Under those circumstances a constant symptom, both in dogs and rabbits, 
to a violently increased peristalsis, with, in the dog, occa- 
Colic» As both the diarrhoea and the excessive pi^ristalsis 
m arrested by atropia, they are probably the result of an action upon the 
{iittttioal ganglia^ The colio in man is probably due to the excitement be- 



40 SYSTEMIC REMEDIES. 

coming so intense as to cause spasmodic contraction of the muscular coat of 
the intestine and consequent arrest of peristalsis, obliteration of the in- 
testinal lumen ^ and constipation. If such be the case, large doses of bella- 
donna should at once give relief. 

The chief symptom of the poisoning in frogs was a progressive palsy of 
muscular origin. The muscle became exhausted on repeated galvanization 
much more rapidly than is normal, and after death was incapable of under- 
going complete post-mortem rigidity. The peripheral nerves appeared to 
have escaped entirely. The heart-muscle shared the fate of the voluntary 
muscles. The muscular action of the poison was excessively pronounced in 
rabbits, but was feeble in dogs and cats. These physiological studies, taken 
into consideration with the results of pathological investigations, render it 
probable that the palsy both in man and in animals is primarily produced 
bj a direct action of the lead on the muscles concerned. 

Dr. Harnack found that in dogs the lead ethyl produces violent excite- 
ment, with chorea, convulsions, etc., evidently due to an exciting or irritant 
action upon the cerebrum, and believes that this explains the saturnine cere- 
bral cases sometimes seen in man. 

Plumbic renal degeneration is evidently the result of a long-continued irri- 
tation, due to a persistent effort at elimination of the foreign substance. 

The pulse in lead-colic is usually very hard and tense. Sphygmographic 
studies made of it by August Frank (^Deutsch. Arch, /. Klin, Med,, xvL 
422, and Ernest Bardenhewer, Berlin Klin. Wochen,, 1877, 126), have been 
thought to indicate a condition of general arterial spasm, and have given rise to 
the very improbable theory that the colic is caused by intestinal anaemia from 
vaso-motor contraction. Bardenhewer found that hypodermic injections of 
pilocarpin relieve simultaneously the pulse and the colic precisely as Harnack 
dbcovered that atropia does. Harnack, however, found that in rabbits and dogs 
the lead ethyl has no action upon the circulation except by direct influence 
on the cardiac muscle, and that it docs not produce vaso-motor spasm. He ia 
probably correct in believing that the pulse of lead-colic is due to an over- 
fulness of the blood-vessels, produced by an expulsion of the blood from the 
intestines by the severe spasm of their coats. 

The following preparations of lead are officinal in the United States Pbar- 
macopoDia : 

PLUMBI OXIDUM— OXIDE OF LEAD. U.S. 

Litharge^ which is prepared by blowing air through melted lead, occurs in 
small yellowish or orange-colored scales, which are insoluble in all ordinary 
menstrua. It is rarely used as a desiccant astringent powder for ulcers, but 
its chief employment in medicine is as the basis of the following preparations : 

Emiilostnnn Plumbi, or Lead Plaster, is made by boiling litharge, olive 
oil, and water together. Glycerine is set free, and the oleo-margarate of lead 
is foniied. Lead plaster occurs in grayish, cylindrical rolls, which become 



MINERAL ASTRIXOENTS, 



41 




ttdhcEiTe at the tempemture of tlic body, and, spread upon kid, is Bomcttmes 
used as a protective to pftrts exposed to pressure, or to siiperficiiil ulcers or 
abmsion^ Emplmtrum Eemusc^ or Resin Planter^ or adheMve or Btickw^ 
piaster, is made by incorponitlng resiu with lead plaster, and, spread upon 
lliien^ is much u^ed iu surgery fur mechanieal purposes. The Emplaitrum 
SapfjntSj or Soup Pluater, h made by the addition of soap to lead plaster. 
It is employed chiefly as a protective. 

PLUMB! ACETAS— ACETATE OF LEAD. U.S. 
Sugar of kad is luade by the action of iicelic acid upon lilhar^e, or upon 
lecta of lead exjiosed to the air. It occurs in tniuspsu-ent, acicular, otlen 
aggregated crystals, of a sweet, styptic taste. It is soluble in water, to wliich 
it usually imparts a slight milkincss. From its snlutiim it b precipitated 
black by sulplnu'ctted hyilrogeu, white by soluble curb* ►nates, chlorides, and 
sulphates, and bright yellow by the iodide of ptitassium. It Is also incom- 
patible with the muciiHge of slippeiy ehn, but scarcely so with that of flaxseed 
ar of pith of sasaafras. 

TUEBArEimcs. — A solution of the acetate of lead is used very largely in 
ftcute external injfmnmatioiin as a sedative and astringent lotion. Althougli 
clieraically incompatible, it is freriucntly combined very advantageously in 
these cases with opium. As a t^Hi ci>uc'entrated solution acts as an irritant^ 
llie strength Air use on the eye should not exceed one or two grains to the 
cnitice ; on the skin, ten grains to the ounce. 

Internally, acetate of lead bus been employed very largely in hfmorrhige : 
indeed, Pruf George B. ^V^lod commends it as the most valnablo of all 
ngtmts in hcmopft/8t^ (Tkerapeuiioi^ vol. i. p, 158). I think it is now, 
iOwercTT ranely used ibr this purpose. Its chief use at prcMmt is in dtarrlnea. 
On ac^Mumt of its sedative properties, when the purging is attended with in- 
flamnnitiou it is the most serviueable of all the astringents; and, owing to 
the promptness of its action, it is also very valuable in cases with profuso 
Berons discharges. In f/j/aeuter^ it is very useful whenever the dischai^cs 
bare become copious. The dose is from two to five grains, always in pill, 
repejited pro re naia. Tlie mpp<mtork$ ( Snppomtoria FlnniLi, U* S. 1870) 
contain each three grains. 

Ll<|roa PlUMBI SUBACETATIS.— The Solution of the SuLaetfttte of Lfiitdf 
Gonlnrds Extract , as it is sometimes called, is a colorless, limpid liquid, of 
m fwectibh, astringent taste. It is made by bailing litharge in a solution of 
ill itf Icjid^ and has an alkaline reaction. When exposed to the air, 

it ilj*iorbs carbonic acid and de[K)sits the carbrniate (>f lead, the neu* 

Ira] aoetAte being left in solution. In its action upon the human organism, 
GuDlard's extract resembles very closely the simple acetate of lead ; but it 
is BffTcr nsHil internally. Externally, it is a favorite application in ciises of 
sprains or ttruiscs, as well as in superficial iuflauimation. For this purpose 
it rctjuires dilution, Mid from a ttiudounce to four fliiidounccs of it may be 



42 SYSTEMIC REMEDIES. 

addod to a pint of water. When used upon a raw surface, the strength 
should not be so great. A sedative poultice, which is very highly recom- 
mended by some physicians in the early stages of inflammation, may be made 
by saturating crumbs of stale bread with Goulard's extract diluted with four 
to six times its bulk of water. This poultice must be applied cold. The 
officinal Liqiun- Plumbi Subacetatis DilutuSy or Dilute Solution of the Sub- 
acetate of Lead, is of the strength of three parts in a hundred. It is too 
weak to be of much value. 

Plumbi Carbonas, U. S., or Carbonate of Lead, is a heavy, white, taste- 
less powder, insoluble in distilled water, but slightly so in water containing 
carbonic acid. It is used solely as an external sedative application. Kubbed 
up with linseed oil, it constitutes white-lead paint, and in this form, or in that 
of the ointment ( (/n^uentum Plumbi CarbonatiSy U. S.), it is a most efficient 
dressing for fresh burns. Care must be taken in its use, however, when a 
large surface is involved, as lead-colic has been caused by its absorption. 

Plumbi Nitras, U. S., or Nitrate of Lead, occurs in white, nearly opaque, 
octahedral, very heavy crystals, soluble in alcohol and in seven and a half 
parts of cold water. It is used chiefly as a disinfectant. Dissolved in water, 
it forms Ledoyens Duinfectant Solution, It acts by decomposing the sul- 
phuretted hydrogen, itself being converted into a sulphuret of lead. It is 
said to attack actively the soldering of pipes {Report on Hygiene^ U. S. Navy, 
1879). Its chemical reactions are similar to those of the acetate, from which 
it may be distinguished by a mixture of it and sulphuric acid striking a red 
color with morphia. The nitrate of lead is frequently used in onychia 
maligna. The dead part of the nail should be cut away, and the pow- 
dered nitrate thickly sprinkled over the surface ; after a few days the slough 
separates, leaving a clean surface, upon which the new nail usually soon 
forms. Sometimes more than one application of the remedy is required, 

BISMUTHUM-BISMUTH. 
The metal bismuth is never used in medicine in its simple or motallio 
form. 

BISMUTHI SUBCARBONAS— SUBCARBONATE OF BISMUTH. U.S. 

(BiOjCO,, HO — 2Bi,08CO„ H,0.) 

A white or yellowish-white powder, tasteless and odorless, totally insoluble 
in water, soluble with effervescence in dilute nitric acid. The mode of its 
preparation is too complicated for discussion here, the chief object of the 
various steps being to get rid of the arsenic, which very generally contami- 
nates the metal. The same assertions may be made in r^ard to the prepsr 
ration of the BiSMUTHi Subnitras, or Subnitrate op Bismuth, U. S., 
a heavy white powder, odorless, with a faint acid taste, and a decidedly acid 
reaction when applied to moistened litmus-paper, insoluble in water, soluble 
without effervescence in nitric acid. 



MINERAL ASTJiIXOE\TS, 



43 



FMVeiOLOOiCAL Action. — The actions of the subuitmte wuti of tht? sub- 
carbonat43 of bismuth are so exactly similar that the}* can j»nictu.jLlly be con- 
gidcred as one thing ; and for the suke of brevity I gliall npeuk of liicyso salt* 
simply us bismuthj meaning thereby these preparations!, Oifila and other 
of the old observers attributed to bismuth violent irritant properties, slating 
that severe sjiiiptoiDS, and even deiith, sometimes lullowed its inge:stiou. 

Thena can be no doubt that the results noted by these authorities were due not 
to the bismuth, but to the ajsenic with whi^h it wsxs conUuninated. Notwith- 
standing all the care of modern phannaty, bismuth even yet oecasionally con- 
taiiL» arecnic, and I have seen it produce from this eause bloody pur^jing. When 
^ure, luiwever^ it is free from any irritant properties, and is a feeble astriu^nt 
and even a sedative, and can be taken without injur}' in iudt-finite quantity. 

Hie officinal ^dts of bisuiuth are so exceedingly insoluble that it has been 
generally believed tliat they are not absorbed ; but the researehes of JIM, 
Bergcret and Mayenc;on (Journal de rAnatomie^ 1873, p. 242) stronjijly in- 
dicate the wjntrtkry to this. According to this authority^ if a piece of paper 
be wet with a solution of sulpho-cyanidc of potasttiuoi and dried, it afFurda a 
mcfit fcensitive and characteristic test for a soluble salt of bismuth, — a beitu- 
lifwl yellow spot appearing at the point of contact. Availing themselves of 
t}m ti^t, MM. Bergeret and >layenf;on have found that when the subiiitrate 
of Wawuth is administered the metal can always be detected, after a few 
hourgs in the urine. TIjcy have also discovered it in the serous exudation of 
dixf^tsy.aud have proven that when a few grains of the salt mentioned are given 
to mbbtts, in from twenty to thirty minutes it can be found in the urine, 
kJi]iie>'B, spleen, blood, and muscles, and even eight days after the administra- 
tion can be detected in all the tissues. Five days after the exhibition of a 
l^immme of the subnitrate to a man, they Riund traces of the n^etal in the 
limer and kidneys ; but the analysis of the body of a woman dead sixty -two 
dsjB after the ingestion of two grammes yielded only ne^tive results. 

TuiniAPEUTics.^ — The preparatiuris of bismuth nre of great service in 
rarious forms of irritation of the alimentary canal. Tliey are very useful to 
alUv ly^nitihff dependent upon gastric irritation. In simple neuralgic fftiatric 
pain follnwing eating, especially when occurring in feeble, badly-nourished 
BubjcctST tkisruuth is of^en of great .service; and even in carctitoma it may 
jAllinte by alleviating pain and vomiting. In pyrrxsf* it is sometimes sueceas- 
ful. In simple diiwrhan of tmtation, and in the chronic diarrlnift of camps, 
the bismuth preparations are often very efficient ; and in the clironio howel 
' lititM of children, especially as seen in the summer seiison, given with 
^ ^ li. they are almost invaluable* Topically, these preparations may be used 
with advantage as dcsaccant astringent applications in kiicorrhcta^ in gonor 
rharn^ and in irrihdilfi extfrtml ulcers. 

Ai»M tNisTiiATlON. — In order to be efficient^ the bisnmth preparations must 
be given in much largec doses than they were formerly used in. To infjiuta 



44 SYSTEMIC REMEDIES, 

live to ten grains may be administered at a dose, and to adalts from twenty 
grains to a drachm. 

BiSMUTiii CiTRAS. U.S. — The insoluble ciVra/e 0/ 2»i^i^A is not used 
in medicine, but has been introduced into the PharmacopoDia for the pro- 
duction of the Bismuthi et Ammonii CitraSy U. S. The citrate of bismuth 
and ammonium is a soluble salt, which is much more astringent than the in- 
soluble preparations of the metal, but at the same time more irritant. It 
lacks the peculiar virtues which grow out of the insolubility of the sub- 
nitrate, but has been used to some extent in doses of five grains in chronic 
diarrhoea and in acute diarrhoeas of relaxation. It should be given in 
watery solution, repeated every three to six hours, according to the exigen- 
cies of the case. 

OEBII OZALAS. U.S. 
The oxalate 0/ cerium is a white powder, insoluble in water, alcohol, and 
ether, but soluble in sulphuric acid. It has been employed in mcdicuie quite 
largely for the relief of vomiting, especially when dependent upon pregnamnf 
or other forms of vterine disturbance. Its action on the economy has not 
yet been made out, but it may be tried with some hope of success in cases of 
nervous or dyspeptic vomiting. The dose is one to three grains, in pill, three 
or four times a day. 

ZINOUM-ZINO. 

ZiNCi Sulphas. — Sulphate of Zinc, U. S. — W'AiVc vitriol occurs in irreg- 
ular white masses, the pure sulphate of zinc in minute, transparent, four- 
sided, prismatic crystals, which effloresce slightly in dry air, and are soluble 
in two and a half times their weight of cold, and much less of hot, water ; 
insoluble in alcohol. The taste is styptic and peculiar. 

Therapeutics. — The sulphate of zinc is in weak solution a stimulant 
astringent, in concentrated form an active irritant. Taken in doses of thirty 
grains it acts as a prompt, efficient mechanical emetic. In smaller doses, of 
two grains, it is sometimes given in pills as a stimulant astringent in chronic 
diarrhoea with ulceration. 

Toxicology. — Sulphate of zinc in large doses acts as an irritant poison, 
producing violent vomiting, colicky pains, diarrhoea, prostration, etc. The 
symptoms which it causes are almost identical with those produced by the 
corresponding salt of copper. Alkalies and their carbonates are the chemical 
antidotes to it, producing insoluble precipitates. Eggs and milk should also 
be exhibited, and the symptoms treated as they arise. Chronic zinc-poi- 
soning, if it really exists at all, is very rare, and the metal seems to be 
used with impunity in cooking utensils. Dr. Schlockow, however, affirms 
(^Deutsclies Med, Wochensch.^ 1879, 208), that the zinc-smelters rarely live 
to be over forty-five ; dying, sometimes with catarrh of the bronchial or 
alimentary mucous membranes, or, in other cases, of a peculiar nervous 
affection, which commences with burning superficial pains, exalted sensi- 



^flNEnAL ASTRINGENTS, 



45 



bilitj, and reflex activity in the legs, and afterwards puts on still more 
clcftrtj tlie features of myelitis. 

Z(\'CI Oxiprai Venale. — Commercial oxide nf zinc 13 n snow-white 

powder, obLaioed by buruiri^ the uictul in the iiir. It should be used owly 

i in pharroacy. The purt oxide (ZiNCl Oxibum, U. S.) is made by healin^^ 

the carbonixte until ihe water aud acid are driven off. It iss u ycllowifili- 

while powder, insoluble in water, but soluble without effervescence in dilute 

TBERAPErTics. — The oxidc of 2inc is uned extcniidly as a mildly a^trin- 
gciit,slif^htly stimulant^ and desiccant applieutiuti lu skin diseases and to idcrrA. 

I \VTieu given continuously in small doses it is believed to act as a tonic and 
alterative upc>n the nervous system* It has also l:>cen i^ommmided aa nn 
mi^ringcnt in chronic catarrhal diarrhita of adults iind iiilunt8, uiid hai?t been 

I laf}gi!]T used in tpilepstf and in chtyrea. The dose is two to fifleen grains. 

f The ointment ( Umjuentum Zinci Oxidi^ U, S* — one part to four of bcnzoin- 

I aletl lard) is espectially useful in chronic eczema. 

Zmci Cardonas Pr.^cipitatus. U-S. — Precipitated earhonate of tine 
I in ttitended to replace the uM impure native carbonate, calamitte. It is nmde 
by precipitatin*^ the sulpbutc of zinc by the carbonate of sodium. It is a 
wbite powder, closely resembrmg in its properties the oxide of zinc, 

ZiNCl AcETAS. XJ.ii.— Acetate of zinc is made by the action of acelio 
acid upon the comujercial oxide of zinc. It occurs in white, micaceous crys- 
lak, which effloresce in a dry attuoHpbere and are very solnble in water, Tito 
tastv is astringent nnd metidlic. The acetate of zinc resembles in its physio- 
logtC4il iind therapeutic qunlities the sul|]hate, but is probubly somewlmt less 
•Gitve. It is cfueOy used in collyria (one to two p^rains to one fluidounce), 
aod as uu injection (dve to twenty grains to one ffuidounce) in gonorrlKia, 

Cadmium is employed in medicine to some 6li<;ht extent in the form of 
' tt« w^lphala^ which is stated to resemble closely the sulphate of zinc in its 
tberjipontic properties. It has been especially u»ed as nn astringent stiniu- 
laQi tu collyria^ made by dissolving half a grain to four grains in an ounce 
of rofic-walcr. Strangely enough, some pbysic-ians who have employed it 
elate that it has I en times the strength of the sine salt, others that it is about 
I equiTalcnt to it. 

OTTPEITM-OOPPEE. 
crrni sulphas— sulphate of copper, u.s. 

The ffulphat6 of cjoppor occurs in blue, transparent, slightly efflorescent, 

1 rbotuhoidal priaios, or their fragments. It dissolves in four parts of cold and 

I in ! " '* r, but is insoluble in aJcohoL With ammonia its solu- 

' lioj 1, white hydratcd protoxide of copjK^r, which redissolves 

fhett an exeeas of the alkali is added, forming a rich deep-blue solution. 



46 SYSTEMIC REMEDIES. 

Physiological Action. — In very dilute solation the sulphate of copper 
acts locally as a stimulant and mild astringent ; in a more concentrated form 
it is an irritant; in powder it is a very mild caustic, which is scarcely capable 
of destroying sound tissue. Taken internally in very small amounts and 
continuously, it is thought to have a corroborant influence upon the nervous 
system. Prof. Falck (JDeutsches KUnik^ xi., 1859) has found that the sul- 
phate of copper acts upon pigeons, dogs, rabbits, etc., as an irritant neurotic 
poison, producing great depression of temperature, with progressive general 
paresis ending in death, apparently from failure of respiration. When the 
copper salt was given hypodermically, vomiting was not produced ; although 
when it was exhibited by the mouth, emesis was very violent and persistent. 
In doses of five to fifteen grains it acts upon man as an irritating emetic, and 
in larger amounts is an irritant poison. 

Therapeutics. — The chief internal use of sulphate of copper is as a 
mechanical emetic. As it is more irritating than sulphate of zinc, it acts 
more rapidly and in smaller dose. For the same reason, however, it is not so 
safe as the white vitriol, and cannot be repeated so freely when its action fails. 

As a stimulant and astringent it is occasionally administered, in pill form, 
in chronic diarrhcea with ulceration. In small repeated doses it has been 
used in various nervous affections with doubtful advantage. 

The chief value of the so-called " blue stone'^ is as an external application. 
When applied in solid form to ulcers, it destroys flabby granulations and 
exerts a powerful excitant influence. Its solution acts more feebly, and is 
sometimes employed as a dressing for indolent ulcers, but more frequently as 
a stimulant and alterant to mucous membranes, as in granular conjunctivitis. 

Toxicology. — The symptoms of acute copper-poisoning generally come on 
in about a quarter of an hour afler the ingestion of the poison, but may be 
postponed for from one to two hours. They consist of violent vomiting and 
purging, accompanied by very severe colicky pains. The matters vomited are 
greenish or bluish, the stools glairy, mucous, and at times bloody. There is 
a very strong taste of copper in the mouth, and often constant expectoration ; 
excessive salivation and bronchial secretion are stated by Galippe {^Etude 
toxical, sur la Cuivre, Paris, 1875) to be characteristic. Death may occur 
in a few hours, preceded by convulsions, paralysis, delirium, anaesthesia, and 
other symptoms of great nervous disturbance, seemingly as the result of a 
direct action of the poison upon the nervous system. Sometimes a tendency 
to syncope is very marked. The urine is usually lessened or suppressed. 
Black urine, due to the presence of hsemoglobin without unaltered blood- 
corpuscles, has been noted ; in this ease, after death all the tissues were found 
stained with altered blood, and evidently destruction of the blood was an 
important factor in the fatal result (N. Y, Med. Record, xxi. 5G7) ; fatty 
degeneration of the liver was also found. If the patient survive for twenty- 
four hours, jaundice nearly always shows itself. After this, profound depres- 
sion with nervous symptoms may develop and end in death ; but not rarely 



MtlfEliAI. ASrJllKQKXTS. 



47 



^m cipi 



m favorable bsue results, in which ca^c the ^ymiitoma ot gaslro-iuteBtiQal 
mflaiuiuwtioD with fever develop theriisulvcs. The copper h said to be elim- 
inaleii more freely with the salivary aud intestiual seeretioua thuu with tlie 
urine (Giilippe, I^k. cit,^ p. 41J. 

Ab the actiou of the sulphate of copper Is ejteeeditigly rapid, any antidote 
to be of avail inuj*t be given at once and act quickly. Milk and eggs are 
aloiost always at hand, and are the most efficient antidotes. No time sliould 
b« loei ill att^raptins; to separate the yolk from the white of the egg^ but 
die c^^ tihould be broken into a bowl as quickly m posi^ible, a little water 
a4dedt atid the whole stirred up and exhibited. The dose should be repeated 
•irreral times, especially when there is votuitiug. Soap or a fixed alkali may 
ht gii'eu. The yellow jor^wiu^ of potash ^ when pure, is harniltisa, and pre- 
etpitates instantly an insoluble compound of copper from solutions of its stilL 

ben it is to be had in time^ it ruiiy therefore be usiod as an antidote to the 

l^bate. The treatment of eopper-poisoninji after tlic adniiiiiHt ration of the 
antidote consists in meeting the indications us they arise; opium should be 
used freely. When death occurs, the results of gastro-iutestiiml iiiflammatiou 
are usually found ; sometimes the intetstine has a decided bluish tint, and occa* 
aioaally subomcous ecchy muses occur. In exceptional casas^ it is said, there 
ars DO evidences of inflammation in the allmenttiry ctinal.* Fatty degeuer- 
atioo of the liver has been noted {^N, Y. MciL Rtc.^ xxt. 567). 

If chronic copper-poisoning ever exist among workers in the metal, it must 
be very rarely. The chief symptoms are asserted to be *^ a coppery laabe in 
the mciuth, giddiness, pain in the bowels, vomiting, occasional diarrhoea, 
and wasting of the body," Dr. Clapton {Mtdlcttl Times and Gazette, June, 
l€»C8) has pointed out, as characteristic, a ^reen line upon the gums ; this 
WAS also observed by Prof. Taylor, but its constancy is not assured. Thus, 
a green liuu Has found on the teeth of all but two or three of a number of 
workers in the metal examined by a committee of the Loudon Clinical Society 
(^TrunKdctionSj 1870, p. l;i), but there was no line on the gums of any of 
tl)cin. Gttlippe {he. cii,) has brottght forward much evidence to prove the 
non-existence of chronic copper-poison ing. Both he and Drs. Burey and 
Biacom have found the metal almost without influence upon dogs (ArchivcM 
de Plifffioioff, Aorm. et Palh.^ 1877, t. Iv. 183), Galippe ( GfJ^iptes-RenduM, 
t- Ixxxiv. 718) fed himself for one month on food containing a large amount 
of cnppcr without causing any symptoms of intoxication. On the other hand, 
l>r. Fttutk (^DeuUchrii Kihttk^ ix. ?t7ij) asserts that the acetate of copper pro- 
duces progressive paralysis, with failure of respiration and death, 



a T<^r a fAtftI oa^o of reprnteJ poisoning by copper, with much infarmntion of value to 
c4)«aiic«iil CJiperia, ic6 La Frnnee MitUcnlt^ Soplumbor, 1^74, ftbatrjiett'il in Half- Ytarl^ 
ComywHtiutm, Jun. IS75, BouriaGVPtt« *nd Yvon (Rfrue ScitHti/Iqnet p. 859, 1874) found 
two hiiD(lre<t »nd nlsHj-flve milligniiuuies of moliilHa copper in tho livi^rof «i woman 
«tbo li&d tjiken the &aiiBOQiao*l lulphatc lUrve munihn previoaalj. Minutti qaiuiUtiM of 
oopp«r exlit la tht aormftJ ham»n bodjr (B»il, dt Thirap,, xoiiL. 88). 



48 SYSTEMIC REMEDIES. 

CuPRi AcETAS. U. S. — Acetate of copper is in deep-green, prismatic 
crystals, yielding a bright-green powder ; whilst the impure BvhacetcUe^ or 
verdigris^ occurs in masses of a pale-green color, which are often composed 
of minute silky crystals. Both these acetates closely resemble the sulphate 
in physiological, therapeutical, and toxicological properties, bat are a little 
less active. 

Cuprum Ammoniatum. — The ammoniated copper is made by tritu- 
rating together the sulphate of copper and the carbonate of ammonium. It 
occurs in deep azure-blue masses, with a strong ammoniacal odor and styptic 
metallic taste. It is soluble in water. In overdoses it acts as an irritant 
poison. In small doses (one-half grain to two grains three times a day) it 
has been used as a tonic to the nervous system in epilepsy and other diseases. 

AEGENTUM-SILVEB. 
ARGENTI NITRAS— NITRATE OF SILVER. U.S. 

This is officinally prepared by heating together silver, nitric acid, and a 
small quantity of water. It is a heavy anhydrous salt, crystallizing in trans- 
lucent, shining, rhombic plates, and having a styptic, exceedingly metallic, 
corrosive taste. It is soluble in its own weight of cold water. Muriatic acid 
or a soluble chloride throws down from its solution a white curdy precipitate 
voholly soluble in ammonia. For external use the crystals are melted and run 
into moulds, where they harden into round, grayish, brittle sticks, about the 
size of a goose-iiuill, and having a radiated crystalline fracture. These are 
the officinal argenti nitras fusus. As only the pure salt will make well-formed 
crystals, the impure products are always manufactured into the preparations 
just named, which should therefore not be employed internally. When the 
nitrate of silver, either in substance or solution, is exposed to the conjoint 
influence of light and of even a minute portion of organic matter, it turns 
black, and is converted into an insoluble substance, which has been believed 
to be metallic silver, but is more probably an oxide. For this reason the white 
stains which it first makes when applied to living tissues soon blacken. 

Physiological Action. — ^Nitrate of silver coagulates albumen, and, when 
applied in its pure state to living tissues, acts as a caustic, coating them over 
with a white almost membranous film. The caustic action is, however, not 
a deep one, because penetration of the salt into the tissues is soon prevented 
by the thick and tough skin or stratum which is fonned. When applied in 
a dilute solution it acts as an astringent, constringing the vessels and over- 
coming relaxation. Its local action, however, is not simply that of an astrin- 
gent, but is certainly peculiar and apparently alterative to nutrition. 

When taken internally in sufficient dose, this salt, by virtue of its corro- 
sive action, is a poison, producing gastro-enteritis ; but it also acts directly upon 
the nervous system. Orfila and other of the earlier observers experimented 
upon it by injecting it directly into the veins of animals. When exhibited 



MINERAL ASTRINGENTS. 49 

in this way, it must, by coagulating the albumen of the blood, produce 
thrombi, to which the subsequent symptoms are in greater or less measure to 
be ascribed. This method of experimentation can therefore throw but little 
light upon the action of nitrate of silver when taken into the stomach. 

It 18 evident that in the stomach the nitrate of silver cannot long maintain 
its integrity. Dr. Bogolowsky has found ( Virchows Archiv^ Bd. xlvi. p. 
413) that when the nitrate is added to a peptone it is readily dissolved, and 
that the solution formed does not coagulate albumen.'*' That in this or in some 
other analogous form silver is absorbed is proven by its having been found 
in various internal organs and by the discoloration which follows its pro- 
tracted use. When it is exhibited for a long continuous period, the skin 
often acquires a peculiar bluish slate color, which may become very dark, and 
in decided cases the conjunctiva and even the mucous membrane of the mouth 
are involved. The silver is found in all the tissues of the skin except the 
rete Malpighii (Neumann, Medizen JahrhiicJier, 1877, 369). According to 
Dr. William Pepper, the staining of the skin is always preceded by a dark 
line upon the gums(7Va/w. Philad. Coll. Physiciatis, 1877). -Both Heller 
and Orfila failed to detect silver in the urine of animals taking it ; but prob- 
ably it is eliminated, though slowly and in very small quantities, by the 
kidneys. 

By an elaborate series of experiments, M. Chas. Rouget (Archives de Phy- 
siologies July, 1873, p. 356) has shown that upon all animals from a crab to 
a d4>g the soluble salts of silver act as a poison, causing in mammals vomiting 
and purging, and in them and the lower animals violent disturbance of the 
motor functions, as shown by paralysis and convulsions, and of the respiration, 
ending finally in death by asphyxia. This is in accord with the observations 
of other investigators. MM. Rabuteau and Mourier have found that the 
almost instantaneous death which Charoot and Ball first noted as following 
the injection of a large dose of the nitrate of silver into the veins is due to a 
direct paralyzing influence of the drug upon the muscle of the heart. M. 
Rouget has never seen this form of death follow the hypodermic or internal 
administration of the poison, the heart always continuing to beat for a greater 
or less length of time after the cessation of respiration, and also retaining its 
irritability. 

As already stated, both convulsions and paralysis are present in acute ar^t/- 
ria, or silver-poisoning. The convulsions arc severe, generally tetanic, and 
according to Rouget are plainly reflex. A peculiarity noted by Rouget is 
the persistence of the convulsions after the complete abolition of voluntary 
movements. M. Curci affirms that they are due to excitation of the motor 
tract of the cord, and that this is preceded by a similar influence upon the 
i«<*nsury tracts {London Med, Record, 1877, p. 72). 

• For recent studies of this character *c»* Ise^lun Neumann {loc. cit.)y alau A. v. Frag- 
at«iD (/yrr/iM A7mi. Wochtn., 1877, 294). 



50 SYSTEMIC REMEDIES. 

The death is due, in argyria, to cesisation of the respiration ; Boaget (2oe. 
cit.^ p. 351) even states that he has witnessed the suspension of the latter 
fiinction in the frog whilst the activity of the reflex moYements was much 
beyond normal. In the dog and in the frill-grown cat this asphyxia is accom- 
panied by an outpouring of mucus in the lungs, pulmonary congestion and 
cedema being found on post-mortem examination. Two theories have been 
propounded as to the cause of the asphyxia : one, that it is simply due to 
the choking up of the lungs by the congestion and the excessive secretion 
whose origin is an altered state of the blood ; a second, that both the asphyxia 
and the lesions in the lungs have their origin in a direct action of the poison 
upon the nerve-centres. 

The first view has been especially supported by Krahmer and by MM. Ha 
buteau and Mourier. Unfortunately, I have not seen the original papers of 
these physicians ; but, according to Rouget, the basis of argument of Krahma 
is simply the ecchymoses which he found in horses dead of the poison, whilst 
that of Rabutoau and Mourier is the fluidity of the blood after death, and the 
existence in it of globules which, on account of their solubility in ammonia, 
were believed to be the chloride of silver. The French observers were, how- 
ever, almost certainly mistaken in their belief that these granules were chloride 
of silver, since ammonia dissolves hseniatin as freely as it does the cliloride. 

In 1864 Charcot and Ball {Gazette Midicale^ 1864) made a series of ex- 
periments in which a silver salt that did not coagulate albumen was injected 
directly into the blood. They noted not only the respiratory embarrassment, 
but al«o that the hinder extremities were suddenly paralyzed, and concluded 
that both the asphyxia and the lung-trouble were due to an affection of the 
central ner\'ous system. In 1869 Dr. Bogolowsky, of Moscow, studied 
( Virchoics Archiv, 1869, Bd. xlvi.) the action of a peptone of the nitrate 
when used hypodermically. He found, on examination of the blood of a 
poisoned animal, that the spectrum analysis (loc, cit,, p. 415) betrayed 
nothing abnormal ; that the red corpuscles appeared paler and their outline 
more delicate than normal ; that the white corpuscles were natural. On the 
other hand, Rouget {loc. a/., p. 361) examined microscopically the blood of 
animals poisoned with the nitrate of silver, and found it perfectly normal. 
The only conclusion to be drawn from all this seems to me to be that at 
present there is no proof whatever that the symptoms of acute argyria are 
due to alterations in the blooH. That the embarrassment of respiration is 
not due to local lesions in the lungs is abundantly shown by the experiments 
of Rouget, who found that whilst in all animals these respiratory symptoms 
are very prominent, in only a few species are decided pulmonic lesions found 
afler death. From all these facts I think it highly probable, if not altogether 
certain, tliat the theory propounded by MM. Charcot aiid Ball is correct. 
That the motor disturbance is centric, not peripheral, in its origin, is shown 
by the fact noted by Rouget (loc. cit.^ p. 354), that the muscles and nerves 
preserve their excitability afler the arrest of the respiration. 



MINERAL ASTRlSQESrs. 



51 



The Tariom facts which have been thus far brought forward in regard to 
ihe physiological actioQ of silver, aJthouj^h iiitcrtasting to the toxioologiiit, 

fc very little reforcrice to \i& th«?rapc'utjc use, since it is never employed to 
Jiicc an acute constitutiuiml influence. 

The action of the drug when exhibited eontinuoualy for a length of time in 
doses has been investigated by Dr. Bagolowsky upon dogs and rubblU. 

I found that it pr<xJueod liiss of appetit^^ wasting, sliglit lowering of bixlily 
temperature^ diarrhoea, diminution of the quantity of urine passed, with iu- 
ci^eflAe of ita specific gravity and often with the presence of albumen^ and 
transitofT paralysis. How far fliome of these symptoms were due to the diret-t 
oontftitutiona] action of the poison, and how \\\x to derangement of the dig(^tion 
dependent upon its Io(^ in6ucuce, is pcrhafjs an open ijucs^tion. The local 
ustlon waa avoided, however, as umch a^ poS8tble^ by the ujsc of an albuminate 
or of ihe double phosphate of silver and aodium, which tlue?? not coagulate 
albumen. Comparative examinatious of the blood showed that the haemoglo- 
bin waa reduced by more than one-third. The blood wu« also rendered very 
apbifltic, as waa betrayed by the tontitatit tendency to the formation of eechy- 
moi^ca. A» some one has iiuggeated that the silver in these cases replaces the 
rroii of the blood-eorpnscles, Dr. B«»gol*>wgky made a chemical examination 
iif the latter, but failed to find any tracer of silver in them, — no doubt be- 
Lmuse it Wiis not thero. The sulid tissues were found, after death from 
ehronic ajgyria, t4j Ixi in an iidvanced stage of degencratiftn, whicli espeirially 
affeetinl epithelial structun^s. The first change was swelling and opacity of 
the cells, with obscuration of the nucleus. After this came fatty degeni^ra- 
tiim, fatty gli^bules in the cell, /estructi*iu <tf nuclcns, and finally of the oeO 
ttaeUl The liver and kidneyif were profoundly intiueneed, as was also the 
miiscnlar structure, e^peeinlly of the heart. Tlia^e results obtained by Bo- 
golDwaky have been in ihe main corroborated by A. V. Hozsahegzi {^Arch* 
Exp^, Fitth. Phnrrti., ix, 2^5). 

Th'! ttuiinaury \vliich has been here offered comprises all our knowledge of 
the physiological action of the preparations of silver. Unfortunately^ it d(X^ 
HOC titniw much liglit upon their therapeutic use. The results of the ehronic 
poisoning are so closely analogous to those produced under similar cireum- 
flfanoes by antimony, arsenic^ and probably other metallic poisons as to indi* 
cata that silver given internally acts upon the nutrition of the body, — in other 
p mnia, thai it is an nltefatttte, 

ToSBAPEtrrics^ — By far the most frequent employment of nitrate of silver 
is iborapeutica is for ica k»eal action, either upon the surface of the body or 
i2]xin those muaiua membranes that can be reached directly by the drug. 

As a simple vum/ic, the salt may be used whenever only a su|>erliciid ticUon 
i» r»juirod ; for reasons already given (page 45), it is useless whenever it is 
neec'tsar}' to prwJucc a deep eschar. Aa a caustic and an alitmttive^ it is 
applitHJ in solid form to many ulcerated tur/aces, for the purpose of destroy- 
kg tfuperficial dMued tisaue and of substituting, when the eeehar eeparat«a, 



52 SYSTEMIC REMEDIES. 

a healthy for an unhealthy action. As an antiphlogistic^ nitrate of silver 
acts not only as an astringent, but also in some way not clearly understood. 
In the various inflammations of the mucous membranes, such as conjuncti- 
vitis^ /aucitisy laryngitisy urethritis^ etc., it is employed very frequently, not 
only in the stage of relaxation, but in the beginning of the attack. In con- 
junctivitis, the solution employed should not, under ordinary circumstances, 
be stronger than one or two grains to the ounce ; and it should not be used 
at all if any corneal ulceration exists, since a deposit of silver is liable to 
occur and to produce opacity. In /ancitis, the strength of the solution may 
vary from thirty to sixty grains to the fluidounce. Even a saturated solu- 
tion can scarcely be looked upon as caustic to the more robust mucous mem- 
branes. In ordinary cases of sore throat, the application once a day or every 
alternate day is generally sufficient. It is best made by means of a good- 
sized camcl's-hair brush, each part of the inflamed surface being distinctly 
touched, and not the whole simply daubed or slopped over by means of a vciy 
large brush or a sponge probang, as is often done. In severe cases it may be 
necessary to use the solution twice a day. In laryngitis, the solution may 
coiitiiin Irom ten to twenty grains to the ounce, and should be applied with a 
brush by the aid of the laryngoscopic mirror. An attack of urethritis may 
sometimes be aborted in its forming stage by the injection of a strong solu- 
tion (grs. xii to fji) of the salt; but the practice is of doubtful expediency, 
since when it fails it greatly aggravates the trouble. In the advanced stages 
of go}iorr1icea, weak injections (grs. i or ii to fji) are often very serviceable. 

Many years ago (1828) Mr. John Higginbottom originated the practice of 
treating eri/sipclas by the nitrate of silver, and his plan has received a great 
deal of commendation from authorities, but certainly has not been generally 
adopted by the profession. One or two cases of bad results, from ulceration 
of the skin apparently due to the local application, have deterred me ft'om 
giving the method a fair trial, and I do not feel able to offer any opinion upon 
the practice. Mr. Higginbottom in a recent essay (London Practitioner, vol. 
ii. p. 34, 18G9) reaffirms the value of the treatment, stating that its want of 
general adoption is due to its being so often imperfectl}' carried out, and gives 
the following directions : 

" The affected part should be well washed with soap and water, then with 
water alone to remove every particle of soap, then to be wiped dry with a soft 
towel. The concentrated solution of four scruples of the nitrate of silver to 
four drachms of distilled water is then to be applied two or three times on the 
infliuned surface, and beyond it on the healthy skin to the extent of two 
or three inches. The solution may be applied with a small piece of cleao 
linen, attached to the end of a short stick, the linen to be renewed at every 
subsequent application. As the solution of the nitrate of silver is colorless, it 
is necessary to pass a little linen, jitst moistened, over every part where it has 
been used, in order to be equally diffused, so that no part may be left untouched. 
In about twelve hours it will be seen whether the solution has been well applied. 



MISERAL ASTRJNOENTS. 



53 



li an J infliuned jmrt b4^ uii affected, the BolutioD muist be immediately reap- 
pliccL Sometimes, cveu aller the most decided application of the nitrate of 
r, the iufloiiimiUioii may spread ; but it is tlieri gcucndly much less severe. 
. b eventually checked by repeated applications. It is desirable to visit the 
pottettt every twelve hours until the infiiminiation is subdued.'^ 

In iuptrficial iujhimmatiom other than erysipelatous I have frequently 
Ufled nitnite of silver in this way, often with great advantage. Freely applied 
to the skin of the whole finger, it will sometimes even abort a commencing 
Jtlon^ or, applied to the scrotum, an fpididymkia. 

Internally, the nitrate of silver is excseedingly useful in stomachic and to 

ft less ext^ent in enteric diseases, exerting no doubt a purely local influence. 

In thnt form of d^spepgia eluiracterized by the vomiting of large quantities 

i of yeasty fluid, it has yielded in my luuids better results than any other 

' remedy ; and the same may be said of chnmic (/ustrifix and of ^antric nicer 

I The rules of udnunist ration are identical in these three diseases. In the first 

plaec^ regulation of the diet is impenitive: if tlie ease be a bad one, all 

eating of tneals should be suspended, and the patient receive every two or 

three hutirs a cup of sweet milk, with sound toasted bread broken up and 

, ihunoughly 9v>ftened in it. Nitrate of silver should be administered in pill 

' A»rtUf one-ciuartiir to one-ludf grain tliree or four times a day, taken when the 

stuuiaich is empty. In very serious cases, when all fiM>d is rejected by the 

Btomaeh^ It is sometimes advisable to allow absolute rest fur two or three days 

to tlnit visciis, the patient being fed by the rectum, and only a little water and 

\fSSb, pf silver with opium being taken by the mouth. Under these circum- 

s, the return to the u^uul method of taking fond must be very gradual, 

al ordy a tabk-«iXM>nful each of milk and of lime-water being administered 

^eiy hour. In ch funic en ten fig or crAltU^ nitrate of silver is sometimes of 

g[reat survice, especially if there be ulcemtiiin. 

For its constitutional effects nitrate of silver is used solely in diseases of the 
iienrr)ua system. It cannot be denied that oocasionally in epilepiftf it hus 
achieved brilliant results ; but the succeasea are certainly far less numerous 
[ tluui the failurefi. There is one serious objection to the employment of the salt, — 
Bcly, the discoloration of the skin which sometimes follows its continuous 
AgniD, it is not understood io what class of cases the drug is of Cifpecial 
viltie, and there is no means of judging as to its applicability to any individuid 
case. When other means have failed, however, the nitrate of silver may be tried 
III rpilq»«y, the patient or his friends being inforinud that although with projier 
prt ' lie cliances of discoloration are very lew, yet it may occur. 

It iujffAmmt/tions of the spinal cord, whether affecting chiefly tho 

I posterior columns and constituting loa/motor ataxta, or the anterior and 

giving rise to pntaphfjia^ the nitrate of silver is one of the few remedies that 

Mtra ever of any service ; although it most fr(iquently fails, yet it olten diK^s 

I, and in some cases has apparently even permanently arrested the disease. 



54 SYSTEMIC REMEDIES. 

Dose, one-quarter to one-half a grain, always giyen in pill form : if it is dedred 
fo act on the stomach, the drug should be taken when the viscus is empty. 

Toxicology. — The symptoms produced by the ingestion of large doses of 
nitrate of silver are partly gastro-intestinal and partly oerebro-spinal. In some 
cases the one series of phenomena predominate; in others, those of the other 
class. In a case at the Hdpital St.-Louis in 1839 (BecWt Medical Jurispru- 
derice^ vol. i. p. 675, Phila., 1863) the symptoms were insensibility, violent 
convulsions, and dilated pupils, with, on a partial return to consciousness^ 
intense gastric pain ; complete restoration of consciousness did not occur until 
eleven hours ailer admission into the hospital, and the coma returned at 
intervals during several days. 

Vertigo, coma, convulsions, great muscular weakness, paralysis, with intense 
disturbance of respiration, are in these cases the manifestations of disturbed 
inner\'ation ; whilst the abdominal symptoms are those of gastro-enteritis. The 
diagnosis can generally be made by the discolorations of the lips and skin, — at 
first white, afterwards black, — and by the blackish or brownish vomit ; when 
the customary antidote has been given, both vomit and stools are generally 
white and curdy. At post-mortem the stomach and bowels are found cor- 
roded, often ecchymosed and with patches of a white or grayish color. Poison- 
ing by nitrate of silver is not common, and I know of but three iktal cases, — 
one in 1837 (Taylor, Priimples and Practice of Medical Jurisprudence^ 
second edition, vol. i. p. 319), one in 1861, a woman killed by fifty grains in 
solution in divided doses, one in 1871, a child destroyed by a piece of the solid 
stick three-quarters of an inch long, in spite of the immediate and free admin- 
istration of the antidote (Scattergood, British MedicalJoumal, May, 1871). 

The treatment consists in the administration at once of large amounts of 
comnwn salty — the chemical antidote, — the constant use of large draughts of 
milk, and the meeting of symptoms as they arise. 

The fatal dose of silver varies very much, according, no doubt, as to the pres- 
ence 0^ substances capable of decomposing it in the stomach. Thirty grain? 
have killed ; and recovery has taken place aft^r the ingestion of an ounce 
(case, Husemann, Hafidbuch der Toxicologies Berlin, 1862, p. 868). 

Chronic argyria^ or discoloration of the skin by silver, is usually unac- 
companied by disturbances of health, although in severe cases the discolora- 
tion affects not only the skin, lips, gums, sclerotic, but even the internal 
organs, such as the liver, spleen, kidneys. It is therefore not due, as has 
been thought, to the chloride of silver, since the latter only becomes dark 
under the influence of the light, but to a deposition of silver itself or of its 
oxide.* The minute quantity of the metal present is shown by the analysis 
of Versmanns ( Yircliows Archiv^ xvii., 1859), who in 14.1 grammes of 

* Aooording to R6z8ahegiiy HermaDn has seen one case in which, preceding the depo- 
Bition of the silver, there were malaise, emaciation, failure of memory, singing in the 
ears, deafness, and spasms of the ocular muscles. 



MINERAL ASTHINOSNTS. 



55 



dried liver fuuud only 00C8 grarame of raetallic silver (0,047 per cent)| 
and iu 8*G gruwmes of dried kidney 0.053 gnmime (0 061 per cent). 
reater or less success has beun chimed for various treatments in argyria, 
in generul they are ecjuoUy futile. Rogers states that blistering will 

;}iten tlie crilor very niuoh, and Kicbmann asserts (Ilusemann, Toxt^ol- 
tyte^ 871) that he has cured two cosc« by the use of potaah baths and of 

ip batliH, each four times a week. The older authorities commend the 

5 of iodide of potassium internally. Dr. L. P. Yandell has reported 
(American Pracf it totter, June, 1872) two cases in which lurj^e do.sc8 of the 
iodide were given for many months for syphilis, and the mercurial vapor- 

hs used at the same time for the same purpose, with the result of a 
plete cure of the argyria. The fading was gradual 

Administration. — Tlie nitrate of silver should always be given in pill, 
ADd, when it h desired to obtain ita coustitutiona] influence, after meals, 
ig the process of digestion ; but when its loeaJ action on tlie alimentary 
«anu] is recjuired, it should be adniinlf«tered one or two hours before meals ; 
Aud if the bowels are to be rtr^iehed^ the pill sJjonld have been made some 
unie, so as to be disBolved as slowly as possible, When it is given in epilepsy 
or other chronic disease, its adjuiuist ration should be suspended hr <mc. week 
at the end of every third week, and its employment should not exteiul over a 
longer time than three months without a protracted intennisaioo. 

Ar^ciiii ni/ras dilulus^ U, S., is a grayish solid substance, often iu crayotib, 
composed of equal parts of the nitrates of silver and potassium. It may be 
uaed as a very mild caustic. 

The oxidt of gihier ( ArqepO'I OxiDUM, U, S.) ia an olive-brown powder, 
very alightly soluble in water, which the United States Pharmacopceia directs 
filial) be prepaa^d by p reel pita ting the nitrate of silver with solution of potassa. 
It has been introduced into medicine as a substitute for the nitrate, with the 
idea that it would accomplish in diseases of the nen^ous system all that that 
drug is capable of, and at the same time not discolor the skin. With our 
present knowledge of tlie method of absoriitiou of the nitrate, this sc'ems 
hij^hly improbable, and it \s contradieted by experience, (Cane, IVdhuL 
Mtd. Tim^Jt, vi. 204.) Oxide of silver is not caustic when locally applied, 
but probably exerts some astringent action, and has been commended in p^* 
rotU. In nervous affections it is probably of equal value with the nitrate. 
The dose is a grain, in pill, three or four times a day. 

The cyanide of silver (Arqenti Ctanidum, U, S.) ia used solely for the 
prej^araiion of hydrocyanic acid. The iodide (Aboenti Iodidltm^ U, S.) 
has been u^ed as an alterative, but is of very doubtful value. 



CLASS n-TONICS. 



There are certain substances in nature which, when taken internally, act 
upon the nutrition of the various tissues so as to restore lost tone, not by call- 
ing into play the vital principle of contractility, but by increasing the power 
in the part. Such substances are known as tonics. They differ from astrin- 
gents in that they affect nutrition, and consequently in the slowness and per- 
manence of their action. They differ in a similar manner from simple stim- 
ulants, and as they do not call into sudden action forces already existent in 
the part, but increase power by increasing nutrition, their influence is a per- 
manent one and is not followed by depression. They are, of course, indicated 
by debility dependent upon impaired nutrition, — t'.e., debility owing to actual 
loss of power. When the debility is due to a sudden depressing influence, as 
in snake-bite, they are of no service whatever. They are especially valuable 
in couvakscence from acute disease ; during the progress of the disorder they 
more often do harm than good. 

Tonics should, of course, never be used when plethora exists. Sthenic in- 
flammatory action is also a contra-indication to their employment ; but when 
inflammation exists with a general stat« of debility, these drugs may form an 
essential part of the treatment. 

The tonics are divisible into several sub-classes, which I shall consider 
separately. 

SIMPLE BITTERS. 

Probably all bitter vegetable substances possess tonic properties, but in 
many of them, as in morphia and strychnia, these properties are completely 
overshadowed by other inherent powers. There are, however, bitter vegetable 
substances which so act upon the stomach as to invigorate digestion, and to 
affect thereby the general nutrition, without exerting any direct influence upon 
other portions of the body than the alimentary canal. These are the simple 
bitters. In ovcrduses they nauseate, and may act slightly on the bowels. 
They appear all to act alike, — differing more in strength than in quality, — so 
that one may be substituted without detriment for another. As they are 
essentially irritiints, inflammation or over-sensitiveness of the alimentaiy 
mucous nicnibnine distinctly coiitra-indicatos their administration. They are 
indicated by loss of appetite and loss of stomachic tone. 
66 



TONICS, 



57 



QUASSIA. U.S. 

The wood of Simaruba cxoelsa, a hirge tree, native of Jan»aic4i, Tliis wood 
is light both iu density and coIoFj eoiuewhat resembling that of the ttiHp-trcc, 
but difitintruishcd by its iiitciist^ly bitter taste. It la kept m the shops iti 
billets and in raspings. The active principle of it appears to be Quasn'n^ an 
intensely bitter, neutral, crystalline principle discovered by Winckler (Repert, 
fUr Phiu^nucie, Bd, liv, 85, Bd. Iv. 85). Shnaruba (U. S.), the bark of 
Sinuuruba offictnaliiij also coutiiini} quossin, and may be substituted for quassia. 

Physiolooical Action. — Quamn la said in large doses to be actively 
fwiflOtioiis to iufieets, and even to mammals (Stille's Tlierapentics^ i. 472 ; 
Hoflcaaann, Die PJlanzeiiifftffe, p. 718) ; but I have met with no detailed 
study of its action except that of L Hup[>e, who experimented upon frogs 
(Dev fetches Klittikj sd.^ lS5r*)* In doses of one gmin it usually produced 
dealh iu a short time. The symptoms were great weakness, wit!i, in most 
Dnvulsiotis and sometimes convulsive tremblings, failure of respiration, 
Uy cessation of cardiac action. The funetiunal aL*tivity of the nen^e- 
trunks was much impiured, that of the muscles to a loss extent. Locally, 
i)uiaau appeared to act as an irritant oa well as a power^ poison to both 
fi«nrous and muscular tissues. 

TuERAPEUTlcs.^ — Quassia is probably the most active of all the simple 
bittern, and may be used whenever sucli remedies are indicated. In cjises of 
i&tt-womiM iu children, a strtaig infusion of quassia ( Jti to Oj) aifords a most 
harmless and efficient injection. Its exhibition should be preceded by an 
liueiiuk of siiuple water, after a stool, so as thoroughly to wush out the rectum 
and allow aooeas to every fold of the rectal mucous membrane. The officinal 
preparmtions ure a tincture (Tuictiira Qwisisi^ — 1 to 9, U.S.), dose, twenty 
drops to a teaspoonful ; a very excellent watery rxXnici {EjctracUtia Qita^siie, 
U. 8,)j which may be given in pills containing from one to three grains ; and 
uid extract {^Extractum Qxtaum Flmdum)^ dose, five to ten drops. 

GENTIANA-GEKTIAN. U. S. 

The root of the Gentiana lutea, or yellow gentiiui of the Alps, This root 
SI'S in the shops either in picecs of viurious sIkc and shape but generally 
§evcnd inches in letigth, or else in transverse slices. The texture is spongy, 
the odor taint but pet^uliur, and the taste bitter. It contains genti&ic acid^ 
which was diiicovcrcd by Leeonte, and is t^istelcss and physiologically inert. 
The jictive principle is [►rub:ibly the cfnttiopiknn of Kromayer, a neutral, 
crystidlinc substance, of an inteust^y bitter taste, 

TufHtAPKlTTlCS. — Gentian is one of the most efficient of the simple bitters, 
and may be mnxl whenever such a remt>dy is intlicated. It is never given in 
iobatance, but in one of its preparniions. These are the cnmpound tincture 
{Tin€iufa Oenttasisn Compoiita^ U.S.), which contains gentiun (1 to 12.5), 
bitter-orajige peel, and cardamom — dose, one fluidrachui to half a fluidounoe; 



68 SYSTEMIC REMEDIES, 

the watery extract {Extractum Gentianm^ U.S.), dose, two to four grains; 
and the fluid extract {Extractum Gentianx Flaidum^ U. S.), dose, ten 
minims to half a fluidrachm. The compound vi/usi*m, formerly officinal, 
was a valuable preparation, containing some alcohol, and much used in doses 
of one to two fluidounces. 

NEOTANDBA. 

Beheeru Bark is the bark of the Nectandra Eodiei, a large tree which grows 
in Guiana and the neighboring parts of South America and is ascd in ship- 
building under the name of Greenhcart. It occurs in large flat pieces, and 
contains an alkaloid, which was discovered by Dr. Maclagan, of Edinburgh. 
According to the researches of Walz {N. JahrL Pharm.^ xiL, 1861, 302) and 
of Fliickiger (Ibid., 1869), this alkaloid is identical not only with Buxia. 
obtained by Faun6 in 1830 from Buxus sempervirens, but also with Pelo- 
sia, discovered by Wiggers in pareira brava. Bebeeria^ or, as it should be 
called, buxia, is whitish, amorphous, inodorous, very bitter, very slightly 
soluble in water, freely so in ether and alcohol, and forms uncrystallinble 
salts. Dr. Maclagan found a second alkaloid, Sipeena^ in bebeeru bark,i>at 
it is probably only altered bebeeria. 

Physiological Action. — Our knowledge of the influence of bebeeria 
upon the system is exceedingly incomplete. Albers ( Virchows Archxv, Bd. 
xxiv.) found that three grains introduced beneath the skin of a lai^e frog 
produced death in six and a half hours. There was first a period of quiet 
with accelerated breathing, then tonic and clonic general convulsions, seemingly 
associated with muscular weakness, but with no increase of the reflex activity. 
Prof. Binz ( Vtrchow's Archiv, Bd. xlvi. p. 130) has determined that bebeeria 
exerts some destructive influence over infusorial forms of life, but that it is 
in this respect not nearly so powerful as the cinchona alkaloids. 

Therapeutics. — Bebeeria was originally proposed by Dr. Maclagan as a 
substitute for quinia in malarial diseases, and has been quite extensively tried. 
It appears to possess some autiperiodic powers ; but they very probably are 
not superior to those of the more powerful simple bitters, and are certainly 
very inferior to those of quinia, so that bebeeria is at present very seldom 
if ever used. The sulphate, which is ofiicinal in the British but not in tho 
United States Pharmacopoeia, may be given in acidulated solution in doses 
of from two to five grains. 

BERBERIS-BARBERRY. 

Under the above title the U. S. Pharmacopoeia of 1870 recognized the 
bark of the root of Berberis vulgaris, a native of Europe. This drug con- 
tains the alkaloid berberina, which, although not itself officinal, is found in 
80 many recognized drugs as to require notice. 

Berberina occurs as a yellow powder, or in fine yellow needles or prisms, 
of a bitter taste and neutral reaction, moderately soluble in cold, freely in hot, 



w&ler, freely soluble Id alcobol. With acids it forms mostly orysioltii&ble, 
goideD-jeUow aalta. 

It« effects upon animak bave been studied by Faick and by Guenste. In 
do^ it produced, when giveD id very large doses, restlessness, convulsive 
tremblingSj thirst, and diarrlioea, and finally partial paj-alysiB of the hind legs. 
Fpciin seven to fifteen grains af it killed rabbits in from eight to forty hours. 
The ayioptoms were increased Frcfjucncy of respiration, and trembiingSi followed 
by decrease of the rate of breathing, paresis, paialysis of the hind legs, great 
dys^nsvL, and iiually couvul^ons. In mau^ as yet^ no ^rious symptoms have 
been recorded as produt^ed by berbeiina. Bucbuer took nearly twenty graina 
without causing anything more serious than a loot^ stool As a bitter tonic 
It has been usee! by various physiciiuis in doses of from two to five grains, and 

I action in this dose appears to be that of a simple bitter. It may be given 

\ piU fumi or dissolvcKi in aJcoboL 

OALUMBA-OOLUMBO. U.S. 
The root of CoccuIub jialmatus, a cJimbing vine of Mozambique. It occurs 
in the gbop in transverse disk-like slices^ oval or circular in outline, one or 
two inches in diameter, of a spongy texture, having a yellow iab surface, very 
bitter taste, and slightly^ aromatic odor. It ot^ntoins a gre4it deal of starch, 
bc^dcs berberina, and, it is said, in lesser amount, Odambia^ a bitter neutral 
principle crystalii^dng in rhomboid prisms or needles. 

TuERAPKCTirs. — A bitter, slightly aromatic tonic^ iisefiil as a stomachic 
I in which a simple bitter is indicaf^. It is not used in substance^ Ita 
Lttons are^ — a tincture ( Tmctura Coluvxhm — 1 to 9, U* S,), dose, one 
to two fluidrachma; and h flmd tixtract {Extractum Calumbm Fluidumy 
U.S.), dose, fifteen minims to half a fluidrachm. 

BUPATORIUM-BONESET. U.S, 

The herbaJ parts, gathered after flowering, of the indigenous Eupatorium 
performtuiii, a tall, coarse composite, recognizable by it#^ perfoliate leaves, 
through whose centre grow the stems and branches. This dj-ug given in cold 
lufuaion (3i to Oj— dose, fji-ii) is an efficient but disagreeable bitter tonic 
ItA chief employment is os a sudorific. The hot infusion when taken fi-ecly 

7e to six ounces) J the patient being well covered in bed^ produces free 
ating, and has been very largely used in "general colds," mmcuhr rfmt- 
msHiamt etc, for this purpose. The only objection to the remedy ia ita 
dlMgreeabl^ imU>, In the d(»se of a pint the infusion has been employed 
M» an emetic. The Jluid extract (^Extmctum Eupatorii Fluidumy IJ,S,) 
HUkj be used in dosed of a fluidrachm to a fluidounce, 

Chiretta* U, S,» the herb and root of a plant growing in the northern 
E of India, ii one of tbe best of the simple bitters, and ts believed by «orae 
exert a peculiar influenoe over the liver. Whenever a simple bitter la 



60 SYSTEMIC REMEDIES, 

indicated, this drug may be employed, especially if a cholagogue action be 
desired. The solid extract is an excellent preparation in doses of one to 
two grains ; the fluid extract (Extractum Chirettm Fluidum, U. S.) may 
be given in doses of five to ten minims ; and the tincture (^Tinctura Chirettse 
— 1 to 9, U. S.) in doses of a fluidrachm. 

CoBNUS. U.S. — Dogwoody the bark of the Cornus Florida, is feebly 
tonic, and has been supposed to be antiperiodic. It is very rarely, if ever, 
used by regular practitioners of medicine, and may be given in almost 
indefinite doses. 

PECULIAR BITTERS. 

These are bitter vegetable tonics possessing other properties besides those 
of the simple bitter. 

PEUNUS VIEGINIANA-WILD OHEEEY BAEK. U.S. 
Wild cherry bark is the product of the Prunus (Cerasus) serotina or wild 
cherry tree, not of Prunus Virginiana or Choke cherry, whose name it bears. 
It occurs in pieces of various sizes, usually without epidermis. The color is 
a reddish cinnamon ; the taste slightly astringent, bitter, and peculiar, re- 
sembling that of peach-leaves. It contains tannic acid, bitter extractive, 
amygdalin, and emulsin. Amygdalin is a nitrogenous, crystallizable, odorless 
glucosidc, of a slightly bitter taste. It is soluble in water and alcohol, but 
not in ether. Emuhin is an albuminous principle, which is soluble in water, 
and, like other forms of albumen, is coagulated by heat, alcohol, acids, etc 
When amygdalin in watery solution is brought in contact with emulsin, it 
is decomposed, forming prussic and formic acids and a colorless, thin, volatile 
oil, which, when pure, has a peculiar agreeable odor and a burning taste. 
According to Liebig and Wohler (^Ann, Chem. Phamu^ xxii. 1), seventeen 
grains of amygdalin yield one of hydrocyanic acid : therefore, if thirty-four 
grains of amygdalin be mixed with sixty-six grains of emulsion of sweet 
almonds, a two per cent, solution of hydrocyanic acid will be formed. 

Physiological Action. — Amygdalin administered by itself is nearly, if 
not quite, without effect upon the organism. Widtmann and Denk (Huse- 
mann, Die Pflanzemtoffe^ p. 688) took as much as sixty grains of it without 
inducing any effect, and their results have been confirmed by Reil and others. 
Lehmann, it is true {Ibid.)^ found that at times fifteen grains of it by the 
mouth were sufficient to cause death in the rabbit, but Kb'lliker and Midler 
have shown that this was owing to its being converted into prussic acid by 
the emulsin contained in the green herbage in the stomach of the rabbit. 

Therapeutics. — In wild cheny bark properly administered there are three 
active ingredients, — tannic acid, bitter extractive, and prussic acid ; and to 
their combined action the general efiiect is due. As the tannic acid is in 



IVNICS. 



61 



soudl quantity, iU influence la not marked ; but probably some of the repu- 
tation which the remedy tbrmtTly enjoyed as being useful in the nij^htnsweats 
of phthisic was due to it. When given in the ordinary dose, I have never 
been able to detect any sedative effect from wild cherry bark; but the in- 
fusion administered with gufficicnt freedom ccrt^iinly ouj^ht to exert such 
infiuence. Pninus Virgrniana is therefore slightly astringent, jscdativc, and, 
owing to its hitter extractive, tonic. It is frequently useful in phtJmia when 
t rohorant i^ needed and at the same time a calmative action nn the neiTous 
system is called for. It may l« used iu hectic /ever Irom any source. 

The in/tiJfion (In/umim Fmni Virginiatix — 1 to 25, U, 8-) is useful as 
an adjuvant to other tonics, especially sulphuric acid, in debUifif with a 
tendency to night-sweats during convalescence from acute disciise. The dose 
is one to two wineglassfuls. On account of its pleasant taste and triuUtional 
reputation, the Ki/rup (iSt/rupuM Pruni Virginxtnia^^ U.S.) is often employed 
as thf* liaius of cough-mixtures. The fluid extract ( Extract nm Prnm I7r* 
pniftnst Fluidum^ U.S.) may be given in doses of from half a fluidraohn] 
to A dradun. 

CINOHONA, U.S. 

Under the general terra of Cinchona the United States Pharmacopoeia 
rf>00§:iiites the ** bark of all the q^ecies of the genus Oincbona containing at 

6t two per cent, of the alk^doids which yield cr3\Htid I liable isaJts,** Under 
name of OfNCUnNA Flava, or Ykllow OiNrnoNA (syn. Calimga 
B<irk)^ the same standard list includes the hark of Cinchona Calisaya ; under 
the name of CixciioxA pallida, Pale Cin'chona, that of Cinchona 
CondamincjL and C. micrantha; under the title of CtNcnoNA rubra, Reh 
Cr^cnoNA, that of C. suc^irubnu 

All the trees yielding fjuinia and its congeneric alkdoids belong to the 
genus Cindiona, and inhabit the slopes of the Andes Mountains from the 
northcni extremity of South America to the lower portion of the republic of 
Bohvia, at an altitude of from five to ten lliousand feet. The bark h col- 
lecttid by pcrsotm known as Cascarillerosj and is exported in largo hundlcis or 
utmally surrounded with raw ox-hide* To these packages the term 
jftH* IS af*plied, 

Tlic Pt/fr Hark occurs in quills or cylindrical rolled piecee, with a p'ayish 
or brownish adherent epidermis. It derives its name from the li^ln fawn- 
isolor of itfi [lowder. 

Tlie Calum/n or Ho^al Yellow Bark comes both in f|uills and flat pieces. 
TIki epidenuis is absent, or, if present, ia loosely attached. The pcjivdcr is 
of a decidedly yellow color, aometimea almost orange. The fractnrc is short 
and fibniQii, presenting: semi-transparent, sharp spiculae, which are apt lo 
become detached and jicnetrate the fingers. 

The Cinchona rubra, or Red Ciiicho^m^ occurs in quills and flat pieces. 
The epidermis is genei-ally present, and is oflen very warty. The color of 



rite 



62 SYSTEMIC REMEDIES. 

the powder is a &int reddish-browD. Beneath the epidermia is in most specie 
mens a distinct, red, resinous layer, which is very i^pparent in cross-sectioa. 

Large quantities of bark under the name of Cartha^ena Bark find their 
way into commerce through the northern ports of South America. For 
descriptions of these the reader is referred to works on Materia Medica. 

Very success^ attempts are being made to cultivate cinchona, especially 
in the Himalaya Mountains, Java, and Jamaica, where many millions of the 
trees have been planted and are thriving. The East India bark is already 
arriving in liondon in considerable quantities, and in a few years the supply 
from this source will doubtless be very large. 

Chemical Constitution. — Besides tannic, kinic, and kinovic acids, and 
other important substances, the cinchona barks contain quinia and quinidia, 
cinchonia and ciDchonidia. Out of these alkaloids quinida and cinchonioia 
are readily formed artificially, but, so far as is known, they do not exist in 
nature. There are therefore two isomeric alkaloidal groups ; quinia, quinidia, 
quinicia ; cinchonia, cinchonidia, cinchonioia. 

QUININA. U.S. 

This alkaloid was first distinctly separated from the other ingredients of 
the bark by Pelletier and Caventou in 1820. When quinia is precipitated 
by an alkali from a solution of its salt, it usually falls as a hydrate, which 
may be crystalline. By sufficient heat the hydrate is melted and the water 
is driven off. On cooling, the alkaloid, now free from water, forms a white, 
opaque, crystalline mass. 

The neutral, officinal sulphate of qmmne (^Quininst Sulphas^ U. S.) occuTB 
in light silky crystals, soluble in seven hundred and forty parts of cold or in 
thirty of boiling water, readily soluble in alcohol, very freely so in acidulated 
solutions, nearly insoluble in ether. The aqueous solution, upon the addition 
of chlorine, and afterwards of ammonia, assumes a green color. According to 
Dr. G. Kerner, if the original solution be colorless and clear and in a clean 
test-tube, one-thirty-thousandth part of the alkaloid can be recognized by thia 
chlorine-ammonia test. When to one hundred parts of the salt, dissolved in 
nineteen hundred and twenty parts of cold dilute acetic acid (sp. gr. 1.042), 
are added successively four hundred and eighty paru* of alcohol (sp. gr. 
0.837) and sixty parts of a saturated alcoholic solution of iodine, crystals 
of Herapathite separate, in the form of right-angled quadrate rhombic 
leaves, which when seen by transmitted light are olive-green, but in reflected 
light are bright metallic green, resembling the elytra of Spanish flies. AVhen 
heated, the sulphate of quinia becomes phosphorescent, emitting a pale- 
green light at 155° to 160° C, and at a higher temperature melts with the 
development of purplish vapors. When the neutral sulphate of quinia is 
dissolved in water acidulated with sulphuric acid, it is converted into the 
soluble bisulphate, which may be obtained in orthorhombic prisms by 
evaporation. 



'/•OJV/CS. 



«3 






Pht»iolooical AcrroN. — Quinine or its salts in jKJwder or solution ai«» 
wheij iipplictl upon ti part denuded of its epidemiis, very active irritante. 
Uj^Mtn tliL' skin they have little or no influenoeT but upon the mucous mem- 
brajiej* they exert a very pert'eptible stimulant or irritant actitJU. 

A. Kulenburg found that when quinia was brought into contaot with a 
snerve it did not cause oontniction in the tributary muscles, but when placed 
iptm the mujcie^^ themselves it induced immediate violent action. He there- 
fure concludefi that it is not a nerve- irritant, but is a rauacle-irritimt. When 
it is aduiinist^red to dogs in auflficiont quantity, it prc*duces restlestsness, foU 
1<jwcii by muscular tramblinifs, which have been compared to those of paralysis 
I iHH, Ions of jiowcr deepening into more or less complete paraly^, great 
i^. -^logea, and cerebral symptoms, such as anie^itheftia, blindness, atupor, or 
Tioleot delirium, dilated pupils, ooma, and convulsions. When the drug is 
intnxiuccd by the stomach, vomitinj? generally occurs^ and at times diarrfaoQa 
bIso,'' Death has been shown by Ueubach to be produced, at least in the 
lower animals, by a failure of the respiration.f 

The first symptoms of cinchonisra, as produced by small therapeutic dosea 
(ten grains) in man, are usually ringing in the ears, slight fulness in the 
bctftd, and perhaps some deafness. With the use of larger dos« these symp- 
loms are iutensilied : the deafness is very marked, disturbed vlsionj may 
•xist, and the flushed face, with the sense of distention in the head, may 
l^int towards a cerebral congestion, which is in some cases relieved by spon- 
epistaxis. In decided einchoni«m, giddiness and staggering in walk- 
arc very c4)mmon. After toxic doses, severe headache, delirium, stupor, 
ple'ic deafness and blindness, dilated pupils, embarrassment of respiratioii| 
eat weukneKs, eonvulsions, paralysis, and finally collapse, may result, 
^her comatuse or delirious. The deafness produced by large dosea of 
line mnially passes off rapidly ; very rarely is there a permanent impair- 
of hearing. Amaurosis, with a peculiar ischaemia of the retinal vessels, 
itM in a small number of cases been produced by very large therapeutic 
iea of the alkaloid (see Archivti of Otholmologtf^ x. 81, 214, 220), 
The minimum fatal dose of <{uinine is not known^but it munt be large, and 
I J varies very n^iich Br, Clnptitn detailH ( Aff^fiWil ThtHtt mul Gazette^ 



•Sea M. F. Mvlior, MSnmirrM dt VActtd4mU, t. xU. p, 723, 184iJ : Ww. 0. Baldwin, 
nf^iVaik Journal of the Medical Seiencett April, 1847 i P. Briquet, Trmii tkiraptuttqu4 
f Qmitr/Htiia, PAriAi 1855. 

Th» |irwettt U p«rliapi &• laitftblo • poiitioa iii in; to notloo ceriaiD rasuai^bes upon 

I relftttoai of iklk&biiifl to protoplajtn. The relation betwdun medieinal subAt&noet aod 

li«*uei upon which ibej set U oertaioly a rcrj clo«e ooet and rcry probably li ohem- 

i in iiM nature. Dr. Ronbaok {Pharm, CntertHcK,, Bd, i., lift iii.) found Ihat rarioui 

BkaMtls nfiniiblj modifj the proporties of albumen, Had believcD that they fortn a cbem 

Al eomitound with it. tinder the influeneo of the poison the albumen coagulatet at a 

J»iw«T temperature, and it dopriveil of lt« aflltiltj for osone. The alkaloida alto 

sipiUttfl ihft albamea from Ita ocouiaed solution. 

I I bare fte«a oompkte tMnporary anaaurosli prodaoad in a ladj bj twelve graiut of 

fealniiie* 



64 SYSTEMIC REMEDIES, 

April, 1864) a case in which a soldier took at one dose an ounce of the 
sulphate, stirred up in some water, without the induction of any more serious 
symptoms than a mild stupor ; a similar case is mentioned hy Dr. Lente, on 
the authority of Dr. WoodhuU ; and a third is recorded by Taussig (Still^'s 
Therapeutics^ vol. i. p. 507). I cannot help suspecting that in these cases 
much of the drug passed through the intestines without absorption. In the 
famous case of Bazire five ounces taken in the course of ten days caused 
death. Von Graefe asserts that he has seen two cases of amaurosis caused 
by quinia ; the suflferer in one instance taking half-drachm doses until six 
drachms were ingested, in the other case an ounce altogether of the drug. 

A close physiological study of quinia can best be made by investigating 
its effects upon the diflferent systems of organs seriatim ; and this shall now 
be done. 

Cerebrum, — According to the experiments of Briquet, a solution of sulphate 
of quinia injected into the carotid will in some cases produce meningitis. In 
doing this, it is evident, the salt acts rather as an irritant to the membranes 
of the brain than as a nervous stimulant: indeed, experimental evidence 
proving that quinia is a cerebral stimulant seems to me to be wanting. The 
chief proof that the alkaloid does act as a stimulant lies in the feet that per- 
sons who have been taking it regularly for some time will occasionally, upon 
the sudden withdrawal of their daily dose, manifestly be less active without 
than with it. Briquet may be right in his belief that in small doses it acts 
as a nervous stimulant, but the proof of his correctness at present is clinical 
rather than experimental. When given in toxic doses to the lower animals, 
probably all of the cinchona alkaloids produce epileptiform attacks. Dr. 
J. Jakoubowich {Revue des Sciences M^d,y 1873) has noticed such effect 
with quinine in dogs, and it has been produced with cinchonidine in various 
animals. Chirone and Curci found that in the pigeon this action of cin- 
chonidine is prevented by ablation of the cerebral hemispheres, but ftof. 
Albertoni objects with much force that these observers gave the pigeon the 
alkaloid too soon afler the ablation, whilst it was still profoundly affected by 
the shock and hemorrhage of the operation (^Arch. f. Exper, Pathol, und 
Therap., xv. 278). Prof Albertoni found that, if the pigeon was allowed 
to recover, the cinchonidine was capable of causing convulsions; also, that in 
dogs with the motor zone of the cerebral cortex destroyed, the alkaloid 
caused epileptiform attacks, and that therapeutic doses do not increase the 
excitability of the cerebral cortex in the dog. The subject is one of great 
interest in connection with the circumj<tauce, noted for quinine by Brown- 
S<^»quard and confirmed by Albertoni as regards cinchonidine, that in epi- 
leptics the attacks are rendered decidedly more frequent by the cinchona 
alkaloids. The present evidence indicates that this increase is not due to an 
influence upon the cerebral cortex, but can hardly be considered sufficient 
to be conclusive. In very large doses quinia without doubt abolishes the 
functions of the cerebrum. Louis Dupuis (^U Action physioL de Quinine^ 



KXICS, 



m 



Ptti*, 1S7T) Found tliat rt-flex action was norrad in poisoned dog.i und n^b- 

bilii> «hlyc)tii;h there was complete Iohs ofst^nsibiltty^ and he natttrullj concludes 

thai the latter was of cerebral orijjitt. The disorders of special sense pro- 

dQced bj quinine seem to be the result of a direct or indirect congestive 

^^Uon upon the peripheral sense organs; since Dr. Kirch ner (SUzttn^s* 

^^ich£€ FhffB.'MetL Gexelh, WUrzh^trg^ 1881, 161) found, in rabbits, cata, 

^Hd gninen-pigs which h«d been poisoned with fpiinine or with salicylic 

^■d, very great conj^e*?tion of the internal ear and of the hibjrinth, with 

Bloody eacodarion, and with, in some cases, the car-drum swollen into a 

Ider-like body by sen ►us exudation. 

Spitttjf X^cfn atid Cenlrrt, — Selilockow was the first to notice a stage 
cre^i^ed reflex activity produced in the fra^ by<|uinia: it-s existence 
ibsequenlly denied by A. Ealeuburg (Rrichert's Archiv, 18tj5)» but 
reaffirmed by If* Heubach ( Central ft. Med. Wmmxch,^ 1874^074), 
by my pupil^ David Certia, who ain*ee in findini.^ that it occurs only after 
minute doses. In his investigations uiade in the Laboratory of this 
livemty of Pennsylvania, Dr. Cerna found that this stage of excitement is 
ibably e:^nsvd by a stimulant influence upon the peripheral sensory nerves, 
did not occur when the abdominai aorta was tied previous to the exhi- 
ion of the alkaloid (Phiia, 3ftd. Times^ x. 493). Two facts, first pointed 
by Dt, T A. Chaperon (PJiUgeri ArcMv^ 18G1J, 295), have been so 
I rfw iKiafitly substantiated that we must accept them as established. They 
In tmaH doaoe quinine causes in the frog a lessening of the reflex 
[ivity, which is removed by section of the inedu!la, hut in large doses it 
Juca-i a pernaanent palsy of reflex activity. The first of these actions 
usually been considered to show that the alkaloid stimulates Setxsche- 
ecntre in the base of the brain, but Dn Sedgwick {Jmn\ of Phj/si- 
y^ iiL 22) believes that the inliibition is such as occurs when a sensitive 
vn isgalvanisBcd, and is the result of a stimulation of the peripheral uffer- 
cardiac pneumogastric nerve codings. He bases his theory chiefly on 
fact wtiicli he has discovered th.it atropia prevents tho primary inbi- 
Son of Ti flexes by quinia* This is however, readily cxphiiiisible without 
adoption of the tlieory of i?cdgwiek, and as the results which ho 
iinod after division of the pneumognstrics are scarcely in accord with 
t>ry, it is still mosn. probable that qninia is a stimulant of Setsehe* 
enlTe* The CJtu^e of the permanent influence upon reflex activity 
not jr«t been accurately determined. Chaperon has shown that the 
^lor nerves are unaffected, but thii^ docs not prove that the spinul centres 
pamlyzed. A. Kulenburg {I^rtcherf's Archiv, 1865) a.S!;erls that vohin- 
moveuieuts pet^ist aflcr reflex actions, and that the quinized frog will 
into its normal position when laid upcui its back, although ordinary 
lejc actiuiis are completely aboli.shed. This, if correct, certainly shows 
^t it is either tlie sensory nerves or tho receptive centres of the cord 
iowj paralysis by quinine paid an end to ordinary reflex movements. So 

b 



66 SYSTEMIC REMEDIES. 

that, accepting the Tarions rcsolUi reached by experimenter8,^it is probable 
that in frogs quinine first excites and then paralyzes the peripheral sensiiive 
nervous system. How far this applies to man is uncertain. According to 
the experiments of H. Kobert {Archiv f. Exper, Pathol, und Therap,, 
XV. 49), very large doses of cinchonine, and probably therefore of quinine, 
lessen the excitability of the muscles. 

Abdominal Organs, — Upon the stomach and intestines quinia acts very 
much as a simple bitter. In moderate doses it stimulates digestion and in- 
creases the appetite ; in lai^ doses it not unfrequently causes nausea and 
vomiting. When there is any morbid irritability of the mucous membrane 
of the stomach or bowels, its irritant action is often very marked, and its 
continued use in large doses has been known to cause gastritis. 

Many years since, M. Piorry asserted^ that a large dose of quinia would 
produce a distinct immediate lessening of the size of the spleen in cases of 
intermittent ; but the testimony of very numerous observers to the contrary 
is so concurrent as to render the truth of his observation highly improbable. 
Several observers'*" have stated that the exposed spleen of an aninud can be 
seen to contract when sulphate of quinia is injected into the stomach, veins, 
or cellular tissue ; but other investigatorsf have failed in their attempts to 
produce this asserted contraction. The experiment necessitates such abnor- 
mal exposure of the organ that only a very pronounced and very constant 
diminution could establish the assertion that quinia produces contraction of 
the spleen, and our present knowledge indicates that the alkaloid has no im- 
mediate decided influence on the size of the organ. 

Organs of Circulation and Blood, — Briquet, who first studied closely 
the action of quinia upon the circulation, found that in large doses it lowers 
the arterial pressure in the lower animals. The experiments have been con- 
firmed by various observers, notably by Schlockow {De Chini Sal/avici, etc., 
Bratisl, 1860), A. Eulenburg (^Reichert's Archivj 1865), and Cerna(foc. cit,j 
194). It has been abundantly proven that the alkaloid thrown into the 
jugular vein, introduced into the coronary artery, or in any way brought in 
contact with the heart, lessens the force and frequency of the pulsations, 
and finally produces diastolic arrest ; also, that this result is not influenced 
by separation of the mammalian heart from the nerve centres, and occurs in 
the cut-out frog's heart. In man, very large doses of quinia (thirty to sixty 
grains) lower the force and frequency of the pulse ; a pulse-rate of forty 
has been noted, and in reported cases of quinia-poisoning the pulse has been 

•M. Piorry, Archive§ GinSrnlet de .XUilecine, 1847; M. Pag^s, Oazette AlfdieuU, 1846; 
also Dr. KUohenmeiBter, Archiv fur Phyniol, Heilkunde, Bd. x, ; M.MosIer, Pntko^oqit 
der Leukaemitf Berlin, 1872, p. 451 ; Jerusalimsky (CVw<r«/6/«« Med. Wlaten., 1876, p. 476). 
Tbo latter observer believes the contraction to be oaudod chiefly by an action on the periph- 
eral splenic nerves and muscles. 

t Magendie {Gaz, Mid,, 1847), and especially L. T. Bochefontaine, BechereheM Expiri- 
mttU, d la CttutractUiti de la Bate, Paris, 1873. 



TON!CS. 



6T 



Imperceptible at the wrist. Under the latter circuuifitancea the pulse rate 
maj be locrea&ed, but tlie earditic force is rc^rluc'ed to a luinimum. The 
fc'idence is cooclusive that both in miin nnd the lower ninrnal.s quinine iu 
Bcicnt ttuiount is a povvertiil dL'presj-ant to the heart* iiiufiiclo or «ranglia.* 
Scbmff (Medain Jahrbiichcr^ 1875) found tliat in the ijuinized animal 
ber gnlvanization of a sensitive nerve nor asphyxia was able to produce 
scul»r eantraetioii and ri^e of bloo4-prpr>surc, and .Jerusaliuisky {^Cftttmlh^ 
t^d. WtMengch., 187Cj p, 470) asserts thut in iVoi^s dtlalalioa of the vessels 
[»uld be seen, so there is some reason tV»r believini: that tuxic doses of 
|uiuia paralyze not only the heart, but abo the vaso-motor system.f Both 
chroff and Jerusalimsky noticed that the fall of arterial pressure produeoU 
quinia is preceded by a rise cif the preasurc, accompanied with ao in- 
i of the cardiac action. The rise of pressure^ if it really occurs, is 
probably the result of a stiuiuhint action ujion the vaso-tnotor centres, as 
Jerusiiliiiisky found that it was not produced after division of the cord. 
lerm^limsky attributes the increase in the pulse-rate to paralysis of the 
inhibitory ap[>aratu», a view which is supported by the assertion of Cerna 
that previous section of the pneumogat^lric prevents the quickening of the 
uLae-rate. 
I have never been able to perceive any depressant action upon the circu- 
lation in man uncr ordinary therapcutio doses (three to five grains) of 
Ekia, and I believe that in tonic doses quinia produced no perceptible 
datloQ of the circulation^ but that ihc largest antiperiodic doses have a 
distinct infldcnce-t 

According to Bonorn and Arvedi^ to Magendie, to Monneret, to Melier, and 

Baldwin, in animals killed with quinia the blood is found to be dark, de- 

fibiinated, fluids and tneapnble of forming a clot. Briquet, however, denies 

ihat this alteration of the blood is constant or even conjmon in f|iiiTna-p(>i8ou- 

^^iag, as he found it in only fourout of twenty-three dog?? so sacrificed ; and he 

^Hbeliercs chat it is merely an accident dependent upon the method of death. 

^^P& a sertoi of analyse^^ apparently carefully made, he found that the continued 

^Fllie of quinine augments tlie proportion of fibrin, but lowers that of the red 

corpuscles. 







• l^mnUDifjnK {Ctuttatb. Jtffrf. UV*»p.**cA., jtviii., 1 880, 529) state* that utropia wUI cause 
iie bt-ftri tirrir<ic<i by i^uinine (o rcoomiuenoe ItB n€tii>ii» 

f M« I'bimne bclitsvci that hy i^umhi the henrl ts nrre«ted in netire dU&tiitioti. Thtt 
lletirj h very improbiiLile. See Hiaista CVoiico t(i flotut/na^ ubftrncrted in Jnnr, Phy^inlttg* 

Mut. €t PfithoU*it., 1879, p. 844. 

lleubuMchr hi A teries of ex[»crttncnLs on the iufliivncfi of gHlviinliixitintt of a icn^itivo 
drvti ufH>n Hie cirouUtiun nftor the exlobithm of miTDJruf, failed tu prove %ny piiriilyiintit 
DtioQ tfftbe drug, ullbou^b in some af bis oxperimcnts the ruflex activity wn« |mr»1.v»(Kl. 

; >uni« itiidt«2< hftiro be<?n miwlo upon tht" frctioo of tbi; driig on the cApilturicM uf the 

iin» l»ut tbo cridiMioe ta m yet contradictory nnd insuflicirnt. Consult Pa^t^Koto^icQl 
I M*tiico- L*iff''i Jtmrnaff 1875, \u S3 i ulao, Archivca nf Medicititf i. 331. 



68 SYSTEMIC REMEDIES. 

Id 1867"' Prof. Binz aDDOunoed the fact thatquinia added to haman blood 
in the proportion of one part to four thousand immediately checks and in a 
short time arrests the amoeboid movements of the white blood-cells. Confirma- 
tion of this has been furnished by Scharrenbroich {Dm Chinin ah Antiphlo- 
gisticum, Inaug. Dissert., Bonn, 1867), by Kemer (quoted in London Practi- 
tioner^ vol. vii. p. 321), by Geltowsky (^London Practitioner^ vol. vii.), and 
by Jerusalimsky {Centralh, Med, Wiu., 1876, p. 476). The minimum ef* 
fcctive strength of the solution has been found to vary in different species of 
animals, and even in different individuals of the same species. 

It is a matter of great interest to determine whether quinia acts in the 
living organism as on the stage of the microscope ; and, to settle this point, 
Prof Binz ( Virchow's Archivj Bd. xlvi., 1869, p. 138) has experimented 
according to the method of Cohnheim. He found that when the mesentery 
of curarized frogs to which quinia had been given was exposed upon the 
stage of the microscope, no accumulation of white blood-cells in the small 
vessels, or passage of them out into the tissues, occurred upon irritation ; or, 
if after a time these phenomena commenced, they were at once checked by a 
suuill hypodermic injection of the alkaloid. AVhen the inflammatory process 
had ulready commenced in a " Cohnheim frog," an injection of quinia would 
cause the wandering out of the corpuscles to cease, and would bring about a 
gradual clearing of the white cells from the choked-up vessels. Prof. Binz 
further took two young cats, and, after poisoning one of them with quinia, 
examined their blood. In the blood of the unpoisoned animal the white cells 
were far more abundant than in that of the poisoned cat. From these facts 
Prof. Binz deduces the conclusion that quinia acts destructively in the system 
upon the white blood-corpuscles, in the same way as when they are out of the 
body. Dr. Geo. R. Cutter (^P»ychological and Medico-Legal Journal, Feb. 
1875) has experimentally confirmed the effect of quinia in preventing the 
extrusion of white blood-cells in the frog's mesentery, and A. Martin (Z>£M 
Chinin ah Antiphlogisticum, Inaug. Dissert., Giessen, 1868)f has not only 
done this, but has also found that the action of the drug is apparent in tlie 
centre of parenchymatous organs, such as the liver. 

On the other hand, Schwalbe J could detect no difference in the blood of a 
cat before and after poisoning by quinia ; and the experiments of Geltowsky 
(Joe. cit.) upon frogs and guinea-pigs havejielded similar results: in idl cases 
after fatal poisoning by the alkaloid the movements of the corpuscles were 
found to be very active. 

These results arc in opposition not so much to the experiments as to the 
deductions of Prof Binz, — deductions which seem to me scarcely warranted 

* Archiv filr Microfcop, Anntomie^ iii., 1867. Consult, also, Experimrn telle Uuter- 
Buchnngen Uber das Weten der Chinimoirknng^ Berlin, 1868; Virchotc*9 Archiv, Bd. xlvi., 
1869, p. 137; lierltn. KliniticheWochentchn/t, Nov. 1871. 

f Quoted by Binz, 17rcAoic'« Archiv, Bd. xlvi. p. 1.37. 

X Quoted by Kerner, Pjiiltjer't Archiv^ Bd. i. p. 203. 



TOMCS, 



69 



P 



iBvestigatioiia. The experiments which he performed in the 
Ciihnheim method at most prove only that poisonous doses of qtiinia pre- 
ent or arrest inflammation. The iocal aecuinulatiun and the out-wandering 
f the bk>od-c»jrpuseles are the result of a locjd infliinimation or irritation, 
and if the qubia should in any way check this it would of course put tin 
ud to the phenomena mentioned. Apiin, quinia might, in the cruq of the 
t, have lessened the pwportion of hlood-eells bj eheckiiig tlioir fonnation. 
The exact nature of the action of the alkaloid upon the white blood- eor* 
iu the body mujst^ therefore, be considered undetermined, even when 
nous doses are UMcd ; when therapeutic doses are employed, the doubt is 
if couj'^e i*till struu*:er. 
It would seem tliat quinia acts also upon other portions of the blood thau 
iQ white corpuscles, Munaasein ( Ueber die Dimmmanen der rothen Btu^ 
rperchen unter verschicdettat^Verhiilttmsen^ Berlin, 1S72) has found that 
fever occurring in the lower animals tlie red corpuscles aic dimiuisliLd in 
«. If in this condition a decided dose of an antipyretic, such as quluia 
»1, be jriven, and the tempeniture falls, the globules resume their 
That the change is due to the full uf the tempeniture rather 
than to a direct action of the drug is, I think, demonstmted by the fiiet of 
itd occurrence whenever the fever-heat is lowered by the application of ex- 
temal cold. The experiu;ents of Manassein, therefore, do not pi-ove l!mt quinia 
exerte any direct action on the red coqiuscles. The investigations of B'u\% 
Archiv fur ExpertmenteJ/e Pittholvffte vnd Fhnnnakologle^ Bd. i., erstes 
«ft, 1873), however, appear to show that the alkaloid lessens the ozonizing 
power of the blood; tor he fuund that in young cats, to whicli he had givtm 
a very large but not fatal do^e of (juinia, the freshly-drawn blood affeeteil the 
tbcture of guaiac much less than it normally should. 

When blood Is drawn from the Iwidy and allowed to stand, acid is developed 
m it. Z u nst { i/c ifni^e zn r Phi/Hitthrfflr dt » Blu tts^^ I na ug . D issert . , B « > n n , 1 80 8 ) , 
who has studied this subject most closely j divides^ the investigation into — study 
of the production of acid in the time from the escape of tlie blood from the 
Tcin to its coagulation, and tjtudy of the slow changes which increase its acidity 
when cHjagulated until putrefaction has fairly set in. Prof Binz believea 
that this development of acid is due to oxidation ^ and by an elaborate series 
of experinients has determined that quinia (ali^o sulphate of behecria and 
ficrate of sodium in ahnost as great degree) inhlbltii these changes very 
gntatly in both their vai'ieties. These experiment*! are in accord with the 
prcviouja ones of A. Schulte (Ceutralhhiit /tir die Mcdicin. Wksemckaflctu 
Kov. 1871); the facts may, therefore, he winsiderod proven. 

If osconiied oil of turpentine be dropped into an alcoholic solution of guaiao 
ia, no alteration of color occurs; but if a drop of blood be added, the blue 
appears at once : <'.«., the blood acts as a carrier of ozone from the turpentine 
U) tlic resin. Prof Binz has found that quinia, even in so small va\ snnonrvc 
part in twenty thousand, has a perceptible influence in preventing this. 



L( 



70 SYSTEMIC REMEDIES, 

Similarly, when into a dilute watery solution of the sulphate of indigo car- 
bonate of sodium is thrown until the reaction is decidedly alkaline, and a little 
blood, and subsequently ten drops of ozonized turpentine, are added, a green 
color begins at once to develop, and in a little while passes into the clear 
yellow of isatin. In this case also the blood acts as a carrier of ozone, and Binz 
and his pupil Ranson6 ( Ueher cimge Beziehungen Jest Chimn zwn Bluf, Inaug^ 
Dissert., Bonn, 1871) have found that quinia also inhibits this action, one part 
of it added to a thousand of the mixture delaying the change of color for an 
hour. In these experiments Binz used a large number of different salts of 
quinia. and found that they acted identically. That the action of the alkidoid 
was on the blood, not on the indigo and guaiac solutions, was shown by the 
fact that when similar solutions without the blood were shaken in the air and 
absorbed ozone, the characteristic colorations of its action were produced just 
as readily when quinia was absent as when it was present. Binz also proved 
that the red corpuscles were the portions of the blood affected. On adding 
crystallized haemoglobin from horses* blood to the guaiac solution he found 
that it acted as an ozone-bearer between the turpentine and the guaiac, and 
further demonstrated that quinia had the power of preventing this action. 

As it is established that quinia exerts a decided antipyretic action (see 
p. 71) in ordinary fever, it is an exceedingly plausible theory that the low- 
ering of temperature is due to a checking of the ozonizing power of the 
blood. To attribute, however, the general medical virtues of quinia to an 
action on the white corpuscles seems to me unreasonable; for from the ex- 
periments of Prof Binz himself upon the lower organisms it would appear 
that quinia acts upon all animal germinal matter ; and it is probable that the 
protoplasm of the nervous system, being more specialized than that of the 
white corpuscles, would be more susceptible of the influence of the alkaloid. 
Further, according to the experiments of Binz, both conia and camphor act 
more forcibly upon the white corpuscles out of the body than does quinia. 
Yet their influence upon the organism is entirely unlike that of quinia. 1 
think these facts are sufficient to show that any theory as to the action of 
the drug built upon the prime fact discovered by Binz would be at present 
premature. 

Antiseptic Action, — As long ago as 1765, Dr. Pringle ( Observations on 
Diseases of the Army^ London, 1765) called attention to the fact that cinchona 
bark, in decoction or powder, has the power of preventing for a time putre- 
faction in flesh ; and more recently the subject has been studied by Mayer, by 
Pavisi, by Hallier {^Das Cholera- Contagium^ Leipsic, 1867), by Herbst, by 
PoUi, and especially by Binz ( Virchow's Archiv, Bd. xlvi., 18G9, p. 68; and 
Unfersuchvngen iiber das Wesen der Chininwirkung^ p. 20), to whose elabo- 
rate articles I must refer my readers for details and references. The experi- 
ments of these authorities have demonstrated that quinia in the proportion of 
one part to three hundred will preserv^e for a long time flesh, meal, milk, butter, 
urine, albumen, etc., and will check very markedly the alcoholic fermentation 



TONICS, 



n 



m iHmej or in syrup. Prof. Binz Las demonstrated tliut thiM antiseptic action 
t§ iluc to a pcJisonous influence exerted by the tjuinia upon t!ie tnngi which 
ore tiie tuimedlate cauae of the cfianges. Aceording to his experiments, the 
lai^ger iiifus<»na, such us Paraniecia and Colpwk^ are killed by a solution of 
i|UiiiicL of the strength of one in eight hundred immediateljj of one in one 
tliuuettiiid after some minuter, of one in twenty thou?(and Jiiler some liotira 
Upoti the ordinary mouM PeniciUium, upon Vibrios and Bacteria^ as well aa 
upuo tJie higher infusoriii, quinia acts with a similar fatality. In the ea^ of 
the Vibri«>s and Bacteria a decidedly stron;^er solution than the one mentioned 
in ro<|iiired lo quiet movenieat. Bochefontaitie {Archiint de Phjxioio^te^ 
Jii]j» 1873) found that a solution of one per oeiiL was needed for ii vigoroun 
«mpid »ciiMii» and that some active j^niiiules eould even be found iti it after 
Utree days. According to Binz, the singularity of the influence of ijuinia is 
•hfywn by the fact that a solution of stiliein, in the proportion of one purl 
tofbrtj^. docs not kill Paramecia and Colpmk. Indeed, these infusoria were 
not even aifeeted by this strong solution of ealicinj and they endured a »olu- 
llou of moqihia of one part to one hutidrcd and twenty for an liour, and a 
firts per cent, solution of strychnia for Bonie miTiute^, Althoutrh fungi will 
ftppQur after a time in ordinary solution of the i^ulphate of quinia, I think it 
nost b6 considered well establiEhed that this and other saltB of the alkaloid 
mxt extremely poisonous to the fun*::! of putrefaction and of other ordinary 
lennentatjons. 

U^tTHM, — In 1871, Dr, Monteverdi announced (AnnaUx et BuUeU'n di la 
Sociiii dr Midechie de Gandj May^ l^^^) *^^i*^* quinia is a uterine stinmlant, 
autsng »t times in the graTid womb oontractions sufficiently riolent to induce 
abortion, and, when given during hibor, intensifying greatly the uterine 
pains, and after labor causing rapid expulsion of tlie placenta and arresting 
i]ti*nuG hemorrhage; aflirnu'ngj further, that in amcnorrhe&a or in nienor- 
rbigia from uterine inertia it« action is no leas marked. Although this has 
bdeo received as new the world over, so long ago as 1855 Dr. John S. Wilson 
(SoHthn-71 Afedicai and Surf/tml Journfd, p. '541, 1855) called attention to 
tlie uterine action of quinine, and in 1SG(> reasserted his belief (Stmfhern 
Journal of Medicine^ Sept, 18liiO)i which in the mean while had been con- 
finned by Dr. J. H. Kich in the Charh^ton Medical Journal and Rrrfttr; 
abd 10 1858 Dr. Jos. J. West (^JSavannah Jourmtl uf Afeflicincy vol. i. p, 19) 
Unyle, ^ Many regard the use of quinine as dangerous and even crimlnnl in 
Mjr diswses in pre^ant women. The belief of these persons is that this 
•oibitaiice exercises a direct influence upon the uterus, cmtning jKncer/id con- 
lracft\ms and expulsion of the f<i?tus. And to supp<*rt this notion they are 
ready to bring forward innumerable instances of abortion after it« us*?^ — ^of 
CMCfl of sudden suppre8sion relieved by a prtnnpt use of the s;unc remcHly/* 
Ho then goes on to say that thei^e abortions, etc, were due tn the inteiuiittcnt 
fever and not to the dnig. Surely this is enough to i*hnw tlmt the oxytoeitj 
ftdiao of quinia was believed in many years ago by numbers of our Southern 



72 SYSTEMIC REMEDIES, 

practitioners. The question now is whether the drug has any such action. 
It is evident that the answer to this should be made out in three different wajs- 
First, Is there any evidence of quinia producing abortion in healthy women or 
in females of other animals? Second, How strong b the evidence of ita pro- 
ducing abortion in women suffering from ague ? Third, What is the evidence 
in regard to the action of quinia during labor ? 

In regard to the first of these sub-questions, the only affirmative evidence 
I have met with is in the experiments of M. Rancillia {L Union Midicale^ 
1873), who saw abortion in two bitches follow the administration of from six 
to nine grains of quinia : aa the pups in one case were already dead before the 
administration of the drug, it would seem that this investigation was not on 
Buch a scale as to be at all conclusive. Moreover, I have given quinia to two 
pregnant cats, in one case in sufficient quantity to cause death, without dis- 
turbing the products of conception. On the other hand, I have met with 
no evidence tliat quinia is capable of inducing abortion in healthy pregnant 
women. Dr. Sayre's case {Amei-ican Practitioner^ 1871, p. 260) is certainly 
no proof whatever that quinia will originate labor, as labor had commenced 
under the influence of the hot and cold douche and other measures employed 
he/ore the quinine was given. Prof. Chiara, of Milan, has furnished (^V Union 
Midicale^ Nov. 20, 1873) very strong evidence that quinia is incapable of 
originating uterine contractions in healthy pregnant women. In his public 
service, two doses of a gramme (15.34 grains) each were given without effect 
daily for two successive days to eight women all in the eighth month of preg- 
nancy. It being necessary to cause abortion, one gramme was given daily to 
one woman for seven days, to another for three days, without in either in- 
stance any effect, so that the labor had to be brought on in the usual manner. 
On the whole, I believe that the first question must at present be answered in 
the negative. 

In answer to the second sub-question, some evidence has already been 
adduced to show that abortion may be so caused. To it may be added the 
assertion of Dr. Walraven (^Boston Medical and SurgicalJoumaly 1873) that 
he has frecjuently seen the exhibition of quinia followed by abortion, the 
record of two cases of such character by Dr. Burt {Medical and Surgical 
Reporter^ 1870), and no doubt the affirmations of others which I have not 
seen. Opposed to this, however, is the overwhelming fact that the great body 
of the profession have for centuries been giving quinia in one form or 
other to pregnant women indiscriminately, and if abortion had been produced 
it must have been noted long ago. Further direct testimony is not wanting. 
Malaria often induces abortion, and Dr. Envin {St. Louis Medical and Sur- 
gical Journal^ March, 1872), Dr. Jas. C. Harris {American Practition^ 
April, 1872), and Dr. A. Russwurm {American Practitioner^ 1871, No. 4, 
p. 127) testify from personal experience that quinia will arrest abortion from 
such cjiusc. Dr. J. A. Ashford {National Medical Journal^ Oct. 1871), Dr. 
Beauchiuup {American Practitioner^ 1870), Dr. Hooker {Ibid,), Dr. J. S. 



f«ll!l^ 



n 




fay (Jbtd,)^ and Dr. A. d*Arcourd (Medical A^ewn and Library^ May* 187M) 

uve given the alkaloid to hiindrods of prognant wonieti in largo doMOi^ without 

Uthyf testijDOnj niight be ndduuod ; but it eeeins to me iucredible, 

be fiice of daily exporieut-o, that even the largest tberapcutie doses of 

luiuia arc ubortifacieut in malarial fcvcm or in befdth. 

In regard to the third gub -quest ion, at the time of the writing of the lost 
redilioD, the evidence, although greatly preponderating in one direction, waa 
scarcely sufficient to be decisive.* At preaeut, it seems established that qui- 
nine ID full doses (ten to twenty gniins) is a very jwwerful stimulant to t!ie 
Qtcrioe contractions during labor The pains it pruduees so exactly Mimulate 
be natural ones as to indieate that they are not so much caused by a speeifio 
etion of the drug, as by ita arousing the genend nervous forces of tho 
^atem« Be this as it may, most of the leading accoucheurs of this city and 
Df New Vurk are accustomed to rely upon quinine io cases of uterine inertia 
Dtu exhaustion. 

Kuiueys and EUminatum, — The manner in which quinia finds entrants^ 
nUi thtf blood hae been especially studied by Dr. Kerner {loc. cit.). As the 
i»tnc juice m very neid, it is evident that the alkahdd will be rapidly dissolved 
the stomach aiid be put into the conditions most favorable for it^ absorp- 
if, however, the salt of quinia escaf>e iWym the stomaclj into the iutes- 
, it will be liable to be preeipitatod by the alkaline juices, fts well sis by die 
bOe, whose acids fonn very instil ubie salts with it. The presumption is there- 
bre strt>ng that, when gastric absorption fails to take place, at least a portion 
'the r^uinia will pass out with the fieccs. That this actually docs occur has 
Ifccen proven by Kerner and others, who have fuuiid the alkaloid in theoxcre- 
iient of persiins taking it. As the blood is tilkaline, it would appear probable 
bat the quinia salt so soon as entering it would be precipitated. That this 
not occur, according to the researches of Kerner, is due to the Bolvent 
' of tho gases contuined in normal blood. 
The authority mentioned found that one thousand parts of blood which was 

I'fibrinatcd and deprived of its gases, at a tempej'aturo of 36^ C. dissolved 
an himr only 0*3^^8 part of pure quinia. Water eaturated with carbonic 
id gas dlssulves the sulphate of quinia pretty freely ; and Kerner also experi- 
cntally determinefl that when a neutral solution of a sidt of quinia is added 
a very dilute solution of carbonate of sodium no precipitate occurs. Il 
nould appear, then, that the quinia is held in solutiuo in the blood by reason 
^^ the loosely -combined carbonic acid gjis in that fluid* 
^H II has b^eu proven by the analyses of Landerer {Repeiiorrum fUr Pkar* 
^Biad^, Bd. XXV,, 1836), of Diet! ( Wuner MedizinUch^ WmhenHchriJ}, 1852), 
^Hf Briquet (,/oc. ctV.), of Binz, and of De Renzi {HnlL Thirap.^ xci. p. 45), 
^Hiat quinine ceca]>ei» ^m the body through the kidneys. According to Bri- 



* For d«Uuli of Ibe o?ideiic« the render is referred to the last edilba. 



Coaault ttlio 




74 SYSTEMIC REMEDIES. 

quet, it may generally be found in the urine half an hour after the adminis- 
tration of a large dose. Its removal, according to the researches of BinE, 
goes on slowly, for it is stated (toe, cit,, p. 167) that in six experiments only 
a little more than two-thirds of the ingested quantity was excreted in the 
first forty-eight hours. Further, De Renzi has found it in the urine seven 
days afler the ingestion of the last dose. Dr. L. Thau, however, in three 
experiments, out of the 4.4586 grammes of the alkaloid which were given 
recovered from the urine passed during the forty-eight hours 4.3 grammes, 
so that only 0.1586 gramme remained unaccounted for. A portion of this 
residue was perhaps lost in the chemical operations ; but it is probable that 
some of the quinia is eliminated through other channels than the kidneys, 
since Prof. Binz has found it in the saliva of a poisoned dog, and Landerer 
{Buchner's Beperforium, 1839 and 1842) states that he has detected it in 
the urine, sweat, tears, milk of nursing women, and in the serum of drop- 
sical effusions, whilst Albertoni and Ricnzi find it abundant in the bile 
when it has been taken by the mouth, but not when it has been given hy- 
podermically. Dr. Thau determined that from a third to somewhat less 
than half of the ingested quinine escapes from the body in the first six 
hours, and that in the first twelve hours about three- fourths are ex- 
creted.* 

Banke was, I believe, the first to notice that quinia produced a great de- 
crease in the elimination of uric acid. This fact has been confirmed by Dr. 
G. Kemer, who has made a very elaborate study of the action of the alkaloid 
upon renal elimination, with the following results. When about nine grains 
of quinia were taken in divided doses during the course of the day, the urea 
was decreased not quite one-eighth, the uric acid to a little less than one- 
half, the kreatinine was slightly increased, and the nitrogenous material de- 
creased about one-ninth. When a very large dose (thirty-eight grains) was 
taken in the morning, the urea and the kreatinine were each decreased about 
one-fourth, as was also the collective nitrogenous material ; the phosphoric 
acid was lessened about one-fiflh, and the uric acid about four-fiflhs. Zuntx 
(quoted by G. Strassburg, ArchhfUr Exper. Path.^ BJ. ii. p. 343) found that 
twenty-five grains of quinine reduced his elimination of urea nearly forty 
per cent. The experiments, upon the dog, of Rabuteau (Bulletin TJUra- 

♦ Dr. G. Kernor {P/lUger'9 Archiv fUr Phyniologie, 1870) oKserts that the quinia as 
excreted is in an amorphous, uncrystailizable furm. He ti\»o h)i8 diocuvercd in the urine 
of persons taking quinia a peculiar oubstance, sometimes amurphouts, sometimes in acioular 
prismatic crystals, fiee from bitter taste, possessing the quinia inflorescence, which he 
believes to be a derivative formed in the body from the ingested alkaloid. He has not 
been able to get this substance in such quantify as to analyze it or further examine it, but 
has produced a principle {dihydroxyle quinia) which he believes to be identical with it by 
acting on quinia with the permanganate of potassium. An elaborate series of experiments 
have shown that the dihydroxyle quinia is physiologiouUy inert. This dihydroxyle quinia 
must be produced in small amount, if at all, as there is abundant evidence that quinia is 
largely excreted as quinia (see Ph. Jour, and Trann.f ix. 125). 



TONICS. 



75 



peuHfue, L liiY. p. 475) and of Hermann von Boeck ( Untermchmgen ilhcr 

die Zcneizting det EitceUscs im ThierkJjrper^ Jluoich, 1871), confijm thia 

deoTOBBe in the elimmiitioD of nxea* Contrary to what might have been 

ed, Stni&burg (luc, ciV,), in an ekborate series of experiments, found 

it qtiiiiia hiid no very decided cfl'eet upon the elimination of «arbonie auid 

iher iu healthy or in fevered rabLits. 

TllERAPEriTics. — At present our estimate of the vdue of qiiinia in diseaafe, 

our knowledge of its therapeutic use, rest eolcly upon clinical observation. 

not as yet able to apply what information we have of ita physiylo^ieiil 

uor, indeed, are we even able to explain its known clinical aclion by 

its observed effects on the healthy organi&m. 

On aeci»unt uf its power of arresting or preventing putrefactive femienta- 
lO by killing the microscopic entities whith produce such changes, Prof. 
has recommended it in the so-called septic dUtttst'9, The chief evidence 
he produces is in some ten experiments made upon dogs and rabbits. 
each of these experiments two similar an'mmls were poisoned with putres- 
nt liquid^; and to one of the pair (|iiiuine was freely adniiniBtered. In two 
the ciDchonized animal recovered, whikt its fellow perished ; in three 
pcrimentfi neither of the animaJa died ; and in the other five triak the cio- 
ized animal lived fn>m two to twenty-four hours longer than the other, 
lese cjiperimcnts are certainly too few and indecisive to prove in any degree 
Prof. Biiiz s view. To my mind they indicate very strongly that quinia has 
DO such influence over the disease [w he claims for it. If living germs in 
the blood were re^dly the cause of the septic symptoms, and quinia killed 
«uch gerrns^ its action would be as manifest and as unmistakable as it is in 
intermittent fever. The results of Prof Binz's exj^eriments indicate no such 
specific section, but rather that the quinia in such ca&es docs good by sustain- 
ing the nervous system, or in some other unknown manner. In pt/s^mki in 
man, quinia has been fre(|uently employed, but exerts no specific action. 

It has not, that I know of, becu proven that therapeutic doses of qainia 
lowpr, to any marked extent, animaJ temjierature in the health}^ man. Dr. G. 
^^IKemer and Dr. Jiirgenson have each noticed that full doses of quinia appear 
^^Hn i healthy man not to afi*ect sensibly the temperature^ but to prevent the 
^^kiBvhich normidly occurs from exercise. Thus, in Kerner's experiment, 
^^^ffSxi gymnastic exercises, which when performed in his ordinary state 
eleviit4»d his bodily temperature 2^ C., affect&d the latter to the extent only 
«f 0.2^ to 0.35 '^ C. when quinia was freely exhibited. 

Even Or. C. Liehernieist4-*r (Deutschea Archiv filr Klmkchc Median^ Bd, 

M**, 181J7) ackuiiwlcdges that numerous experiments have shown him that 

^c alkaloid has no constant action on the Intdily heat in health, and de- 

**^la a case in which forty grains iidmiuistered within seven hours caused no 

of temperature. The same authority claims, however, that by a 

Wge uuniber of experiments he has demonstnit^?d its power of lessening 

r-Ueat» In one hundred and seventy-eight observations in t^plmd feccff 




76 SYSTEMIC REMEDIES, 

twenty grains of the quinine having been given daring the night, the morning 
temperature was lower than that of the previous evening by, on the average, 
1.63^ C. On one hundred and seventy-^ix different occasions a scruple of 
quinine was given during the day ; sixty-nine times the temperature was 
lower in the evening than in the morning, ten times it was the same as in the 
morning, and ninety -seven times it was higher than in the morning. A com- 
mittee appointed by the London Clinical Society ( 7Vaii«ac^«bw«, vol. iii., 1870, 
p. 201) experimented with the drug on about fifty cases of various diseases. 
They assert that the antipyretic action of large doses was very decided, 
appearing within from one to two hours after the exhibition of the drug, 
and lasting from a few to many hours. In a very recent publication Lieber- 
mcister asserts that he has given some ton thousand doses of quinine as an 
antipyretic and has almost unbounded confidence in it. He insists that from 
twenty to forty-five grains must be given within the hour, and not repeated 
oftencr than once in twenty-four or forty-eight hours. 

Naunyn and Quincke {Reichert'a Archivfur Anatomie^ 1869) found tliat 
sometimes quinia prevented the development of fever aft«r the division of 
the spinal cord in animals, but in other cases failed to do so. Binz (^London 
Practitioner, p. 4, 1870) has achieved similar results: he says that if the 
conditions of the fever are too favorably constituted the effect of the quinine 
fails thoroughly. The drift of our present clinical evidence seems to indicate 
that quinia exerts in febrile disease a decided antipyretic action, which is 
especially manifested during those stages of disease in which the natural 
tendency is towards a lowering of temperature. In typhus and typhoid fever^ 
scarlatina, severe erysipelas, rheumatic hyperexia, etc., after the use of the 
cold bath (see Part II.) twenty grains of the alkaloid are often very effi- 
cacious in preventing a rapid return of the excessive fever. If the experi- 
ments spoken of above be correct, this reduction of temperature must be due 
to an action on the tissues and not on the central nervous system. It would 
seem, however, more probable that quinia acts as an antipyretic by stimulating 
the inhibitory chemical centre ; but decision of this must be reserved for future 
investigations. As an antipyretic the drug should be used whenever there is 
serious elevation of temperature, except it be in cajses of simple inflammation 
of the brain or its membranes. All antipyretic remedies appear to act more 
strongly on children than on adults ; and accordingly Dr. Kapmund (Deufschet 
Klinik, 1874, p. 51) has found quinia of the utmost service in serioiis dis- 
eases of children with high temperature, especially lohtdar pneumonia. Much 
of the failure which has hitherto attended its employment undoubtedly has 
been due to a faulty method of administration. 

As a simple tonic, quinia is used by every one ; but I have never been 
able to see that the ordinary combination of it with iron is of much more 
value in simple cases of debility than iron with quassia or other simple 
bitter ; but if, as is probable, it be true that quinia lessens to a very great 



TONICS. 



11 




I e xtent tlje climiDation of nitrogen, t,c., the consuniption of tissue, the general 
^Hr&/cdcc has a good foundntiim, 

^H When given in very lar<re closes, cjiiinia, as has been already shown, acta 

^Kb 2l powerful depressant, and as such has been used by Erit^uet and other 

^■Trcuch physicians in rhenmatttmi. Aa much as sixty or seventy grains a 

^^ay have been given, and it U beyond dispute that under the influence of 

these heroic doses tlie symptoms of inflammatory rheumatism have oilen 

rapidly abated ; hut the nu'thnd has found little favor out of France, and iB 

less efficient and more dangerous than other plans of treatment now in vogue. 

In infiammatciT^ rhcnmatigm^ after the acute symptoms have abated| when 

the patient shows evident signs of weaknetJSj especially if there be profuse 

vweating during sleep, fifteen grains of cpii nine dully are often of great service, 

Vurious theories liave been brought forward to account for the wonderful 

S^we? quinia has npou all forms of mahirhd discuse; but, as we know 

[>thing of the nature of malaria or of the method of its action, and as wo 

1 very partially informed jis to the efl'ects of cjuinia upon the heakhy or- 

ij it seems to me jTerfectly futile to endeavor to explain why it averts a 

of intennittent. I shall not, therefore, occupy sjaice with such dis- 

cmsion. The present seems, however, the fitting place to notice the discovery 

_4>f Dr. H. Bence Jones in rt^ard to the existence of a body similar to quinia 

I the animal organism. 

ainiA and its salts have the remarkable prtiperty of converting the eheni- 

I'luys of the s[)eetrum into light, or, in otlier words, of rendering visiblo 

he ordinary invisible mys of the solar or other spectrum. Connected with 

bifl laet i« probably the phenomenon known as the fluorescence of cpnuia* 

Hien a eolorle^ watery solution of one of its salts is examined, a pale-blue 

lio© upon the surface is very noticeable ; nnd Prof Stokes has shown that 

olution of quinia h;is the power of entirely stopping certain of the rays of 

ght, so that when a beam is tranj^mitted through it to light up a second 

of the solution this latter displays no fluorescence. Br. 1 1. Bence 

{Lfcfttre^ on Pathoh^ and Thenfpeufics^ London, 1867) has found 

when tlie electric light is used this test is so delicate that one grain of 

he alkaloid may be deteett'd in l,450,t100 grains of water. He has also dis- 

pvered that man and aninialH are pervaded by a sukstanee which, in its action 

light and in many chemical reactions, very closcJy re^mbles, if it be not 

pcnticjJ witli, quinia. Believing this substance to be probably an alkaloid > 

» has given it the name of anhntd gitinoiduie. Drs. Edward Ilhoads and 

Filliam Pepper, Jr. {Penmi/hania Jfmpiud Reports^ vol. i., 18G8), have 

pnde observations upon ten cases of malarial fevers in which no quinia had 

en used, and have found the fluorescence of the blood to be from to H, 

end of from 3 to 6, which is said to be normal. The significance of tliesc 

mlts is at onoe apparent; but, before sufficient grounds shall have been 

btaiucd upon which to buiJd a theory, tar more extended researches on the 

'taHance of the fluoreficence in health and in diseases other than malarial are 





78 SYSTEMIC REMEDIES. 

necessary. Especially is this the case since Dr. ChalTct {Schmidt's Jakr- 
hiicher, Bd. cxli. p. 152, from Gazette ffebdamadaire, 2d series, t. v., 1868) 
has found that this fluorescent body exists in yarioos foods and even in wine, 
and is therefore probably not of animal bnt of v^etable origin. 

Quinia in its relations to malarial /ever may be considered first as a pro- 
phylactic, secondly as a curadve agent. 

The value of the daily use of quinia to persons exposed to a malarial 
atmosphere has now been thoroughly tested in all portions of the world. In 
North and South America, in Europe, in Africa, in India, the prophylactic 
powers of quinia have been tried on the largest scale in connection with the 
military and naval services, and the testimony b unanimous in favor of the 
drug. A single citation will serve to illustrate this fact.'*' Dr. J. B. Hamilton 
(^Indian Medical Gazette^ Nov. 1, 1873) reports the case of a battery of 
one hundred and thirty-five men, quartered at Jubbulpore, East Indies, in 
the same barracks with an infantry regiment. Each of the artillerists received 
three grains of quinine every other day; to the infantry none was given. 
The result was that whilst three hundred out of the five hundred men of the 
regiment were sick at one time with malarial disease, at no period was more 
than four per cent, of the battery affected. The dose of quinia as a prophy- 
lactic may be considered as three grains a day, or possibly, in very deadly 
climates, three grains in the morning and two in the evening. 

In intermittent fever, when there is sufficient time, it may be well to pre- 
cede the quinia by a mercurial or other purge. If the expected paroxysm 
be so near that there is not sufficient time for the acdon of the purgative, 
the antiperiodic should be administered without previous preparation of the 
patient. The value of purgatives in obstinate intermittents, as an adjuvant 
to quinia, is often overlooked, although in some cases the employment of pur- 
gatives, and of such diuretics as cream of tartar, seems to be almost essential 
for the successful use of quinia. 

When there is necessity for prompt action, the antiperiodic may be given 
in a single dose, or in any other method that the circumstances of the case 
will allow ; but ordinarily the best plan is to commence the exhibition of the 
drug about eight hours before the expected paroxysm, and to continue in 
hourly doses until from three to four hours before the attack is due. 

In pernicious fever, or malignant malarial poisoning, no time should bo 
lost after the first paroxysm in getting the patient cinchonized, as it may be 
uncertain whether the attack be of the quotidian or tertian type. At least 
thirty-five grains of the alkaloidal salt should be administered during the first 
tweuty-four hours of intemiLssion, and twenty-five grains duriug the second; 
in very severe types of the disease much larger doses even than these are 
necessary, less than fifty grains of the drug sometimes appearing to do but 
little good. 

• See also K. M. Downie, M.B., Indian Medical Journal, March I, 1872. 



TONICS. 



n 



In reim'ttent or hlllons fever it may often bo advisable to give purgaiivea 
ttd febrifiigejs but it b not pro|*er to delay the exhibition of the ant i period i a 
911 their acvount. As soon m the remission has appeared, the exhibition of 
qutniu should be begun. Local infliunmations or even severe eerehral synip- 
aius occurring during a remittent fuvcr are no contra-indicatiuns to the use 
the specific. Wlien gastritis exists, other channels of entrance than the 
oujach should be empluyed, on account of the local irritant action uf quinia. 
When the symptoms in remittent fever are severe and seemingly eontino- 
8, it may be not only proper, but necessary for the saving of life, to exhibit 
liiinia freely during the period of fever. In large doses the alkaloid is prob- 
bly antipyretic aa well as anti periodic, and I do not know of any theoretic 
' clinical objection to ita nee during the period of fever. 
In vinhnial inttrrmtttent jieuralgia, as in all other forni.« of abnormal 
unnifestatiuns of malarial diseaj^e, quinia is efficient, although it may be 
necessary to use it in large doses. 

In hrnralgia which, although not dependent upon uinlaria^ assumes the 
Dt^^rmittent tyjje^ quinia will often terapomrily set u-side the paroxysmal 
ittacks, and sometimes effect a cure. The same fact may be sttitcd in broad 
ni* as true of all non-inalartal mtcrmiUent affections. In the great ma- 
only of such cases, unfortunately, the action of the quinia is only temporary. 
^any controlling power is soon lost. 

Pirious idiusynera?5ie3 exist towards quinia. Pruf. Kuramitsas asserts 

bat in some persons it causes hsomaturia {BuIL TJdrap,^ xcvii. 53) : it not 

krcry rarely causes vesical irritation, and it is said that in some pL'i)ple {BriL 

^td. Jour,, W,, 1809 J Berlin. Klui. WocL, 1877, 29^ ; Fhihu AM, Timei, 

IG6) a few grains given internally suffice to produce great (udenia of 

be ace and limbs, accompanied with a pronounced erythematous rash, in 

ome cases closely resembling that of scarlatina {A^. Y. MaL Record^ xxi. 

W27), the whole subsiding in a few days with dci^quamation of the cuticle* 

Local Uge of Quinia, — The effect of quinia upon the lower organisms has 
suggested it« local use in varloui disorders nnppoited to depend upon the pree- 
pacc of such entities- Thus, Dr. Henke (DeuUches Archivfiir Klin, Med., 
1 xii. p. 630), finding some peculiar motile cella in the sputa of whouphig* 
v^hf employed inhalations of quinia with asserted good results. Dr. Henke 
\ not, however, the first to suggest cither this fiingoid pathology of whoop- 
ag-cciugh or the use of quinia. Prof Binz in 1870 (^American Jaumcd of 
%$i€trivM and Discatct of Wmurn^ iii.) claimed that quinia had a specifio 
itlioti in whooping-cough, provided it was given in large doses in solution, so 
\ In come in contact with the mucous membrane in its passage through the 
liarynx; and in 1S71 Letzerich ( /6»V/., vol, iv. p. 761) announced that 
uping-cough was due to a fungus in the lung. Prof. Dawson (I hid., 
iBT3) has confirmed the value of the method of Prof. Binj ; but, if the fun- 
theory be — a8 I do not believe — true, the plan of Henke must certainly 
! Uie better one. 



80 SYSTEMIC REMEDIES. 

Again, Hehnholtz recommended the local use of quinia in liay fever^ 
believing that disease to be dae to a fungus, and much testimony has been 
brought forward as to the value of the treatment. A weak, tepid solution 
(gr. j to iii — fji), as nearly neutral as possible, should be freely applied by 
snuffing it up, or, better, by means of Thudichum's douche. If the value 
of quinia in whooping-cough and in hay fever be established, it by no means 
follows that the theory which originated the use of the remedy is true. The 
alkaloid is certainly a stimulant to the mucous membranes, and in the later 
stages of gonorrhcRa the topical employment of its solution (gr. v to x — T^i^ 
is often very serviceable. 

Administration. — Owing to its bitter taste, sulphate of quinia is gen- 
erally given in pill, which may be made with gum, or simply by adding a little 
sulphuric acid to the alkaloidal salt and quickly rubbing up the pas^ mass 
into pills before it hardens. Whenever a rapid action is desired, the quinine 
should be given in powder, or in solution made by adding a drop of dilute 
sulphuric acid for every grain of the salt. In the use of pills of quinine, 
care should be exercised to see that they are soft and fresh, for when old 
and hard they not unfrequently pass through the bowels unchanged. The 
ready-made " sugar-coated" pills kept in the shops should be avoided, as 
uncertain in their action. The taste of the powder is best covered by 
chocolate or by liquorice. 

"When sulphate of quinia is given hypodermxcaUy it acts with much greater 
promptness and apparently with greater force than when administered by the 
stomach. Albertoni and Ciotto (^BuU, ThSrap., xc, p. 403) found that 
when they injected it into the jugular vein it failed to appear in the bile, 
but when they administered it by the mouth it was freely eliminated with 
that secretion. Biliary salts of quinia are so insoluble that their re-absorp- 
tion must be effected, if at all, very slowly ; hence possibly the superior 
efficiency of the hypodermic method. The local irritant action of quinia, 
however, forbids its hypodermic employment, except in cases of great emer- 
gency. Given in this way, it very generally produces great local disturbance 
(abscesses, ulcers, etc.), and in several cases has caused fatal tetanus (2>>n- 
don Lancet^ 1876, i.). When it is so given, care should be taken to have 
an excess of acid (tartaric — the best) in the solution, to prevent precipitation 
of the quiuia by the alkaline juices of the cellular tissue. The hisidphate 
of quinine (^fjnininse. BUnfphas^ U.S.) is .soluble in 10 parts of water, and 
should be preferred for hypodermic use : even its solution should be acidu- 
lated. Ten grains of quinine injected under the skin are probably equivalent 
to fifteen grains given by the mouth. 

The hydrohromate of quinine {Quininx Ift/drohromas, U.S.) is soluble 
in about 16 parts of water and in 3 parts of alcohol. It is stated that a 
ten per cent, solution in a mixture of alcohol, 25 parts, water, 75 parts, is 
not irritant when used hypodermically. 



TONICS. 



81 



The lannate ofqninia^ altliougli not officioiil^ has been UBcd to some ex- 
tent, and is certainly not inefficient. It lias the great advantage of not being 
disagreeable to the palate, but i^ lesH active and less certain than the more 
soluble 8ftita of the alkaloid^ and is also much Blower in its operation. If given 
at all, it sbcmld be Id doses one-third greater than those of the sulphate. 

QciNtDiH-» Sulphas. U- 8. — Sulfthatr. uf gmnidine occurs in long, 
shining, silkj^ acicular crystals, soluble in 130 parts of water at 62^ F., in 
JG parts at 212^ ; readily soluble in alcuhut, nearly insoluble in elher It ia 
f basic salt, like the sulphate of rfuinia, readily taking another equivalent of 
acid. It behaves like its isomer with chlorine and ammonia, but is dtiitin- 
gciitfhed by rotating light powerfully to the right, instead of moderately to 
the left. It prf)bably closely resembles quinine in its physiological and theni- 
peutio properties, and is an efficient antiperiodic ; the dose is about one-third 
larger than that of quinine. 

I}frxim quitiui, s brown, amorphous substance, derived from ehinoidino, is 
said to answer all the tests for quinia except to polarize to the right. It \h 
probably an impure quinidia. 

CINCHONIN^ SULPHAS— SULPHATE OF CINCHONINE. U.S. 

The pure alkaloid cinehonia crystallizes in pri.sms and needles. The offici- 
OJiJ gutphah' of cinehonia is in short oblique pi ianis of a very bitter t:iste, sol- 
uble in fifty-four parts of water, more freely in boilin^jr water, readily soluble 
ta ttleohfpL From \t& solution in ehlorinc-water it is precipitated white by 
Ainmoniii. Bill's test for it consists in adding the ferrocyanide of jx>tassium 
in slight excess to it^ solution. A yellowish -white curdy precipitate is the 
result. On gently heating, this redissolvcs, but is again deposited, when the 
liquid cools, as abundant golden-yellow crystals. 

PjirsiOLOOiCAL AcTFON. — The physiological action of cinehonia is similar 
but less powerfol than that of quinia. Thus, Oonzon (quoted by Huse- 
nn) bus found that its action on infiLsnriaand on f«innentation is similar to 
but weaker than that of its sister alkaloid, and that on the movements of the 
wliiti* b!ood-corj>usclc^ its influence seems trjinslent. llj^on dogs, according 
to Bematjcik's cacpcrimcnts, the lethal dose of cinehoniti is to that of quinia 
Its 5 is to 4. The history of cinehonia in tlte organism appears, therefore, to 
be parallel with that of quiniiu 

TtiKRArr.UTics. — As an {iiiti periodic, cinehonia exerts a similar influcnco 
to quintA, but is probably about one-third WL'akor than that alkaloid, and 
isiti£t be used in correspondingly larger dose. I)r. J. B, II am ikon {loc. eii.) 
nOirmsi as the result of oxpeiimeut that cinehonia as a prophyluctic against 

• Fcir An t-Uborato dfioueiioa of the thempoutio ralu« of ibis toJt, ie« Bvlhiin d§ 
tAt^dimis, r&Hi. 1873. 



82 SYSTEMIC REMEDIES. 

malaria is even superior to quinia. As a tonio I have never been able to 
perceive that oiDobonia acts differently from quinia. 

CiNCUONiDiNiB Sulphas. U. S — Sulphate, of einchonidine ooeurs in 
white, silky, lustrous needles or prii^ms, odorless, of a very bitter taste, sol- 
uble in 100 parts of water, freely soluble in acidulated solutions. It polar- 
izes to the lefl, and is not fluore-scent. No dose studies have been made of 
the physiological action of the einchonidine salts, but it is probably very 
similar to that of quinia. Abundant clinical experience has shown that it is 
a reliable tonio and antiperiodic, apparently equivalent to quinia if given in 
doses one-third larger. It has been claimed for it that it produces less dis- 
agreeable symptoms, both gastric and cerebral ; but Dr. Rafferty, who has 
administered three hundred ounces of the sulphate, affirms that it is more 
apt to cause nausea and vomiting than is quinine. 

Chinoidinum. U.S. — Chtnoidm, or Quxnoidin^ is a blackish substance, 
with an almost resinous fracture, which is obtained by the evaporation of 
the mother-liquor after the crystallization of the alkaloids out of it. This 
substance contains probably amorphous quinine and cinchonine, besides 
quinidine and einchonidine. It is an excellent tonio and antiperiodic, and, 
on account of its cheapness, is largely used in some of the eleemosynary 
institutions of this city. It should be administered in about double the 
dose of quinine, and is most efficient in solution, but, on account of its taste, 
is often given in pills. Its solution should be made with acetic acid and 
water, aromatics being freely added, as it is apt to cause nausea. 

The U. S. Pharmacopoeia recognizes for use as a tonic an infusion of bark 
(^Infusum Cinchonse — 1 to 16.6), dose, a wineglassful ; a tincture of the 
yellow bark ( Tinctura Cinclionse — 1 to 5), dose, one to two teaspoonfuls ; a 
compound tincture ( Tinctura Cinchonx Composita — Ruxham's Tincture)^ 
which, as a tonic, is the best preparation of the bark, and b a very elegant 
remedy in convalescence, in doses of one tcaspoonful to a tablespoonful ; and 
also a fluid extract and a solid extract (^Extractum Ctnchonx Fluidum and 
Extract um Cinchonas) y the doses of which are five to fifteen drops or grains 
respectively. 

AOIDUM PIOEUM*-PIOEIO ACID. 

Picric or Carhazotic Acid is not officinal, but has been used to some ex- 
tent in medicine. It occurs in pale, yellow, shining scales, but is employed by 
the therapeutist only in the form of a salt, on account of the deleterious 
influence of the pure acid on the gastric . mucous membrane: the picratc 

* Piorio Acid does not really belong in this chapter, but, as it has attracted most atteD* 
tion as an antiperiodic, in the ignorance which exists as to its physiological action, I have 
Introduced it. 



TONICS. 83 

of potaasiiuii, of sodinin, or of ammonium may be ijused ; but the lost is the 
one generally chosen. 

Phtsioloqioal Action. — ^The only detailed study of picric acid known 
to me is that of Dr. W. Erb (Die PUerinmure, Wiiraburg, 1865). This 
obeenrer found that the daily use of a grain (for ninety days) of a picrate pro- 
duced, in a rabbit, yellowness of the conjunctiva, of the inner surface of the ear, 
and of the urine, with an occasional slight diarrhoea and great loss of weight. 
wiUiout any elevation of temperature. After a time the animal seemed to grow 
accustomed to the remedy, so as to regain in great measure its flesh. Three 
grains a day caused, in about two weeks, the death of the rabbit with symp- 
toms of inanition. All the tissues, except the nervous, were stained of an in- 
tense reddish-yellow color, as was also the urine. Eight grains produced fidling 
temperature, weakness, diarrhoea, collapse, and death, sometimes preceded by 
tremblings and even convulsions, in about twenty-three hours. Most of the 
tissues were stained yellowish-red. The most remarkable physiological effect 
of the poison occurred in the blood. The blood of animals slowly killed by 
% picntte was of a dirty-brown color, with distinct nuclei both in the red 
Uood-disks and floating fVee in the serum. M. Erb found that this alteration 
in the corpuscles occurred during life and was accompanied by a decided in- 
crease in the number of the white corpuscles. These alterations in the blood 
were apparently the cause of death, and seem to have been due, so far at 
kisst as concerned the red disks, to a direct action of the poison upon the blood ; 
for Erb found that identical or very similar alterations occurred in these cor- 
puscles when the blood was mixed with the picrate of sodium outside of the 
body. 

Erb found picric acid to act on man as on the lower animals. Twenty-four 
hours after the ingestion of fifteen grains of it the yellow color was very plain 
in the conjunctiva, the skin, and the urine. The temperature was not ele- 
vated, and gastric disturbance was usually absent, but sometimes it was severe. 
As with animals, so in man, picric acid was found abundantly in the urine. 

Pro£ Binx ( Virchows Archtv, Bd. xlvi. p. 130) has found that picric 
add exerts upon the infusoria an influence similar to, but much feebler than, 
that of quinia. 

Therapeutics. — The carbazotate of ammonium has been strongly recom- 
mended by various authorities in malarial disorders; but in the experiments 
of Erb the result was so n^^ive that the possession of any antiporiodio 
powers by the drug is doubtful.'*' As an anthelmintic^ the picrate has also 
been coDunended ; but Erb found it powerlci^s in cases of tmiia^ and for the 
destruction of the round-worm and thread-worm there is an abundance of 
safer and even more efficient remedies. A matter of the gravest importance 
is the asserted efficiency of the remedy in trichiniasis, Erb has produced 

• Confiilt Drut9ehe9 Klimkf 1855, No. 40; Medical Timet and Gnzettey Sept 1862; Nevi 
Btmediet, 1873; Gazette dee H6pitauje, x\y. p. 116; Ohio Medical Ilecorder, 1877. 



84 srSTEMJC REMEDIES. 

slow poisoning with a picrate in rabbits which had been fed upon affected 
meat, and, on examining their bodies after death, found the trichina every- 
where, even in the walls of the intestines, in very active life. On the whole, 
the testimony so £ir seems to indicate that picric acid has no value as a thera- 
peutic agent. Erb affirms that in robust adults from nine to fifteen grains 
a day may be given for a long dme with safety ; but I would fear the effects 
of more than half that quantity, 

AROMATICS. 

There are certain remedies usually spoken of in treatises on Materia Medica 
under the general head of tonics, which might more properly be considered 
local stimulants, acting, as employed in medicine, upon the alimentary canal. 
These are the so-called aromatics, substances dependent for their virtues upon 
the presence of a volatile oil. 

The volatile oils are essentially local irritants, causing when taken into the 
mouth intense burning pain ; when confined upon the skin, rubefaction, blis- 
tering, and finally, if the contact be very prolonged, more destructive changes. 
Internally, taken in very large doses, they cause burning pain in the stomach, 
increased activity of the circulation, and a species of intoxication. In suffi- 
ciently large quantities they are irritant narcotic poisons. When administered 
in therapeutic doses they act almost exclusively upon the alimentary canal. 
As compared with that of the simple bitters, their influence is more powerful 
and more transient. They do not permanently increase the digestive power, 
but simply increase action for the time being. They are employed chiefly 
— to give pungency to bitter tonics ; as carminatives, to stimulate the intes- 
tines to contract upon and expel flatus ; to prevent the griping of purgatives ; 
to disguise the taste of medicines, and to render nauseating drugs acceptable 
to the stomach ; to act as condiments, and aid in the digestion of the food. 

Injected into the circulation, the volatile oils lower the blood-pressure by 
depressing the heart's action, and even in comparatively small doses may 
cause immediate diastolic arrest. In this respect oil of cloves is one of 
the most powerful. The heart-action is undoubtedly direct and upon the 
heart itself: other muscular structures would seem to be similarly affected, 
as H. Kobert has found that the oil of mace directly lowers muscular excita- 
bility {Arch.f, Exp, Path, und Therap., xv. 22). 

Some of the tonic drugs containing a volatile oil also have in them a bitter 
principle which modifies their action. Such drugs may be known as armnatic 
bittern; as bitters they arc less powerful than such dnigs as quassia, and are 
especially indicated where the stomach is delicate and easily nauseated. 

Inflammation of the stomach or bowels is the chief contra-iii3ication to 
the use of aromatics. Unlike the simple bitters, they are often very useful 
in diarrhcca of nervous irritability or of relaxation, when no decided inflam- 
mation exists. 



TONICS, 



85 




There is one pmpeny which is pruhubly eoamioti Ui all tlie iirumutic oils, 
ojttd whjeh njuy tlierefore be alluded lo at this place with propriety, — viz., the 
power of producinj^ loenl tinoostliesia* In China the oil of peppermint has 
lonj* been used lucally in lieural^a; and my own experience with our native 
oil \b in accord with that of Dr. A. Wright {London Lancet^ 1874, it ; 
0€ef *lao, Gaz, Mid,^ 1874) in finding it efficient in ueuralcj^a and subacute 
rliaiiQsaiis ui. A rag soaked with it should be laid upun the part, and wheu 
die burning is no longer endurable cosmoline applied. The power of oil 
of cloves in benumbing seneilivc dentine or exposed nerve-pulp is well known. 
Altogether, the subject offers an iuvitiog field for investigation. 

AROMATIC BiriERS. 

AKTHEMIS. TJ.S -CHAMOMILE, 
Roman or true Clitimomile. is the dried fluwers (*f Aiif hemis nobilis, a com* 
poiJte of Europe. They are soiuctimcs single^ souietiineti double. The single 
are mon? iironiutie than the double florets. Chamomile contains a bluish or 
sumctlmes grceuiah volatile oil, a bitter principle, and a small amount of 
laaiiiu. Matricaria or German Cfhumomik is the flowers of JMatriearia 
QiHimiiuina, which are decidedly smaller than those of the ordinaiy chamo- 
mile^ and have a htrongcr, less agreeable f>dor and taste. Their volatile oil is 
very similar to thiit of chamomile. 

Therapeutics. — An excellent stimulant tonic; eaf>ecialty useftil in con- 
Vide^cence. The dose of the inftiMon {Itt/ti^uni AiUhemidii^^ii& to Ojj 
la oiiii to two wineglassfuJs before meals. 

Skrpkntaria. U. S. — Virginia snake root is the root of Aristolochia 
Bcrp**ntiiria iind of A. reticulata, small herbal plants of tl»e United States. 
It occurs as fine brittle rootlets attached to a smiill head, of a camphuraceous 
odor and taste, and contains a volatile oil^ a yellow ish-^reen rcsin, and a 
bitter principle. It is an elegant stimulant tonic, especially ui^eful i\n an 
adjuvant to more powerful bitters* In overdose it h mild to cause vomiting, 
and even purging. The done of the line/ are (Tinciura Strpentarist^X to 
10, U. S,) is one to two fluidrachras; of i\iQ Jiuid extract {Extractum Ser* 
jptftiarm /7»iViiiwi, U. S,)| twenty drops. 

Cascarilla, U.S., is the bark of Croton Eleuteria, a shrub growing in 
til** Wi»t Indies. This bark occurs in (juills or roiled pieces, and is to be dis* 
linguishcd by its outer grayish and inner deep -chocolate surface, by its spicy 
titter lasto, and the plcitsant mu«k-likc odor which it gives whilst burning. 
It contains tannin, volatile oil, and cusciunlltn, a neutral, bitter^ cryHtallizahle 
principlt:. It« iherapeuuc action is very similar to that of serpentaria. The 
doee of tlie in/mion. {hfmum Coicarillm — Jt to Oj) is a wineglassful 



86 SYSTEMIC REMEDIES. 

TRUE AROMATICS. 

OiNNAMOHUM. U. S. — Cinftamon is the bark of Cinnamomum Zeylanicum. 
a native of Ceylon, and of C. aromaticum, growing in China. The finest 
variety of cinnamon, that fVom Ceylon, occurs in long, closely-packed quills of 
a thin, very aromatic bark. Cassia Barkj or Chinese Cinnamcm, is coarser, 
more broken, and less aromatic. Both variedes contain tannic acid and a yd- 
lowish volatile ail ( Oleum Ctnnamamt, U. S.), which on account of ite great 
fragrance and very pleasant taste is largely used, in doses of from one to 
three drops, as an adjuvant, or to disguise the flavor of less agreeable drugs. 
Cinnamon water (Aquu Cinnamomi — f^ss to Oij, U.S.) is used solely as a 
vehicle. The spirit of cinnamon (Spiritns Cinnamomi — oil 1 to 10, U. S.) 
is administered in doses of half a fluidrachm; the tincture (^Tinctura Cinnor 
momi — 1 to 10, U. S.) in doses of one to two fluidrachms. 

Fnlvis Aromatums. U.S. — Aromatic Poucder (cinnamon, ginger, carda- 
mom, uutniegs). An elegant carminative powder; dose, ten to twenty grains. 

Caryophyllus. U. S. — Cloves are the unexpanded flowers of Caryophyllua 
aroniaticus, a tree growing in the Molucca Islands. This aromatic, largely 
used as a spice, contains an exceedingly pungent volatile oil, officinal as 
Oleum Caryophylli, This is a yellowish oil, becoming dark by age, which, 
besides being used as a carminative and aromatic, is frequently employed 
to benumb sensitive dentine, or even exposed pulp, in caries of the teeth. 
Dropped on a piece of cotton and placed in the cavity, it will very frequently 
cure toothache. Dose, one to two drops. The infusion^ or clove tea (^In/usum 
CaryophyUi — 5ii ^o Oj), is made with boiling water; the dose is a wine- 
glassful. 

Myristica. U. S. — Nutmeg is the kernel of the fruit of Myristica mos*- 
chata, a tree inhabiting the Molucca Islands. The nutmeg contains both a 
fixed and a volutilc oil. Mace ( Macis^ U. S. P.) is the arillus or outer imper- 
fect supernumerary coating of the seed. It contains a volatile oil identical 
with that of the nutmeg. The nutmeg is possessed of narcotic power, and 
it is said that oue or two when taken will produce a dreamy, half-uncon- 
scious condition. I have found that injected into the juguhir vein the vola- 
tile oil produces in the lower animals profound narcosis with abolition of all 
reflexes, and, finally, death from paralysis of the respiratory centres. The 
dose of the volatile oil (^Oleum Myristicm^ U. S.) is from two to five drops. 

PiMENTA. U. S. — Pimento, or Allspice, is the unripe berries of the Eugenia 
Pimenta, a tree, native of the West Indies. It contains a green fixed oil and 
a volatile oil {Oleum Pimentse, U. S.), tlie dose of which is two to five drops. 

Cardauomum. U.S. — Cardamoms are the fruit of the Elettaria Cardar 
momum, which grows in the East Indies. They consist of tough, seemingly 
fibrous, generally more or less triangular capsules, containing a number of 



TONWS. 



St 



Alf Imrdf vety aronuitic seeib. The capsule is itself dry and ta^tisless. In 
RineTce cardainoiiis atx? divided into three varieties, according to their 
AcconHng to Troniirisdorf, tho gecd-s contain, besides 10.4 |>er cent. 
' fixed oil, 4.6 fKT cent of a colorless, highly aromaticj volatiJe oil. Car- 
damom is a very grateful arctmatic, much le^ stimulating and hcatiug than 
DQ8t of the otliur substaoccs of itd class. The duse of the ttncturt^ ( ISnc- 
CarJnmftmi — 1 to G.<>, U.S.) ib half a flnkimehm, The compound 
ncturt ( Tinctura Cardaniomi Q/mp^wttn, U,8.) is a very elej^^uit addition 
i or vehicle for, tonic medicines ; doac, one to two fluidraehnis, 

ZiNorBKft. U.S. — Ginger is the dried rhizome or root-sto<:k of the Zin- 
jibcr ofiieiuale, growing in the East and West Indies. Green Ginger is the 
Vc«/i rhiakjiue. The Bhitk Ginger \& the root^tock dried with the epidermis 
the Whit^ or Jtunaica Gintjcr is the same, deprived of its epidemiiii. 
fresher ginger is, the greater is its power, and by time and exposure it 
ome^s eompletely inert. Its active principles are a soft^ acrid, aromatic 
jitt, and a yellow volatile oil. Ginger is much used in domestic medicine 
s a stimulant carminative in colic ; given in hot water, it is also used as a 
odorific and stimulant in the pain due to midilvnlj/'mppressed menstntfition. 
It IS often added with udvunUige lo other remedies in dtftfjKpsia, The «yr'</) 
frupiis Zlngihr^rin^ U. S>) is used ooly us a cordial drink or vehicle, lu 
cs of frum half a fluidounce to a finidounee. The tincture ( Tittcfura 
^dn^heru — I to 5, U. S.) is the most eommouly employed ; the dose Is half 
tteuspooDful to a teaspoonful. The dose of th^Jlidd extract {^Extradum 
^dngiltcri^ Fluidmn^ U.S.) is ten drops. The olcaregin (^Oleorcsina Zingi- 
jf U- B.) is employed as a stimulant addition to tonic pills ; the dose is 
half a minim to two minima. 



iroody 



PiPEft. U, S. — Black Pepper is the unripe berries of the Piper nigrum, a 
vioe-like plant growing in the Eas^l Indies. White Pepper is the ripe 
eft, stripped of their skin and dried. It is much inferior to the ordinary 
^y. The active principles (^f black pepper are a soil acrid resin, a pun- 
fiery, volatile oil, and pi peri n. 
In 181!) Oersted discovered Piprrin {Ptptrlna^ U.S.), which crystallizes 
»rless, ^lt>tening, four-fiided, truncated prisms, of a neutral reaction, but 
lie of combining with acids to form salts. When pure it is tasteless; hnt 
commonly it has a burning taste, due to the presence of some of the 
le oil of pepper. Tiic f>os»ecssion of very active antiperiodic proper- 
* hail bf^eu claimed for pifKirin, and it was for a time employed in intcr^ 
Utent fever; hut it luks fallen into complctG disuse. The dose as an anti- 
odio is four grains reiieatcd once or twice during the inten^al between the 
pan>X}'sms. According to tho observntions of Prof 11. Krouecker and of 
llerr Flicas, piperin in the frog paralyzes the peripheral ends of the bciiwry 



icliktile 



'^m 



88 SYSTEMIC REMEDIES. 

nerves (Archiv /Ur Physiologie^ Leipzig, 1882, p. 111). Pepper is verj 
largely used as a condimeDt ; but, as its taste is more hot than aromatic, it 
is rarely used iDternally iu medicine, except as an addition to simple bitten 
or to antiperiodics, generally in the form of the officinal oleoresin ( Oleorenna 
Piperis), the dose of which is- a minim. In atonic dyspepsia the latter 
preparation is an excellent adjuvant to tonic pills. 

Capsicum. U.S. — The U.S. Pharmacopoeia now recognizes only the 
small, less than an inch long, very fiery fruit of Capsicum fastigiatum, the 
African Peppery or Chillies, The large, bright red, conical or ovate, com- 
paratively mild peppers of the market are from C. annuum ; they are some- 
times known as West India peppers. Capsicum contains as its active prin- 
ciple an exceedingly acrid oleoresin. The name of Cupsicin has been applied 
by dififercnt observers to the oil, to the resin, and to their combination, but 
should, I think, be dropped, as having no definite meaning. 

Capsicum is a very powerful local irritant, its oleoresin when applied to the 
skin producing in a very few minutes intense pain and redness, and finally 
destroying the cuticle. In the alimentary canal it acts in a similar manner: 
thus, moderate doses produce merely a pleasant feeling of warmth in the 
stomach, whilst overdoses may cause gastro-intestinal inflammation, with 
severe pain as well as vomiting and purging. The chief use of Cayenne 
Pepper is as a condunent ; yet it is often added with advantage to tonic pills 
to increase their immediate action on the stomach. When there is habitual 
feeble digestion, with flatulence, its free use on food may do good. In ady- 
namic disease^ especially as occurring among drunkards^ capsicum is ofleit 
very useful by stimulating the stomach up to the point of digesting food. 
Locally^ either as the diluted tincture in a gargle, or applied in powder or 
tincture by means of a swab, it is useful in severe tonsillitis^ especially in 
that accompanying scarlet fever. 

Administration. — The dose of capsicum is four to five grains in pill 
form ; of the officinal Oleoresina Capsici^ which is to be preferred on account 
of its lesser bulk, from half a grain to one grain. The infusion (^Infusum 
Capsici — 5ss to Oj) is used as a gargle. The tincture {Tinctiira Capsici 
— 1 to 20, U.S.) is employed locally, and is sometimes administered in 
half-fluidrachm doses to drunkards {Extractum Capsici Fluidum^ U. S.). 

Oleum Cajuputi. U. S. — The Oil of Cajeput is obtained from the leaves 
of the Melaleuca Cajuputi, a tree growing in the Molucca Islands. This vola- 
tile oil is of a green color, peculiar fragrant odor, and burning, camphoraceous 
taste. It is not very irritating to the skin, and is exceedingly destructive to 
low forms of life, and consequently has been used as a parasiticide externally, 
and even internally against the Ascarides. I have never used it except as a 
carminative and aromatic stimulant in cases of intestinal pain and spasm, 
and in serous diarrhoea. When employed in these affections in combination 



TOMCS. 



with cblurufurm, camphor, and opiuiii^ it is vcrj cfiieient As a countcr-irri- 
UaC, It litui been nst^d in rlwumatisni; as a stimuknt to the skin, in psoriam\ 
U€He rtmiceu^ und pityrituU, The dose internally h from ten to fifteen drops. 

AUKANTtI AmABI CoitTEX — BiTTER OrANOE PeEL, U. S.— They?M*c/ 
extract ( Extract urn Aurnniti Amari Fiut'dum^ U.S.) and the titiditre 
(Tuieiurtt Aaranfii Atnart) muy be ^iviin respectively in doses of twenly 
mioimaatid a fluidrachm. AiJRANTii DuLCis Cortex — Sweet Orange 
Pekl, U* S. — Of the synip (Syrupus Aurant{i\ U. S/) the dose is a dessert- 
^pooDful, of the tiucfitrf {Tiruiura AnntrUn Dulcts^ U.S.) u teaspoonful, 
Th« orange peels are tfiemselves scarcely medicinal, but are o^uinal os af- 
fordiDg prepanitions much used as vehicles. LiMONis Cortex, U.S., or 
Lemou Peel {^Spirit u a Limonis^ U.S.), is also used for flavoring purposes. 

AcUAXTII Flores. — The flowers of the orange are ofEcitial for the 
pff^eparaliou of the Orange Floicer Water — Atpta Aurantii Fiorum^ U.S. — - 
which in o^ni m an elegant vehicle, free from medicinal properties. 

Tlie fniils of the fullowitig uinbclhrurous plants, Ftcniculum vulgare, 
Curum Carui, Coriandrum sativum, Pimpinella Anisum, are ofiicinal under 
the retipcetiye munea of Fa^niculum (Fennei)^ Girtmi (Caraway), Corian- 
drum ( Corifiiithr)^ Atns$tm ( A nine). They all depend for their virtues upon 
vcilafil*;! oils which are ofBciual Tlie Oil of Auii^e of couiiihtcc is ehieflj 
tU<! product of a Chinese tree, the Ulieitim Anisatum, or Sttir Anise, from 
whose five- to ten-rayed capsular fiiiit it is obtained by distillation. The 
Atptn Firntculi and Spirit un Anm are officinal All of these fruits and their 
preparations may be used as carminatives and stomaehies. 

The herbal portions of Uie following mints are oflSeinjd : Lavandula vem, 
Bosnuuinus officinalis, Salvia offieitudis, Mentha piperita, Mentha viridis, 
MeJIssa officinalis, Tlicy are respectively known as Lavender {Lnmndula\ 
Rimemary {Rfjmiarinus)^ Sage (Salvia), Peppermint (Mentha Piperita)^ 
Spefirmint {Mentha Viridin), and Halm (i/e*/i*«*a), Tlie most important 
preftarattons of tliein iire as follows: Spiritus Ijavandnlse Composite — 
fXmpound Spirit of Lavender^ a ver)' clej;j;imt and ajrreeable stomachic and 
Ctirdial ; dose, a flutdrachm to half a fluidounce, Aqna Mmthse Piperitst — 
Prpperminf W^jtcr^im^ A^pta Mentha Viridis — Spvarmiftf ltV(/rr, both very 
fl^jucntly used na vehielcj*. Spiriftts Mentlim Viridi» and Spirit ug Matthm 
P$^»rrUm — Essence of SpearmiiU and Essence of Peppermint, used ua car- 
iDiii»ttV66, in doses of from ten to twenty drops. The oils of lavender,* 



• MM. Movulo And BruyUot b»vo utodied to game extent the pbjiiologiGiil ftctlon of 
ili« oil* or liktcndcr« rQeciQiLry, uiAT^joram, ikud A»pw {Liit<a»dHta iifnea L.) {DhU, Arad^ 
Mo^. M/iL Brux*iU*f 1879, 55S}, Iq froge thcjr cau^e genemtly (>»ral)i<is wUh lu«» of 
r«(lex fl«tivitj, the niu«ulet being intact, And the sentitive nerTouii Hppnriitua Hffectcd 
hmt^rm tho motor, Upoii the higher atiiiuajj n eitnilAr effect waa produced, except that 
«ril4iif romtoArj oiiuc«d epU«ptiforin convoliioat. 



90 SYSTEMIC REMEDIES. 

rosemary, peppormiiit, and spcarmiDt are also officinal, and may be used in 
doses of At)m three to ten drops as carminatives. Sage contains tannin. 

The volatile Oil of Gaultheria ( Oleum Gaultherm, U. S.) is used for 
flavoring purposes. Calanituty the rhizome of the Acorus Calamus, also 
contains a volatile oil, and its infusion is sometimes used as a carminative. 

EUCALYPTUS GLOBULUS. U.S. 

The Eucalyptus globulus"*" is a large tree, native of Australia. The leaves, 
which are alone officinal, contain, besides tannic acid, a volatile oil, which, 
when pure, is nearly colorless, of a warm mint-like taste, with a bitter after- 
taste, and a very peculiar mint-like odor. It is freely soluble in ether, alcohol, 
and the fatty oils, and is obtained by distillation or by acting on the leaves 
with ether. It does not undergo oxidation into a resinous mass on exposure 
to the air, and is remarkable for its power of resisting the influence of con- 
centrated sulphuric acid. It has been affirmed that the leaves of Eucalyptus 
contain also an alkaloid ; but Rabuteau {Bulletin TtUrap.y Ixxxiii. 549) has 
fairly demonstrated that this is an error. All the virtues of the remedy 
probably reside in the volatile oil, which is in greatest abundance in the 
leaves. According to the researches of Stanislas Martin (Bulletin TMrap,, 
Ixxxiii. 453), the oil is entirely absent from the bark of plants grown in 
Southern France and Corsica, but exists in that from Australia and Algeria. 

Physiological Action. — Locally, the oil of Eucalyptus acts as a de- 
cided but not very intense irritant, and the first efiect of large doses is 
burning in the mouth and fauces, with increased secretion of saliva, followed 
very soon by a feeling of warmth in the stomach. 

The general efl*ect of the same dose of the oil appears to vary considerably 

* Attention wa« first called bj Labillardidre to the value of the Euoaljptua globulus in 
1792, but it was not until 1860 that M. Kamel commenoed the culture of the tree in Paris 
and induced the Prefect of the Seine to order its culiivation on a large scale. Since that 
time it has been largely introduced into Europe, Algeria, South Africa, and California, 
and in some of these countries planted forests are now growing and spreading. Tho tree 
is remarkable for combining extreme hardness of wood with a rapidity of growth as- 
serted to be about five times that of our ordinary trees; it is even affirmed that shingles 
made of it are fire-proof. Its capability for absorbing and evaporating water is also 
extraordinary, and to it has been attributed the freedom of Australia from malarial cli- 
matic influences. Indeed, it is stated that a tree will evaporate ten times its weight of 
water in twenty-four hours, and numerous examples are given in which swamps in Europe 
and Algeria have been rapidly converted by it into dry ground. It is believed to destroy 
malaria not only by draining the soil, but also by yielding balsamic exudations to tbe air: 
however this may be, there is at present very strong evidence as to its power of rendering 
infected districts healthy. As, however, the oonsideration of this belongs to the subject 
of hygiene rather than of therapeutics, the reader is referred for detailed information to 
the following memoirs: Regulus Carlotti, L* Eucalyptiiat ton Rang parmi let Agentt de la 
Matiire MidicaUf Ajaccio, 1872; M. Gimbert, L* Eucalyptti* Globulutf ton Importance en 
Agricnltnrty en Hygihie et en Mideeinef Paris, 1870; Waterer, Bulletin de In StfciStS 
d^Acelimatationf 1872; London Medical Recordf Deo. 1873; London Lancet^ ii., 1877. 

Under the name of Eucalypsinthe, a liquor distilled from its leaves has appeared in 
European commerce. 



TONICS. 



91 



^ia 1 

■oft 
Voce 




"in,* 



diiTi*rent individuals ; but the following summary comprisos tbc facto as 

Hmrly as may be. Aft^?r the ingestion of from ten to twenty drops, a period 

'of mental and phjsiesd activity is often apparent^ followed by a feeling of calm 

And serenity. Bj somewhat Lirgor doses, or in susceptible pciscjiis by the 

doses mentioned, increased dieturbaDoe of the digestive orgiuiis, ending utleu 

-ia loose stools having the odor of the oil, with au^meutAtioti in the frequency 

nd force of the pulse, is produced. Gublcr adds to these symptonis inci'easo 

Fof temperature ; but in Gimbert's experience febrile manifestiitiuns, although 

occasionally occurring, were not usually present. In some eaj^^es the medicine 

sets rery disagreeably, producing violent cardiac palpitations or Intense head- 

che : how fiir these are direotly dependent upon the drug, or are sympa- 

etto upon its local action on the stomachy i^ uncert^itn. If the dose be 

led, or if a larger amount be takeu at once, a period of sedation mani* 

s itself^ the pulse loses its force, luid the animal temperature ia abated. 

After doses of seventy -five grains, Biaz noted nunibne^ of the Itmbs, with a 

ling of excessive weight in them. If the use of the remedy be persisted 

'in, % Bini^Q of asthenia is indue^jd; the teuiperuture falls as mueh as a degree 

ud & half, and the pulse even to fif\y (Gimbert, Archiwjn Ghi4rnles^ 1873, 

lxxi< Hl)i the rL«pimtinn becomes le?^ frequent-, the niuR'uhir we^tknea*: is 

I Wtreme, so that raising the arm to the mouth is painful; the sensiitions are 

blunted, but the intellect Is absolutely unaffected. In an old man who t«ok 

Peij^hty dnjps, the |^K)wer of inntiun nlmoBt di«apf»eared, and he affirmed that 
he loajt for the time being all gcn^^e of the presence of his limbs^ so that he 
iras anconadous of possessing them when ho shut bis eyes, dthough his 

*rulellect was perfectly clear throughf>tit. 
Upon the lower mamnudia the oil of Eucalyptus appears bo act precisely 
irtt doed on man. According to the experiments of Gimbert, the hypoder* 
fflic InjoelioD of the oil ih immediately followed by a period of excitement, 
iiicmingly in great meiusurc due to the intense locid irritation; afler about 
all hour, if the dose has been sufficiently large, the animal bt^ns to 
hie and totter in walking, the breathing grows more and more slow and 
tthir, the limbs give way, the ears drcwp, the muscular weakness becomes 
and, and death, preoeded otlon by partial convulsions, oceui's through 
e of respiration. In Gimbcrt's exjierimcnts the heart idways c<3ntinued 
\ beat after breathing had cejised. As the motor nerves and the musdes 
aincd their functional power ni\er death, the failure of motility and reflex 
ivity must have been central, and Gimbert concludes that the drug in toxic 
v\b therefore a piu^yxaut to the sfunal cord and the medulla. This oon- 
Soil was also attntned experimentally by Bluz (BriiUh Jifedical Journal^ 
lh74). Various observers accord in stating that, afi^-r tiixic doses, there 
In animals, a decided fall of temperature. It would appear from the 
Iciperimeuts of Hermann Schljiger that, after hypodermic injections, the 
Itempcniture sometimes rises, probably as the result of the local irritation 
]{DmFhffswL WtrL Eucal.^lob.^ Inaug. Dips., Gottingen, 1874). The same 



92 SYSTEMIC REMEDIES. 

observer noted that the arterial pressure was greatly lessened. As this fall 
occurred after paralysis of the parvagum, by section or by atropia, and also 
after vaso-motor paralysis by section of the cord, it must be due to a direct 
action upon the heart. This was confirmed by the direct influence of the drug 
upon the cut out heart of the frog. The oil is probably eliminated by the 
lungs, skin, and kidneys. In the experiments of Prof. Binz, the day after 
the ingestion of seventy-five drops, the breath smelt of the drug, and the 
perspiration of amylic alcohol. The urine began to have the odor of the 
oil an hour and a half after its ingestion, and continued to have it for thirty- 
six hours. Dr. Gimbert states that the odor imparted to the urine resembles 
that of violets, and is very similar to that caused by turpentine. 

Binz states that upon the lower infusoria the oil acts even more power- 
fully than does quinia, and its antiseptic properties are without doubt very 
great (Gimbert, Archives Ghiirales, xxi. 137). Mosler {Deutsche^ Archit 
fur Klin. Med.^ 1872, x. 160) affiniis that in dogs whose spleens wore ex- 
posed, injections of tincture of the leaves of the Eucalyptus produced a 
decided contraction of the viscus. According to Gimbert, the excretion of 
urea is enormously increased by the use of the drug. 

THEEU.PEUT1C8. — The chief use that has been made of Eucalyptus is as 
an antipcriodic. So far as I know, Dr. Joseph Keller ( Wiener Medizinische 
Woclienschrift, xxii., 1872) has employed it upon a larger scale than any one 
else. lie used it in four hundred and thirty-two cases, of which two hun- 
dred and ninety-three had suffered from previous attacks. Of the tertians 
75.57 per cent., of the quartans 70 per cent., and of the quotidians 67.89 per 
cent, yielded to the remedy. He recommends it as especially valuable in obsti- 
nate cases in which quinine has been taken again and again. Lorinser ( Wiener 
Medizin. Wocliejuchrijlty xix., xx.), Haller ( Wiener Medizin, WocJtenhlaUj 
xxvi.), Bohn (Berlin, Klin. Wochensc/irijl, 1872), Carlotti (loc. cit.)^ Cortan 
{Montpellier Mddiccd, May, 1872), Gimbert (loc. cit.), Gublcr (Joe. cit.)^ 
Tristany, of Spain {Buchner's Repertorium, xix., 1870), and others, bear 
more or less urgent testimony to the value of Eucalyptus in malarial dis- 
eases; whilst Bnidell (Bulletin Thirapeutiqne^ May, 1875), Seitz (Bayer, 
arztl. Intell. Blatt. 1870), and Papillon (Gazette Ilehdomadaire, 1872) 
affirm it to be of comparatively little or no value. The weight of testimony 
is vastly in favor of the possession of decided antipcriodic powers by Euca- 
lyptus; but it is exceedingly improbable that it will ever supersede the 
cinchona alkaloids: where these have failed, or for any reason cannot be 
taken, it may be used with good hope of success. 

Gimbert, Gubler, and Carlotti all claim excellent results from the use ot 
Eucalyptus in bronchitis^ both acute and chronic : in the first variety it is 
not to be given until the acuteness of the symptoms has been relieved and 
free expectoration established, which, as a rule, is about the end of the 
second week. The remedy is also asserted to be of value in asthma^ and 
even in catarrJuil phthisis. As the oil is eliminated by the kidneys, it 



TONICS. 93 

oomefl into contact with the nrino-genital mucous tract, and has been em- 
ployed in affections of the same ; it seems to be less active than copaiba, 
and the results obtained in gonorrlicta by Aron (Schmidt's Jahrhucher^ 
Bd. clvii., p. 239) were not very good. The remedy appears to be safer 
than copaiba in the early stages of the disorder. The drug has also been 
employed in hemorrhages^ in intestinal catarrh^ in nasal catarrh, and similar 
disorders ; it seems to act somewhat similarly to turpentine in these cases, 
but to be less stimulating. G. Schleinitz has employed (he oil with asserted 
good results in antiseptic sur<;ery, using a guuzo saturated with a five per 
cent, solution (Berlin, Klin, Wochensch., xix. 524). 

Administration. — The oil ( Oleum Eitcalt/pti^ U. S.) offers the most 
eligible preparation of Eucalyptus : in bronchitis from four to ten drops of 
it may be given in emulsion or capsules at intervals of two or three hours , 
as an antiperiodic, from half a drachm to a drachm may be exhibited two or 
three hours before the expected paroxysm. The saturated tincture made 
from Australian or Algerian leaves is efficient ; dose, a drachm to half an 
ounce. The dose of the Jluid extract (^Extractum Eucalypti Fluidum, 
U. S.) is one to two fluidrachms. 

MINERAL TONICS. 

FEERUM-IRON. 
Since iron constitutes a necessary integrant portion of the red blood-cor- 
puscles, it is a food rather than a medicine. A very largo proportion of the 
various articles of ordinary diet contain a trace of it ; and as, according to Quo- 
venne, it is very rarely to be found in normal urine, it must accumulate in the 
system. When, however, the supply, from any cause, is insufficient, or the 
power of digesting and assimilating it is impaired, or an abnormal excretion 
of it oc»curs, or by direct discharge it is drawn off from the blood, as in hemor- 
rhage, a less than normal amount of it exists in the body. When this is the 
case, the condition ordinarily known as anstmia existing, the circulating fluid 
contains comparatively few red disks. It is this state which constitutes the 
great indication for iron. Under its use, if the cause of the anosmia be pre- 
vented from operating continuously, the color returns to the checks, because 
there is an absolute increase of the hacmato-glubulin in the blood. Thus, 
Prof. Simon (Animal Chemistry, London, 1845, Syd. Soc ed.) reports a 
case of chlorosis in which, under the steady use of iron for sixty-four days, 
the globulin increased from 30.86 parts to 90.80 parts per tiiousiind, and 
the haematin from 1.431 parts to 4.598 parts per thousand ; and Cutler and 
Bradford (^?iicr. Journ, Med, Sci,, 1878, p. 78) have obtained confirmatory 
results with Malassez*s tubes. This increase is certainly due in part simply 
to the supply of the peculiar food of the red corpuscles ; but it seems prob- 
abje that the iron acts not merely as a food, but also as a veritable stimulant 
to the organs which produce these bodies. Since, however, we have no 



94 SrSTEMJC REMEDIES. 

definite knowledge as to the early history of the red disks, it is evident 
that any theory as to the method in which iron increases their number must 
be a mere conjecture. It has been generally believed that iron, given to the 
healthy subject, would induce a condition of excess of the red blood-cor- 
puscles. Recent exact investigations, whilst somewhat in discord, offer evi- 
dence calculated to unsettle our belief. The experiments of Nasse {Lond, 
Med, Record^ 1 877, p. 498) upon dogs are in favor of the older view, whilst 
those of E. C. Cutler and E. H. Bradford are in opposition to it.* The first 
observer giving iron with fat, noted not only an increase of bodily weight, 
but that the specific gravity of the blood rose from 1052 to 10G0.8, and the 
amount of the metal in the blood from 0.477 to 0.755 per thousand parts, 
both the result of increase in the corpuscular element. Cutler and Brad- 
ford experimented upon man, using the tubes of M. Malassez, the result 
being slight diminution of the red blood-disks. As, however, the experi- 
ments were only two in number, and the subjects not under complete oontrd 
as to conditions of life, their observations can hardly be considered conclusive. 
It appears to be a well-established fact that one of the functions of the red 
blood -corpuscles is to convert oxygen into ozone, which is the efficient form 
of the element in the system (see paper by A. Sasse, Vierteljahresschrift /Ur 
Prakt. Ili'ilkunde, 1866, zweiter Band). The oxide of iron outside of the 
body certainly possesses an ozonizing power similar to that of the red disk. 
Thus, a spot of iron mould, i.e., iron oxide, on linen will in time destroy the 
fabric. The reason of this is the corroding action of the ozone which is 
slowly generated by the oxide of iron. From a similar cause a fleck of rust on 
a bright surface of steel will steadily enlarge and deepen. It would seem a 
priori probable that in the blood iron acts as it does out of the body. If this 
be so, by increasing oxidation an increase of the iron in the blood should 
cause elevation of temperature and increased elimination of urea. The studies 
of W. Pokrowsky ( Virchow's ArchiVj Bd. xxii.) have shown that, in cases of 
anaemia, afler the exhibition of iron the temperature does rise, even when 
in the beginning it was not below normal, and that simultaneously there is 
an increase in the daily elimination of urea ; and the experiments of Botkin. 
as quoted by Sasse (I have not seen the original), establish the same fact in 
regard to healthy men. The increased oxidation cannot be due simply to au 
increase in the number of the red corpuscles, for whilst the latter accrues 
slowly, Pokrowsky found that the temperature sometimes rose within five 
hours afler the exhibition of the first dose. It would seem, therefore, that 
iron acts directly on the blood as an ozonizing agent. 

* Drs. V. H. Meyers and F. Williams {Arch. Ejtper. Path. u. Pharm., xiii. 7ft) ba\-© 
studied the effects of enormous do»c» of the tHrtrnle of iron nnd sodium upon the lower 
animals. Both frogs and mammals are killed by it: the symptoms in warm-blooded ani- 
mals being vomiting, purging, great fall of the blood-pressure, muscular weakness, finally 
coma and death. The experiments show that the heart is not much affected, but tha ^ 
motor system and the spinal -motor centres are paralysed. 



TOiV/OT. 



05 



Iron in very minate quantity (Qucvenne, Mimoire mtr F Action ph^stolo^ 
\ ti thivapendqm dm FeiTn^ineux^ Arch. <ie Pfit/sioL^ de ThirapeuHque 
? tf *i7^y*>iie, Oct, 1S54, p, 93) is at tiroes present in normal urine, and the 
eadiibition of it as a raedicitie increases the percentage. According to the re- 
aeaichea of Quevennc (p, 95), the elimination of the ordinary medicinal soJta 
of iron is always very slight j but the experiments of Bccrjuerel {Simon*$ 
Chemisfrjf, vol ii. p. 2G4) are not in accord with this. The amount of iron in 
Ihe nrina was found by him to vary, in those taking femiginou.s jkreparations, 
f cry gwatly and unaccountably from day to day, but the eliminaliun com- 
menced as soon as the administration. According to Querenue^ the haloid 
I escape tn the urine mueh more freely than do the other preparations, 
AJiDQSt all of the prepamiioii^ oi' iron are more or less a.striugcut^ and when 
J in the blcod very probably exert a direct influence upon the tiiii^ueS) contract- 
^H ing them not merely by iucrca^iDg their t4>ne| but also by acting on their 
^■titid contractility. 

^H Tlie preparations of iron may be divided into those which are soluble and 
^B those which are in^tuble In water* At fit^t sight it would appear that the 
^P former class of preparations would be those most readily absorbed. The 
^ experiments of Quevenne (loc. ct't/) have, however, demonstrated that these 
loluble prcparutions are largely preeipitutcd Jay the gastric juice even when 
it is strongly acid* This precipitate is probably an albuminate, mixed, when 
tibi gsstric juice is alkaline, with die oxide of the metal. It has been fmrther 
[ deatoQfitratcd by Quevenne that these precipitates do not yield so large a pep- 
omtai^ of material to the acid gastric juice as do somo of the insoluble salts, 
j According to Mialhe (tVimi/e appiitptie, Paris, 185(3), utter tlie entnuice of 
liio iron salt into the blood its power of acting a& a ferruginous tonic depends 
upon its capability of being decomposed by the alkalii« td' the bhxid in such 
a way as to give origin to iJbuminates, From these considenitions it would 
ik^pear that the ijuestion of solubility in water is of very little importance io 
I choice of a chalybeate. Quevenne has demonstrated that the reduced iron 
I the largest percentage, and, as it is nearly free fii^^m ajitringency, it is 
^ the best chalybeate. If a soluble preparation be desired^ the ammo* 
Tqic or potaaao tartrates are very unirritating. If Mitscherlieh be correct in 
his deductions, the protoealts are more readily absorbed than tlie sesqulsalts, 
i tod consequently should be preferred as a general rule.* 

When iron is exhibited in the usual doses, but a small proportion is absorbed, 

I he remainder escaping with the faeces, to which it impai'ts a black color. This 

bliu;k color is due to a conversion of the iron into tannates and sulphnrets ; 

(lie tannic acid of the first compound beiog derived from the food, the sulphur 

I of the second from the intestinal gases, 

Tiiertji PEUTics. — The chief indication for the use of iron is the existence of 



• 1 hftr« It^ft thif «i in earlier editions, althougb U ecems to me thiC the «ubjoct of tb« 
iborpiioci of iroa ujge&tljr needf re-iaveiligntion ; ac« alto Berlin. Klin* trocAciur^., 



96 SYSTEMIC REMEDIES. 

anmmia; the oontra-indication, a state of plethora: on these points sufficient 
has already been said, and the peculiar actions of certain salts will be consid- 
ered under their respective preparations. The preparations of iron which are 
recognized by the U. S. Pharmacopoeia are unnecessarily numerous. 

Ferrum Reductum — Reduced Iron. U.S. — ^This preparation is also 
known by the names of Ferri PulviSj Iran by Hydrogen^ and Quevenn^t Iron^ 
and is as a chalybeate the best of all the various medicinal forms of iron. It 
is made from the subcarbonate (sesquioxide) by exposing it at a white heat 
to the action of hydrogen, which takes away the oxygen and leaves the pure 
metallic iron. It occurs as a light, iron-gray, tasteless powder, which should 
be completely dissolved by dilute sulphuric acid without yielding the odor 
of sulphuretted hydrogen, and when touched with a lighted taper should 
ignite and burn to the brown oxide of iron. If it be black, or if it fail to 
answer the tests given above, it is impure, and indeed, as offered in the shops, 
not rarely it is entirely spurious. Of all the efficient preparations of iron it 
is the freest from astringcncy. The dose is from two to five grains, taken in 
pill form after meals. As it is entirely tasteless, it is frequently given to chil- 
dren in chocolate-drops or lozenges, which are taken as confectionery. 

Ferri Oxidum Hydratuji — Hydrated Oxide op Iron. U. S.— 
The Hydrated Sesquioxide of Tron^ made by precipitating the tersulphate 
with ammonia, is a reddish-brown powder, which is used solely as an anti- 
dote to arsenic. For this purpose it should be freshly prepared, and should 
be so moist as to constitute a magma. Its virtues are deteriorated by age, 
even when it is kept under water, and are entirely destroyed by drying. If 
the solution of the tersulphate of iron be not at hand in an emergency, the 
perchloride will yield just as useful a product, and carbonate of sodium may 
be substituted, if circumstances necessitate it, for the ammonia. The pre- 
cipitate falls at once, and may be washed by putting it in a piece of muslin, 
squeezing out the original fluid, and then pouring on some fresh water. As 
the sesquioxide of iron is perfectly innocuous, it should be very freely admin 
istered when used as an antidote, especially since it only acts when in excess. 
A teaspoonful to a tablespoonful of it should be stirred up in water and taken 
at once, the dose being repeated several times if necessary. The Ferri 
Oxidum Ilydratum cum Magnesia^ U. S., differs from the hydrated oxide 
in containing magnesia, which is substituted in excess for the ammonia as a 
precipitant. As magnesia is not at all irritant, and is itself antidotal to 
arsenic, this new preparation offers decided advantages over the older anti- 
dote. It should be given promptly and freely. 

Ferri Carbonas Saccharatus. U.S. — Saccharated Carbonate 
OP Iron. — This greenish-gray powder is made by precipitating a syrupy 
solution of the sulphate of iron by bicarbonate of sodium. Throughout the 



TO yics. 



W 



■ tubsequent washing, and dunog drying, sugar is kepi oonstfintly present in 

Iai^ Minouiit, so as to prevent the absorption of oxjf;en, nnd tbe consequent 

L toiiTerston of the protocarbonate into the Bcstjuioxiile, This is a very good 

I cbajybeate, nearly free from astringency, and may bo given in doses of from 

three to five grains, in pill form. PHuhn F* rrt Componittr^ U.S., contain 

tht prr>to€arbonate of iron and rayrrh. They are sometimes used in auaamia 

with atnenorrb(Ba ; one to three pills three times a day. The MUtura Ferri 

K ^>ftyK»iVa. U,S., is a Uc|iiid preparation containing aub^tantially the sume 

I t^i^TtHiient^s a3 tbe compound pills. Dose, one to two tablespoon fills. 

P FxRRt SIJLPHA&— Sinj>HATE OF Ikon. U* S. (FeO,SO, + 7H0 - 

Fe^Oj -\- 7H,0.)* The pure protoftulpbat^ of iron is made by dipeolviag iron 

in diJute sulphuric acid. It occurs iu transparent efflorescent rhombic prisnis 

€3>€ a pole bluish-green color and a metallic styptic taste. The sulphate of iron 

is WL. ^ery decided ajstringent, and in a concentrated form and sufficient amount 

aeCs as an uritant poison, producing vouiking^ purging, and gnstro- intestinal 

inflaa^nmation. Extermdly its solution (five to twenty-five grains to the fiuid- 

LEicn' J tj^ Uikxl as an astringent lotion. It has been especially recommended 

tiliU fonn (5i to Oj) in crysipcliiM. As a simple ehalybciitc the sulphate 

of irc»n should never be used. In chronic diarrkKjea it is sometimes cmpkiyed 

A tonic astringent, Dose, five grains; in the form of the dried sulphate 

I-^^Wti' Sulpha* ExMiccatm^ U. S.), three grains. Ftrri Su/phag PrfrcipU 

tr§e^€M, U, S,, is simply a pure ferrous sulphate obtained by precipitation, aad 

*>**jr be used instead of the older preparation, 

XtiOUOR Fkrri SuBsuLrHATis— MoNSEi/fc; Solution. U.S. — The Boh- 
^^fi tif the §nh*iilphate [of the se^vjuioxidc] of iron (ofk*n incorrectly called 

lutiftu uf the persulphate of iron) is a moat powerful astringent and styptic, 
Is used solely as such. It is but slightly irritant, and is the best of all 
"*<? astring«;nts for staunching hemorrhage when it can be applied directly 
^ tile pirt, 00 in external wounds, or in hmnatemcM». Tn homorrhage JVoiu 
^^ «tomaeh, t<*n drop."? of it may be given in a t,ablespoi:mful of water, the 
^^^^^ lieiag repeated as necessary. Applied by means of tlio atamijcer, it 
^0|\^.rj ^'^ery efficient in humoptt/sU. In such a ease the fluid Uv Ikj atomiKcd 
••*OiiId Imve the strength of from five to twenty drops to the ounce. The 
*^«*«thition should Irwjt from five to fifteen minutes, and be repeated at intervals 
" ttn hour or longer. It is very c^ejitial that the liquid should bo finely 
P'»lvrruEcd, 

T|r' Snfitdfjn o/ the TentdphaU [of the Scsijuioxide] of Iron is also oflici* 
'"^, under the title uf Liquor Fkrei Tkrsuli'HATIS. Owing to its irritant 
*^t.i<Mi, il ia lised in ph;irmacy only to make the sest^uioxide prcparatious. 

TijccT^RA Fkrbi CriLORiDi — Tincture of Culobide op Irojt, U*S., 
the BesquiehJaride of iron, murintic acid, and alcohol, and, from 
T 



98 SYSTEMIC REMEDIES. 

the reactions of the last two ingredienta, muriatic ether. It is prepared 
by adding alcohol to the officinal Liquor Ferri Chhridi, and is a reddish- 
yellow, astringent, irritating, somewhat corrosive liquid. It is an excellent 
chalybeate, possessed of peculiar properties, probably in some measure due to 
the ether which it contains. It is a diuretic, increasing often very decidedly 
the daily urinary secretion. It appears also to exert an astringent influence 
upon the urino-genital mucous membrane, and is frequently employed with 
tincture of cantharides in gleet In chronic Bright' s disease it ijs often of 
very great service as a chalybeate diuretic. In erysipelas it is constantly em- 
ployed with remarkable results, controlling the disease in a manner not yet 
understood. Analogy has suggested its employment in other adynamic affec- 
tions, such as diphtheria and pystmia^ but its value in these diseases is much 
more doubtful. Locally it is used as an astringent in sore throat ; for this 
purpose its strength should be reduced at least one-half. As it is very de- 
structive to the teeth, care ought to be exercised in its use about the mouth, 
and also in its administration. The dose is from fifteen to thirty drops, given 
afl a chalybeate three times a day ; in erysipelas, every two or three hours. 
The orange-yellow crystalline deliquescent Sesquichloride of Iron (Ferai 
Chloridum) (Fe,Cl, — Fe,Cl,) is officinal, but ijs very rarely used. 

Syrupus Ferri Iodidi. U.S. — The Syrup of Iodide of Iron contains 
7.33 per cent, of the dry protiodide of iron in the fluidrachm, and is made by 
shaking iron, iodine, and water together, and adding hot syrup. It is a trans- 
parent, greenish liquid, of a sweet, ferruginous taste. It deposits no sediment on 
keeping, and should not affect the color of starch. If it strikes a blue color with 
the latter substance, it contains free iodine. The syrup of iodide of iron is 
a favorite remedy in those cases of anasmia in which there is a distinct scrofti- 
lous taint. It is believed to possess the peculiar alterative powers of iodine, 
conjoined with the tonic properties of iron. It is enormously used in scrofu- 
losis occurring in ansBmic children ; but it certainly possesses no advantage? 
over a ferruginous tonic and iodine when given separately but simultaneously 
Indeed, it seems to me uncertain whether its use is as effective as the sepa- 
rate administration of iodine and iron. The dose of it for a child two years 
old is five to ten drops ; for an adult, thirty to forty minims. As it affects 
the teeth very seriously, it should always be freely diluted when taken, and 
the mouth should be well washed aft^r its administration. 

Ferri Iodidum Saccharatum. U. S. — Saccharated Iodide of Iron is 
a yellowish-white or grayish powder which represents the chemical and 
medical properties of the corresponding syrup, being prepared by a parallel 
process. It may be substituted for the syrup in doses of from two to five 
grains given in pill form. 

DiALYZED Iron. — Ferrum Dialysatum, — This is a clear, neutral, nearly 



TONICS. 



99 



UstdeflS, dark-red liquid^ prepared bj dialysinj; a solution of the chloride of 
iron. Its exact chemical oomposition is uncertain. It cotjCaiiia a luinata 
proportion of chloride^ and it is possihle that the iron exists m a basio 
oxych!oride. It bears dilution with pure water, but fa at once precipitated 
by alkalios, almost all soluble salts^ and many organic substances. As the 
troD oside in tbia oondition is unable to pass throug;h antraal membranea, it 
has been asserted that it cannot be absorbed. Clinical espcrience »howa| 
howcTer, that it ia absorbed^ and it, a priori, seems certain that the clialyzed 
iron mufit undergo change the moment it enters the st^miach. In what form 
absorption takes place we do not know. The tastelesHoe^s^ bannlessneaa to 
the teeth, comparatire freedom from astringency, have rendered it a favorite 
chalybeate, notwithstanding its feebleness ; the assertion frequently made 
bat it never constipates is an error. It Bhould never be used in combina- 
ion. The dose ia twenty to forty drops. Bialyzed iron seems to be the 
, antidote at command for arsenic. It is harmless, and in cases of poison- 
tig a tahlespoonful should be administered at once, and repeated pro re nata 
(see PhllwL Med. Tunes, voL viii, pp. 104, 151, 335). 

There are four oJBcinal Citrates of Iron, all soluble in water. Two of these 
(Ferri Citras and Fkhri kt Ammonh Citras) occur in garncty-red scales, 
kiid ai\5 simply mild chalybeates. Dose^ five grains. The Citrate of Iron and 
}uiniti (Ferri et QutNiNiE Citras) is in transparent scales, varyiiisr from 
idish brown to yellow if^h brown in colorj wiifi a tint of green. The Citrate 
Iron and Strychnia (Feuri et Strychnin.e Citra-s) contains one per 
ent of stTychnia. 
There are two officinal Tartrates of Iron (Ferri et Ammonii Tartra8 
4md Ferri et Potassii Tartras), Iwth occurring in gamety scales, and 
J able in water. Dose, five grains. The Lactate of Iron (Ferri Lactas^ 
,LS.) occurs in green i4«h -white crystalline crusts or grains^ Bolub!e in forty- 
sight parts of water. It is a good chidybeate. Dose, five grains. There 
t officinal Phospfuttes of Iron^ which may be used in five-grain doses. 
aRi Pno8PeAS is a bright slate-colored insoluble powder. Ferri Pyho- 
SOSFBAH IS an excellent preparation, occurring in apple-green scales, dome< 
hat soluble in water, und nearly free from astriogeucy and ferruginous taste. 
The Ammonio -ferric Alum (Fehri et Ammonii Sulphas, U. S.) occurs in 
rctahedral crystals, of a pale violet color. It is freely soluble in water, is 
astringent, and is only used in atonic leucorrhota, in which affection 
rkcd benefit is often gained by the exhibition of it in five-grain dt>ses rhree 
fty. The Bromide of Irmi (not officinal) has rect^ntly been highly 
Bded by Dr. Da Costa in chorea and incontinence of urine in children 
iicat and Sur^ictd Reporter, 1874), He gives, to a child, five grains, 
lived in syrup, and rapidly increases the dose to twenty grains. In a few 
b, I have found it useless in chorea. 

MANaANESE*— The Biack Oxide of Manf/atme (Manoani Oxidum 



100 SYSTEMIC REMEDIES. 

Nigrum, U. S.), and the Sulphate (Manqani Sulphas, U. S.), have been 
supposed by some to possess therapeutic properties similar to those of iron* 
The metal manganesium certainly exists in the blood, but its salts have 
failed to gain the confidence of the profession, although highly recom- 
mended by Harmon, of Belgium, and by P^trequin (^Noiwelieg Recherches du 
Manpah^, 2d ed., Paris, 1852, also Bulletin Thirapeutique^ March, 1852) an 
an adjuvant to the chalybeates. In Dr. Garrod's experiments upon anosmia 
{Medical Thne$ and Gazette^ 1863) the preparations of manganese failed to be 
of service. C. C. Gmelin is said ( U, S. Dispensatory) to have found the sulphate 
act as a powerful cholagogue on the lower animals ; and Dr. Thomson statee 
that it is a purgative to man in doses of one or two drachms. Dr. Leand 
affirms {Glasgow Medical Journal^ Jan. 1865) that the oxide of manganese 
is therapeutically equivalent to the preparations of bismuth excepting in 
that it does not constipate, and that it may be used with advantage in goo- 
tralgiay pyrosis^ and similar stomachic derangements. 

AOIDUM SULPHUEIOUM-SULPHUEIO AOID. U.S. 

Oil of Vitriol (SOjjHO — H,SO^) is when pure a colorless, heavy liquid 
(sp.gr. 1.843). On exposure to the air it rapidly absorbs moisture and 
becomes less dense. When its specific gravity is 1.78, it deposits ciystals of 
the bihydrated acid at 28° F., and may burst the glass in which it is kept. 
Owing to its great affinity for water, it is used in chemistry as a dcsiccant. 

Physiological Action. — Concentrated sulphuric acid is powerfully cor- 
rosive of both animal and vegetable tissues, abstracting the elements of water 
and leaving the carbon untouched. It consequently blackens organic matter 
at the same time that it destroys its texture.* When administered in thera- 
peutic doses and absorbed into the blood, it is converted into sulphates, and 
us such, so far as is known, is eliminated. 

It escapes by the kidneys, as has been proven by Dr. H. Bence Jones 
{Lectures on Pathology and Therapeutics, London, 1867) in r^ard to large 
therapeutic doses, and is attested by MaukopfF as occurring af^r poisoning. 
As, however, the amount of elimination by the kidneys seems to be slight, 
it is very probable, as Dr. Headland {Action of Medicines^ London, 1852) 
conjectures, that it is excreted both by the lower bowel and by the skin. 
Locally applied, dilute sulphuric acid is an astringent, and clinical experience 
proves that it exerts a similar action when taken into the system. Under 
such circumstances its astringent influence is most marked upon the skin and 
intestine, — parts which are believed to excrete it : it is therefore possible 

♦ The observation of Ore {Comptet-Henduif 1875), that considerable quantities of dilute 
acids can be injected into the blood without causing congulation or serious disturbance, 
has been confirmed by Dr. Paul Guttman {Virchow^t Archiv, Bd. Ixix. p. 634). The 
acid is probnblj at once neutralised by the alkali of the blood. 



TQNICSL 



101 



tkat tills aoiioti b in a measure local, aod depondent npoB the preaence of 
the excreted acid.^ 

THSaAPSUTlCS. — Concentrated Biilplitirici acid is not rarely used as an 
€BdiaTOtic« for whicl» purpose it is mixed with fiuoly-puwUered charcoal so us 
%o fon» a paste. Appropriat^sly diluted, it hjis been uBcd as a stimulant and 
astringent lotion In venereal and other indolent ulcer&. Internally^ sulphuric 
acid is very useful as an astringent in colliquative sweats (night-^weais) and 
in profuse Bermts diarrfweas. I have used it with great advantage in the 
sudden serous vomiting and purpng of infants known as cholera infantum. 

It has been employed with advantage in cholera^ and a remarkable series 
of obiwrvatioua by Dr. R, G. Curtin {Fhilnddphia Medical Times^ vol. iii. 
p. 04U) at least furuijih ;j:ood reasou for further testing its powers as a pro- 
phy lactic agiiinat this disease. The facts recorded by Dr. Curtin are as 
fijHows. A very severe epidemic of the diaease ceased iu the Insane Depart- 
ment of the Philttdelphiu Almiihouse within twelve hours after the luuaticis 
^ till put upon the free use of sulphiirio acid lemonade ; the only new ctise 

er this being in a man who refused to use the prophyhtctic. Two days 
after the use of the sulphuric acid was stopped, two new cases occturred, and the 
epidemic was again aiTestcd by the use of the acid. In the Biirgical wards 
of the Hospital Departmeiit the acid was used irom the beginning of the 
epidemie \ and these waids^ although in no way isolated^ were the only parts 
of * * *riUion nnvittlted by the disease* 

^ , I acid was formerly used iu henwrrhagm^ but is now rarely em- 
ployed. It is^ I think, much less efficacious than some other remedies. In 
d^poinoniug the dilute acid is an efficient antidote, and it has been 
by M. Gcudrin (Dr. Bennett, Ltrndon Lancet^ 1850) as a remedy 
ia ehtcnuc lead'ptftsomn^. Aa, however, he combined its internal exhibition 
with the daily use of warm sulphur-baths, it is doubtful how much of the 
mOGfiflBful re^idt was due to its aetion. It is difficult to perceive how it can 
do good in these oases, and I do not think the clinical proof that it does so 
has as yet been bnmght forward. 

Toxicology, — ^Vhen swallowed In conoentratcd form, sulphurio acid acts 
ire poison. Death from collapse has resulted in two hours tiiid 
in Medical Timet and Gazt'ttCy voL i., 18(53), but usually the 
oourso of sulphuric aeid poisoning is much more protracted, the fatal result 
having been delayed iu some cases for several months. The usuul symptoms 
aro pain in the mouth, throat, and epigastrium, violent vomiting, often of 
t^irry matters, with symptoms of coUapHeT sucli ui* cold extremities, feeble 
ippressed voice, and clammy skin. The mind is generally dear to the 



nh atrllon uf lurge }jut not corrofivo doie« of nilnunil iiuids Ufvon antfnnl? has boen 
Ut iomo exttiril AtutJitfd by Dr. P. Hofmelater {fMujer, Mtd. Wftchtmeh,^ 1879* i v. 75). 
t)«n.ik. h« btnov«i< rciultf from ospbyxU, duo to the acidi ilea (ion in thci bltKMl uf the alkm* 
lioe m\\Mt wbich wrTe m vebiales la earn ing ibe cftrbunio ivcuU froia the tiaeues. 



102 SYSTEMIC REMEDIES. 

last. Profuse, and sometimes bloody, salivation is commonly present The 
parotids sometimes swell as early as the fourth day, and Maukopff {Syd, Soc 
Year-Book, 1863) has seen suppurative parotitis apparently induced by closure 
of the duct of Steno, retention of secretion, and consequent irritation of the 
gland. The later symptoms are those of ulceration of the oesophagus and 
stomach, and need not be dwelt upon here. The larynx is often profoundly 
affected. There is a very marked increase in the amount of sulphates in the 
urine, which may be albuminous and contain granular casts. Desquamative 
nephritis may be developed several days after the subsidence of the first 
symptoms. Thus, in one of the cases reported by Maukopff, urine which 
had ceased to be albuminous on the third day became so again on the twen- 
tieth, with a simultaneous development of casts containing blood-corpuscles ; 
after death tubular nephritis was found. Another sjrmptom noted by Man* 
kopff was intercostal neuralgia. 

After death, greater or less destruction of the oesophagus and stomach, 
or of the air-passages, is found. The black color of the slough is a diagnostic 
sign which an examination of the mouth will sometimes render available 
before death. 

The most important part of the treatment of sulphuric acid poisoning 
consists in the immediate and free exhibition of the antidotes, which should 
be given in milk or in water. The best antidotes are chalk, magnesia, white- 
wash, and soap. Christison condemns the use of the alkaline carbonates, 
because they are themselves irritating. As, however, in these cases time is 
a matter of vital importance, if the alkaline carbonates be the only antidotes 
at hand they shquld be used unhesitatingly. 

Administration. — Sulphuric acid should of course be given properly 
diluted, and with the requisite precautions to prevent its injuring the teeth. 
It is best administered in the form either of the dilute (^Acidum Sulphuri- 
cum Dilutum — 1 to 9, U. S. ; sp. gr. 1.082 ; dose, ten to thirty drops) or of 
the aromatic sulphuric acid (^Acidum Sulphuricum Aromaticutn — 1 to 5, 
U. S.). The last preparation contains alcohol and aromatics. Its dose b 
from ten to twenty drops. 

AOIDUM HTDEOOHLOEIOUM-HTDEOOHLOEIO AOID, U.S. 

Muriatic Acid is a colorless aqueous solution of hydrochloric acid gas, 
having the specific gravity of 1.160, and containing rather more than 33.9 per 
cent, of the gas. The muriatic acid of commerce commonly has a yellowish 
tint, produced by sesquichloride of iron, or sometimes by organic matter. 

Physiological Action. — In its concentrated form muriatic acid is highly 
corrosive, but less so than either sulphuric or nitric acid. Its astringent 
properties are not all decided, if indeed it really possess any. As it prob- 
ably is one of the natural acids of the stomach, it would seem as though it 
ought to be capable of aiding digestion. It also appears to have influence 



i 



TONICS, 



103 



over the glandular system of the alimentary canal ^ mcreasitig by iU action 
their normal secretions, 

Thbrapeutics. — In ttomacluc </y*/>^#*a, muriatic acid, witli or without 

pepsin, la often useful by aiding in the digestion of the food. In other cosee, 

where the dyspepsia is ifitegtinaj^ with a t<^ndency to diarrhoea and loss of 

appetite, muriatic acid combined with strychnia and some aromatic, such as 

[impound tincture of cardamom, is often very advantageous* In low /emr$ 

use of mineral acids has been highly extolled by various authoritiea, I 

ttve seen a number of cases treated upon this so-called ** Swedish pbin/* and 

live never been able lo perceive that the acids do any retd good. 

Locality diluted muriatic acid h.is been recommended by Bretonneau in 

itphiheriti. He employed a mixture of one part of the acid to two of honey ; 

&lder practitioners have used it of full strength, withj it is claimed, good 

It should he applied by means of a little mop, scrupulous care being 

cisod to prevent any of the acid from coming in contact with porta not 

ftrntect^l by false membrane. 

ToxicoU)or. — Muriado acid, ajs a poison, is similar in its effects to, but 

y powerful than, sulphuric acid, recovery having occurred after the ingestion 

of an ounce of the officinal acid [BrMon Medical and SurgicalJournal^ vol. 

XV.). The treatment is similar to that of poisoning from other mineral acids. 

AjJiiiNiSTRATlosr. — The acid is best given in the form of the officinal 

^^^Andum Uf/drorfdoricmn Dtlutnm (Jiv to Oj ; sp. gr. L038). Dose, ten 

^Bo thirty drops^ properly diluted. 

^ AOIBUM NITBIOTJM-NITBIO AOID. U.S. 

A liquid of the specific gravity of 1.420, which as first made is colorlessi 
^^l)Ul by exposure to the light aci|iiircs a yellow tint. It oxidizes all of the 
^pconunon metals except gold, and is exceedingly corrosive to living tissue, 
which it iitains an indelible yellow. When diluted it converts most animal 
lodv^etable substances into oxalic, malic, or carbonic acid. 

PliYSlOLOGlCAL ACTION, — Whf'n applied to any portion of the living 
ot]gmJsm, nitric acid acta as a most powerful chemical caustic. When very 
greatly diluted, it is a simple local stimulant, with very slight astringent 
powers. Owing to its chemical activity, its vapor was at one time used as a 
dii«inff?ctant ; but it has been superseded by other substances. Taken inter- 
nally in wnall amount, it acts as a stimulant upon the glandular system of 
the alimentary canal, and in serous diarrhoja appears to exert an astringent 
I» flue nee. It mninis to me very probable that these effi?cts are local rather 
than euiistitutionaJ, due to a direct action of the acid upon the muc<ius mem- 
brane of the bowel. On entering the blood, nitric acid must be converted 
mto a nitrate- In regard to it« elimination we have hut Utile definite infor- 
mation, but it probably oeeapos through the same channels as does sulphuric 
acid. 
TaEBAFEimcs. — ^Nitric acid is used quite frequently as an escharotic, 



iwrriii-- 



104 SYSTEMIC REMEDIES. 

especially in cases of chancrei and venereal xnr other v>arU, In its employ- 
ment care should be taken to protect the sonnd tissue by oil, or, still better, 
by a layer of soap. It may be applied by means of a splinter of wood, or, 
if it is to be used more freely, by a little mop. When it has penetrated as 
deeply as is desirable, washing the part with warm soapsuds will prerent 
further action. Very much diluted (five to twenty drops to the ounce), it 
forms a good stimulant lotion for indolent ulcers. It should not be employed 
as a mouth-wash, on account of its destructive action on the teeth. Of course 
this does not apply to its use as a caustic in cajicrum oriSy in which, as in other 
forms of acute gangre^ie^ such as phagedenic chancres and hospital gangrene, 
it is very eflficient. In these cases it must be applied thoroughly. 

Internally, nitric acid has been used in low fevers, but with doubtful 
advantage. In dyspepsia^ in chronic hepatic congestion, in the oxalic acid 
diatJiesis, in the dyscrasia of constitutional syphilis, nitric acid has been 
employed with advantage, but is much inferior to the nitro-muriatic acid. 

In 1826 Dr. Hope claimed for the Acidiim Nitrosum a specific action in 
serous diarrhoea,, including the sudden acute diarrhceas of hot climates, and in 
the chronic dysenteries originating under similar circumstances. The formula 
he employed is as follows : R Acidi nitrosi, f 3i ; Misturae camphorae, f Jviii ; 
Misce, et adde Tinct. opii, gtt. xl. S. — A fourth part to be taken eveiy 
three or four hours. Under the name of Hope's Camphor Mixture a prepa- 
ration similar to this has been much used, but has gradually lost the confidence 
of the profession, chiefly, I believe, because on theoretical grounds the original 
formula has been departed from. The Nitrous Acid of the shops (^Acidum 
Nitrosum, Edinburgh Pharmacopoeia) is an orange-red liquid, which may be 
looked upon as a solution of nitric oxide in nitric acid. When it is diluted 
with water it is after a short time converted into simple nitric acid. For this 
reason it has been customary to substitute nitric acid for the Acidum Nitro- 
sum of Hope's original formula. It should be noted, however, that the latter 
only provided sufficient of the remedy to last a few hours, and, as the reaction 
which has been spoken of requires some time for its performance, I do not 
think that theory in truth warrants the change. Practically I have failed 
absolutely with the new formula, when immediate relief was afterwards ob- 
tained by the use of the medicine prepared according to the old plan. Made 
in this way and used whilst fresh, Hope's Camphor Mixture is a very efficient 
though disagreeable remedy in diarrhceas connected with disordered secretion 
of the liver and other glands of the alimentary canal. 

Administration. — The dose of the strong acid is from ^vq to twenty 
drops ; of the diluted {Acidum Nitricum Dilutum — 1 to 6, U. S. ; sp. gr, 
1.068) from fifteen to sixty drops. 

Toxicology. — When taken in a concentrated form, nitric acid is a cor 
rosive poison, exceeding even sulphuric acid in violence. The symptoms so 
closely resemble those induced by the latter substance that it is unnecessary 
to detail them here, as is also true of the treatment. The distinguishing 



TONICS, 



les 



f ehumcter is to be found in the color of tbo affected tissues, wliich in nitrio 
Bcid poisoning are staiucd of a deep yellow. 



AOIBUM MTRO-HTDEOOHLOEICUM-HiTEO-HYDEOOHLOEIO 

ACID. U,S, 

This preparation is made by mixing tliree parts of nitricj with five parts of 
fuuriatic muL If the acid be sufficiently strong, an orange-colored lif|uid is 
brmed, wiih the evolution of intenaelj-irrilatiiig vapors. After standing for 
I of time, the red color changes to a gulden yellow. It is in thiB stata 
Jnited S twites Pharniacopujia directs the acid to be used* By longer 
Staading the goldtm yellow becomes ^ewton^yfillow, and the odor of chlorine ia 
■almost entirely lost. These changes are hastened by Hght, bot will occur in 
tie dark and in well-stoppered bottles. Although the goldun -yellow acid ia 
iirected by the PharmiKiopoeia, yet careful clinical studies have convinced me 
bat the acid act« much more efficiently when freshly prepared and of a deep- 
color. Id some cases it has seemed to me useful only when in the latter 
brm. The lemon-ycUow acid is nearly valueless. 

Physiological Action. — In concentrated form nitro-muriatic acid ia 

Kceedtugly corrosive. Our knowledge of it« action in small doses is purely 

dmioal, and will be spoken of under the head of Tlierapcuties. The chemistry 

' the acid is so complex and uncertain that no rciisouiible conjecture can be 

Ic us to die form in which it is absorbed or the method of its escape from 

body. That it is absorbiMl in iridic form is proven by its occasionally 

cing salivation, even when upplieJ to the skin by means of batbii. 

TheraI'ETJTICS. — The remedial value of nitro-muriutk" acid depends chiefly 

[JO the j)ower which it possesses, to a much greater degree than any other 

iX the mineral acids, of influencing the action of the liver and other glandular 

the alimcntiiry canal Originally prt>poscd by Dr. N* Scott, of 

^ in the chrome hepatitis of hot cluuatcs, it has been used with great 

fitico^s by Anueaiey, Martin^ and other famous India surgeons. The remedy 

ircmid gecm not to be indicated in hepatitis with high fever and a tendency 

lo mpid suppumtion so much ai> in the slower i\»rm of the affection, which 

Honoally ends in chronic enlargement and induration of the viscus. In the 

bitual Cf/n^c$(ioH of the liv^ occasionally seen in this climate I have used 

$1 with the most marked benefit In the still milder affection known aa 

• initotiineuij'* whose pathology is probably a U>r|)id eondiiion of the small 

of die alimentary mucous membrjme as well us of the liver, nitro- 

Btic acid has yielded in my hands most excellent results. That the 

rcme<iy dues act u]>ou the liver is proven by the fact that in these cases it 

wtnetiiues produces violent bilious diarrhoea. WTieu jaundice depends upon 

c^wtructiou or upon any of the severer organic diseases of the liver, the acid 

ia of little if any use ; when, however, the jaundice depends u|Mjn torpor of 

lluf liver, or even when it is catarrhal in origin, the remedy miiy lie of great 

Even in the early stages of cirrhosis, whilst the Ever is still enlarged, 




106 SYSTEMIC REMEDIES. 

nitro-muriatic acid should be tried, as in some cases apparently of this char- 
acter great benefit has been derived from its use. 

In those forms of chronic diarrhoea in which the disease is really an intes* 
tinal dyspepsia, nitro-muriatic acid may be of the utmost service, benefiting 
and even curing cases which have resisted all other treatment. As the effecfc 
of the acid is not a sudden one, it is evident that it acts in these cases not ss* 
an astringent, but by restoring the normal digestive power. 

There is a morbid condition, probably dependent upon defective primary 
assimilation, in which the chief symptoms are general malaise, a feeling of 
weakness, a lack of elasticity, a very great depression of spirits, in which 
crystals of oxalate of lime are generally to be found in the urine, and in which 
nitro-muriatic acid produces in a few days a surprising revolution. 

As a " blood-purifier" the acid has been employed in constitutional syphilis^ 
and in various ulcerative skin-affections. In these diseases it no doubt does 
good by improving digestion and increasing glandular action, but there is no 
reason to believe that it is a direct alterative. 

Administration. — For reasons which have already been given, when 
nitro-muriatic acid is administered internally it should be freshly prepared ; 
and, as the changes which have been spoken of take place more rapidly when 
the acid is mixed with water, the officinal dilute nitro-muriatic acid is an in- 
eligible preparation. As light hastens its deterioration, the strong acid should 
always be kept in a dark bottle with a glass stopper. Directly afler mixing 
the acids the evolution of gas may be so great as to necessitate its being 
allowed to escape. After six or eight hours, however, the bottle should be 
closely stoppered. The dose of the strong acid is from ^yb to eight drops, 
properly diluted, and taken through a tube after meals. 

In chronic hepatic diseases the external application of the acid seems to 
give even better results than its internal use. In India, according to Sir 
Kanald Martin, the bath is used as follows : 1. Take Hydrochloric acid f 3iii, 
Nitric acid f Jii, Water f Jv. Mix. Two gallons of water and six fluid- 
ounces of the above mixture suffice for a bath, which will keep fit for use 
during three days, provided half a Quidounce of acid and a pint of water are 
added morning and evening. The bath must of course be given in wooden 
or earthenware vessels, and if it becomes necessary to warm it only a portion 
should be heated, and the rest then added. In urgent cases the whole body 
may be immersed in the bath ; but generally a foot-bath is preferable, the in- 
side of the thighs and arms and the hepatic region being at the same time 
sponged. The bath should be repeated twioe daily, lasting each time for ten 
or fifteen minutes. 

I have had no experience in this method of using nitro-muriatic acid, but 
have derived great benefit from the application of the acid over the hepatic 
region. My plan has been to wring out a large piece (eight by ten inches) 
of spongio-piline, or of canton-flannel (several layers), in a lotion of a strength 
varying, according to the irritability of the patient's skin, from one to three 



TONICS. 



107 




nidrachins to the pint, and to apply tlris over tlic rij^ht hypochondnuin, 
^vering it with a piece of oilod silk iiuppnrtcd by a baudagc. The applica- 
Qn fiotnetimes causes a prickling seiisatiou, and after a time may produce a 

ofufie local Bweating, The dreeing Diay be lefl on froin hulf aii hour to an 
r, Mhd be repeated three or four times a day; &ome patients can wear it 

DOst oontiuuously. 

ToxicoLOGT, — \Mien taken in poisonoua cluBes, nitrLvnmriatic acid pro- 
nws symptoms and results similar to those following the ingestion of nitric 
ud. The color of the stain produced by it la yellow, and its antidotes are 
he same as those of other mineral acids. 

Lactic Acm (Acibum Lacticum, U. S.) appears to be the natural add 

the gaistric jaioe, and may with propriety be used as an adjuvant to pepsio 

doeea of half a draclim three times a day. W* Preyer, conceiving that sleep 

due to the presence in the blood of the results of tissue change, amongst 

which \s lactic acid, experimented with it and its m)da suit, nnd announced 

lat they acted as powerful soporifics upon both man and the lower unimaU 

Cen t ralb , Med. Wissenx, ,1875,p. 57S). A ecord i n g t o h is atat emen t a , w i th t he 

!eep came deep, slow rcf^pi ration, wkh lessening of reflex activity and of the 

il3' temperature. Sub8e(|uent paj>en3 by Dr. E. !Mendel (Deutsch. Med. 

'ochfns,, 1876, No. 17), Dr. Erier ( Centralb. Med, Wis^ens.^ 1876» p. 658)^ 

Dr. Fischer (Lond. Mtd. Rtctyrd, 1S77, p, 193), Dr. Lothar {Virchom'* 

rchh^ Bd. Ixvi. p. 120), and Dr. Senator (^Berlin. Klin. Wothens.^ 1877, 

537), have shown that the hypnotic jwwers of lactic ueid and its sidtB are 

Ty fi'eble and uncertain. The large do»es used also are very prone to pro- 

irritation of the nHmcntury canal, and Senator noticed the production 

amatic pains. From three to nine drachms of the lactate of sodium 

lay be given at a doae. 

PHOSPHOBUS, (P.) U.S, 
Phosphoms is a translucent, when pure nearly colorless, hut usually alightlj 
jlowitth, highly inflamuiabte elementary body, which is tasteless, but possesaed 
r a ^leculiar alHaeeous odor. It is obtained trom tlic phosphate of calcium of 
ilcined lH>ues, by taking away the lime with sulphuric acid and deoxidizing 
be rt«iduum by heating with charcoal. It k insoluble in water, sparingly sol- 
uble in ether, absolute deohol^ and the »3ils, freely sty in chlorofiirm. It takes 
Ire at. 100^ F., and melts at 108^ F. In the shops it is in cyUndricid sticks, 
t>vered with a whitish layer, and having when cut a waxy consistence and 
When properly treated, it h converted into several allotropic forms, 
be red phosphorus, black phosphorus, and the crystallized metidlio phos- 
horuji of Hittorf. The first of these is the most important ; it is brittle, 
not t-ake fire at ordinary tempenitures, and is said not to be poisonous. 
Physiological Action.— The physiological action of phosphorus in 
bcra^jeutic doses is probably entirely different from that wliich it exerts when 



108 SYSTEMIC REMEDIES. 

in larger amounts. It is a constituent of most of the more important tissues, 
and is especially abundant in the nonre-centres. Like iron, cod-liver oil, etc., 
it appears to act when given in minute quantity as a stimulant to the nutri- 
tion of the tissues, into whose composition it enters. So far as the nervous 
system is concerned, this assertion rests chiefly upon clinical observation ; but 
Dr. Wegner ( Vtrcliows Archiv^ June 22, 1872) has experimentally demon- 
strated such an action upon the bony tissues. He found that when adult 
animals were fed upon minute doses of phosphorus tJie spongy tissue in the 
long and short bones was thickened, and the compact tissue rendered more 
dense. Afler a time new tissue was deposited upon the inside of the shafts 
of the long bones, in some instances until the marrow-cavity was obliterated. 
The action upon the bones of growing animals was even more marked. 

Phosphorus was at one time believed to be a diffusible stimulant, and it 
possibly may exert such an influence. In the acute nervous exhaustion of 
typhoid pneuinonia I have seen it apparently act very favorably in this way. 

For reasons to be hereafler adduced, it is certain that in poisonous doses 
phosphorus acts as phosphorus, and when it is administered therapeutically 
it certainly enters the blood in its elemental form, and, I believe, acts as such. 
Dr. Wegner advances the following reasons for believing that it does not act 
as phosphoric acid so far as the bony tissues are concerned. First, no similar 
action can be obtained from phosphoric acid unless from eight hundred to one 
thousand times the proportional dose be given. Second, the newly-formed 
tissue is at first gelatinous. Third, there is no excess of phosphates in the 
bone. Fourth, when the food is deprived of lime the same new tissue arises, 
but remains in a soil, gelatinous state. 

Therapeutics. — The chief use of phosphorus in medicine is as a nutri- 
ent tonic to the nervous system. In all cases of chronic nervous exhausttoHy 
whether involving the cerebral or spinal centres, it is of great value. I have 
seen marked benefit from its use when the symptoms were not severe enough 
' to indicate organic lesion ; but the most remarkable results have been in the 
cases in which the structure of the centres was apparently deeply implicated. 
In threatening cerebral softening, in myelitic paraplegia from excessive 
venery, it is the only drug which appears really to affect the nerve-centres. 

In neuralgia attention has recently been drawn by several writers to its 
virtues ; and, as neuralgia is oflen simply an expression of exhausted nerve- 
power, the use of phosphorus is commended by reason as well as by experience. 

It is probable that it may be of value in some cases of impaired vitality, 
although the nervous system be not obviously implicated. Dr. H. Eames 
(Dublin Journal of Medical Sciences, Jan. 1872) states that he has obtained 
p;reat benefit from its use in obstinate skin-affections, such as lupus, acne, and 
psoriasis. Attention has been recently called abroad to its use in cataract,* 

♦ Dr. Tavignot, Revue de Thirapeutiqne MSdico-Chirurgieale, August and Septomberi 
lS71;'Prof. Gloppi, Oiomalt d^O/talmolo^a, abstract in N. Y, Medical Record, 1872. 



TONICS. 



109 



Oo ftcoauDt of its marked loflueDce od the dovdopment of bone, Br. 
Wagner suggested tta use in osteomalacia and id rickef*, and I>r, Frieze gUitCji 
(AniMi. A7m. HocA,, 1877, p. 437) thai he has had britliiuit succu^ia from iU 
UM ill combination with irrm id eeTeral cases in which urdinury trcntinent 
had Ikiied, Prof. Samuel B, Percy hns used jihospburua succeaafully for 
rspeited juruncular eruptions (I^ize £gsa^j Tramt. Amrr. Med* Ab90€*^ 
1872, p, 659). 

Toxicx>LOGY^. — T}»o ingestion of a fatal dose of phiiephorua is not fuUowed 
bj any eontiible effects for aomo time. After, however, from three to twelve 
bottus a scn&c of wciukneas and of general wretchedne« manifosta itself, and 
in a lutgc proportion of the eases (aocording to Lcwin ci|^hty-eight per cent.) 
Is leoompanied, or soon followed, by vomiting. With the emcsiii there ia 
aaasea^ and in most cases the imtient soon eomplnins of abdominal pain, the 
MTrrity of which, however, never equals that of corrosive pi:>iBoning, The 
iDattcTB \^omitcd oonsigt uf ftMxJ, mucus, and bile. During the first eight nr 
ten hours they often ainelJ strongly of phosphorus, and are luminous in the 
daric. The vomiting may persiiA during the whole attack, but generally 
ecMRB on the seeoud or third day, to reappear with the subsequent jaundice, 
when ooffeeHJolored vomit from exuded blood is ejected. The pain, which in 
iB08t eases abutes with the vomiting, often spreads fn^m the epigastrium over 
the whole abdoman, and in rare instanees is paroxysmal. If it reappear in 
the I»tt«r eU^'^f it is upt to affect aspeeially the right hypochondrium, and 
ti affiociatcd with decided tenderness in the region named and in the epigas- 
trium* 

fThc tongue is whitish or abnormally red, sometimes furred, There is 
gioerally hver, hms of appetite, and thirst I^Iaukopif has noted a morning 
and evening temi»erature of from 37*^ C. to 30° C, and from 37.4° C. to 39.8* 
C. nsspectively. During tJie latter part of the case there is very oft^^i a IB- 
markable fall in the temperature, which is generally, but not always, a pro- 
cursor v>f death. Tlie lowest point I have seen noted wa» 31 J2° C. (88.2^ R ) 
aomo hour? before dojith.^ In some cases fever is altogether abscDt or comes 
on just before death. f 

Tlie fitools are at times normal in character and frecjuoncy, but there is 
gtnemlly diarrhcea or constipation, with flatulence. Latxs in the attack the 
pttisag^ are io most cases very Light clay-colored^ or even whitish, and ex- 
ocptlonnlly they are bloody. In some cases they are phosphofCMenti, 

Jaundiei* comes on in from thirty-six hours (casos report^ by Haukop^ 
Wiener Mrdizi/i. Wochaisclm/t^ 18G3, and by Tiingel, K Unuche Mittheiltinfftn 
1XIJI tier Mrdiciju Ahtlheilung dcs AUgemein. KrartkenhayseA in Hamburg^ 
1301 ) to five da^TJ (Lebert and Wyss, Archtteg GeiUrakjtf Gth series, adi., Sep- 
t4^mber, 18GB) after tlie ingestion of the poison. In most cases it appears Erst 



■ Sm OMt of Hr. Btttimnnnr Arifkiv dtr Heilkmtdtf 1871^ p. 257. 
t S««eaM of Ct^DCiilu, S^ttenham Soe^ Vtar^lfookt 14I8»'70, p. 4H* 



STSTEXriC REMEDIES. 







pi. 

it^ 

Dr. 

as ]•' 

actio 

thou 

bone, 
but r«.iuB 

Tiii:i 
ent toiiicr 
whether ii 
Bccn marki 
'to indicate 
cases in wl% ' 
In thrcatQ||4 
vencry, it \^ 

In ncurai^ 
virtues; andy 
power, the ua^ 

It is probahig 
although the Oi] 
(Dublin JounuLi^ 
(a*eat benefit frozu 
psoriasis. Attoui 



♦Dr. Tavignot, Rf 
1871;'Prof. Gioppi, G: 



-^ Stuxiidme? the urine gives previous warning of it 

»« Ujt^- 15 with it a decided and palpable increase ie 

T1.13. taj pass, if the patient live long enough, intc 

samiTtiZ :f the bulk of the viscus. The severe nervou^»— s 

f r«^* ireloped until after the jaundice, although earlj*^^3^ 

* irt ^frequently anxiety, headache, giddiness, and^E=J 

r. r fT«c sleeplessness. Tlie more pronounced nervous ^^^ 

ifcsirliaL which may be wild and is very frequently 

^tf W it-in^ inflhi^ in coma and death, occasionally preceded by 

z X' Taylor, the latter are a certain sign of approach- 

f ^atfnlly, partial spasms and fibrillar contractions of 

vjnr. although there is always, in not too rapid cases, 

I -h^ TohiDtaij muscles. Death sometimes takes place 

■ ■.r^pM jod caiidiac paralysis, but more commonly the patient 

fm 1 ^Mxal failure of the respiration and circulation. 

t is by a gradual amelioration of the symptoms, and 

B apt to be impaired for some time. Apparently 

convalesce unexpectedly, and TiingeJ states 

Bar take place even after violent delirium. 

Jwavs much affected by the poison. Very commonly 

. ,iJiBmi»n»> *n«' sometimes it contains sugar. As was first 

« Huk and Leyden (Die acute Phosphorvergiftung^ Berlin, 

^ma» !»«*">» bile-acids, as well as biliary coloring-matter, 

^^ jjjnnJ in the urine. Not unfrequently a cloudy sediment 

^ -^ of epithelial cells, often tinged with bile, is deposited. 



-fill jDHWOmes 



^jdLiyw— 



(Mg^^9 Arehiv, Bd. iiL p. 1) and other observers have 
the urine of dogs poisoned with phosphorus, and 
are sometimes to be met with in the human 
generally follows, but may precede, the icterus. 
appanntly oonstant constituent of the urine is the 
been found in the urine inside of renal epithelial 
(Sohati, Prag. Med. Wocheuschri/t, 1882, 



^ ^8— k BymptomB pandlcl with those commonly seen 

Mtoi that he has seldom seen albuminuria in ani- 

of the kidneys was profoundly altered. Orfila, 

1 that the only effects following the injeo- 

Ignlar ran of an aninud were the cxhal^- 

■ilmoaaiy inflamnution : on examination 

mi^ wu found in the lungs. Ludimar 

raftw/ttr KUn. Med., p. 198) have 

ndwEo amet of tho oil in the 

' ^th labsequent oxidation 

nleoted in the fonn of 



TOMCS. 



lU 



\ fine emuMon, the characteristic Bjrniptoms and post-mortem appearances of 
lphosphonis-p<jlsonmg reawlt. 

I some instances phosphonis-poi soiling presents Byroptonis quite different 
the fy^jical array » Death may take place in a few hours, and in such 
I jaundice is not generally prt'seot (case, London Lancet^ 1879, ii* 31 1), 
Zeidler reports a death in IVirty two hours, from suppression of urine^ with 
collApse and erotic deUriuHL In a case of BolUnger's (Deutuckeit Archiv/Ur 
KUn. Medidn^ Bd. vi,, 1870) the chief symptoraa were vomiting, join and 
tenderness over the ahdomen, great weakness of pulse, gradual ly*devel oped 
paralysis of the legs, and death, without jaundice, in four and a hiilf days. 
The autopsy revealed hemorrhagic effusion between the membranes and the 
Eptnnl cord, and also into the sheaths of the proximal portions of the spinal 
nerves* 

In women, fatal doses of phosphorus very commonly produce a bloody 
..peeudo-meustrmd discharge, and when pregnancy exists almost invariably 
tioe abortion or miscarnage. 

The older toiicologists spoke of an erosive gastritis as a common result of 
bhosphorus-poisoning^ hut it is now well established that such affection is 
rarely induced by the drug.* As was first pointed out by Virchow 
[Virehow'g Archiv^ Bd. xxxi., 1804) there is universally a gastro-adenitis, 
ihich caoses the gastric mucous membrane to be thickened, opafjue, whitish, 
lyish, or yellowish-whit«. Under the microscope the epithelial cells appear 
irolkn and filled with grannies and oil-globules, and in very advanced 
eneration the c<;lls complet<}Iy break down. This gastro-adenitis is not 
iue to a local action of the phogphorus, because it occurs when the poison 
I introduced through other channels than the mouth. The duodenum and 
ntestines suffer similar changes. The liver is generally very much enlarged, 
able, and light^jolored ; sometimes it is mottled, and sometimes portions 
it are deeply stained with bilcf The cells are gorged with fat-globules, 
Q&d in some cases there are small-celled int^ri*titial thickenings due to hyper- 
dama of the trabecular tissue. The galbbladdcr may be full or empty. In 
ed cases the liver undergoes atrophy, with destruction of its secreting 
The kidneys, especially in their cortical portion, suffer a degeneration 
Dilar to that of the liver, the epithelium becoming enlarged, granular, fatty, 
md finally undofgoing destruction. The voluntary and cardiac muscles, the 
fipleen, the lungs, and probably all the tissues, partake of the universal fatty 

icgcnerationj which Wegner has shown to involve even the minute arterioles, 
• It wt»ttld ftppcftr probable that If it occurred »t nil it would l>e in rapidly fiitiil ofues; 
UTllJigel did not find it ia a patient dead in nine houra of phoiphorui-poiaoDing.*-' 
7wiimr'» Afxhiv, Bd, %%%,, 1864. 
t Aoeordiog io rc*carcho4 made bj Br. Emile Ronst^aa In tlie Pathol^gtcsal Laboratorjr 
of ihi» Univcriiljf of Punnaylrania, the first anatotnioal ohangoi in the Uv«r occur ia tho 
I of tbe lobules around the hepatic vgid. 
t Mopn of tbo pr«seat work dooa oot allow Qf a full di«€Uiiion of the pathologjr of 





112 SYSTEMIC REMEDIES, 

The blood is often profoundly affected, becoming very dark, losing it« 
power of coagulation, and apparently suffering also in its corpuscular elements : 
for ecohymoscs are almost universal, and bsematin crystals are occasionally 
found in the viscera. In the case of Concato (he. at.) the white corpusdes 
were observed during life to be increased in number, and ^e red to be 
diminished in size and altered in form. The eochymoses occur in all parts of 
the body, but are apt to be especially pronounced in the mediastinum and the 
serous membranes. Schiff has found that in dogs, after death from phoa- 
phorus, the blood docs not pass into the veins, but remains in the arteries 
(Archiv/iir Exper. Pathol, und Therap., Bd, ii. p. 347). 

Dr. Mayer states that when very large doses of the poison have been taken, 
the blood and even the urine (?) may be phosphorescent ( Canstatt's Jahtf- 
hencht, Bd. v., 1862, p. 123). 

The elimination of bile-acids in the urine shows that the jaundice of phos- 
phorus is caused not by an arrest of secretion, but by an occlusion of the 
biliary passages and consequent resorption of the bile. Dr. 0. Kohts (loc. ctt,) 
has apparently demonstrated that the occlusion is most frequently due to the 
duodenitis involving the common duct, so as to obliterate its lumen by the 
swelling of the mucous membrane. In some cases, however, it is probable, 
as believed by Wyss, Alter, and Ebstein, that a catarrhal inflammation of 
the minute gall-ducts is the cause of the jaundice, and also that the result is 
in part effected through pressure upon those ducts by the swelling of the 
glandular and trabecular tissue.* It is proper to state that Demarbaix and 
Willmart (Presse MMicale, xxi., 1869, and Schmidt's JahrhUcher, p. 152, Bd. 
cxliv.) insist that the icterus is not really hcptogenous, but hscmic in origin, 
chiefly because they have found ha&matoidin in the urine. This fact, however, 
proves only that the blood is altered by the poison : it does not disprove the 
liver-origin of the jaundice. 

Acute phosphorus-poisoning so closely resembles yellow atrophy of the 
liver that their clinical distinction is sometimes difficult, nay, impossible. 
Distinct phosphorescence in the breath, vomit, or stools would of course be 
direct evidence of poisoning. This phosphorescence, however, very otten 
cannot be detected : according to Vetter ( VirchovDM Archtv, Bd. liii. p. 186) 
it can be rendered more evident in the vomit, stools, etc., by acidifying with 
sulphuric acid and warming in a shallow dish. When death ensues during 
the first week of phosphorus-poisoning, the enlarged liver affords a distinctive 
proof of poisoning ; but when the case is more protracted, the atrophied liver 

phopphorue-pnieoning. The render is referred to the following papers : Etudes climqueB 
et erpSrimeHtaU§ §ur V Empoitonnement aigu par le Phonphore, Par Prof. H. Lebort et 
Dr. 0. Wyss. — Archite$ Ginii-aleHf Sept. 1868. Zur pntholoffftchen Anatomic dcr actiUm 
Leberatrophie nnd tier Pho»phorverfji/tungt \on Dr. Otto Bollinger. — Detituchet Arch./, 
Klin, Med.f B<i. t., 18(J9. Ueber Jcterut bet Phonphorvergi/tung, von Dr. 0. Ku\\{».—lbid, 
* For an elaborate discussion of the cnu8o of jaundice, see KobU's Memoir, Veuttehf 
ArehiVf Bd. v. p. 108 j consult also thai of Dr. Bollinger, Centralblatt/Ur die Med. Wi*9,, 
1809, and Deuttchet Arekiv, Bd. ?., 1869. 



TONICS. 



113 



of pluKplKiras caDDot be distingiiislied from that of the natural digease. The 
Ejmptoim during life rarely^ if ever, afford sufficient ground for a positive 
diignosk The lull in the gymptoms after the first onset of the disease hap- 
pcwj more generally in phosphorus-poisoning than in yellow atrophy. Yet 
Ihe clinical diffenjnces between various coses of either affection are greater 
chaa tliose which have been relied upon lus »eparuting the two affections. 
Eoliler ha aAserted that Q^yniiiudelie ueid in atropliy of the liver replaces 
thfl sarco-lactic acid of phosphomst-poisoniiig^ and stress has been laid upon 
tlieaflaeried fiiets tiiat in the natural disease leuein and tyroBiu are present in 
ihuid&QOe in the urine, whilst in the poiifoning they are absent. In yellow 
ilropL)', however, tyroein is not nnfi-equently absent from the urine, and leuein 
piweut in very small amount, whilst both principle«i may be present in 
phospiionisi-poisoning.* In regard to the acids in the urine, very careful 
obemicftl analyi^is would in any case be neocssary to di^termioe their pre^ 
•ftCe, and sufficient evidence is certainly not yet fijrthioiuiog to tihow that 
either of them is really characteristic. Chemical examinsitton is ther<?fore 
ibiolfitely necessary in all medico-lpgal cases. (For discussions of the 

aMpMwiB between yellow atrophy and phoisphorus-poi^oning, sec Kohler, 
SyJenham Year-Book^ 1870, p. 455 ; Schultzen and Ries^ Annfilm des 
Baliti. KranlceiihauMs^ Bd. xv., 1869 ; and especially Dr. I. 0<<dikov8ky, 
WW MfnUzin, Pretse, xm,y 1872, abstracted in ScJimidf'g JakrhUchcT^ Bd. 
«^v. p. 15. For eases in which the queatiou was Icgidly rai^sed, investi- 
gutod^iad discussed, see Schmtdf'sJahrb., Bd. exli. p. Uil ; Sj/d. Yfnr-Hool\ 
1832, p. 430; Annales dUt/phte, Jan. 18t»9.) According to M. Poulet 
(Coi. Mid. de Patigy Aug. 1872) phosphorus h eliminated as hypophospliorio 
acliind the jK>isoning can be recoj^nizod by heatini: the urine witli nitric acid 
to uttlciualion. If hypophosphorie add be present, as dryness is reached the 
laiituru suddenly bursts into a flame like a packet of matches* 

It bus of late yeiirs been dt'inuntitrat*?d that phosphorus passes into the 
Wood oi |ihosphorus, and nut in the fomi of j>hos|j!ioric add or other com- 
pOiuuL In poiEouing-eases in men the breath is said sometimes to be dis- 
tinctly phosphorefloent ; and in animals Bamberger has found phosphorus in 
tlicllood, and Hu^emann and Mamie in the liver, two or three htmrs iiiler 
lt« iiigcjtion ; Vf . Dyhkow sky {hfoppe-S^'t/lfTs Mrdidnmh-chemisehm Unfer- 
««cA«ii<^, Heft i. p. 54) has detected it in the blood and liver ten hours atler 

IgagHartion ; and other observers have demonstrated its presence in alnu^i^t 
' the ti£8UG& It seems probable that to t»tjmtj extent it finds entrance 
>th© circulation by being diissolvcd in tlit; various fatty mutters contained 
D> the alimentary canal. At the temi>eniture of the body, however, it yields 
ftottadant vapors, and Bamberger has demonstrated that these readily inid 

•(W» \Wi€ner Jtf«fl, Prttte, 1S72; Schmidt'» Inkrh,, B<l. 160, p. 127 J Bd. 195, p. 
^3<^). hot. Owikovikj beriov«s ibiiC the piineiplo* Appear habitually about tbe Rixth day 
ofl^tp^^i^niQg^ when th« liver ii still enUrged. 

8 



114 SYSTEMIC REMEDIES, 

rapidly pass through animal membranes. He has found that defibrinatcd 
blood, when separated from the fumes of phosphorus only by an animal mem- 
brane, rapidly becomes saturated with the poison. Dybkowsky (loc, cit.) has 
confirmed this, and it cannot be doubted that in a similar manner living blood 
absorbs the poison from the alimentary canal. 

W. Dybkowsky {Hoppe-Seylers Medicimsch-chemische Untersuchungen^ 
Heft i.) renders probable the theory of Schuchardt {Henle und P/eu/er't 
Archil^ N. F., Bd. viii.) that the phosphorus to some extent in the ali- 
mentary canal, but much more largely in the Teins, is converted into phos 
phuretted hydrogen, and that some of this compound and some of the phos- 
phorus itself is oxidized in the venous blood, so that phosphoric acid, besides 
phosphorus and phosphuretted hydrogen, is emptied into the arterial blood ; 
further, that the last two compounds are oxidized at the expense of the 
arterial blood and the tissues it feeds, and that the poisoning is due to this 
deprivation of oxygen. For the details of the experiments upon which 
these conclusions rest I must refer the reader to the original memoir.* 

The indications for treatment in phosphorus-poisoning are very evident 
It is plain that no medication can influence the terrible organic lesions in 
duced, and that the primary object must be to prevent the absorption of tho 
poison. Emetics and purgatives are, therefore, of prime importance. As 
phosphorus is soluble in oils, no fatty matters should be allowed either in 
the food or medicines. As an emetic, sulpliate of copper should always 
he chosen. 

The minute particles of phosphorus adhere so closely to the alimentary 
canal that they cannot be dislodged by mechanical means, and an antidote is 
urgently demanded. For the purpose of oxidizing the poison, Duflos sug- 
gested magnesia usta and liquor chlorini, and Scherer the chloride of lime ; 
but in practice these substances have been found of no value, on account of 
the slowness of their action. 

The oil of turpentine, originally proposed by Andant (Journal de M^de- 
cinc de Bruxelles, 18G8-69) as an antidote to phosphorus,f has been largely 
used by experimenters, with apparently contradictory results, which, as is now 
known, were due to the employment of different varieties of the oil. Tliei-e 
are in European commerce three varieties of turpentine, — the rectified, the 
German, and the French. Jonas (lAebig wnd Wohiers Annakn der Chemie^ 
Bd. xxxiv.) found that whilst the pure oil has no effect upon phosphorus, 
the acid French oil forms with it a crystalline, spermaceti-like mass. This is 
soluble in ether, alcohol, and alkaline solutions, and has received the name of 
turpentine-phosphoric acid. It is said to be eliminated by the kidneys un- 

♦ M. Lccorch^ {Arvhivei de Phytiohftjie nonnnle et puiholtujujnef tome i., 186S, tome ii., 
18C9) believes that phosphorus acts in the blood us pho:^phoric acid, but docs uot efitablish 
his opinion. For a discussion of this, see Dybkowsky's paper. 

f For cases, see Gmttte llebdowudaircy 1874; Schmidt's Jahrbiicherf Dd. 169, p. 126 j 
Med, Times and Gaz,, 1876, ii.461. 



TOMCS. 



115 



i^umged, and to exert no deleterioua infiuence. The elaborate experimenta 
of Vetter on dogs and rabbits gave results in accord with these fucts, fur he 
found the rexjtified and German oils to b^3 of no value in ])ho8pliorus-p*>ison- 
ing, whilst the cnide acid French oil was distinctly antidotal K(M*hler, 
however, asserts that when the German oil has not been rectified for some 
time, it acta upon phosphonis. He believes that the oU aets partly by oxi- 
cilsing the poison j ajid partly by converting it into the harmless turpentine- 
irons acid* One part of the oii must be given for 0.01 part uf the 
inia. (^Detroit Hemew^ 1873; trom Mcd.-Ckirur<f. Ranthchatt^ June, 
1873u) The ordinaiy American oil of turijentine, as wc41 as the Canada 
Bakntn^ appears to be of no ajitidot^U value in phosphoruii'poisonlng. 

Aa was pointed out by 31 M, Eulenborg and Guttmann {AcrU, LtfrratHr- 
liait, 18GS, No. 12, quoted in Sydenham Year-Book, 18C8, p. 450), and 
subsequently by Prof Bamberger ( Wirner Medizuuscfic Pre»$e^ Jan, 1872 ; 
VtrchoicB Archib\ June, 1872), phtjsphunis in a solution of a soluble salt 

copper becomes immediately black, owing to the formation of a photH 
of the metal. Prof, Bamberger {he. ciL) also asserts that, whili^t this 
change b very rapid, that bduced by turpentine is a slow one, and, from 
aa elaborate series of expierimenta upon animals, concludes that a^pper is 
much the more valuable and certain antidote. In human poisonings then, 
Stdphate of copper should be given in dilute solution, tliree grains every 
five minutes until vomiting is induced, Afler this, if the French oil be 
acoesable, it may be given freely in emulsion. Otherwise, sulphate of copper, 
with opium to restrain the cmcsis, should be administered in such doses as 
the stomach will retain. Sulphate or citrate of magnesium should be used 
as a quickly-acting purge, and symptoms as they arise should be judiciously 
treated* 

Matchmakers and other artisans who are exposed by their occupations to 
the fumes of phosphorus suffer from chronic poisoning, which, whilst in manj 
cases it profoundly affects the vitality of the sufferer, is especially distin- 
guished by the occurrence of necrosis of the upper or lower jaw. It has long 
been known that those artisans who have bad teeth are especially liable to bo 
icriously affected, and the experiments of Wegner have demonstratt'd that 
the necrf>sis of the jaw is due to the local action of the vapor of phosphorus 
upon tlie part. He f^iuud that when rabbits were kept in an atmosiphere fult 
of the fumes of the poison no necrosis ever occurred, unless, by means of an 
unsound tooth or an artificial wound, the atmosphere had aooess to the bone. 
If such access were, on the other hand^ allowed to any bone of the body^ 
periostitis and subsequent necrosis resulted. Further, when rabbits received 
continuously small doses of the phosphorus by the mouth, no necrosis occurred 
even after wounds which laid bare the bones. As phosphonis-uecrosis iKilong? 
to the province of the surgeon rather than of the physician, I will not dis- 
cuss it further here. 

Al>sifNifiTRATiON.— Phosphorus may be given in pill or in 8*jIuU( n. The 




i 



116 SYSTEMIC REMEDIES. 

Oleum PhospKoratum^ U. S., coDtaining one per oent. by weight of phos- 
phorus, may be given in doses of one to three minims in aromatized emulsion 
or in capsules. The Pilule Phosphoric U. S., or officinal pills of phosphorus, 
contain one-hundredth of a grain each. In regard to the dose of phos- 
phorus, I have found that many stomachs will not bear more than the 
fiflieth or even the hundredth of a grain, as given in the liquid form ; but 
I have oflen given as high as the twentieth of a grain. Dr. J. A. Thomp- 
son has used it in much larger doses (^London Practitioner^ July, 1873), 
prescribing one-twelfth of a grain as an average dose, and in one case having 
given as high as one fourth of a grain every four hours without injury. On 
the other hand. Dr. Anstie has seen slight poisoning from three-fourths of a 
grain taken in small divided doses during seven days (^London Practitioner, 
Aug. 1873). 

ZiNCi PiiosPHlDUM, U. S. — Phosphide of Zinc has been largely used 
with asserted good results as a substitute for phosphorus. According to the 
researches of Yigier (^BuU, Therap,^ xc, Jan. 1876) it would seem that the 
phosphide yields its phosphorus within the economy, probably to form a 
phosphuretted hydrogen. He found that it killed rabbits more quickly than 
did a corresponding dose of phosphorus, and that both symptoms and lesions 
were identical in the two cases. The phosphide should be given in pill or 
granule. The dose may be considered as one-twentieth to one-twelflh of a 
grain. Prof Seguin recommends doses of from one-fourth to one-sixth of 
a grain. « 



CLASS m-OARDIAO STIMULAI^S. 



The tenn cardinc stimulants \b here iised to desigiiate a number of medi- 
cines which, when given intcrnidly^ increase the power and foree of the cir* 
eolation, and are' used by the physician ibr sach purposes. There are some 
Btibetojicca which are heart-stimulants in reality, but which possess other 
properties in so great a degree as to overshadow their cardiac relations, and 
Are not used by the physician to affect the circulation. Such medicines ar© 
considered in connection with those powers which give to them their clinical 
value, and are consequently not included in the present c1qss« Some of the 
i of this class are slow in (heir upcmtion, some more rapid. Some 
increase in the pulse-rate, mrna lower it. It is evident^ then, that 
no gencml indications can be luld down for their use, but that medicines so 
«livef«e tnu^t be studied individually. 



AMMONIA, 

Ammonift is a colorless, irrespinible, bi^ldy irritant gas^ of a strong alka- 
line fraction, extremely soluble in water. It is obtained upon a large scjde &» 
s^ waste product in the manufacture of coal gas, and is officinal in the Materia 
Medica list of the U. S* Pharmacopceia in the fonn of the Btroiiger water of 
ammonia^ aitd the muriate, carbonate, nitnit^?, and sulphate of am in on i ion. 

PHireiOLOorcAL Act r ox. — Locally applied, ammonia is a very powerful 
irrirant. Wlien inhaled, it causes intense in-itation, and finally inflamma- 
tion of tlio mucous membrane of the air-passages, imd its solution, if kept in 
iXfntact with the skin, reddens, blisters, and at last produces even sloughing 
of the parts. When ammonia is injected into the veins of animiUs in con- 
Biderable quantities, it causes violent convTilsionS| with remarkable disturljance 
of the respinition, followed, if the dose has been large enough, by death in a 
X&rj abort time. (F, Lange, Archw fUr ExpenmenL PatUfd. vnd Tlier.^ 
Bd. ii. p. 3C8; V, FeUz et K. Rittcr, Jouninf ck P Anatomic H dc hi Phynoh^ 
1874, p. 32*5; Funke, Pji'dgerK Arcfnv, Bd. ix. p. 426.1 The respiration, 
If oot intcrff^red with by the tetanus, is enormously accelerated, Billroth 
Irchiv/Ur KiiH. Vhtrnrg.y Bd. vi, p. 421) states that the temperature falls 
uously in animals p*>isoned with annnnnia, 

Kewpirntum. — Where a small rjuuntity i»i' ammonia is injected into tne 
lilood of an animal, the breathing is greatly accelerated ; after larger doses n 
period of arrest of respiration occurs in ex])iration (Funke), at once or in 

I cours*^ of a few seconds, and precedes the hiirrietl brciitbing. In regard 

the effect of section of the pneumogastrics u])on the respimtory action 
of ammonia there is some disagreement : i\m^^ in Funke^s observations the 
primary arrest of respiration was always present, whilst in the experimenls 
uf Lunge it was always absent. Both obsen'cra note, however, that section 

117 



118 SYSTEMIC REMEDIES, 

of the pneumogastrics does not interfere with the increased rapidity of the 
breathing, and Funke especially remarks that the change from the slow, deep 
breathing of divided vagi to the extremely rapid respiration of ammonia- 
poisoning is colossal. Our knowledge of the physiology of respiration is 
hardly sufficient to warrant a positive deduction ; but the fiwts noted indicate 
very strongly that ammonia is an intense direct stimulant to the respiratoiy 
centres in the medulla oblongata. 

Circulation. — The chief practical interest in the physiological action of 
ammonia centres in the circulation. It is chiefly as an arterial stimulant that 
it is used in medicine, and clinical experience assigns to it a powerful but fuga- 
cious action on the heart. The only experiments on the subject besides my 
own that I have met with are those of Lange. When the drug is injected 
into the veins of animals there is a momentary fall of the arterial pressure, 
followed by a sudden, decided rise, and a corresponding increase of the pulse- 
rate. These phenomena are independent of the convulsions, because, in Lange*8 
experiments, they occurred in curarized animals. According to Lange*s studies 
the rise of pressure is not due to any stimulation of the vaso-motor centre, 
because it took place equally after division of the cord, — 1.«., after the sepa- 
ration of the arterioles from the vaso-motor centre. The increased arterial 
tension which follows the exhibition of ammonia must therefore be due to an 
action either upon the heart itself, or upon the peripheral vaso-motor nerve- 
fibres, or upon the muscular fibres in the coats of the arteries. As in Lange*s 
experiments the increase of the pulse-rate did not accompany the rise of press- 
ure after section of the spinal cord, it would seem to be caused by a stimulant 
action upon the accelerators of the heart, which are of course paralyzed by 
spinal section. The fall of arterial pressure, which immediately follows the 
injection of ammonia into the jugular vein, is probably due to a direct action 
of the concentrated poison on the heart. Previous section of the vagi does 
not prevent it, and when the dose is sufficient it is replaced by permanent 
diastolic arrest of the hearths action. That it is not produced by spasm of the 
pulmonic arteries is shown by the fact that when death occurs the left; heart 
is found full of blood. When administered in toxic doses, ammonia, prob- 
ably, has some effect upon the hsomic corpuscles, for Felts and Ritter fbund 
that the blood of a dog killed by the poison not only did not contain any- 
thing like the normal amount of oxygen, but even when shaken up with the 
gas refused to absorb it; further, under the microscope the red disks were 
found to resist the action of acetic acid to a markedly abnormal degree. 

Motor System. — The convulsions already spoken of as being produced by 
iinmionia are not cerebral, since Lange found that they occur equally after 
division of the cord ; nor arc they peripheral, since, in Funke*s experiments, 
tying of the artery of a limb failed to arrest them in that part, wliilst section 
of the nerve was followed by immediate quiet : they must be spinal. Am- 
monia, in toxic dones, acts, therefore, as a stimulant to the motor function of 



CARDIAC SUM VL ANTS. 



119 



the apioal cord, lieighteDing, as baa been proven experimentally by Fimke, 
iU reflex activity, 

BHnnnatifin. — The volatility of unimoiiia ntid the extreme fugaciousnesa 
of ltd tttitiun would seem to iitilk'ntu its eliuiimition by the lungs; but Felti 
ud Kilter {Iik^. cit,^ p. 'X2?*) Ciittnl to find it in the breath of a piwoiied 
uad, and the resrurehcs of IL Bence Juries? appixrently demcmstrat** that 
at ksagt a portion of it \& oxidizeii in the system {Phiiosopincal Transaciiomf^ 
Ijuodoii, 1851 ). The la^t ohj^erver found, to ]m surprise, that even hinro 
do906, (kr from increa^sin*; the alkalinity of the urine, avcm at timea to lieighten 
(oddity. It oecurrod to hbi that the axnuionia nu'i^ht be oxidized ; and \m 

[>rdinfrly found that the natuml prnduL-t of its oxidation, nitric acid, a|tpear8 
la the urine aller the exhibition either of the aunnonia itself or of it^s tarti-ate, 
carburiDte, or Tutniafe. It is pn>l>al«ie tlint i^oine pctrlion of the animoniii 
is, in cotijuncUon with earbotiir* aciJ, er inverted into urea.* 

TUERAPEUTICS. — Externally, ainuionta h nmdi used m a conBtitucut of 
irritating liniments, and, on account of its effideiiey and eheapnesSj is very 
valuable. By inverting a watcli-gluiij^ full of the Ktrouger wat^jr of ammonia 
npcm the skin, a blister omy be mi^d in a very few minutes; but, m the eftbets 
of the application are very apt to be severe, the use of it h justifiable only 
aoder rare circnmBtanees, 

Intcniallj the chief indication fVtr the use of ammoin'a is ftiflitre of the 
ht^rt** action. The more sudden and purely functional this is, the more eifi* 
cacious is the remedy, which sbuuld in such c^scs be not only administered 
by the stomach, but ijhould alsio be inhided through the nostrils, as the local 
action of the irritant vapor uixin the unieousj membrane has a very aroUHing 
inflacnee. When the failure of the cireulntion depends upon a slow and 
peiTCtcnt cause, as in ail^uti7nfc Jeter s^ ammctnia is not generally ust^fuh but 
nmj be empinyed as an adjuvant to aleuhol in the crisis of the disiirder. 

Iq poi»onin^ hy vent/mons iterpfrtts^ anunonia has been largely used, but 
uertjiinly Is in no sense antidotal, since, according to the experiments nf Dr. 
Fayrer (Jitdian Annals uf MvfUcttl Sctruce^ 1872), mixing it with the poison 
bcfons injeeting the latter into au aniniid does not in any way delay the fatal 
rcsulL As an ailjnvant to other more powerful stimulants, and especially to 
alcoliolf ammonia may be useful in these cases. Pr. G. B. Hal ford, of Mel- 
boamc, Austndia, has claimed {^Mtlbourne ArgrtK^ 1872) that when injected 
bitci the veins its effects in poisoning from snake-bite are very extra ordinary ^ 
■od »veruJ caises of recovery after its use in this manner have been rep(>rted. 
It is far from ec*rtairt, however, that thette ctisea would have died had no medi- 
cnriMTi been praetiticd ; and Dr. Fji^Tor stnt<*s that in an extended series of 

' Tho rvttiliuii of auiuhjiiIu to the formntlon of urea u of vueh purely p)iyeiolugiua1 
^Ivtt^L. hUil ito difioiiHsion wouM require §o rauclt ftpnoo, thut I diiimbtH M with the foU 
owluf rvfiirnrutigii, whioU will givu lUe rr*i<ler a jtuRlfieat key to ihe literature : Ar^h. £'-t- 
!*<#, hifh. rt. f^ktttm.^ »., viii., x. 125i xii. 77; Zcit9tht\f. /*A^*v>foj/. Chtnut ii. 29, iv, 36j 



mtk 



120 



sfsteaMic remedies. 



experiments upon aniiiiiils he hoB not found ita injection to be of any tmow 
Ammonia cannot, therefore, he considered a specific in snake-poisoniDg ; butv^ 
as the injection can do no barm, it should be practiced, yet never to the ex* 
clmiiou of other measures. 

In failure of the heart during ans^thcski* and in pouoning other than 
from snake-bite, hypodermic injections of ammoniaf have seemed in i 
number of reported ca.ses to be of very jrreut service. The same may be 
Bald o£sitJdrn coUapxe in disease, us sometimes is »een in the exanfhrmuta^ 
in eholerUj and not rarely in pernicious maiarial /ever^^ or after Eurgical 
aperattoits or {tiJurjetL Froin fift-een to twenty *fivc minims of the aqua 
ammonifB fortior^ diluted with fuur times its bulk *»f wuter, should be thrown 
directly into a vein of the arm, and repeated in fifteen minutes if necessary. 

l^of. Stille and other authoriiiea claim fur ammonia an antidotal influeuce 
in aleoholiu intoxicittion ; but that it can relieve absolute druiikenneBS is, I 
think, very doubtful. iVmmunia appears to have a tendency to act upon theJ 
mucous meDibrane of the lungs, and may bo used as a stimulant expectorant < 
in adynamic jiccttiral inflammatioiis, us in typhoid pneumonia* As a stxmu* 
laut antacid, it is frc(]uently of service in cases of fieadache &om gcuUric 
aciditt/. 

Toxicology. — When taken in large amounts, ammonia acts as a violent 
eorroftive poison, producing generally abdominal pain, vomiting, bloody purging^ J 
and other symptoms of gastro-enteniis, with convulsionf!, collapse, and tiualljl 
deatli. In some cases symptoms of impending suffocation, resulting in death 
from asphyxia, have occurred, and at the autopsy intense redness and congeB- 
tion of the bronehial mueous membrane have been present, due no doubt to ^ 
the irritant having found its way into the bronchi. The intellect may be clear 
to the very moment of death^ or stupor, and finally ei»ma, may be developed. 
In the rare instancoiJ in which death has tiiken place within five minutes from 
the ingestion of the poison, the fatal result has probably been brought aJ*out 
by ojdema of the larynx. When the sufferer survives the first few hours, 
recovery may occur ; but death sometimes happens long allejrwards from the 
organic lesions which have been prcKluoed* The treatment of poiatining by i 
ammonia couHigts in its iieutmlization as soon as possible by vinegar or oUier 
dilute acid, and the meeting of indications as they arise. If the mdema of 
the glottis Ikj tlircutening, tracheotomy t^hould at once he performed. 

Adaiinistration.- — There me four officinal prepiutitions of uncombiued 



* Prof. Sidney Ricg^r {Practitioner, xxvti.) finds that Atamonia nddtMl to tbe fi'og heart 
depresjied with ohlorofons, iodoform^ «tc., baa a vory |>ronuQii(iod eflfect in re-eptublifhing: 
its net i 00. 

t Soc huUm\ Mefiicnl Gnzetit^ Jane I, 1872; Mettieat Time* and Gnteittf Kov. IST2; 
Chicttf/n Mcdir.ftt Ja»mal, 1872 J London Mtdteat Recttrd, i., 1873; L*Ah*ilU M^dirtthf 
Aug. 1874 J Jlnrh'n, Ktin, Woch«n0chnj>, No, 24, 1874; Archtvew 04M4ruU9, ii., 1874; 
London Lmif^et, 1879» *i. 158j JVVw l&rX* MhI, Itet., xv. 532, 

% Se« Dn Zuelzer, i?erM« dv Thirnp.'Mtd.-Chh'ur,^ July 1, 1873. 



CARD! AC STIMULANTS. 



121 



firaoi 

M 



I 



aminotila iteolf, — Eamelj, Aqua Ammonije Fortiob {Stronger Water of 
Ammonia), gp. gr. 0,900, Aqca AmmonIjK { Mrj/er of Attnnom'a), E^p. gj. 
0,95D, Spiritus AwMONi-f^* (iSptViV o/ Ammomtt)^nnd SpiiiiTtrH Aiimonue 
AboMATICCS) or ^rcwiafi'c Sptrii o/ Hartshorn as it is usually cidlt'd* 

To reduce llie fltreiigth of the first of these pi'cparutiona to that of tlie 
seoaDd requires the aJditloti of one and a half uutuiiurre gf water. The E$pirit 
m of vai^'ing strength^ but ia eomewhat weaker tliun the simple water. The 
aromadc flpirib coutaina both ammonia and \is carboimte. For hypodermio 
use the waters of ammonia are to be preferred. The ^^lii-its, c«peciidly the 
mromM^Cy ore best suited for iutenial u£ie. Tke dune uf the simple spirit in 
Imm twenty-five drops to a t^i^aspoonful, pri>purly diluted* 

The Carbonate of AmtmniHJti^ IJ. S, (AMAfONii Cakbonas, NH^0,C0, 
NH^,) ia the beat prepamtiou fur continuous use aud in typhoid pneH' 
It occurs in wlutc, UiirLslucent, fibrous masses, whieh oo expasure 
booomo opaque aud eff^oret^ceiit, parting with ammonia and passing from a 
aaatjui* into a bi-carbonatc. It is soluble m four and a half times its weight 
of water, and may be given in solution in doses of frum five to ten grains, 
repealed pro re nata. 

The NUrrUe of Ammmmtm (AiiMONll NiTRAS, NH,0,NOi— -NH^NO,) 
is officinal for the preparation of niti-ous oxide; the Sulphate (Ammonii 
Sulphas^ NI1^0,S(>j, — 2N11^,S0^), for the preparation of AmmomO'/nrria 
Ahtm. Tbe Muriate of Ammfmia will be eonHidcred elscwlicre, 

ALCOHOL U.S. 

Absolute nleohoh n**,. alcohol frtni rrom water, is a colorless, volatile liquid, 
boiling at 172^ F., not congealed by a cold of — IGG** F., and having the 
specific gravity of I) JDd. It is nut oflieinalj and is nevcT used except for 
chemical purjMises. 

The U. S. Pharmacopoeia recognizes AtoonoLf containing 94 per cent, 
of absohtTo alcohol, and having the specific gravity of 0,820; Ahcouoi* 
DtLrxcH, Dilate Afcohof, containing 53 per cent* of alcohol, and having 
llie specific gravity of 0.928. 

Alcohol also exists in the officinal SplRlTtJS Fbumknti, or Whisky, and 
SpiRirrs Yixi Gallici, or Brand y» which are obtained rea|tcctively by the 
distillation of fermented grain and of fermented grapes, and should conUiin 
ftom 43 to 50 per cent, of nb^lute alcohol, and in tbe officinal Vinum 
RlTBiKUif, or Red IFwuf, and Vindm Album^ or White Wine, 

For modidual use, brandy should be at least four and whisVy at least two 
years old. 

Alcohol ia formed out of sugar by fermentation ; but, as a discussion of the 
nahinJ history and chemii»lry of this process, to be of value, would occupy 
much epacc, the reader is referred for it to works especially devoted to 
chemistry and to materia mediea, 

Phtsio LOGICAL AcTloN, — The phenomena induced by the ingestion of 
alcohol are, unfortuuately, so well known as to make any description of them 



122 SYSTEMIC REMEDIES. 

here unnecessary. I have not met with a close experimental study of the 
order in which the nervous centres are affected, but it is scarcely doubtftd 
chat alcohol acts upon them as docs ether, excepting that the latter substance, 
being much more volatile than the alcohol, is consequently absorbed and 
eliminated much more rapidly, so that its influence is more evanescent. I 
know by experiment that the vapor of alcohol is capable of producing the 
stupor known as anaesthesia, and, further, that this ansdsthesia may bo 
deepened into death, accompanied by all the phenomena of fatal ether- 
narcosis. The experimeDts of Mommsen (^Arch.f. Pathohg, Anat.^ Ixxxiii. 
243) would seem to show that alcohol acts slightly upon the peripheral motor 
nerves, as he found that wheD brought into contact with them it augmented 
their excitability. 

It is a well-known clinical fact that alcohol given to healthy men increasep 
the frequency, and, to the fingers, the force of the pulse. The very careful 
and elaborate experiments of Parkes and Wollowicz upon man, with the 
sphygmograph, indicate that there is produced by brandy an increased rapidity 
of the ventricular contraction, with shortening of the period of rest or dias- 
tole. The tracings furnished, however, no distinct indications of increased 
arterial pressure. Dr. H. Zimmerberg found that enormous doses of alcohol 
reduce both the pulse-rate and force. Afler section of the vagi the alcohol 
lessened the arterial pressure without affecting the pulse-rate, whose slow- 
ing in the normal animal would therefore seem to be due to inhibitory stim- 
ulation. It is plain that Zimmerberg's experiments apply, not to therapeutic, 
but toxic, doses of alcohol. J. Dogiel affirms that by moderate amounts 
of alcohol the arterial pressure is at first increased and then diminished. 
During the latter state the vaso-motor centres are found incapable of re- 
sponding to stimulation. The rate of the heart-beat is stated to be at first 
increased, then diminished, then increased ; the first increase being owing 
to the stimulation of the accelerators, the diminution to stimulation of the 
par vagum, and the final increase to paralysis of the same. The action of 
alcohol upon the circulation has been carefully studied in the Pharma- 
cological Laboratory of the University of Pennsylvania by Dr. J. D. Cas- 
tillo (^Phila, Med, Times, xi. 45). He found that in moderate doses the 
drug caused great increase in the rate and force of the cardiac beat and 
corresponding rise of the arterial pressure, and that these phenomena were 
not affected by previous division of the pneumogastrics, of the accelera- 
tors, or of the spinal cord. These results are in direct contradiction to 
those of Dogiel. It should be noted that Dogiel does not give any experi- 
mental evidence for his conclusions, and I believe myself that the work of 
Castillo is accurate, and that small or therapeutic doses of alcohol increase 
the pulse rate and the arterial pressure by directly stimulating the heart 
Castillo agrees both with Dogiel and Zimmerberg in finding that large 
doses of alcohol diminish very greatly arterial pressure, but believes that 
the full is solely caused by a direct depression of the heart itself. He 
found that the lowering is produced after section of the cord, and that 



CARDIAC STIMULANTS. 



123 



when iL isYcry pronounced galTanic irritntioD of tbe sciatic causes a rise of 
pressure, showing that the vaso-motor centres are intact. It maj be oon^ 

-pj red estublbhed thiit overdoics of afc^thol direct! t/ defrre&s and paralyze 
'-arUmuscU : hut it yet seems probuble tbttt the first rise of urteriul 
1 -"iirs and the ufter-fall are in part due to an influence exerted upon the 
v.i>4>- motor centres* 

Owing no dcmbt to the sensations of warmth induced bj ita local action on 
the f(tonaach and by the increased activity of the circulation in the extremities, 
alcohol haa been looked upon as a promoter of animal heat. As lon^ ago a^ 
184B, howeyer, Dum^ril and Demarcjuay asserted that afler the adniinistra' 
ticfii of large doses there is a fall of temjK'rature. Of htte years much atteo* 
tion has been given to the subject, and [Kisitive ri^^ults have been achieved 
Aa almost all experimenters are in accord, it does not seem worth while to 
oeeujiy space with a distussion of tlnj history uf the subject, liefcrcnoee are 
given to the iirincipal original memoirs.* 

It is certainly dt'monstnitod that lethal doses of alcohol produce in animals 
a Ikll of temperature whidi often amounts to 5° C, and that even when in* 
tojueatiou or alcoholic narcosis is alone induced the depression of temperature 
may amount to 3*^ C. The proportionate dose necessary to produce distinct 
nenrouii ^yuiptoms is cnormoua in the lower animals as compared with man ; 
yet, afler the ingestion of amounts of alcohol which are not enough to cause 
Dtoxication in the animal, the fall of temperature is slight, — nirely more than 
° C., and according to Kuge (loc. cit>^ p. 2G5) usually from ^^ to |" C. 

The experiments of Richardson show that in some cases very minute doees 
of alcohol increase slightly the temf>erature (}** F. in mammals, 1^ F. in 



^ Fur thase desiroui of looking up the litenatmro of the iabject, the follovriog refcrettoea 
•r« gtreii : 

Iff. 8w D»Flf, TranMtiHhn9 Amertcnn Mrrlicnl AMocintion, IBib, p. 577. C BoUvioTp PjlU- 

r^t Ar^kiv fUr Ph^^iahtfit, p. 370, lf?n9 ; Obernier, Ibid., p. 19% Um, A. GodfHo, De 

fAi<iu^^ •*>» A^'tion pkya%filofjitju0, ««« AppHcationa thirapeuHqHti; PnHft, 1860, C. lloovicr, 

Wirkmnij tier AUohot au/ die KUrptrttrMpertttuft Bonti| 1869. MimaaAeint CentrtithtatI /Ur 

dU Mtd^ WiMtti§rha/tmi, 1S6D. P» Eu^c* FiVeAoie't Arckir, Bd, z!ix. p. 2^5, C* Bin^ Vir* 

#lp*r'f Arrhh, Bd. lU p, 153; London /Vrtc^ih'««rr, Tol. liL, 18(i9, irol. ▼., 1870; Jmtmat nf 

Anau*my andf Pk^tioloff^t voL riii*, 187ii p. 232; Sit»Hitgtbtrichtt dwr nuderrktrnvtchcn 

vG^itUfk*ift fur Natttr- und Jititkunde, Mrdit> StiftUm^ July 21, 187.1. Browu-S^quard, 

o^mnl dt la Phtftiulojjfir, 1S59, p. 4<JT. Jocobi, Deutsche* KUntk, 1857. T*obe»&hicbiD, 

thtri** Arrhiv/Ur Anatomi^f ISftfl. Hitigrr and Kioknrdfiii Landon Lancet, I$($ft, p. 2DS. 

jthjtrdtoo, Mtdical Time* and Gazetttf rol. ii. p. 704, 1809. Purkri iJid W<jllowios, 

iTt^AHMicfif'^t o/ th§ Boyat S'ffietjtt 1870, Anstlc, StimtdnnU and Xarettti'e*^ London. 

Itiitiicr, Vebrr die Wirkun^ det AlkohoU au/ die TcMptnttitr dee Geitunden, Inanguml 

' t»i*«rnAtJuii, abitr»«t«d by Bin* lu Virckvit'e ArthiVf Sept, 1871. C. Bouvicr, CentruWlutt 

fUr die Med, Wieeeue^cha/ttHt Deo. 1871. I, S. Lotnbiird, A<«3 York Mtdttni! Jminmlt 

Juni*. IBOj. Subjusk!, Veher die dee AlkohoU, Chtunt/onae nmd Ethtre Biajtuee an/ 

drtt tkifHtehem Onjaniemve, iDnagurikl l>i»sertAtioa« Dorpnt, 1805. S. Rabou, Btrlinm 

l[hwiei:he Wt>cktneckri/tf \%1\, Eftdxicjiiwskt^ CVufrnfA/al^ /iir r^e Med, Wineennchtft^Ht 

n. OttttAir StrAJtburg fu»e ia fever), TiVcAoir** XrcAit?, Bd. li. p. 471. L. Lcwin, 

'C^tramaH /ttf dU Mtd, Wieetntek^ften, Ko, 38, 1874. 



124 



SrSTEMIC REMEDIES. 



birda). Aa Tegards animiil beat, alcohol octA upon nmn as upon the lower 
aninials. Afler doses ouly Huflicleiit to increase tlie activity of the eirculi^ 
tion, proWblj as a reBult of iIiIe mcraise^ there is sotuctinies i\. very trifling 
esaltatioQ of temperature (Farkes and WoUowick), After larger doses there 
IB a slight fall of temperature^ aud when full iutoxicatian la induced this fall 
may amount to 3^ F. (Ringer fuid Rickardii), 

Upon animals suffering from pyaimic fever Bouvier and sub^cjuent ob- 
servers have found that tdcohol exerts a decided antipyretic action, very large 
do8<M of it lowering the temperature as much as 8J° C., and altogether pre- 
venting the occurrence of fever if narcosis be produced before the develop- 
ment of tlie latter. In fever in man alcohol exertij a similiir influence, but , 
in order to make its antip3*rctie action decidedly manifest, doses so lar^e as 1 
be toxic juust be given (Ringer and Rickards), It has boon noticed both 
in man and in the lower animals (Bunvier) that when the individual is accus- 
tomed to the free habitual use of alcoiiol the tempcraturo is scaroely aflfected 
even by large doses. 

Vciy recently, Dr* Frans Kiegel (Peuitehes Arehw fUr Ehn. Mtdicin^ 
1873) has made a very elaborate ori^nal investigation upon men, eompri^ng 
as many as eighty-six experiments, and has arrived at the following txjnclu- 
sions, which are in exact accord with what waa already in type when hi<< 
memoir came to hand. As they embody the whole subject in a few words, 
and may be received as absolutely demonstrated, I offer no apology for inter- 
polating them here : 

"1. Alcohol, even hi moderate doses^ in many cases causes a lowering of the 
tempemture of the body. The amount of this diminution averages as a rule 
only some tenths of one degree, 2. Only exceptionally is there noticed an 
elevation of the temperature consequent upon the administration of alcohol ; 
not nnfreiniently, at least afler minute doses, there is no noticeable change. 
3, The diminution of temperature in convalescents ia, as a rule, leas than in 
healthy subjects, or it may be alt<»gethcr wanting. 4. In those who habitu- 
ally drink alcoholic stimulants, the depressing influence of alcohol upon the 
temperature is almost always wanting. 5. The frequent repetition of the 
doses of alcohol diminishes their lowering effect upon the temperatnro*j 
6. The imiount of diminution of temperature is directly proportional to 
dose of alcohol given, 7« The depression of temperature caused by alcohol 
is for the most part of but short duration, and the temperature soon returns 
to its previous grade," 

The effect of ulcohol upon the formation of animal heat was first properly 
studied by Dr. Bevan Lewis (Journai of Mental ScL^ xxvi. 20). He 
found that after the exhibition of alcohol in the rabbit there was sometimes 
a primary lessening of heat production of very short duration, which was 
followed by a marked increjvse in the heat production. In some cases heat 
dissipation more than kept pace with this increase and the bodily temper^! 
ature fell ; in other instances the bodily temperature rose, showing that heat * 



CARDIAC STIMULANTS. 



IfS 




roductlon was excited more than heat dbsipation. Oaloriuiotriciil cxpeti- 
b«i}U miide by myself and Br. Hoiebert have arrived at Biuiikr results, 
but before it can bo shown exnctly how alcohol affects thennogenosis further 
imeotation is needed. It may be that the increased heat generation is 
BpJv the result of the rapid burning up of the alcohol kiself. The great 
yi of bodily temperature whieh occurs aOer toxic doses of the drug seema 
tr> me to be clearly due to excessive heat dissipation , which in turn is the 
result of vaso-tnotor paralysis.* 

The effect of alcohol upon the elimination of carbonic acid by the lungs 

has been investiguted by several observers, with different results. According 

t reseurehes of Booker ( Bcitrdtfe. zitr Iltilkitnde Imbt^mthve zttr Krank" 

tnusfniitttl und Arzutatcirkunffn Lehir^ abistractod by Claude Bernard 

in Jmtfmal de Phannticie, torn, xv., 3d series, 1849), of N, S, Bavia ( Tratu 

octioTiM of the Amertcnn Medical Association^ 1855), of Ifammond (Phytic 

fj^ical Memoirs, Phibidelphia, 18C3), und of M. Perrin (An-hives G^nerales^ 

series, tome iv,), there is a decided lessenijig in tlie anitjunt of carbonic 

i g»s exhaled. Dr, E. Suuth, huwwer, found that small doses of alcohol 

the elimination of the ga^, althougli brandy, whisky, and gin always 

pod the production. It is probable that the action of the small doses of 

taken wjay vary, as it is reiidily conceivable that by chocking or aiding 

tigestion, by in6uenctng the circulutton, or in some other way, they may at 

I exert an indirect action which shall overcome any direct influence they 

I, Be this as it may, the weight of evidence appears ti> be at 

preseot in favor of their usually dimiu limbing the elimination of carbonio 

•dd; although the matter cannot be considered as entirely settled. 

One of the most important facts to be determined about alcohol is ita 
iafluenee U|Km the excretion of nitrogenous material. Backer is commonly 
btBered to have expetimen tally determined that it lessens the excretion of 
nraft. I have seen only an abstract of the original paper. In it this is not 
positively asserted, but seems to be inferred. Br. Hammotid has pci-fonned 
-• veiy elaborate series of experiments upon himself: first, when just sufficient 
i taken to maintain the weight of the body ; second, when more than 
Dough for that purpose was ingested ; third, when not enough was tiikeo. 
' all these circumstances, urea, chlorine, and phosphoric acid were leea* 
nod is amount by the ingestion of alcohol. Parkcs and Wollowic« (foe. 
L) affirm that their experiments gave a contrary i^esult. In examining the 
Ifeports of their experiments I find, however, that on one of the days the man 
ng the alcohol had a chill followed by fever. If this day he omitted, the 
verage daily excretion of urea during the alcoholic period was 34,35 grammes ; 
ittring the time when brandy was taken, 34.8 grammes ; and during the water 
i, 35.02 grammes. The ingestion of alcohol seems, therefore, to have 




* FroC Bfdi'i exp«riii]Miti and fnfereneei iipoa this tubjoeti In tbe Hght of rMenl 
irUflfice, ff «m of no riUiw. 




126 



SFSTEMW REMEDIES. 



reduced the eliraination of urea bj about ten graiua a day. Recently very 
carcfiil experimcBta hiive been made by L. L. Rioso (^Ilojfmann tthd 
Schwalbes Jahresb.^ 1881, 357) «poii two persons under rigid conditions. 
Tbe exhibition of alcohol was followed by great lessening of the exeretioo 
of urea, and to a less pronounced degree of uric ncid, chlorides, pliosph ' 
and sulphates, and at the same time an increase of the bodily w.i 
These results are in strict accord with those of IJiimmond, and it must 
be considered fairly proven that alcohol causes a threat lessening in the 
excretion of the produf:t» of tissue waste* 

From the time of Liehig's cdchrated classification of food until the appear- 
ance of the nieiuoLr of MM. Lallcmandj Duroy, and Perrin, uigested alcohol 
was almost ufiivcrsjilly believed to be burnt up in the body* These latter 
observers asserted, however, that alcohol escapes unchanged from the body^ 
not only because they were unable to detect in the blood or tissues any of the 
results of it** oxidation, such as aldehyde or acetic acid, but also because they 
found it unchanged in tbe ejtplred air, the sweat, and especially in the uriuc. 
The results obtained by the French investigators were, however^ seriously 
questioned b}^ E, Baudot {^U Union MedicaU^ 18G3), who demonstrated that 
tbe chromic acid test which Duroy and Perrin bad relied on for detecting 
alcohol in the excretions is so delicate as to reveal .165 grain of alcohol in a 
quart of water ; and Baudot further afBrmed as the result of twenty ex- 
periments that except after immense dose** tbe amount of alcohol eliminated 
by the kidneys is so small as practically to amount to nothing. In 1866 Dr. 
Schulinus (^ArcMv der JleilkunJe^ 1866), by a very elaborate and laborious 
investigaliou, confirmed the results of Baudot, showing that alcohol taken 
into tbe blood finds its way by exosmose into all organs in similar proportion, 
and does not c&cape through the kidneys unless in very Iriflhig amounts. In 
several experiment's be fuund that one-fourth of the ingested alcohol bad dis- 
appeared from tlie body alter from two to three and one-fourth hours, and, 
as but a fractional portion of the lost amount was elimiimted, he concludcsd 
that it must have been burnt up. AdoJph Lichen { Annah-n tier Chemie m 
IVtamiffct'ej 1870, vii., Supplement. Bd. p. 236) has in a number of experi- 
ments arrived at results similar to those of Schulinus. 

In 1865 a number of expenmcnts yielded to Anstic, of London (Stimit^ 
tants and Narmlics (reprint), Fbiladel]jhia, 1868), similar result.^, and also 
demonstrated that the eliminution from the lungs is exceedingly trifling. 
Thudichum investigated the matter on a large scale in 1864, and again with 
tbe assistance of Dupr<5 in 1866 (Tenth Report of the Medical Officer of the 
Privy Connciiy London^ 18G8). In order to avoid the fallacies of tbe chromic 
acid testj tbe alcohol was obtained from the uriJie by repeated distillations. 
In tbe first instance forty-four bottles of wine, containing four thousand 
grammes of alcohol, were drunk by thirty-three men, out of whose urine, 
oollectcd during the next six hours, ten grammes, or only 0.25 per cent. 
the ingested alcohol were recovered. In the experiments of 1866 the 



JSUft 




VAHDIAC STIMULANTS, 



substantially the fiamc, but, g^xiter cnre bciu^ taken to get akscilut^j 
mccuttkcy and to avoid loss during distillatiun, 0.82 per c^nt. uf the lUimuiU 
■dministcred was found in the urine. Quite recently^ Subbotln (Zeidtchnjt 
fUr hiologk^ viL, 1871 ; SchmiWs Jahrbilcher, 1872, Bd. cliv. p. 2iU) b&B 
oaiide jin apparently close experimental study of the subject upon six rabbit^^ 
mild has shown tl^at elimination conLLnues for a longer time than had been 
generally believed, and that twice as much of the alcohol escapes by the akin 
nod lungs as by the kidneys. In one experiment he found that Ifi per cent. 
of the alcohol escaped unchanged in the first twenty-four hours ; eliniioation 
after this time, although perceptible, amounted to very little. As he^ like 
Ijdlemand and hia colleagues, experimented with }^>oisonou6 do^es^ his results 
ooofimi nilher than ciDntradict those of Baudot, SchuliuuSj Anstie, Tbudi- 
cbant, and Duprd ; for it is manifestly evident that afler such doses ciimina" 
tion would be proportionately greater than afler smaller qutuitities, as there 
naturally must be a limit to the powers of the syi;tem to o^tidize alcohol, 
Ptof R, D, Edcs, in hit* experiments (^Boston Medical and Surgical Journal^ 
^872, p. 347), found that afler stnall doses the amount of eUmination by 

) bnrdth is great<*r than that by the kidneys, although the contmry holds 
irhero large amounts have been administered : in either case the total amount 
dituinated was but a small percentage of that ingegte-d.* Final 1}', Anstic 
(LoHthm Pmctitwntr, July, 1874) hiis recently repeated his experiments, 
ring the method of SubbuLin^ and even t^ubjtcting u dog, which bud been 
liking for Sf>me dnya very much larger amounts of alcohol than ha had 
illtEiiinated by skin^ kidneys, rectum, and lungs, to disttllatiou, with the results 
i»f conlirunng his first experiments and of finding no '^ residual alcohol* — 
•,e.» alcohol left in the body — worthy of mention* 

l*hesc concurrent invest igationsf certainly demonstrate that but a small 
prt)fK>rtiou of ingested alcohol is either eUmifiated from or accumulated in 
the body, and conse(|uently that it must be oxidized in the body, and in some 
ees partake of the nature of a food. It hits been objected to t!iis that 

one has as yet bt-L-n able to detectj in the blood any of the ordinary 
pruduets of Ita oxidation j the probable reason of this is, however, that 
llie oxidatbn is carried us it were at one hound to its ultimate cud, the 
production of water and of carbonic acid. A strong corroborative proof that 

obul is largely consumed in the body is furnished even by the cxporimcnta 

Lalleinatid, Duroy, and Perrin themselves, for they proved that elimina- 



• Prof. Eili-4 relifrd upoo the cbrouiic ooid itBl, which Dint ftiterts to be faUBcioas. 
In tho espcriraenti tniule by Slcnbacb and Schmidt, under Prof. Bias's direction, alc(>hol 
ottld not hm dotoctod in the breath, nnd Prof. Hinx bellcvofl thmt no vlimlniitioD of it 

eun from ttie loaj^t. Ho dodaros that the odor of tho breath after drinkm|£ la not 
tkmi of (dtfohol, but o{ th« i«theT< and other rolaille principles of the viirioLLi Kquldtt imblboda 

1 I heHere Ihcso reiiulu hove alio boon confimiod bj Wohler, Jmtruat tfe* Pmtjr^Wj xi., 
bat I bAv« nul Mxra the oHginul paper or uny abntriU't of it. 

X l»ucb*k ( Vifttfljttkr, Prakt. Heiik,, Bd. liJ.. 1953) did not, fli he thought, domonrtrnte 
th« i»tmruc& ut ttldehjrde in thti blood of ft&iiniil^ poisoiiod With akobot. 



128 



SYSTEMIC REMEDIES. 



"ion ocascd, or at least could not be detected by the most delicate tests, hefur^. 
the alcohol had all escaped from the body. 

A very strong confirmation of the theory that asserts the oxidation of 
alcohol in the body is found in the researches of our countryman Ihr. H. 
Ford, whose experiments have, however, not been repeated, and therefore, 
although apparently carefully performed, lack the absolute authority of com- 
plete confirmation. Dr. Ford {N, Y, Mtd, Journ.y Jan. 1872) has worked 
upon the supposition that the hepatic sugar must be converted into alcohol 
in the body before its final destruction, and, using large quantities of blood 
of animals, has sought by repeated distillations to obtain alcohol from it.^ 

Pushing his researches still further, Dr. Ford used various tissues as the 
substances to be distilled. He also made elaborate calculations, based on the 
carbon ingested and on the carbon exhaled, as to the amount of alcohol 
which ought to be found in the capillary blood of the lungs. The resnltR 
are expressed in the following table : 

Alcohol in the capillary blood of the lungs : 

r calculation based on '^ cordon t'n^e^^" • . 0.5403 

I " " '' ''carbon exhaled'' . . 0.5794 

*' putrescent lung-tissue (mean of ezp. 8, 9, and 11) . . 0.3819 

fresh " ( " " 12, 13, and 14) . . 0.3076 

putrescent thoracic blood (mean of ezp. 1, 2, 3, 4, and 5) • 0.7625 

fresh " " (mean of table) .... 0.0841 

putrescent liver-tissue (exp. 6) 4.3138 

fresh '' (mean of ezp. 25, 26, and 27) . 0.0190 



The important facts seemingly established in the above table are: the cor- 
respondence between the amount of alcohol in the thoracic blood as obtained 
by calciilation and by experiment ; that the smallest quantity of alcohol is to 

* Space Is wanting to describe in detail the very elaborate methods employed by Dr. 
Ford. The tests which he relied on, to prove that the liquid obtained was alcohol, were the 
chromic acid test, the peculiar inflammability, and the optical appearance of the alcohol 
in the conducting-tubes at the time the distillate commenced to boil. In order to pre- 
vent any possible oxidation of the alcohol during the process, Dr. Ford sometimes added 
sulphuretted hydrogen. The results of ten experiments are shown in the following 
table : 





WHfrht of 
Blood. 


Interval 
from 

Denth to 
212°. 


Tempera- 


Weight of 


Weight of 


Weight of 


WHghtof 
Alflohol 


With or 


No. 


ture when 


Firxt DIs- 


Final Dis- 


Alcohol 


for lu,000 


without 




distilled. 


tillHtion. 


tillate. 


obtained. 


parts of 
Blood. 


BS. 


15 


fl970 


60 m. 








0.0660 


0.0032 


without. 


16 


97:t4 


66 


loio 


1602 


0.8416 


0.0198 


0.0203 


without. 


17 


J»137 


70 


100.3 


1636 


1.6218 


0.0606 


0.0662 


with. 


18 


92:J6 


77 


99.6 


1623 


3.6130 


0.0444 


0.0480 


with. 


19 


89H8 


60 


99 


1656 


2.e«i9« 


0.1367 


0.1609 


with. 


20 


8W>4 


60 


98 


1565 


1.7320 


0.0760 


0.0S68 


with. 


21 


9423 


45 


96 


1660 


1.8722 


0.0708 


0.0761 


wilhoat 


22 


9112 


61 


98 


1650 


0.9562 


0.0360 


OJSSi 


without 


23 


273;iO 


48 


98 


14(t50 


10.6883 


0.2988 


o.nfn 


with. 


24 


36300 


61 


99 


17600 


14.0606 


0.6662 


01669 


with. 



VARDIAC STIMVLASTS, 



n^ 



I obUinod from fresli Uver-tiseuo, the frrctitest from putrescent li ver- tissue , 
in wliicli the plyeogeti nniat liuve unxlcrgooe tbrmentfttion. The fresh thoracic 
blottd was blcHxi which had not traversed the lungs ; the putrescent ihonicic 
blood of course represented the eanie blood with all its sugar fermented. 

Tlieee roeearches of Dr. Ford nre certainly corroborated by the discovery, 
first miidCf I believe, by A. Lieben {Atinalcn dcr Ckem. und Pharvt., 1870), 
dikoitgh usually uttributed to Dupr^* (The Doctor, Feb. 1, 1873), that 
B sabetAnce exactly rescuiblin^^ iiUoliuI exists in very minute f|unntlty in the 
urine even of teetot«ilen*,* M. Beehaujp ( I^ntlon Lfincrf^ 1873), apparently 
itithout a knowledge of the work of the other chemists, obtained^ fi'ora the 
urine tif pensons who had not taken any alcoholic beverafte for a Iohl'^ time, 
•Jcohol in sufficient i|uuntity to burn it. As Lieben alfto found tlmt this sub- 
atMice exists in the urine of dogs, hordes, and lionB, and A. lliijcwpki ob- 
taioed it from healthy rabbits (Archw fiir Phy»i(ilogie, xi, p. Vl'l, 1875), 
tt8 existence in the normal or«raniFm must be eonsidercd demonstrntt^cl* 

Upon the nervous system alcohol exerts a powerful infiuence. Its effcctfl 
upon the cerebrum are too well known to require elaboration ; but it may be 
mentioned that I. Dogiel {he eit,} haiB found that in frog« the reflex susccp- 
tihility is at first somewhat, and afterwards decidedly, diminished by largo 
doiied of alcohol, and that the seosory and motor nerves are similaj-ly affected. 

The question of the effect of ulcohol upon digestion is an important one* 
There c^n be no doubt that very large doses hinder digestion. According 
to the experiments of W. Buchner {fhnUck. Arch. f. KUn, Afctl.y xxix. 
537), ten per cent, of pure alcohol does not affect artificiiil digestion, whilst 
beer, even diluted, retards it. The use even of small doses of alcohol 
ieemed to delay digestion in a few experiments made by washing out the 
etomaich a fixed time after a meal taken sometimes with, somelimcfi without, 
doobolic drink. The methi^d is, however, too crude tg allow much weight 
ta the expcrimente ; for it is possible that alcohol may lessen the rapidity 
with which the fo<»d leaves the stomach, and therefore aid in the thorough- 
neas of gastric digestion. Certainly every^duy experience teaches us that in 
Bmall amounts wines and liquors enable the bon vivani to digest more than 
ia natural or proper. 

From what has been said, it is certainly deducible that alcohol in small 
amount Is an arterutl and cerehrfil gfimvknit^ increasing functional activity 
in the nervous and circulatory apparatus; is n/ootl, in the sense that it is 
destroyed in the system and yields force which is utilized by the organism ; 
b. when in soflieient quantify, a retarder of tissue changes, ohecking the 
excreliun of nitrogen. 



^ It li uf4rt«<l Chat llic idbit&Dce ** it not &1oohoL It p&iwi ovor dftrlievL 

prci4uot« of (ttiitiUiilloJit yields fLcetio ftcid oa betn^ oxidizedf rcducr^ tunic of 

p»bi*iiuiu wki«o dilute sulphuric Add it prcfttnt, and itii ftqueouj^ Murion hni^ n i^iwer den 
tity tliAD irafor. It fumlKlies iodoronn, and exisu in tho urine In u very nuiiill qutinrlty.** 
Pt>««e»itif the phyi1««l and obontical «btti'tveir«r» uf ifcl<»i*bol« to urdimiry tuimU it ip nlcubul, 

W 



130 



SrSTEMW JtEMEDIES. 



If nlcuhol be oxidized in the hodj, aod be a food, as it seems to me is 

clearly proven, it must of course generat4? force, meosiirttble by the modern 
^taudiird of the heat-unit. A little culcuhitiou will &how the iniportarioej or 
rather the ^rteut amount, of the generated force. According to Duj>r6 {Lon- 
don Pnictitifmer, vol. ix-, 1872, p, 33 )^ one gmmmo of lilcohol oxidized in the 
body evolves 7184 umX^ of heat, whilst tljc siune wtMght of lean beef givti^ off 
only 14S2 unit« of heat. It has been estimated that 9.3 ounces of leiio beef 
— equal to about two ounces of alcohol — will supply the neoefls;iry foree to 
maintain the circulation and r&spi ration of an average man for one day. That 
IB, four ounces of strong spirit will suffice for this purpose. Since to the 
ubility of furnishing material whose conf^uroption shall give power is added 
the ability to restrict waste and lo stimulate the fiiuctions of circulation arid 
of the nervous system, it is evident that in alcohol we have a mo«t important 
means of sustaining the system during the strain of an acute exhausting 
disease. 

TuEiiAPKUTtcs. — Our knowledge of the physiological properties of alcohol 
shows that its chief therapeutic value in acute disease m as a stimulant, a 
temporary Impart er of power which shall enable the system to stand some 
utrain of like duration, — ^to bridge over some period of weakness. 

The cases to which it is especially adapted may be divided into three classes. 

Flri^t. Those in which there is a temporary loss of heart-power, as in 
fainting fr(»m e3Lhaustioii, loss of blood, or other cause. In these cases tlie_ 
alcoholic stimulant should, if possible, be given hot, and not much dilttt( 
with it should also be exhibited some more rapidly-acdng diffusible stimulant 
such as ammoniiL 

Second, Those acute diseases in which the powers of the system are in danger 
of being used up; to aid in the digestion of food and in the maintenance of 
power. Alcohol J as \\\\b already been stated, is to a certain extent a food, but it 
will not of itself sustain life for a long time, and should in adynamic disease 
alwMVs, unless for specLil rcAisous, be combined with milk, or occasionally 
with eggs. One great source of its value in these diseases is the power it 
imparts of assimilating food, and in milk-punch are funiishcd the stimulant 
to digi^tiun and the most perfect f(M>d kuown for digestion, TliL* use of 
alcohol is apart from its office in the lowest stage of fever as a heart- and 
nerve-stimulant. Employed fur this purpose it is useful in all stag*^ of the 
ad^iinmh ftv€rs^9^.n^^ as h/phm and typhoid. By the exhibition of three or 
four ounces of milk every two hours, with one or two drachms of brandy or 
whittky, from the beginning of the attack, in many cases the develtvpmeut c^ 
the severe adynamic symptoms may be prevented. 

In the advanced stages of disease?, when the ti/phoid ttate is well devel* 
oped, alcohol should be given boldly, — to quiet by atimulation the nervous 
and circulatory systems, — to afford a food which shall in a measure replace 
the natural pabulum, — to aid in the digestion of milk and other simple nour- 
ibhment,^ — to aid in lowering tcniperature by checking the tiiisue-waste of 




CARDIAC STIMULAATS. 



131 



f^Tor: in a word, to enable the system to stand the drain upon its vitRl 
ciwere, and at the same time to check such drain. 

perlj administered, it alwajs promotes, not nrrcstfi, secretion in thv^t^ 
The gnide to the amount given i^hould be the effects produced ; so long 

it lowera temperature and pulse-rate, moistens the dry tongue and skin, 
nd f^tilets the nervous disturbance, it does good ; if, however, the tongue 
j^^ws drier, the pulse puts on an angry , bounding character, and the patient 

omcs reetle^ and uncag}\ Ftimulation is being pushed too far^ nnd tlie 
^amount exhibited should be lessened* The antipyretic action of aJcohol haj* 
euggwtcd its use in all eases of high teni|M?rature ; a8» however, this is only 
one of its actions, and as it is not decided unices very large doses be given, 
alcohol cannot be employed as a gen end felirifuge. True arterial excitement 
and sthenic inflammation certainly contra-indicate its use. The rule may be 
laid domi as follows: high temperature ban indication for the use of alcohol 
t)niy when other symptoms also demand it; in itself higli temperature is 
never a contra-indicutioQ to alcolioL In acute sthentc dmascsy after the pro- 
gressive stage has passed and the results of the disease simply remain to be 
overcome^ alcohol and milk will often save life* Thus, in acute ptiemtmnia^ 
when so much consolidation has occurred as to render it doubtful whether the 
exiidefi matter can be removed, or in aUcess^ when large amounts of pus have 
formed, the demand may be very great for alcohol as a food and as an aide* 

digestion, and sometimes as a stimulant, 

TlunL Those in whieh there is a depressing agent. In many forms of 
pouoniVi^, alcohol may be used with signal advantage simply as an arterial 
and nervous stimulant, to overcome the influence of a depressing agent* Thus, 
in mahe*bit€ the unlimited use of it affords, with the liypodennic use of am- 
monia (sec Amnumia), the best method of treatment. Recently it Inis been 
Terr strongly recf»mmendcd in pt/ftmin by Dr. Theodor Clemens, of Frankfurt 
{DeiitMche Klititk^ 18T4, 1875), who states that he has seen eight cases of a 
severe tyj»e recover under the adminihiration of red wine in as large amotints 
as the patient would drink. In potmniny by aamiie^ rtTtttntm inridf.^ or 
other similar substance, whore death is threatened through failure of the 
heart^power^ alcohol iii some furni h imperatively needed. In all these cases 
of acute depreieion threatening a fatal issue, it should be administered freely, 
not much diluted, and, if convenient^ hot From one to four ounces of 
'. ' ' ' nuld be given, re|)cated evciy ton or fifteen minutes, until slight 
ii -ru convalescence, or death has resulted. 

What has been said up to thb point in re;:nid to the therapeutic action of 
alojhol has luid reference? to acute disease. The value of the drug in some 
ch^>uic diseases cannot be doubted ; but in prescribing it the physician should 
never lose sight of the possible danger of producing a habit far worse in its 
fruits than death itself 

In chronic nmral^ia/m fit/pochondricuUj in jnehmcholia^ temporary relief 
may scvmetimcs be obtiiined by the use of stimulants ; but the very relief 



wSmm 



132 SYSTEMIC REMEDIES. 

afforded doubles the temptation to the frequent use of the alcohol, and, as 
the system becomes habituated to its action and the dose has to be more and 
more increased, the habit of frequent stimulation grows almost of necessity 
into drunkenness. For this reason I do not think the physician is ever jus- 
tified in prescribing alcohol for its narcotic stimulant effect in these cases. 
The chief legitimate uses of alcohol in chronic diseases are to aid in digestion ; 
to furnish a food which, without any digestive effort upon the part of the 
system, shall be absorbed and shall take the place of more ordinary food ; and 
to check excessive tissue-waste. Of course these indications exist only in 
such diseases as are either dependent upon or closely associated with a con- 
dition of system in which the general nutrition is depraved. In purely local 
affections the use of alcohol is rarely called for except in the last moments 
of life, when it may always be employed to afford relief and to protract for a 
short time the strugj;le. In chronic dyspepsia, alcohol adminbtered with 
the food often aids very materially in the assimilation of the latter ; but care 
has to be exercised in prescribing it, for the same reasons as were given when 
speaking of the use of stimulants in melancholia a moment since. In many 
cases of chronic neuralgia^ not as a narcotic stimulant, but as a food and a 
stimulant to nutrition, alcohol is ollen of the greatest service. The danger 
of establishing a fatal habit in this disease is, however, excessive. In almost 
all cases in which alcohol is called for in neuralgia, cod-liver oil is also indi- 
cated, and it is generally best to exhibit the two remedies together, so as to 
obtain the easy assimilation of the oil and to guard against evil moral results. 

In plithisis and its congener scro/ulosisj there can be no doubt as to the 
great value of alcohol ; and in the latter stages of consumption its judicious 
use as an antipyretic narcotic stimulant to lessen the sufferings of the patient 
is perfectly justifiable. During the chronic movements of the affection, 
alcohol taken with cod-liver oil, or in small amounts with the food at meal- 
times, conduces not so much to the comfort as to the well-being and recovery 
of the patient. 

The question as to the propriety of the daily use of alcohol by healthy 
men is at present a very serious one, involving so many moral and politico- 
moral issues that it cannot be fully discussed here. Suffice it to state, as 
obvious inferences from our present knowledge of the physiological action of 
alcohol, that the habitual use of moderate amounts of alcohol docs no harm ; 
that to a certain extent it is capable of replacing ordinary food, so that if 
the latter be scanty, or even if it be coarse and not easily digested, alcohol, in 
some form or other, is of great advantage ; that in all cases it should be taken 
well diluted, so as not to irritate the stomach ; and that wine or malt liquors 
ai^ certainly preferable to spirits. The experience of Arctic explorers has 
certainly shown that alcohol has no hcat-'jroducing power, so that at a time 
when it was believed to have such influence by physiologists the Northern 
navigators had learned that the free use of spirits, far from enabling a man to 
withstand habitual exposure to intense cold, very materially lessened his power 



CARDIAC STIaMVLANTS. 



133 



Ou the other hand, the experience of dmost every trout- 
fifihennan or ^port^inan hus satkfied hiui tlmt spiiita do liave power to provt^iit 
""^ catching cold** under sudden and uriacciLstomed exposure to wet mid ci4d, 
and that b<)iiamb«d extremities will become wanu and have their proper feel- 
ing return under the influence of a glass of whisky. There ia, however, 
nothing strange or contradtirtory in these experiences, and they are both in 
Strict locord with the present knowledge of the phyaiolo^eal action of the 
dil^ Afl is often the case, the fact« were practically made out, however, 
bdbre science could Btjlve the apparent puimlox. A» has been abundantly 
abown, alcohol huit no heatini; povt^cr ; but the chLfl of hudden expo^urc^ the 
Boflerin^r hcnuiubcd extrcuaties, the brotichtiiH tlmt {>crhap8 follows, all mean 
Bimply thi^: tjjat, m the result of the cold^tbc blood leaves the surface and 
the extrtonities^i the circulation falla in the outpotsta^ aud^ aa a consequencei 
uppresscd perspiration — i*.e., susjfondcd function of the skin — ^and internal 
ongestions result. The relief aflordcd by the ^spLrius^ an well as the preven- 
tion of sickness^ is due simply to the power of the remedy in maintaining 
the circulattou nnd keeping the external surfaees warmed by the constantly- 
renewed currcntis of fresh blood from the interior of the body. 

Owing to its stimulant and antiseptic properties, alcohol constitutes an 
excellent dressing for wounds, whether accidental or surfrieal in their oriiiin. 
It would se*im also to lessen pain by a local aneesthetie eflect ( Horvulle, Gaz. 
Er4 J/opihtuXy Sept. 1878). Strong surgical testimony ns to the local valui* 
wbibky has been given by Drs. Blair {Ghn^ow Med. Jmir.^ Feb. 1870) 
and Snesserott (PhtUi, Med. Timen^ vol. iv. p. 774). Lint soaked and kept 
ootuitantly wet with spirits is to be packed on or in the wound. 

Administration. — Almost enough haii been ulri?ady mid upon this pointy 
but a few further reujarks seem appropriate. When stimulantit are us^ed ta 
sastsin tiie sinking jHiwers in poisoning or in dLsease, the amount given 
Bhaald be almost R*lely regulated by the effects. Thus, in ^nake-bite it may 
be neocasaiy to give a pint of whisky in the course of an hour ; and in low 
fbvera I have eoen the greatest benefit result, and life apparently saved, by 
the exhibition of a qujut of spirit* a day. The rule in always to be gov- 
6flied by the eflfeetfl. In pois ning, one, two, three, or four ounces, us the 
0M# may seem to need, shituld be exhibited every ten nunutcs, until some 
effeet Is produced or matters become hopeless. In low fevers half an ounce 
to an ouncic should be given every one, two, or three hours, pro re nat*iy the 
{iraetitiuner watching the rcs^ulti^, us alRuidy i^pokcn of. 

The <(ue»tiou of choice, of course, comes up in every case as to which of 
the spirit!* sliall be us*ed. I have never been able to p*erccive any difference 
in their aciitm (gin, of courbc, being excepted ), save only that sometimes one 
mfge^sm better with the stomach than the other. This has seemed to me to 
d^paild ftimply upon the pcrHurjul likings of the patient, to which then^fore 
thi choioe may well be lel\. In sudden collapse, some of the wines with a 
Ttaj high hoin^uct are believed to be more stimulating, on account of the 



iU 



134 



SrSTEMW REMEDIES. 



etliers whicli tbey cont^iin ; but I Lave had no experience with theiu. It 
convttleficeuce, atid for habitual use id hwilth, wines jire preferable to spitits, 
— ^more at^'eable, more tunic, an J leys apt to lead to excessive mdulgenoe. 

When a mild stiinulaut is wanted in the beginuiug of fevers, especially if 
uiilk-puiich seema too *'h(iavy/* ivine wJu^i/ may be Bometimea used with 
udvantage. It is madu by pouring a iialf-pint of sherry or madeira into a 
pint of boiling milk, stirring thoroughly, and after coagulation had ocourred 
strziining off the whey, which may or may not be sweetened, according to tht; 
taste of the patient. Mtdkd wine is often very grateful to patients aa a 
change. It b made by beating ao eg^ up thoroughly with throe fluidounoes 
of sheny and adding a like ijuautlty of wator, which must be actually boiling 
when poured in. Vkampagne \& useful In patleiiU with delicate stomachs, 
espteciahy il' uause-a or vouiitiug actually exists^ and also may be empl<»jed 
with advantage in sudden failure of the vital powers^ especially in elderly 
periwjns. It must always be very ** djy/* i*.e., as free as possible from sugar. 

Miik-punch is prepared by adding iVom a desaertopoonful to a fluidouuee 
of brandy, whisky, or rum, according to the degree of stimulatiou required 
and the taste of the patient, to three fluidouuces of milk, with sugar and 
nutmeg to taste. The addition of a tablespoonful of lirue-wator is not rec 
nized by the palato, and renders the beverage more acceptable to the btoaiacll 
when the lattor is weak. 

Eyfj-itogg is still more nutritious t!mn milk-puneh, but is ** heavier, and 
is usually rejected by the stomuch if given teo freely. It is made by beating 
up thoroughly iho yelk of an egg with five fluidounces of milk and half a 
fluiduunce to one fluidounce of spirits (add half a flutdounce of lime-water 
if required), and adding u sufficiency of sugar, with hnuUy the white of the 
egg previously thoroughly bentcn into a froth. 

ToxiooLoay. — The acute form of alcoholic poisoning in its minor de 
18, unfbrtunateiy, an hourly occurrenee almost in every village, but that futj 
results are not absolutely so rare as is generally l>elieved is shown by tha 
fact mentioned by Taylor, that in four years (18G3-67) thirty-five deathsl 
fixjm this source occurred iu England and Wales, It is worthy of note that 
in some fatal cases convulsions have preceded dc*ath {Phila. Med. Ttnun^ 
vi, p, 4C3)« The absolute diagnosis of acute alcoholic poisoning wheu the 
patient is simply seen in the advanced stage of deep eoma cannot be made out» 
The odor of liquor upon the breath or about the person is simply a proof that 
the subject btis been driuking, not that the symptoms are caused by alcohol. 
The manifest at ions are merely those of profound compression or oongestion ofg 
the brain, of apoplexy, of opium-poisoning; and a man who has been drinking^ 
only moderately nniy have been struck down with apopk-xy or poisoned with 
opium. Dr. Hughlings Jackson has recorded a case in which the alcohol im- 
pregnated not only the breath but the urine also, and in which the patient was 
lefV to ileep it off; but at the post-mortem a clot was found covering nearly 
the whole of one hemisphere. Afler death in acute alcoholic poisoning th<f 



CARDIAC STIMULANTS, 



133 



h, is found very much congested, and sometimes ccchymosed. The treut* 
ment coosist^ in the evacuation of the stomach, the use of the akoniulo but 
and oold douche, aud the usuul mechaolcal methods of orousiDg a uarcotised 
patient. 

TEEEBIOTHINA-TTJEPENTIKE. TI,S. 

White Turpentine is the cuuciute olcMrc^iiiu ubbuned by incising tliii Pinua 
palo^rifi and other species of pine. The supply in tJic American market 
comes ahnost exclusively from North Cawhoa iind other of our Suutheni 
Sutca, It is rarely^ if ever, itself used iu medicioe, but by dUtillution Ls 
sepaiated into a volatile oil and a regin {Rosin)^ iirhieh is offieloal under the 
naine of i?cfi«a. Roalu is used iu riiedieiiie solely iu the furmiiti^jn of cer* 
tain plasters, chief amyng which m the Emplasfrum Resiu^^ U.S., AiiltcKive 
PlaMer^ or, in ordinary language, " Sticking Plastery* which is fonned by 
; rosin to lead plaster. 

OLEUM TEREBINTHIN/E— OIL OF TURPENTINE. U.S. 

This is a yellowiah, highly-inflammable oil, of a strong peculiar odor and 
A hot hi tin g taste, moderately sulnble in alcohol^ freely so in etlier, very 
slightly so in water. By heating with muriatie acid it is converted into a 
red lii'^uid and a white crystaJiine subatance, which, from it8 reijembluuce to 
camphor, has received the name o^ artificial camphQt. Turperjtine h remark- 
able for having the property of absorbing oxygen and convertiug it into yxoue. 

Pbysiolooical Action. — Turpentine is a powerful irritant, causing in 
a very shurt time iuflammatioo in any tissue with which it cornea in contact* 

When taken by a healthy fKJrsctu in moderate di^hn^^ it jtroduees a !!*ensc of 
warmth in the stomaeh* ^on followed by exhilaratioD, and, if the amount be 
Mjfficient, giddiness and even a species of in toxical tion. The pulse is increased 
tn force and firecjucncy. The turpentine e^-apcs from the body through the 
lungs and kidneys, imparting its own odor to the breath, and that of violeta 
to the urine. Although sevcnd recorded instances prove that turpentine is 
vnpnible of producing death, yet cases of serious poisoning by it are rare, and 
a lethal result exceedingly so. The symptoms noted in jMjisoning by it are 
mottt of them coDftant, but vomiting and purging are present in s^ome cases 
aful not in others, Unctmsciousness is geuendly complete, and in some cases 
bi accompanied by dilated pupils ; the urtne is very much lessened in tpiantity, 
oHeu bloody, not rarely suppressed ; the skin is sometimes di-y, SLtmctmieB 
niuist ; the pulse is feeble, rapid, and genendly regular. The intense irrita- 
tion of the uriiio-ireuital organs iu some cases has been indicated by constant 
priaj»ism and efforts at micturition. 

The lethal dose must be very large, but is not detinitely known, since reeov- 
ery from four ounces in an infiuit fourteen months old haj* been reported. Iu 
Dr. Mauud's ciise {Anmtalrc de Thinipttittiiim^ 1840), death waa snp|>osed 
to have bcHin produced iu an intemperate woman by six ounces; and l*hilip 
Niall has recorded au instance of death produced in an infant iburteen 



iB«fa 



136 SYSTEMIC REMEDIES. 

weeks oM by turpentine, of which half an ounce was thought to have been 
taken {Lotulon Luncet^ March, 1869). 

Turpentine appears to be a stimulant to the ciroulation and to some of 
the nerve-centres, but further study of its exact influence is still needed. 
R. Robert {Cenfralbl. /Ur Med, Wissens,, 1877, p. 129) found that in 
moderate doses it exerted a powerful stimulating influence upon the inhibitory 
reflex centre, and also elevated the blood-pressure by stimulating the vaso- 
motor centre. Very large doses appeared to paralyze both of the centres 
spoken of, causing decided fall in the arterial pressure. The respiration 
was first increased in frequency, but later strongly diminished. The blood 
became very dark and the heart was finally paralyzed. The vagi and de- 
pressor nerves did not appear to be afiected, nor did indeed any of the 
peripheral nerves, or the muscle. Dr. Hoppe (Journal fUr Pharmacod^ 
namilcy Bd. i. p. 105) concludes that the vaso-motor nerves are the first to 
feel its influence. 

Upon the kidneys turpentine acts decidedly, causing, according to the size 
of the dose, increased secretion, or symptoms of renal irritation, such as pain 
in the back, and strangury, with a diminished excretion of bloody urine. 
Leon Crucis {Dela Tiribinfhine, Paris Thesis, 1874) has made some experi- 
ments which indicate that when tui-pentine is given in toxic doses to rabbits 
it increases the coagulability of the blood and gives rise to numerous minute 
hepatic and pulmonic thrombi. 

Therapeutics. — Externally the oil of turpentine is very much employed 
as a powerful counter-irritant It is useful more especially when it is desired 
to act upon a large extent of surface. When a very intense permanent local 
impression is required, a blister is to be preferred. Thus, in pleurisy a blister 
may be used, in bronchitiSy turpentine stupes. In preparing the latter the 
turpentine should first be warmed by setting the vessel containing it in hot 
water, then a piece of flannel, just previously saturated with hot water and 
wrung as dry as possible, should be dipped in the turpentine and again 
wrung out. It is then ready for application, and may be lefl on from 
fifteen minutes to half an hour, according to the sensitiveness of the skin. 

Another local use of the oil of turpentine is as an addition to enemata. 
From a teaspoonful to an ounce of it mixed with double its amount of olive 
oil renders opening enemata much more active, especially in causing the ex- 
pulsion of flatus. Turpentine enemata containing much of the oil in a small 
bulk are also constantly used with good efiect in arousing the system firom 
stupor ari:sing from narcotic poison or similar causes. 

In ulceration of the bowels^ turpentine taken by the stomach is often very 
efficient, probably acting locally in the intestine, and in simple gastric ulcer 
the very best results are sometimes derived from its use. In a single large 
dose (f3i^ to f^i with an equal amount of castor oil) it is a very efficient 
vermifuge, especially against the round-worm. It also may be used as a 
stimulant in low fevers^ particularly when the tongue is dry and red. 



CARDIAC STIMULANTS, 



I3T 



In typktnd or enteric /ever it witlioul doubt acts as a local stiimilaiit to 
this akerutcd bowel, besides influencing tbe j^neral condition of tbe system. 
There arc two conditions or stages in the diseases named in which it is 
aspeciAlly uaefid, — indeed, is of incHlculiible service. About ihc end of the 
Beoond week the tongue sometimes kitonjcs very dry, red, chajiped, perhaps 
coated in the centre with a brownisli fur, find ut the same time marked 
loeteoTis&i develops. Ten drops of tuipjiitiuo every two hours during the 
Jay Aud every three hours during the night will in the majority of cases 
remove the bad s}inptoms not^d. That the action of the oil is largely a local 
one is shown not only by the arguineiits of the introducer of the practice, 
Dr, GtHjrgt! B. Wood, but alao by the value of the same treatment when 
, ,, itiwrrham persijits after the acute stage of the fever has jiasscd. When con- 

leso(*noc is protracted, when there is a constant tendency to the recurrence 
of diarrhoea^ when^ in other wttrds, the ulcers of Peyer*& patches are slow to 
head, turpentine acts almost as a specific. 

In tjfpht/id hronchiiU nud pneumoma^ especially as Intercurrent In typhus 

rpr and sinular diseases, turpentine applied externally and taken internally 
I often very usieful. The some may be said of the low iiirms uf pucrpertU 
/rver. In thL** disease the abdomen should be kept covered with fomentations 

the oil and of waj-m watej' alternately, the counter-irritant being used as 

ristontly a£ a proper regiir<l for the skin of the patient will allow. Inter* 
naJly it should Itc given in very large doses (f5*^) every two hours. 

In heniorrhagc^ from the stomach, bowels, or lungs, turfjcntine has acquired 
celebrity, but is hardly so much used as formerly. It is in the ataxic cases 
that it is useful. I have very rarely employed it, as the oU of erigeron has 
seemed M'eu more efficacious, and is much more fikasant to the patient. In 
ffmfjmra hxnufTfhapcti turfjentine has been highly praised. 

CatAN TirRp£MTlNE, the product of the Pistaoia tcrebintha^ hiis boett 
ty highly commended by Mr. John Clay as a reinedy in internal cancer. 
^ have known of its ui^e in one case of uterine cancer, in vviiich most iiston- 
Ubing results have followed its employment, and believe it should have a 
thorough trial. It is essential that the remedy be genuine ; six grains of it 
may bv administered three times a day continuously for many moutlis. 



DIGITALIS, U.S. 
Tlie leaves of the Digitalis purpurea, or fox-glove, of the second 3*enr*8 
growth. Tliese are large leaves, of a dull pale green, with whitish down 
underneath, and have a bitter nauseous taste and a faint narcotic odor. 
Digitalis yields both to water and to alcohol. M. Ilomylle discovered in it 
I peculiar bitter principle, which has been abundantly proven to contain the 
cdical Yirtut^ of the crude drug, and, under the name Digital in (DtoiTA- 
LINUM), in now officinal in the U. S. PhannacopoDia. As prepared according 
ta the directions of the hitter, it is a whitish or yellowish powder, odorless, 



138 



SrSTEMIC REMEDIES. 



but of a very bitter taste, nearly insoluble ia etber and lo water, readily 

soluble ID alcohol and in acids. With murititie acid it mukes a ydlow 
Bolutiou, which soon chaDges to green. The officinal prepiiriition is made 
by a process copied after that of M. Henry and M. HonioUo. It crystallixea 
with great difficulty, aod imperfectly. Nativelle, in 187 1^ announced (^BuUrtm 
de VAcad, Roy, de M^d^dne^ LS71, vol. xxxvi.) to the Academy of Fraooe 
that he had discovered a process by which crystallized digitalin oould be 
prepared, and received the grand prize of Orfila, 

Cry stall iztible digitalin {Journal de Chhme Midkah^ 1873) occurs **tu 
short and deliLiitc ueedle-shaped erj'stalsT and possesses an intense and per- 
sistent hitter taste. It ia but tdightly soluble in water, soluble in twelve parts 
of cold and six of boiling alcohol of 90°^ less soluble in al)s«^lute alctdiol^ and 
nearly insoluble in ether ; very soluble in chloroform. It Ls rapidly diissolvcd 
by a solution of chloraJ hydmte, the solution becoming greenish blue in color. 
The concentrated mineral acids dissolve it, hydrochJoric acid producing ao 
emendd-green color, sulphuric acid a green which if gutyected to the action 
of bromine fumes changes to a dark red, nitric acid a yelhiw, nitro-tuuriatic 
acid a yellow changing to an obscure green, and a mixture of equal porta of 
sulphuric and nirric aci»k a rose cMih>r changing to a deep violet. When heated 
on platinum, it melt*?, swells up^ becomes brown, and disappears without leaving 
any traces. It contains no nitrogen, but is composed of 51.33 per cent, of 
carbon, t»,85 per cent, of hydrogen, and 41.82 per cent, of oxygen." 

According to Ch. Blaquart (L* Union Pharmacenitque^ Nov. 1872), ten |)er 
cent, of crystal I izable digitulin can be extracted from the crude drug, which 
probably contains twelve per cent, of it. The question whether this sub- 
stance is the pure active principle of digitalis is of course an important one. 
The French commission reported as the result of physiological experinienta 
that it produces in man and animals effects similar to those of the amorphous 
digitajin, but that it is much stronger than the latter. Tbis conclusion baa, 
bowever, met with some opposition. M. Gubler {Bulletin de CActuL Roff. de 
Medeciney vol. xxxvil. p. 404) denies that this crystallized digitalin is stronger 
than the amorfihous preparation, and M. Vulpian in tlie subsequent discussion 
asserU^d that in experimenting he had found them of equal strength, and 
Ch. Blaquart (/wc. c*V,) in bis experiments arrived at a similar result; yet 
one-ninth of a grain of it is said to have been given to an adult without 
causing a toxic effect.* M<f^genind and Daremberg {Lomlon Medical Record^ 
1873, p. 278) have found the crystalline variety the stronger. Dr. Boucher 
\xf^rm?i (Gazelle. MidicaU^ 1874) that the crystallized digitalin is readily 
convertible into the amorphous or granular variety ; but he also asserts {^L*:$ 
Mmtdes^ July^ 1872) that it is a complex body.f This assertioii is coti- 

^ Fur I ho pmoeM of tQEinuriiGtDrc, ace Boittou Medleal and SttVfjicnl Jtmrtinf^ p^ 35, IS73. 
t a. Bauchardat {fiulL Thirnp., xc. p« 81 J cftUi Attention tu (he fiwt tbat cryetiUlUed 
iligiUllDi} duc£) uot, (Lud RiQurpbouA digitaltn doea, polarize tight. 



CARDIAC STIMULANTS. 



139 



I 



fiiTDdd by sevend cliemmtB^ especially by 0* Schtniedeberg (Archw fUr Ex- 
periinenL Pathologie und FharmttLol,^ Bd, iiL p. 19), whoiiffinns that there 
ins \n digitaliji four active prmciples ; Digkoxm^ the moat active of ull, 
wblch coDfltlttttes the greiiter bulk of NativeUe's cryataUked digit^dm; 
Di^ifafetn; Di^iialin ; and Dlgiiomii.^ For a particufar account of tbes« 
mibstanc4J8 the re4ider ia referred to the paper of Schmiedeberg.t Tl**-* only 
pmcticaU conclusion at presont poeaiblo is, that it ifi best to use only ufficinid 
preparations, such as the tincture, which represent the crude druf^.J 

PuvsiOLOOlCAL Action. — To the therapeutiiit the interest in the physio- 
logica] action of digitidis centres chiefly upon the circulation. The drug does, 
however, exert a direct influence upon the apparatus of voluntary motion 
which is worthy of notice. In toxic dosses it lowers reflex activit)^, lUid in- 
duces htifeiiude, prostration, muscular irenihlings, and sometimes convulsiuns. 
Thut the muBcles themselves are affected has been pn»ven by the researches 
of Yulpian, of Dybkowsky and Pelikaii, and of Gourvat, all of whom have 
found that the muscles of frogs poisctned with diti^italia respond more feebly 
than is normal to gidvauic currcnta. The nen'ous tissue has, however, been 
foucd by Gourvat to be more susceptible than the muscular, the nerves losing 
their functional power scwner and more completely than tlie muscles. 

Aj the result of an elabonite experimentiil study (Rrichert's Archiv /Ur 
Aftaiotntc, 1871, p. 252), Dr. A. Weil concludes that digitalis first lessens 
reflex ajclivity by directly — 1\/?,, independently of its action on the circulation 
— exciting the inhibitory reflex centres of Sctscheuow, and after a time by 
dirocUy juindyxing the spinal cord. The experiments upon which tliis con- 
dufiioQ was bused are divided into two series, in the first of which it was fouud 
that idier suudl toxic doses of the poison great diminution in the reflex activity 
of the frog was apparent in from ten to twenty minutes, and continued until 
the de&th of the batrachian ; but that this diminution for from twenty-five 
ttintites to on hour was immediately suspended by section of the cord high up, 
the reflex activity retuniing at once to its normal state ; that after large doses 
the reflex movements were almost abolished in five minutes, and continued 
YUitil death, but at any time duriug the first ten or twenty minutcB could at 
once be restored by section of the upper ctird ; that, both after large and small 
toxic doses^ a time finally eume when divi^iiHi of the cord hud no power to 
restore the lost reflex tunctious. These experimeuts have been ccuifirmed by 



* Ififfiialire»in ftnd foxir«iiir «rii derivfttSrei rceptsctivfilj frDm digital in and iJigiitixia 
of S«hml«d«berg. A itudj of Iholr pbysiologiottl aotioa m«jr be fouud id Arck^ £^per, 
rntkt>L «l Pharm,, Bd. ir, p. 19K 

t Consult tkUQ Sehmidt'9 JahrbUchtr, Bd. clviii. p. 234, for &b«trftot of theiii hj Nloolfti 
Gon* of Doq>at. 
t DigiUmia is aJMrted to form th« bulk of tbo lolubia dlgitalla of oommercOj and to 

* Ibfl tttiov M •tipoHtH^ tbe iiGtiv« pH&oipIe of soap-burk. As sftpoDiD hhM bec^n Appar- 
totlj deiDon*tml«d to b« tbe phyaiological ftotagoDUt of digitalii, it is oridcDl tbiit tb« 
wboU malTcr i§ i-:tce«dinglj eootus^d; and that tbe coDolmioo ld tbe text ia tbe ool/ 
Ofic tbftt can »t preaeot be rcMbed, 



140 



SrSTEMlC REMEDIES, 



Dr. Meilmizen (ArcL fUr Phjsiolog., vii,, 1873). The second of Dr. Welles 
series of cxperimeuts were directed to discovering^ whether the action upon 
the iuliibitory reflex centres and the cordVas a direct ouc, or was winply the 
restdt of the altered circulation. In this part of the inrestigationj the hearts 
of frogs were cut out^ or their motion arretted by the local application of a 
concentrated aclution of the nitrate of pota^ium, or rendered slower by a 
dilute solution of the same salt^ and the effects of these various procedures 
upon the reflex activity were studied. It was found that slowing of the 
heart's action did excite the Setschenow's centre, but not to nearly so great an 
extent as did digit^dis^ and that minute doses of digitalis Bonietimes stimulated 
the Set8chenuw*8 ganglion and lowered reflex activity before the heart wa^ 
sensibly afl'ected. In regard to the spinal cord it was proven that when 
the heart was killed by the local action of putaah the reflex functions of the 
spinal ganglia remained intact for a much longer period than when di^^itiUii 
was administered^ 

Ctrcniatiou, — The action of digitalis upon the heart of the frog was, 
believe, first invehtigatt?d by M, Vulpian {^Comptvs- Rtndus de la Soc. deBl 
1855, p. 70), who has been followed by numerous observers, among whom ma; 
be mentioned W. Bybktmsky and E. Pelikan {Zcttschrt/i fur Wimfiucfui 
Zoohffk^ Bd. xi,, ISOli), A. B. Meyer (^ArLeitfn aux detn Fhifsiologisch 
IttMtitut til Zurich, quoted by Boehra), Legros and Legroux (quoted by 
Gourvat), Claude Bernard (qiiotcd by Gonnat), Eudolf Boehm {PjllUjerg 
Archiv/iir Fftj/m/ifjf/u, Bd.v., 1872), Ilomolle (Architr^ Generahs dt Mide^ 
cine, July, 1801), Gourvat (Gazette Mtdtcaie de ParU^ 1871), Fothcrgill 
Di^itfiftSf London, 1871), Fngge and Stevenson (/V, Rot^til Soc,^ London | 
vol. xlv.), J. F. Williams (Arch. Exper, PnthaL vnd Plmrnu, xiii. 1)* 

The statements of thefle investigators agree in all essential pointi?. One or 
two of them have oecasionally noted a primary brief acceleration of the heart's 
action \ but the rarity of tt« occurrence shows that it has beon probably 
produced by some extraneous unnoted influence. 

The first distinctive action of the drug is a marked lessening of the nam- 
ber of cardiac beats per minute, due to a prolongation of the diastole, which 
may be complete, but is more generally divided l>y an abortive attempt at 
ventricular contraction^ The systole is abnormiilly energetic, so that the ven- 
tricles become white as the last drop of blood is squee»ed out of them. As 
the action of the drug becomes more intense, the rhythm of the heart is very 
much afl'ected, the ventricle and auricle no longer beating in aceonL At the 
same time tlie diastole generally becomes iinpcrfect, one portion of the ven- 
tricle maintaining its systolic spasm, while the rest dilates. Thus, the extreme 
apex may remain hard and white during the diastole, and even hernial pro- 
trusions of the ventricle may occur. Finally, the heart xa arrested in systole; 
and as the muscle so hardens, of oounse all its power of responding to eloo- 
trit^l or other excitants is loit 

In suuie mrc iustauecs, instead of the above seriea of phenomena, the 



o£^^H 




CARDIAC STIMULANTS. 



H] 



periods Uiroiit:;li4rut are prolonged and quiet, and afler several periods 
of rcbxatioti, lastiDg fur ten ur twenty eccouds, final djusti:)lic arrcBt nrnj 
occur. 

As l»odi Boehm (op, cit.^ p. 163) and Dybkow^ky and FelikaD (lac ciL\ 
hare found that the slowing of the heart's boutj the inereaiied energy of ouu- 
tnctioD, the irregularity and find s^t^tolic arrest, are produced hy digitidb 
afler divLtioQ of tlic ?ugi and de^ti-uetioii of the ^pitiul eord^ and a^ botli 
Ackonuaim (quoted by Boehni^ op. ciL^ p. 158) and Hlu'Iiih have found that 
the pandyxing of the j^K^ripht-ral ends of ilie vagi by atitjpia does not prevent 
the phenomeDa just alluded to, it is evident that the drug aeU direetly upoD 
the heart-niuselo itself, a oc*ncIu8ioD which is coiifirnierl hy Euleiiburg and 
j^hreDhaus (quoted by Dr. T. Lauder BruiiUtii, On Digittdis^ Loudon, 1808, 
p» SI), who found that digitalig, when locally applied, acta at onoo upon 
llie heart. On the other hand, the inliihitory activity of the pertphera] ends 
of the pneumoj^astries ia without doubt increased by the drug. There is no 
0tage in which stimulation of the vagi does not cause diastolic arrest In- 
deed, D}bkuw&ky Hiid Pelikati have seen galvanization of the nerves produce 
mch rekxatioD in the auricles afler the ventricles had already become per- 
aiaoeiitJj contracted* Further, Boehm has found that a Btimnlation of the 
pneiiiaogaatrics which vs iosuffieient to make itself felt before poisoning 
wiH^ aHer the exhibition of digitolb, cause diaatolie arrest lasting for many 
mmuieft. 

It appears, therefore, tJiat the peripheral cardiac inhibitory apparatus shares 
in the atiojulant aetioD of digitalis ; and as Boehm has found that diastolic 
arrest oaver takes pluce in frogs poisoned with the drug^ afler section of the 
Tigi, it is probable that this rare mode of death is really due to super-exci- 
Ution of the inhibitory cai-diac nerves. 

Budolf Boehm {op. cif.y p. 170) has investigated the influence of digitaliB 
Q|)OQ the working power of the heart when freed from all connection with 
the central nervous system. By using the method of Ludwig and Coats, he 
abtaiocd as a constant result that the amount of work done was increased by 
mall doees of digitalis ; tiiat afler large doses a similar increase was followed 
in a short time hy very great diminution in tiie exjH*nditure of power by the 
heart, a diminution apparently due to imperfect diastole and consequent non- 
fldiuii^aD of aerum into the vLscus. By direct experiment with an artificial 
circulation Dr. Williams has proven that the cut-out frog's heart actually 
puts out much more force than normal under the influence of digitidia. 

The elahomte experiments of L. Traube ( Gcmmmflie Bcitrii^e zur Patho' 
to^ie nnd Phygioh^k, Bd. i», Berlin, 1871) upon warm-blooded animals 
ahowrd that in dogs moderate do«es of digitalis produce increased arterial 
pressure, with lowering of the rate of the cardiac pulsation. When toxic 
do?«^ were nse<l, these phenomena were followed hy increase of the pulse- 
frcqucncy and fall of the arterial pressure, which, however, did not com- 



142 



SrSTEMW REMEDIES. 



ineiice at the same time, since the maximum pressure TFas not leached iinti] 

the pulse \niA risen above the orii^inal, normal point, 

Boclin* {he. ctt.) hiis coTifinucd tliese results^ and lias also noticed a veiy 
mtirked dicrotic pulse, evidently due to an abortive ventricular contraction 
during diastole, precisely as occurs in frogs. 

Tbe experiments of Brunton (he, cit,) and of Gourvat (loe. cii.^ also ane 
in accord with those of Traube ; so that it may be considered proven that in 
ninmmals moderate doses of distal is produce rise of arterial pressure with 
diminished pulse-rate. 

Prof L. Traube has found that, after section of the vapi, di«n talis is in 
warm*blouded animals, with mre exceptions^ incapahle of reducing the pulse- 
rate, and, contrariwise, that wlien the pulse-frequeney has been r**dueed by 
the drui^r section of the nerves causes an immediate and very marked rise in 
the rate of puIs;ition, I believe Boehm* has experimenially confirmed tliia; 
and in the single experiment of Gourvat a similar result was attained. 

The conclusion would seem to be inevitable, that in mammals the reduc- 
tion in the pulse produced by digitalis is directly or indirectly owing to an 
excitation of the peripheral inhibitory apparatus. The occasional reduction 
of the pulse-rate after section of the pneumogastric shows, however, either 
tliat the iuliibitory nerves in some animals find another path thnu the pneu- 
mogastricB, or else that there is an aJditiomil — ^sometimes inoperative, some- 
timea efficient^ — cause of the reductiou of the pulso-rate. As it has been 
shown that di*^talis L^ capahle of slow in jr the beat of the isolated heart of 
the fro^, it would appear prohriblo that it may exert a similar influence at 
times, in mammals, upon the cardiac muscle or its contained ganglia. 

Although digitalis does increase the muscular energy of the heart., it seems 
scarcely jx>ssihle that the enormous rise of pressure produced by it can be 
owing to this alone. This a priori reasoning has received experimental 
confirmation from ]MaIan,"f Fothergill (ioc. ciV.), Gourvat (/be. eit.)^ Acker- 
man n (Ik'her die WirkuHf/en der Di(^ita!i»j in Volkmaniis Sammlunf^ Klitii* 
scher Vorirage^ No. 48, Leipsie, 1872), and Boldt {Liangnral Dissertation^ 
Schmidt's Jahrhucher^ March, 1872), The first three of these investigators 
have found that the arterioles of the frog's web as seen under the mien> 
Hc*ope undergo very decided contract ion after the systemic use of digitalis ; 
and Ackermann states that if the ahdomen of a nibbit be opened so as to 
expose the ai'tenes of the mesentery, a very marked contraction, even to the 
partial obliteration of the lumen of the veasela, can be readily seen to follow 
the exhibition of digitalis. 

Boldt experimented upon curariied frogs after the manner of Ci^hnheim, 
and found that the first ejfeet of the digitalis was marked ecm traction of the 
arterioles. 



» Ilia IdnguAgo i« fuch oa to leave tho pdot iom«ifhiit doubtful. Op. fit., pp. 188, 189. 
t Quoted bj Fotbergill (op. ciV.), 



CARDIAC STIMVLAyrS. 



143 



Acconling to Bachin^ Traube foiitid that, if the spine be divitliHi, digitalis 
IB pnwcrlcss to tncrtiasc the arterial pressure, although lessening, m usual, the 
pnbe-nitc. The same authority also stat^^s that Bczcdd has seen an execssive 
mi of the arterial prtswnre erkHue iniinedlately upon the division of the spinal 
cortj in an animal under the influence of digitalis. Further, in hfs own ex- 
periroenta Buebtn has attained fiinitlar results, or, in other words, has found 
chat after separation of the suuill vessels from the vas^>niotor nerve-centre, 
dtjnCalid does not increase arterial pressure. 

The»e experiments would seem to prove that digitalis acta upon the v^seU 
hy stitntilAtltig tho vaso-motor centres in the ba^ of the brain ; but thej 
hnrt been contradicted by Aekcrmann (op, cft.^ p* 397), who state.** that he has 
tnany lima* eut the Rpinal cord and without exception found a very marked 
riM uf arterial pressure follow the injection of digitalis. Unfortunately, none 
of Iheee eacperinients have, that I am aware of, been published in detail, 
and it 10 therefore impossible to analyze or to re<MiDeile them; but GrlirB 
(SchmifJf'g Jahrhiicher^ Bd. clviii,) expresses the opinion that Aekermann 
did not fully divide the cord in his experiment^- Gorz himself found that 
ft rise is produced by digitalin after division of the cord, but of so small an 
ftmount as to be readily accounted for by the increased power of the heart. 
Pr* J. F. Williams (Arch. ICxper, PatkuL m. Pharm.^ x'nu 1) has also found, 
after reduction of blood-pre^sure to zero by clilorul, chat digitalis will cause 
rise of pressure. This dues not, however, throw much liirht upon the vaso- 
motor action of the drug, because by enormous doses of chloral the heart 
is ftltuost as much afTected as is the vaso-motor system. Drs. Brunton and 
Heyer (Journal of Analomt/, p. 138) injected digitaliu into the ear of a 
labbit whose cervical sympathetic and pueumogastrics had been destroyed, 
but were tinabte to obtain any satisfuictory result ; there was certainly no 
OODBtatit perceptible con traction ^ akhough e^ometimes the vessels were seen 
to empty themselves more rapidly tliun before the injection. Whilst we 
are not in the position to consider as absolutely disproven the theory of 
Profeesor Ackermann, that digitalis acts directly upon the peripheral vessels 
tlieaiaelvefl, the probabilities are strongly against it. 

From the crvidence whtcH has been brought forward, it may be consid- 
ered as definitively proven that in mammals digitalis in therapeutic doses is a 
powerful stimulant to the circulatory Bystem. 

The foUawing proposition expresses our present knowledge, and probably 
m Twy dose to the truth : 

DigiitiiiM i« moderate doses stimidateM the musado-motor portion of thM 
htittt (probably its contained ganglia), uicrtaMtM the activity of the inhihitory 
nppftratuM^ and probably caujies contract inn of tht^ nrfrriobA by an action on 
the vano-motor centres in the cord. As a consequence of the first action, 
the cardiac beats become much stronger; as the result of the last, there is 
narroiriiig of the blood-paths, and to the passage of tlie vital fluid an in- 



ii^ 



144 



STSTE3IW REMEDIES. 



raoiiif^H 



creased resistance, which, acting od the already excited inhibitory system, 
aidB in the slowing of the pulse. 

According; to ray own experience, decided therapetitio doses of digitalift, in 
mnn as in other mummali, produce great reduction and sometimes dicrotigm 
of the pulse, ftod increase the size and force of the wave ; at the same time 
the arti^rial tension is augmented. Poiijunous dosee induce, after a tiuje, 
increase of the pulse-rate, with smallnees and weakness of the ware and 
lowered arterial pressure. 

Sphy;nnopTJrihic studies of the effect of digitalis up*>n persons sufleriJis 
from viirious acute and chronic diseiwes have been made by M, Legroux, M. 
Jiordirr {Bufhtin Tltrrapeiitiqtfe, 18«]8, p. 110), Constantine Paul {Bttlletin 
TlUrapatfiquc^ 18t>8, p. 193), and Paul Lorrain (Jaurtial de PAnatomie H 
ih In /*hi/sioh^ie^ ISTO). The pmbloms offered by these gentlemen are so 
complex as to render a detjiiled study ulnjost impc*ssible ; but, as a whole, 
tlicir tracings seem to confirm my personal experience* Paul Lorrain calls 
attention to the fact that when tlie drug has reduced the pul&e*rale Teiy4 
greatly a ?fr(tiid ab^irtive systole can, on auscultatirm, sometimes be 
occurring during the long dia^stole, and some of his sphygmographic ti 
are markedly dicrotic. It is evident that in man the second systolic mov^^ 
ment occui's precisely as in animals ; and it seems very certiiiti that the 
propo'^ition framc<i for the lower mammals applies also to man. 

When the pulse haa been reduced by dluitalis to forty or Mtj a minute^ 
the change fmm the recumbent to the erect position will not infrequently 
suffice to alter at once its character, so that it will become feeble, small, and 
one hundred and fifty per minute. The experiments of Tniube, which have 
already been mentioned, afford an explanation of this phenomenon so simple 
that it can scarcely be else than true. Tlie action of the drug in euoh a case 
is verging upon the point at which the pulse-rate increnses and tlie arterial 
pressure falls, owing tx) the partial paralysis due to over-stimulation. Whilst 
the patient is recumbent, the Hue is not passed over, but the udditioual stimu- 
lation of the erect position carries the circulatory system beyond the limit of 
simple stimulation, and the over-effccta of the drug are at once manifested. 

The influence of digitalis upon the urinary secretion m health has been' 
stadied by numerooa obaenrers, with such diverse results as to prove that the 
action of the drug on the kidneys is so inconsistent and varying as to render 
it probable that it is in great measure indirect rather than direc-L Thus, 
Jbrg, Hammond (Proc. BioL DejfL Acad, Naf, Sciences^ PhUa., Dec 1858), 
and Brunton (ioc. ctt,} have fouwd tlie secretion more or less decidedly 
inoreajied, and Homolle (ArchiveJi Giniraie^, July, 1861), Winogradoff 
{Virchow*9 Archiv/Ur Anatovilc^ Bd. xxii., 1861), Stadion, and, according 
to Brunton, also Krahmer, Kluyskens, Vassal, and Shohl, have found it either 
uninfluenced or diminished. 

The urea in the apparently very careful experiments of WinognnWff 
Hoc, cit,)^ of Stadion {^Pra^er Vicrttljfihnckri/t fur die Prakiischc IIvU'- 



CARDIAC STIMULANTS. 



145 



, 1862, Bd. Ixxil), and of llamuinnd (he, a't.)^ was diminiahedi whOo 
in the almost equally elaborate cxperitnents of Biunton {Joe, ctt.) it was 
iDCreased. AH four obaen-ers noted k*i«tieiiing of tbe cliloridea. IMt^gorand, 
Ufflng the crystallized digitalin of Nativelle^ fouud Ins tLriiie inci*oiised twenty- 
fivB pQT cent, but his urea duniuished twenty per cent Auguste Meusnier 
has sought without success for sugar in the tirine botli of imtients taking 
large doses of digitaJk and of ralibits poisoned vvit!i the dmg (^L\lciton de la 
Dt^itale Mur la Fonctioti ^iffcr^nntjttey Pam Thesis, I8G8). 

It is Tery certain that f(rxic doses of dtgitalis lower the temperature a 
number of degrees in healthy tnon and animals. It would ^eeni, fn>wcver, 
that the fall of tempemture is general ly, if not always, preeeJed by u rlne, as 
hid been noted by Boulej «nd Ueynul, by Dumeril, Demanjuay, and Lecuhite 
(quoted by Brunton), by Uirtz^ by Legroa (TVt^c, 18GT, quoted by Goiirvat), 
md by Goun^at (Gazette MkUatk tU Par is, 1871, p* 572). 

The effect of therapeutic do»m in the normal condition has not been 
closely studied, that I am aware of. But in a number of cases, chiefly of 
poeumonia, Z. E* Coblentz (La Digxttde comme Afftni anttpyrMtqite^ Stras- 
bcmrg Tliesis, 1882) found that about twelve hours aAer the fall of the pulse 
there was ali»o a fall uf temperature. The tendency of our present knowl- 
edge ia to connect the changes in temperature induced by digitalis with the 
ngGB of the circulation ; and it seems very possible that therapeutic doset 
In health will be fouud to increase bodily heat, although in fever they may 
diminish iL 

TUEBAFSCTICS. — The chief clinical use of digitalis is in diseases of th« 
heajt ; and from what has been said in regard to its physiological action it 
logicaJly follows that rt should be useful in loss of cardiac power* 

When the aiuacle of ihe heart is for any reason unequal to the task set it, 
ikta systoles become rapid and imperfect, and by this irregular action thft 

Dtrieles, neither c«miplelely filling nor emptying themselves, increase the 
dibttmiamnflnt. IJndiT these circunistanc*es, digitalis, by lengthening the 
dliislolie pauses and increasing the force of t!»e s^^toUc contractions, causes 
the ventricles to till themselves in the one and to empty themselves completely 
in the other aet By subduing irregular action through the inhibitory nerves, 
by energiiing the muscular power of the hc;irt*wallsj the remedy La of incal- 
eolalile tfervice, and, increasing artmal tension all over the body, causes the 
disappeonujce or lessening of jjyniptoms due to low pressure in the arteries. 

It is a higical nuoessity, if our reasoning as to the physiological action of 
digitalts has led to a correct result, that the drug should be of the greatest 
iierrioe when the lesion is simply loss of carJinc power; and clinical expe- 
rience tallies with this a pnbrf argument. In mtmpk dilatation^ or la trimph 
/atlttre o/ the cardiac muscle without valvular lesion, the results of the use 
of digitalis arc rnont fevorable. 

On the other hand, in xlrnple htfpertropht/ digitalis docs harm, and should 
ttever be tieed. It must be borne in mind that although this agrees with 

n 



146 



srsTKMw hemedies. 



what tlic expurimeiiUlist has proven to be the action of digitalia, yet it was 
discovered inde|>etidently as u clinical fact by practitioners. Thus, Nie- 
nieycr, who ridiculed experinienUil therapfuties because he would not take 
the trouble to study them deeply and practically and was therefore incapable 
of understanding them^ — Niemeyer says, *' Digitalia in pure unoomplicated 
hypertrophy is imsui table." 

Valvular lesion of the heart, as is well known, gives rise under unfavonibl<^ 
circumstances to dilatiitioUj but in favorable cases to hypertrophy, or rather 
in the jxreat miijority of cases to hypertrophy with dilatation. FoUowinf^ out 
the priiRi}iles already inculcated^ it might seem at first that the use of digitalis 
in hypcrLrophied hearts with valvular lesion ought to be reprobated. But 
it is known eiinically that di^^talis often does good in valvular lesion with 
enlargement of the heart. The results of logical deductions fronj our physio- 
logical cuiiclusiona as premises are^ however, not really at variance with tliis. 
It must be borne in mind that structural and functional hypertrophy are 
different things: by this Is meant that although a heart be enlarged and abso- 
lutely struuger than nomiaJ, yet it may be, relatively to the work required 
of it, weali. Thus, if 1 represent the normal work of the heart and 1 its 
normal |>owor, if the former be increased to 4 and the latter to 3 the heart 
is really in the position of a weak organ, although possessed of three times 
its original strength. Hence it is that digitalis is often useful in \*alvular 
disease with hypertrophy. In the vast mujority of cases the heart with 
diseased valves is in the position just spoken of; but sometime the work 
advances only to 2 and the strength to 3 ; then the hypertrophy becomes 
exoeasive, and digitalis will increase the difficulty. In almost all cases the 
intsreased power of hypertrophy, unless tlie muscle be degenerated, rendem 
effectual smaller doses tlian can be used in dilatation, and also increases tho 
danger of tlie over-action of large doses. 

In miiral iMu^fficiency and in miiral stenosis digitalis is often of great 
service. It is evident that in both instances the valvular lesion leads as itM 
first result to pulmonic hyperemia. How does the digitalis lessen this ? In 
the case of stenosis^ the diastole being lengthened by the remedy, the auricle 
is afforded more time to empty itself inta the ventricle through the narrowed 
orifice^ and at the same time is strengthened Ln its contracting power; evi- 
dently , then, the left ventricle when its systole occurs will have much moro 
to contract on than before tbe digitalis was administered, and the amount of 
blood in the eystemic circulation will be increased, — i',e., the amount in the 
pulmonic circulation will be diminished ; further, the right ventricle will 
have greater power afforded it to force the blood through the luu^, — i.e., 
to resist the recoil from the left auricle to which the impeded valve gives 
origin. 

In mitral insujffictenet/ the mechanism is different, but the result is the 
same. The increased power of the systole will throw proportionately more 
blood through the aortic orifice than through the partially open valve. The 



^^r CARDIAC STIMULANTS, 147 

opeoiiig At the insuHioient mltnJ valve ii mudi smaller and move oln^tructed 
thxa the aortic orifice. As the force or nipidity of the eurrent increiisea 
under the Jiction of digitalis, the friction becoTn<*8 greator at both orifices^ but 
tke ratio of increaac is evidently fkr higher in the small choked mitral leak 
than in the wide aortic opening. UcDce the large orifice cotistatitly gains 
uptin the atnaller as the cardiac force is increas«id, and, more blood passing 
into ihc sysiteujic circulatitm, the pulmoriio is relieved. Airiiinj the ri^dit ven- 
tricle uharea the sttiuulunt actirm of the drug* and acta more strongly upon 
the pulmonic circulation, resi^stinir tlie direct backward flow from the uunclc. 

In aortic conKtriction di;;italis i^ usjcful when the henrt-power be^u»s to 
fail. In thei?e cases compensatory hypertrophy^ with slowneaa of action^ ia 
very apt to occur^ or even to bcc<ime excessive : much more frequently doea 
this happen thjin in mitral disease. Again, in aortic imafficitmc^ the pro- 
|lon^*d diiiBtole of digiudis action favors the return of bloLKl to the heart, 
and 13 not advantageous. It is evident that digit4il!s is not so genendly 
a-«fal in aortic as in mitral disease^ nevertheless when the heart-mujicle 
fails, and the hypertrophy is not compeusatury, the drug is useful in both 
aortic stenosis and insufficiency.^ 

From the oonsideraC ions which have been brought forward, it is very evident 
that a knowledge of the relation of the he«'irt mu.^ele to the work required of 
it in any individual cn^e i^ much more necessary to the therapeutint thou to 
lta<»w what valve is disi^ascd. 

In " irritahte hrttrt** of soldiers, a disease or condition of eardinc irritability 
evidently connected with mnncubr weakness^ and very probably dependent 
upon ejEhaustion of the inhibitor)^ nerves, Dr Da QtMa {^Amfrican Jountal 
o/ the Mr.dicitl Sciences, Jun, 1871) found that in the early stages of the 
affection digitalis not only acted better than any other remedy, but even, 
when administfred eoutinuously for »ome time, often effected a permanent 
rmre. When hypertruphy had taken place, the drug was of little u^\ 

The relief afforded by digitiills in not too inveterate cardiuc disease is often 
to a mtTwnri-' perraanentf becanst! the drug may aid very materially In the pro- 
duction of eompeuRitory byj»ertruphy. Dilatation is certainly more apt to 
occur when the muscular fibre is lax and acting feebly than when it is toned 
tip and in vigorous play ; secondly^ the stimulus t^ action in a nuisele is 
almo^ of necessity directly or indirectly a stiuiuluB to its nutrition; lantly, 
and most important, imi>riived systt-mie circulation means in a fur more 
intense degree improved blood-i?npply to the cardiac muscle, as is shown by 
the fcrtlowing considerations. 

During ny stole tlie cardiac muscle contracts so as \o squeeze out com- 
pletely all tlje venous blood from the heart-walls. The arterial blood eutera 
dnrin«! diastole, and the force which drives it into the relaxed walls is derived 
frtitti the arterial system. The coronary arteries arise nearly at a right angle 



148 SYSTEMIC REMEDIES. 

to the aorta : the blood squirts into the latter during systole in an unbroken 
stream, and of course does not enter the coronary artery. But when the 
reflux wave comes, the aortic valve flaps to, and the whole pressure of the 
blood-column forces the liquid into the open cardiac arteries. If the arterial 
system be empty or nearly so, the arteries are not distended sufficiently to 
give origin to a powerful reflux wave, and but little blood enters the coronary 
artery, t.c., the cardiac walls. The dilated feeble heart is unable during 
systole to free its walls thoroughly of venous blood, and during diastole the 
fbrce is lacking for driving in the arterial blood. Digitalis enables the cardiuc 
muscle to free itself thoroughly of venous blood, and at the same time, by 
restoring to a greater or less degree the normal balance of the circulation 
and removing the excess of blood from the general venous system, gives the 
aorta sufficient blood to provoke an active reflux. 

If in aneuritm^ or in general capillary atJieroma, there be increased resist- 
ance to the circulation, and the heart have not sufficient power to meet this, 
digitalb may be useful, but must be employed with caution. It undoubtedly 
increases arterial pressure ; and this increased pressure may prematurely rup- 
ture an atheromatous cerebral capillary or tear open the thinned wall of an 
aortic aneurism. The use of digitalis for the purpose of " quieting the cir- 
culation" in aneurism is of very doubtful expediency. 

In cardiac dropsy digitalis is of service probably not only by regulating 
through the heart the circulation, and by evacuating the surplus fluid through 
the kidneys, but also by an action upon the vessels. Clinicians do not allow 
enough for the rSle of the vaso-motor nerves in dropsy. Without saying 
more as to the clinical side of this question, which I have discussed elsewhere 
{American Journal of the Medical Sciences^ July, 1871), it may be allowable 
to allude to the experiments of Ranvicr {Comptes-Rendmy 1869, p. 1327), 
who found that when the vena cava was tied in a dog, and the sciatic nerve 
of one side cut, (cdema occurred only in the leg whose nerve was divided. 

The use of digitalis in large doses as a cardiac stimulant in syncope or in 
sudden collapse from hemorrhage or other cause is in its infancy. One or 
two cases have been reported in which the happiest results have followed its 
exhibition (case. Pacific Medical and Surgical Journal, 1874, p. 273), 
and it has been given hypodermically with the most astonishing effects in a 
number of cases in my wards at the Philadelphia Hospital. From twenty 
to thirty miuiius of the tincture should be injected into the arm, and re- 
peated in half an hour if absolutely necessary, or one-fiftieth of a grain of 
the digitalin may be substituted. In my experience* the digitalin has several 
times given rise to severe local irritation, the tincture never. 

Closely allied to the last use of digitalis is its employment in poisoning 
by substances such as muscaria, delphinia, and aconitia, which arrest the 

* Local irritation, and even the production of absccsse?. has also been noted by various 
observers besides mygclf. See Witkowski, Denttchet Archir KUu. Med., xviii. p. 142; alto 
Pel, Centralb. Me L HVm., 1877, p. 169. 



CARDIAC STIMULANTS. 



149 



i in diastole. Boehni has shown {PJlUgtr'M Archiv^ Feb. 1872) that in 
digital b-poii^ning of the frog, even when s^^stohc cardiac arrest hns occurred, 
tiie^e suhstauices will oflcn restore the Ciu*d»ac inciveriienta, — a proof that real 
attta^Qism exists m their action ; and Duhie reportit a nix^a^BntUh MMical 
Journal^ Dec. 1872) of recovery after the ingestion of an ounce of Fleming's 
tincturu of aconite, apparently due to the hypodermic injection of twenty 
niiiiims of tineture of di^nLilij* and the exhibition by the mouth of three 
doses* in an huur of a mixture of tincture of digitalis (one drachm each 
du8e), braudy, and amniouia. 

Digitalis is often of great value in various ojcute diseases,'*^ such as m/y. 
namic pnrumQma rmd atlt/namic /ever$j by maintaining the heart*^ aotioru 
It can have no effect upon the diseases themselves, but may help most 
opportunely to sustain the heart during a crisis or a period of strain upon it. 

With the idea that digitalis i& an active antipyrtiic^ it has been prascribed 
in various acute diseases, sometimes with asserted good results. As already 
stated, toxic doses of digitalis at fii-st elevate the temperature ; and pn^of is 
wanting that in healthy men therapeutic doses have any decided influenee in 
dt*preaiing the temperature. There is, therefore, no good physiological basis 
for the antipyretic use of digitalis; at the Bame time, it is very possible that 
it may directly or indirectly lower the temperature in disease. Clinical (>roof 
of this i.^, however, stili wanting. The struugcst evidence in favor of such 
action is fumwhcd by the records of Prof Wunderlich {Mauuai of Mallcal 
Thrrmomctrif^ Sydenham Soc, Translation, p. 325), according to which from 
hiLlf a drachm to a drachm of digitalis, given in divided dose during three 
or four days in the second or third week of severe typhoid fever ^ immediately 
produces a slight fall of temperature in a large proportion of the cases, and 
iometimcs a oonsiderabte fall. This fall is said not to last more than a day, 
when the temperature rises again, but in eases favorably u fleeted does notregHin 
the original height; the pulse is very much lowered in frequency, and remains 
At uniform for four days. It is evident that at least in &t)mc of those 
\ of Wunderlich fl the drug was given about the time natural deterveip 

aoe would ht expected to occur, and that the slight retluctiou of tempera- 
brought about at such time does not argue very strongly in favor of the 
ition tJiat digitalis is a powerful antipyretic in disease. Far more ex- 
tensive and complete observations must be made upon a rising, not a falling, 
temperature, before any satisfactory conclusion can be reached. At present 
the antifjyretic use of digitalis should be purely tentative. In paerj^cnil 
Jcver, Winkel (^Philud, Med. Tiyne*^ 1874, iv.) believes digitalis docs good 
by its actifkn on the circulation, by contracting the arterioles of the uterus 
mud by lowering temperature. 

The propertjT of causing contraction of all uu striped muscular Ebres has 



• CoQBull IlAukel, Brithh and Furtifjn SUUicu^ChirHnjiral Rttitte^ x%\\, &13j Griifl- 
»Ki.vr, />N/J.ii iii>,.,urttf, June» 1873; AnBlie, Z^iM./'»*» /^..'-^i/iVMier, Sept. 1873, 



150 



SrSTEMW RRMEDIES. 



been attributed to di^ talis, and whilst the probabilities are oertiiitily sucli as 
to invita investigation, yet we have no definite knowledge upon die subject. 
Mn Dickenson {Med.-Chir. Tmm.y vol xkix.) claims tliat it has a powerful 
action in causing the uterus to contract and to arrest bcmorrhagB, — a few 
minutes after an ounce and a half of the infusion is swallowed in menorrbafiria, 
flevcre pains resembUng those of the first sbi^e of labor coming on, with a 
momentarj profuse discharge of blood and clots, if tbere be any present, ifil- 
lowed by arrest of the flow for hours. S tad ton (^Stfdctihnm Soc, yenr-BooL'^ 
1862, p. 451) claims that digit^iris is capable of temponiril^' but completely 
anuulhug the activity of the sexual orgaiKs, and that it may be regarded as 
a true auaphrodlsiac, 3L Guunot {PhilncL Mvd. Time^t^ '\\\ 30) makes the 
I iame assertion, and advises the use of the dmg in sperm atorrbica. 

The use of digitalis as a diuretic will be considered under that beading. 

Toxicology, — In poisoning by digitalis, the first symptom uf any severity 
la gcuerally vomiting of mucus and bile, very violent and very often repeated. 
At tlio same time a feeUng of heat of the head, disordered vision, and vertigo 
manifest themselves. The pulse at this time in the horizontal position may 
be full and strong and slow, but on the patient's rising becomes weak and 
rapid. The face is pale. The vomiting continuing, profound prostration 
comes on, the pulse becomes feeble, small, irregular, although the beat uf the 
heart may be strotig and hard. The eyes arc very prominent, the pupils fixed 
and dilated : uecordiug to Tardieu, an almost diagnostic symptom is the blue 
color of the sclerotic. Abundant salivation soinetinies occurs. Intense head- 
ache and pains in the back or limbs aie often complained uf Diarvha'a ia 
very generally present ; the urine may be suppressed. The intelligence ia 
often perfect in the midst of profound collapse, but dclijium more or lesa 
violent finally comes on. Death, usually preceded by stu|Hir or by convul- 
sions, takes pljiec most frc^jucuUy in one or two days, but hiis occurred m 
late as the tenth day, and as early as three-quaiters of an hour.* 

It lA said that in some cases, in which a cumulative action during the medi- 
cal use of the drag baa occurred, the first marked symptom has been 8ynco|>e, 
followed by paralysis of the lower portion of the body, vomitingi diiirrhtea, 
delirium, genemi insensibility, and dt\ith. 

In the majority of cases of digitalis^ioistining the patient recovers. Wlien 
this happens, the symptoms gradually ameliomte. Cai"duic weakness, and even 
a bruit de soitffit^ with more or less exophthalmos, is said to have persiiited 
for weeks in some cases. In poisoning by digltalin the symptoms are those 
of rapid digitalis-poisoning, — violent vomitings intense cephalalgia, and some- 
times rachialgia, irregular, feeble, intermittent pulse, paroxysms of suffocation. 

The minimum fatal dose of digitalis is not known. A large tcaspoonful of 
the tincture is said to have caused alarming symptoms in a young puerperalj 
woman (Tardieu, CHmqiie^ p, 685, Ubs. VIII., Pans, 18G7) ; twenty grain 



^ See OMe reported by M. Barth, quolod hy Tiirdleu* 



CAB£>JAC STIMULAi\7\S. 



151 



>f the extract proved fatal on the tenth day (Jbid.y Oba, W,) \ and two and 
« half grammes of the leaves i» iufiLsion on the fifth day {Ibid,^ Obs. X.) j 
fif^ granules (gr. one^fiftieth each ? J of digitaJin have been recovered fiuui 
{ILid,^ Obs. XII., XIV.); about one*fourth of tt grain of digitalin {GazetU 
Jlebdomctdaire^ Jtily^ 1874) produced very violent but not lethal symptonis. 
In the only final caae of dij^italin-poiaoniog I know of (^Affaire Couty de lit 
l\fmaraia% the amount ingested was unknown. 

The treatment, after the evacuation of the Bt4>maeh and bowels, and the 
very free admitiiiitration of tannic acid, us the best, ol thou f;h unreliable, chem- 
ical antidote, should cousibt in the exliibition of opium, ui' uleoboHc stinmlauta, 
and rest in the horizontal position. I kimw of no recorded experiences with ihe 
antagonistic poisons to digitalis, such as aconite or rnuscarin. As it is posbible 
»hat whilst bo fur as the heart is concerned they may be really antagonistic and 
^et may intensify the action of digitali.son the cord, their use requires caution. 
Two caaes, one ending fatally, of what may be considered chronk digitaliM 
9ninff^ have been reported by Dr. Kohnhorn (Lanctt^ 1876, i. p. 583). 
I symptoms were loss of appetite, tinnitus aurium, vertigo, lowering of the 
fete and force of the pulse, diarrhoea, weakness, general anaemia, and syncopal 
' ftUacks. The only lemoD found at the autopsy was congestion with ccchy- 
iOOB of the gastro-intestinal mucous membrane. 

Administ&ation. — Digitalis may be given in substance in the form of 
the dose being one grain three times a day, and increased until some 
Sisct is produced. The solid extract ( Extra ctum Digit alU, U.S.) is less 
eliable than the leaves ; its dose is one-fourth of a grain. When a mpid 
ruction is desired, one of the following officinal preparations, or the digitdio, 
should be used: In/ttsuni Digitalis (1 to 66,6),^ — do»e, one fluidrachm to 
half a fluidounce; Tinctnra Digitalis (1 to 6,Bi>),— dose, five to twenty 
drop^i Extractum Digitalis Fltiidum^ — dose, one to two drops. ALs/ravJum 
Itigitcdis* Ut 8. — Abstract of digitalis is a gtxtd preparation* twice as strong 
as digiulLs itselfi and to be given in half the dose. 

In emt^rgerjcies where single large doses are administered they may be very 
much hirger than those here given. Thus^ of the tincture two fiufdmchma 
or even half an ounce may be exhibited ; of the infusionj a wincghissfnl. 

Occafiionally when digitjdis is steadily given three times a day continuously 
■n intense action will be suddenly developed. This probably arises from an 
accumulation of the medicine in the system, due to elimination not being so 
ra[ud as ingcjition* Whatever the cause may be, of the fact (case, FhHadel' 
■ ArV/ Medical Times ^ vol. ii, p. 24) there can be no doubt. For this reason, 
aIi^ nL»vcr digitalis is given continuously^ at least every two weeks its exhi- 
bition should bo suspended for three or four days. 

Digitalin of corameroe is a complex body of various composition, power, 
and even properties. There are two distinct varieties of it, one soluble, the 
•jther insoluble, in water. Much of the digitalin sold is inert, and especially 
is this true of *' digitalin granules.'' As the preparation is complex, variable, 



152 



SrSTEMIC REMEDIES, 



ftnd eKpen»LVC, it baa been dropped froin the United St^tea PharmacopcBtaf 
mid uu^ht nut to be used, eapeoiully ast it lias do coueeiviible advantage over 
the 8lable prepitruliuDd of the drug. Even J or h^'podunuic u^ the uuoture 
soems preferdble, as the di^itulit] ^lution appi^urs to undergo change io a 
few hourS} a»d uj^ually eaus^^ mure iriitMion when injecied than does the 
tioeturti. The dose of digital iu is one* fiftieth of a graiD. 



CoNVALLARiA Majalis. — 111 18511 G. F. Walz disoovered in this plant 
two active Bubstances, convaiJttrin and convailamaTm. Of theae the first is 
crystalline, iusuiuble in water, and, aeeorditig to the experiments of Dr. W, 
Maraud {JScJimtdt's Jahri.^ Bd. cxjtxiv, 166)^ when taken in dosea of three 
or futir grainSf acts as a simple purgative. The glucoside oonvallaniariQ tfl 
soluble ill water, and h the principle to wbieh the plant owes its action upon 
the circulation. Murnii' iuund thul it killd by a direct actiun upon the 
boart, und in moderate doaes first filows nnd then qutekena the pulse: pre 
vious divL'siou of the vajii did not interfere witli the development of theee 
phenomena. Tiie ehiL-f i^iudiej? upon the physiological and theru]>outic action 
of the lily of the valley are tho^ of Prof Germain 86e (Bu/4, de t Acad, de 
M6d.^ No. 27, 1882, p. 7t)7) uud of 8. Isacw (^Ilfjffmaim und *Sc7tica/Wt 
JahrL, 1883j 122, from the Ru^iauj. Prof See finds that in the dog it 
firsit slows the action of the heart and iiicreawcij the blood-pressure decidedly, 
the rebspirationa at the baiue time becoming fuller and a little le«8 lTec|uetit. 
If a toxic dose baa been given, the heart's beatis become very rapid and ivr^* 
uhrr, the arterial pressure still being mueb above nornnd; finally, the presssure 
begias to full^ the cardiac pui^itious to grow more feeble^ and death occurs 
through syncope. It is stated that tlie pneumogaetrtc nerves ar^ weakened, 
but iicvt'r pandyxed, whilst the geueral nt-rvous system Ls not affected. In 
man the action of ttie drug upon the circulation Ls ah in the lower animals, and 
there is said to be usually [produced profuse diuresis and sometimes purging. 
In Isaew's experiments upou IVogs with convallamariu, the heart was arrested 
in ventricular systole by two milligrammes of the pure convallamariu, the 
frog continuing to live for a long time, the remedy seemingly having no 
effect upon its general nervous or muscular system : isoluting the heart had 
no effect upon the action of the pi>ison. In the dog the phenomena of 
convaliimiariu-poisouing were as descrihed by Prof S<5e, it being further 
noted that the pneumogastricj^ were not affected j that the pulse was oflen 
dicrotic during the stage of rapid cardiac action, and that the final arre^^t 
was diastolic, the heart-muscle Bot being able to rcspoi*d to the nunst powerful 
galvanic stimulation. The obi^ervaiion that the heart of the dog Is arrested 
in diastole is probably incorrect, as l>r. I. Ott has found that the arrest is 
Bystolic (Archives of Mrd.^ Feb. 1883), and it is highly improbable that 
the action in the frog's and thiit in the dog's heart should be so diverse. 

It is evident that convaJlamarin acts almost exclusively upon the heart 
and its contained ganglia, and possibly also upon the vaso^motor system, 



CARDIAC STIMULAyrS. 153 

althoagh conceroiDg this we have no definite knowledge. Its action is 
evidently stimulant, and resembles in some respects that of digitalis. 

The lily of the valley is said to have been long used by the Russian 
peasantry for the relief of dropsy, and in 1880 Drs. Troitzky and Bojojaw- 
lewsky called attention to it as a valuable remedy in cardiac valvular disease, 
especially when associated with dropsy (^Wratsch., 1880, 47). Prof. See 
recommends it in palpitation of the heart, in cardiac dilatation, fatty de- 
generation, and other forms of cardiac weakness, also in valvular lesions 
with failing heart-power ; in a word, in the class of cases in which digi- 
talis is DOW used. When there is dropsy, its very positive diuretic action 
renders it especially valuables, and in some cases it purges freely, probably 
through the convallarin. The value of the remedy has been confirmed by 
Prof. H. Desplats (Joum, des Sciences Mid. de Lille, Oct. 1882), and by 
several other practitioners. Although condemned after trial by Dr. B. Stiller 
{Wien, Med, Wochenschrift, Nov. 1882), the remedy certainly should be 
carefully studied, first physiologically and afterwards clinically. In cases in 
which it has failed there is reason for suspecting that the preparation used 
has been a bad one. Dr. Marm4 found that the fatal dose of convallamarin 
was, for the dog, 0.016-0.03 grm. ; for the cat, 0.005 grm. ; for the rabbit, 
0.006-0.008 grm. Prof. S^ gives, of an aqueous extract of the whole plant, 
from fifteen to twenty-three grains a day ; Bojojawlewsky, each day an infa- 
liion representing from fifty to one hundred grains of the plant. 



CLASS lY.-OARDIAO SEDATIVES. 



There are certain drugs which are used by practitioners to decrease the 
activity of the circulation ; and it b these which are here considered under 
the heading of Cardiac Sedatives. Many, in fact all of them, possess other 
powers besides those which cause them to be considered under this caption, 
and none of them are in very close accord in these qualities. There is, however, 
a general resemblance in the action of such as are derived from the vegetable 
kingdom, in that they are all sedatives to the motor-nervous system and yet 
all produce convulsions. I have made an especial experimental study of these 
convulsions (Philadelphia Medical Times, vol. iii.), and have found that they 
are cerebral and not spinal, because they do not occur in any part of the body 
separated by section of the cord from cerebral influence. Further, they are 
probably due to disturbance of the circulation at the base of the brain, for the 
following reasons, the truth of each of which has been experimentally deter- 
mined : first, lessening of the circulation at the base of the brain will cause 
convulsions ; secondly, the convulsions produced by the cardiac sedatives do 
not occur until the arterial pressure is reduced about one-half; thirdly, if the 
disturbance of the cerebral circulation be artificially increased by tying the 
carotids previous to poisoning, or in any other way, the convulsions come on 
sooner and are more violent ; fourthly, in some animals the convulsions caused 
by arresting circulation at the base of the brain are feeble and ill defined, whilst 
in others they are violent, and I have found that in species of the first order 
cardiac sedatives produce but slight convukions, whilst in species of the 
second order they cause violent convulsions. 

The indications for the use of a cardiac sedative may be said to be increased 
arterial excitement, sthenic fevers, and severe local inflammations. In order 
that a rational selection of the various drugs may be made for any individual 
case, it is necessary to study how, in these various conditions, relief is afforded 
by an arterial sedative. When there is arterial excitement from irritation, 
or excitement of the heart, the mode of relief is too obvious to need discus- 
sion. It is plain that in such a case a drug should be selected which simply 
depresses the heart's action and does nothing more. In sthenic fever the 
case is different ; here it is desirable to relax the peripheral vessels and to pro- 
mote a flow of blood to them, whilst the rapidity and force of the circulation is 
diminished. A drug which depresses the action not only of the heart but also 
of the superficial vaso-motor nerves b here indicated, and if to these powers 
154 



CARDIAC SEDATIVKS, 



155 



tOiUai a special one of stimuluting the perspiratory glntiils^ lUc moBt perfect 
remedy U obtained. With infliiUTiuEitlon tlie affvut desired la a lessouiog of 
the flow of blood to the part. A simple cardUc sedative may do tliis, by 
lowering the force of the circulution, but a cardiac vitso-motor sedative ia far 
iHonj jM^werful. The blood-vessels of the inflaiDcd part are alreaily dilated^ 
imd consequently attmet blood, ati it were, to the part. If the remedy dilates 
all of the blood-vesfleltj this local attraction ceases, aod blood ia diverted from 
the inflamed tissue. It would appear from the experiments of Ludwig, 
SchilF, and others (La Nazione^ Aug. 1872), that the blood- viwisels, afler 
complete dilatation^ are able tci hold twice the normal amount of blond, and 
Golz, quoted by Fothertrill (Bnfish Mfd^Journ.^ 1873), found the intestinal 
TCfiBela were able to contain al! of the hluod of the body. These facts show 
how by means of an arterial sedative, wliith paralyzes the vaso-motor centres, 
** we can bleed a man into his own blood-vessels,'* or^ in other words, get 
mach of the effect of a venesection by drawing blood from the diseased part. 

AIJTIMOBY, 
ANTIMONTI OXIDUM. U.S.— OXIDE OF ANTIMONY. 
A grayish-white powder, insoluble in water, wholly soluble in muriatic or 
toftaric acid. It is prepared by dissolving the Bulphuret of antimony in 
muriatic acid, adding nitric acid, and precipitating with water of ammonia. 
Its solution iu the stomach is dependent u{>on the acid there present^ and 
coDScquently, being uncertain in its action, it should not be used inteiiially 
— although it is capablo of producing all the eficicta of tartar etuetio, for the 
ItreparattoD of which it was introduced into the Pharmacopoeia. Antimomi 
Sulpf^iiium^ U. S., Antinionii Sulphiduni Putijicatiimy U- S., and AtUiTiwfnii 
Sulphuratum^ U. S., are still more uncertain preparations^ whose therapeutio 
use ought not to be cuconrai^ed. 



ANTIMONII ET POTASSII TAIlTliAS. U. S,— TARTKATE OF 

AKTIMONY AND POTASSIUM. 

Taetar Emetic is prepared by boiling the oxide of antimony in a solo- 
UOD of bitartrate of p<>taiisium. It occurs in the form of a white powder, 
tlie rosuJt of the pulverization of transparent, colorless, slightly effloreswnt 
djtlftls, which are most commonly rhomb ia octahedrons. Its taste is vari- 
oiuttj doacribed: to me it is at first very slight, bnt aiter a time styptic and 
acrid. In some persons it blisters the tongue and lipa after a few moments 
of nontMdL Tartar emetic is insoluble in absolute, but soluble in dilute alco- 
hol, Soluble in from two to three parts of boiling wat^r, and in from twelve 
to fift^ien partji of water at ordinary temperatures. It is incompatible with 
alkallc« and with acids, including tannic acid and substances containing it. 

pHYSlOLOoicAL ACTION. — Locally applied, tartar emetic is an irritant, 
Acting up.iu some Tery delicat^s and susc€ptible skins in a very short time. 



l."6 SYSTEMIC REMEDIES, 

In most instances, however, its continuous application for scTcral days is 
necessary to produce any effect. At first there is simply a redness, accom- 
panied by some burning pain and the eruption of small papules, which shortly 
become converted into vesicles and then into pustules. These are irregular 
in shape and size, varying from one-eighth of an inch to an inch and a half 
in diameter, and are very painful. Sometimes these pustules give rise to 
small sloughs, but generally, if the application be withdrawn, they simply 
give origin to superficial ulcers, which readily heal. 

The only symptoms which are induced by small therapeutic doses (one- 
twelflh of a grain) of tartar emetic when exhibited for a short time are a 
scarcely perceptible diminution of the force of the pulse and an increase of 
the perspiration. 

By somewhat larger amounts of the drug, nausea is induced, and is accom- 
panied in a more decided degree by the phenomena just mentioned. Afler 
large doses, prolonged nausea, violent vomiting and retching, with marked 
reduction of the force of the pulse, great muscular relaxation, and a feeling 
of faintness, occur. At the same time the saliva is generally increased in 
amount, and the skin is bedewed with sweat. 

Afler poisonous doses all these symptoms are intensified. The vomitin? is 
violent, repeated, continuously re-excited by the slightest provocation, and is 
accompanied by burning in the oesophagus and stomach and by colicky pains 
in the abdomen. The matters vomited are first mucus, then mucus and bile, 
and finally, in some cases, blood. With the gastric disturbance occurs violent 
and frequent serous purging, the discharges resembling those of cholera, but 
becoming in some cases towards the last bloody. Cramps may occur in the 
extremity, and, in conjunction with the serous purging, have caused the anti- 
monial poisoning to be mistaken for cholera. The exhaustion is extreme, 
and finally ends in collapse, with thready or imperceptible pulse, pinched, livid 
countenance, suppressed voice, profuse cold sweats, lowered temperature, and 
at last death from asthenia, generally preceded by stupor or convulsions : 
indeed, Taylor reports cases in which wild delirium was present some hours 
before death. The urine'*' in mild cases is increased in quantity, as it is 
also in the banning even in fatal cases, but in such towards the close it is 
generally scanty and bloody, and even suppressed. C. G&thgens found, in 
some incomplete experiments, an increase of the elimination of urea after 
repeated non-toxio doses of antimony (^CentralbL Med. Win.y 1870, 321). 

It is evident that the symptoms just enumerated can be best studied 
in detail under several heads. Before entering upon this, however, it is 
well to premise that the experiments of Viborg {StilWs Therapeutics, vol. 

* What is said ia the text is, I think, oorrect; although authorities differ on this point. 
Trousseau {TraUi ikirapeutiquef 4th cd., vol. i. p. 619) afllrms that it is suppressed; 
Husemann, that it never is suppressed ( Toxicologie, p. 854) ; Tardieu, that it is scanty. 
For a ease in which i( wa$ euppreeeed, see Taylor's Medical Juritpntdence, London, 1873, 
p. 309. 




CARDIAC SEDATIVES, 



157 






E), Buclilidm, Courtcn {IhuL)y Magendie (Ihid.)^ Ackermann (Virchow^i 

Ar€k£nt Bd. xxv. p. 531), Richardson {London Lancet^ May, 1856)| Nobi- 

flij J (Schmidt's Jahrhuchrr, Bd. cxl. p. 24), and Riidziejowski (Rdchert'^ 

A -'^iv/ur Anatomie, 1871), Jind of others, !iav« denioiistmted that tartar 

emetic acts upon the lowor animals precinely as oa miin. 

Circulatimi. — When a sufficiLnit dtjsc of tartar emetic is iiijoeted into the 

frog (Rjidiicjewski, Ackcrmnnu, Nubiliii^), the ciirdmc cootractioDa in a 

fery short time are lessened in frequency and force, and become irregular, 

the auricles pukatiug more frequently thao the yentriclcs, until finally an^est 

oecurs in dia^stolo. After death the irritiibiUty of the cardiac muscle to 

ordiQary stimuli is almost, or more frequently entirely, destroyed j but in 

tbw rec^iot experiments of L Soloweitaehyk (>lrc/i. Exper, Path, u, Pharm,^ 

xiL 440), digitalis placed upon the paralyzed heart caused it to recommence 

\U action; eridence that it is rather the cxcito-motor ganglia than the 

tua&clc fibre which is affected by the antimony. Upon the heart of the 

1 the drug acts as upon that of the frog. According to the researches 

SrAckcrmann and of Ernst Sentz {ICxperimtnia de Rat lone Ititerpnlsus^ etc^ 

KaB. Inang., Dorp. Li von., 1853), the arterial pressure always falls steadily , 

wd ioan extreme degree. The pulse R»mi:timeii seems uuccleratcd at 6r5t^ 

int in the great majority of cases is decrcaHed very decidedly in its rate, 

Dimug this period of slow paW the diatitoUc pauses are extremely long, but 

tbe irniividual beat will iofluenec the meri'tiriat column of the cardiometer 

five tiaies m much as normal. After a while the pulscf suddenly becomes 

'^ty nipid, the force of the heart-l>eat is almost completely lo«t, the arterial 

pressure £ilb to a ujininnun, and in a very few moments diaatolic arrest 

OOMifs. It is evident ihnt the action of antimony upon the heiirt is a direct 

tme, j]3g irritwbility of the muscle is lost, and Ackermann has found thai 

lae cut-tmt heart of the frog is affected by the solution of tartar emetic; 

'Urtiiei'^ the experiments uf Rjiditiejewski have proven that the jwripbenil 

•^'w of the vagi in antimonial poisoning are early more or less completely 

f***J,^'d, so that the diustolie nrii^t eannot be due rj excitation of the 

***bii<jry apparatus,* The depression of the hcart*musclc power does not 

. hovfever, to be the sule cause of the lowering of the blood-pressure^ 

I*" ooloweitschyk has found that galvanization of the Viiso- motor centra 

» powerful current is powerless tu produce any elevation of the arterial 

re at a time when the heart still responds to Bllmuli, The conclusion 

bed that antimony hwers arterial preuure h^ a direct action upon 



^>*1i«pB the preseat if aa fitLmg aa any other pMition to notioe Vat theory of Ntibiling, 

tl»tk MftioQ of Utrtju- emetic npua the heart is owing to the potoah it oonUins, Thi« 

^^ In tUelf Ib ia improbable tbat it woulrl seem laarcelj worthy of discuENioa, wflre \i 

^^^ lh« tust that N(5bili»g iiB^crt^ that thu (..■irlrnto of DCtimony ami ioda ia not pui- 

Dr. lliuixi^ewfki {Utv,eit., 48^) hoA ropoatt^d and sxtcoded tho cxperimeDti of 

*i tag find completely db^troved both the auertod foot and the theory based upou it 

^S itiat the iodri-iftit is ni poisonous as th« potaah-ialt. 



158 



SrSTEMIC REMEDIES. 



(he heart and the vato motor §^stcm^ and tluit it is probably tlie periplieral 
portions of the latter syat^'in which are uffected. 

Nervom System. — A prominent symptom in antimonial poisoning is 
paralysis, affecting to an extraordinary degree the sensory and to a less extent 
the motor aystom* In man the ansesthesia which occurs in animals haa been 
overlooked, but in the advanced stages of poisoning it is no doubt present, 
Rcidzicgew^^ki and Hoioweitschyk have found that the depre^ion of reflex 
activity occurs after section of the cord, and is therefore not due to 
stimulation of the Setschenow inliibitory centre j that it is not prevented 
by tying an artery and cutting off access of the poison to the nerve, and is 
therefore not peripheral It conse«|uently must he spinal, and as both ob- 
servers noted that in the frog and the rabbit volnntiiry movements persist 
after the total abolilion of sensibility and of reflex acdvityi the conclosion 
IS reached that antimony is a piiralysant to the rcctptwe centres or MefiEory 
trad of the spina I cord. 

Iladziejewski states that sensibility is first lost towards thermic and 
chemical irritants, and then towards tactile stimuli. The motor nerves and 
muscles are said to retain their functional power. 

Ibmperatnre. — The influence of antimony ujion the temperature appears 
not to be very marked when the drug is exhibited in ordinary therapeutic 
doses. Thus, Aekermann found that, after doses severe enough to induce 
violent vomiting, no alteration in the temperature could be discovered by 
the thermoniet4*r under the tongue. Owing no doubt to the disturbance of 
nervous and arterial action, there is in these cases, however, a very marked 
reduction of the temperaiure of the extremities. Thus^ in the crises just 
alluded to (Aekermann) the heat of the hands was lowered from 0.2° C. to 
3.5** C. in various persons. This decrensse of the temperature is certainly 
in a measure due to increase of the heat evolution. 

After puisonous doses of antimony the decrease of animal heat is very 
pcrt.rptibk\, provided the victim live sufficient ly long. Thus, in Ackermanii's 
experiments a fall of only 1.6° C. occurred in rabbits killed in the hour, but 
in those that lived five hours the depression amounted to 6,6° C- 

Abdfjmittfd Orgniis. — It cannot be gainsaid that tiirtar emetic acts an an 
initant u[x»ti the alimentary mucous membrane. Although cases (Archhtt^ 
GiHhaks^ Sept. 1865) have been reportcnl in which no lesion has beeu 
found m the stomach or bowels after dcatli from antimony, yet in llie grent 
majtirity of instances very decided indications of viulent inflammaliun have 
been present. 

T)r. Kaflzic'jewski, on the strength of this action, and of two expenmentu 
in which he found the greater portion of the ingested antimony in the vomit 
of the patient, has advanced the theory that the emesis is due to a hx'al action 
of the drug. The persistent nausea^ however, certainly indicates that the 
remedy does not act like the so-cullcd mechanical emetics. Further, the 
vomiting induced in the expcnment of Magendie, of replacir»g the stomach 



CAIIDIAC SEDATIVES. 



150 



of an antaiiil by a Llndder and giving tartar emetic, would seem at first 
dght lij s<-'ttle tlie point coinplctely. Tliia experirn«nt of Muirr^ndiL' baa 
been confirmed by Brintou {Q/cIopadia of Anntomr/^ Siipplcinent^ p. 310 j 
I^omdon Lnncet^ 1853, vol. iL p. 599), who fiirtber proved that when tartar 
^Bletic was injected into the vein of an aniuinl it was very freely and rapidly 
Vljninated by the stomach. Br. B. \V. Richardson (Lmtdon Lftncet^ vol L, 
lS5lS) bad corroborated this^ and has al^o found that a Binitlur elitnination 
follows the inhalation of antiinonietted hydrogen* I think, therefore, it 
must be concedeti — first, that the finding of even a large f[uantity of anti- 
mony in the vomit doea not prove that its action on the stomach is chiefly 
ft local one; secondly, that the emesis is certainly preceded by at least a 
partial absorption. Thia would seem to show that the emei^ii* is purely 
ceotric. The experiments of Moo^o (Schmidt's J*thrhur/ifr, Bd. 169^ p. 
234>), on the other hand, indicate that tbe local uction of the drug is a 
powerful factor in the production of the vomit ir>g. It was found that 
when tartar emetic wa.s administered by the niouth vomiting was caused 
by smaller qaantitiea and more promptly than when injected into the veins ; 
dso that; aHer section of the peripheral vagi in the abdomen^ a reveree 
relation existed between the two methods of administration. If these ex- 
periments be, as they appear, correct, tartar emetic must cause vomiting partly 
by an action on the centres and partly by a local influence upon the Btomach. 
The purging induced by tartar emetic is seemingly an effort at elimination. 
I^ftptnitory Organs. — The respiration in poisoning by antimony is very 
irr«^lar, with all sorts of variations in the rhythm of the act. In the 
advanced stages the pau.^es are often very long, and the inspiration and 
expiration so forced and prolonged that very generally, in animals at least, 
marginal emphysema and subplenrnl ecchymoBes are found after death. 
The origin of the respiratory trouble is probably ?omew!iat complex, the 
chief factor being the direct influence of the drug upon the respiratory 
nerve-centres, and minor eansra the intense venous congestion due to the 
failure of the circulation, and the alteration of the blood itself Upon 
the mnoous membrane of the lunga antimony acts directly or indirectly, 
evvn in moderate doses, as is shown by clinical experience and by the experi- 
ments of Mayerhofer (JVbM«a^<'r« ArzneimiftefMire^ Berlin, IST'K p. 219). 
Th KRAPEUTics. — There are three indications to meet which tartar emetic 
is constantly employed. The first of these it fulfils by virtue of its powers 
as an em«/ic. The discussion of this may be found in the chapter upon 
Kmetics. 

The second purpose for which antimony is used is to depreu arterial 
rxcii^meni. It is chiefly in wflQmniaiwn that tartar emetic is uaed as an 
arterial sedative. In combination with more decided diaphoretics it is eon- 
itantly employed by some surgeons in fever after operations, in gmwrrhata^ 
and in various sthenic inflammatory afl"ections. In pneumonia it has been 
very largely used, forming an essential portion of the older plan of treating 
that diseaie. Aooording to the method of Basori^ four Or five grains a day 



ICO SYSTEMIC REMEDIES. 

were at first given, but rapidly increased to twenty-four or even thirty gralnf 
daily. Although by the aid of opiates and careful dilution a species of tol- 
erance was often obtained for these heroic doses, yet veiy projierly the plan 
has l^n abandoned by modem therapeutists. As tartar emetic if adminis- 
tered in sufficient quantity to depress markedly the circulation causes generally 
intense nausea and often purging, I think it is inferior to aconite or Teratrom 
viride when it is desired to depress the circulation very decidedly in pneu- 
monia or any other disease. 

Owing to its action upon the mucous membrane of the bronchial tubes, in 
the first stages of bronchitis tartar emetic is an invaluable remedy. After 
free secretion has been established, other expectorants are, I think, of more 
service. The value of antimony as a diaphoretic depends largely upon its 
action on the circulation. Minute doses of it are constantly employed to 
increase the efficiency of fever-mixtures. It must always be borne in mind 
that it is a powerful depressant, and is therefore to be employed only in 
sthenic cases. 

As a counter-irritant^ tartar emetic is used only when it is desired to pro- 
duce a slow, persistent, and at the same time veiy decided impression. For 
ftirther discussion of its application to disease, see chapter on Rubefacients. 

Toxicology. — The general symptoms produced by poisonous doses of 
antimony have been sufficiently described. There is, however, according to 
authors, a form of antimonial poisoning in which neither vomiting nor 
purging* occurs, the symptoms being simply intense prostration, cold clammy 
sweat, a sense of oppression in the chest, with the respiration at first in- 
creased, then diminished in frequency and embarrassed; a rapid feeble 
pulse, after a time becoming slow, intermittent, and irregular; delirium, un- 
consciousness, tremblings, and clonic and tonic convulsions (Husemann, 
Toxicologie^ p. 853). 

Tardieu {loc. cit., p. 608) states that in some cases of tartar emetic poison- 
ing a rash exactly resembling that produced by the external application of 
the drug has appeared all over the body on the fourth or fiftih day. 

As already stated, in the vast majority of cases there are to be found, after 
death from antimonial poisoning, very decided traces of inflammation of the 
stomach and bowels; in some cases, however, these appear to be wanting. 
The venous system is generally very much engorged, and the viscera are 
intensely congested. Magendie asserted that in animals poisoned by tartar 
emetic the lungs are always ftill of portions apparently hepatized ; but Ack- 
ermann (loc. cif., p. 544), in twenty experiments, found only some marginal 
emphysema and subpleural ecchymoses, with, in one or two cases, spots of 
atelectasis in the lungs. The assertion of Magendie, therefore, is too swoop- 
ing; but it is true that, in a large proportion of fatal cases of antimofiinl 

* Husemann states this. Although vomiting is absent in these oajtes, purging is gener- 
ally present. I do not remember to have seen the report of a caie in which it was absent 



CARDIAC SEDATIVES. 



161 



poisoning, empli^ecmsi, pulmonary npriplcxy, atelectnsifl, or other structural 
legions of the lungs exist. The hlocxl umially coagrulatea ira perfectly. 

I>r, Saikow^kj ( Virehnw'jt Archii\ B(J, xstxiv, p. 73, 1S65), of Moscow, 
\u& found that when iinimals nre fed upon antimonio acid (one-half to one 
gnmme dailj) or other preparations of the metal for from fourteen to nino^ 
tteii ds^ the liver, kiducya, and evnn the he:irt under*^o a fatty degenera- 
tion; aba that there is a lessening of the amonnt of glycogen in the liver, 
and in Btune caaes even a tcital dliuippoarance of it. Tins has been eorifirmed 
lij Pfttiik Orohe and Moslcr, who state that iu the duchy of Brunsvi'ick the 
pMianLiy give to the gee*e, when produeing the famous fatty livers, a ocrtdn 
quantity of the white oxide of antimony every day. 

Till* ni'niiinum Iktal dose of tartar ometic is not koown. Three-quarters of 
1 grain in a ehild, and two grains in an adult, have proved fatal ; but iu the 
Litter case eitriusie circumstances favored the result (Taylor, Guf/'n Hospital 
MepffTft, Oct 1857, an analysia of thirty *»evGn fatal cases); two hundred 
grains have been recovered from (oaao, Ta^fh/i Medical Jnrigprudence^ 1873, 
p. 309), 

Chrome Ptmontn^, — According to Mayerhofer {JTeUer*^ Archiv^ 1846, 
quoted by Taylor), the symptoms following the crtminal administration of 
fimall dose8 of tartir emetic at intenrals are nausea, mucous and bilious 
Tomiting, watery purging, ofWn followed by constipation, small frequent 
polsCf and asthenia^ deepening into death from eichaustion. 

The treatment of antimonial poisoning eonsista iu washing out the ali- 
mentary' canal with large draughts oT tannic acidj — the best known antidotei 
^-and in the use of opium and of internal and external stimulants. 

Abjcikisttiation. — The sudorific dose of tartar emetic is one-twelflh of 
a grain, the emetic dose one-half to one grain, repeated every twenty minutes 
ut neccsairy. The Antimoniol Wine ( Vinum Aniimonn^ U.S.) contains two 
grftins of tartar emetic In the ounce. The emetio dose is half a fluidounce* 
The Vf^neHfnm Anli'moatt Ctnrt^ir emetic, one part in five) is employed ex- 
ternally, a« a counter irritftnt. A small quafihiy »,< spread upon a linen rug 
and Isiid ofMjn the f^kltu or a little of it may be well rablii«d in twii-e a thiy. 
Whenever it is persrstently used, there comes on, sooner or later, a peculiar 
bttming or tingling pain, which Is 'very .shortly followed by piwtulatiou. The 
of the dnig is very persistent as well as severe, t^o that the remedy ii 

plicablc only to a few ease^ in which An action of the kind spoken of is 
required. Care must be exercised not to continue the application too long, 
i&Bl severe and obstinate ulceration be produced. 



VEEATEUM TIEIDE. U.S. 
'The n»ut-!»t4jek of Veratniiu viride, a coarse perennial herbal plant, indige- 
nous to (f)j Northern United States. It is a large tapering rhizumo, an inch 
or two in length, lofls than an inch in thickness st the bsse, and having a 

U 



IC2 



SrSTEMIC REMEDIES, 



bitter ucrid tORte. It contftms two alkaloids, jervia and trratrtnilia, whicli 
ure m clo^ly tLssociuted with the resiti us to be separated from it with great 
diffiuuhy, Tlie nature of these alkaloids has htKjn the subject of much db- 
cusaiou iiuiong t;hcmists, Mr. Charles Bullock was, I believe, tlie first to 
Bepuruto them oue from the other, and to prove the inert uess of tlie resitn. 
Id ftooordunee with the belief of Mr, Bullock that iliese alkaloids were dis- 
tinct from all previously discovered, Dr. George B. Wood named thcni viritlta 
and verattoidta. Dr. Peugnet subsequently showed that vindia was identi- 
cal with jervia, previously described by Simon, from veratnim album, Mr. 
Mitchell {Proc, Amer. Pharm. A^oc,^ 1874) confirmed this, and concluded, 
with Peugnet and Bullock, that verutroidiu is distinct from veratria. Re- 
cently (Ani^r. Jonrn. of Pharm., 187 "i, p. 1) Prof. Woruiley has arrived at 
the conclu-sion that veratroidia is identical with venitria. Without intending 
to deny the conclusions of Prof. Worinley, I shall, in the present edition, 
allow the text of the old edition to stand, so far as concerns the names 
employed to represent the two alkaloids of veratnim viride. Jervia is so 
closely united with the inert resin that it is separated from it with great 
difficulty. 

Pu YiJiOLOQiCAL AcTiON.— In treating of the physiological action of vera- 
tnim viride, I sliali first speak of the effects of its alkaloids singly. When 
an animal is poisoned with Jervia^ the first symptom manifested is slug- 
gishness, as shown by a divSpo^ition to be quiet, accumpanied by distinct signs 
of muscular weakness. In a little while peculiar rapidly-repeated thrills run 
through the muscular system, so that the animal trembles violently. Aller 
& greater or less length of time the animal becomes unable to stand, from 
weakness, ajid at or before this period violent convulsions appear, — general 
clonic spasms without rigidity. The convulsions alternate with intervals of 
relaxation, and as the animal grows more profoundly prostrated are less severe, 
but they continue in most cases up to death. Even when they are most vio- 
lent, force is evidently wanting. The animal is totally unable to raise himself 
from the ground ; the pigeon drives himself forward upon hia breast, the rabbit 
puslies himi^elf along on his belly^ or lies upon his side and kicks into the 
air. Sensation appears to be beuumbed only very late in the poisoning, and 
eonseiousucss is preserved almost to the last. The pupils are not affocted. 
There is no pui^ing or vomiting, but id ways profuse salivation. Iie$pi ration 
ceases before cardiac action, so that death probably takes place from asphyxia. 

The circulatiLMi i.s profoundly affected. The pulse is generidly, if not 
always, lessened in frequency, j^ rot? iWtti (he animal lit quiet. When there 
are convulsions, or even when the tremors are marked, it becomes very rapid. 
The arterial pressure is greatly lowered, falling progressively from the begin- 
ning to the end of the poisoning. The fjrce of the indmdual beat appear 
not to be much altered at first. 

In an elaborate series of experiments {Pltiludelphla Medical Timts^ vol/ 
Iv.) I found that jervia had little or uo effect on the pneumogastrle nerve 



CARDIAC SEDATIVES, 



163 



since it acts as iiRjaJ after those nerves bave been cut, and gal van i ami ion of 

the p:ir vKii^m in uniinals prof<juudly affet'ted by tbe poison prtxluced the 

■al itirdiac result*. Further, when tlie eord \\'il< cut very high up, so as to 

Jyxe the aecelenitora, jer\'Li still loKSoned liie polse-nite. Aa it was also 

|>rDVeii that the alkaJoiJ lessens the arterial pres^ture aflber division of the cord, 

r.^e., after vaso-motor paralysis, tmd also tliiil it pamlystes the lieartof the frog 

or tiirtle when phieed direetly upon it, it follows that jervia lowera the fiirce 

iiti4 fre |Tieticy of the cardiac i ents iudependently of its nerves, by a direct 

acticio on the cardiac muscle or its contained piuj^lia. When the nerve-trunks 

w^re pilvanizcd in an aiiiuuil pc»i.suned with jcrvia, although the pain-cries 

\ that the afferent nerves wore not paralyzed, little or no rise occum»d 

) arterial pressure* It seems, therefore, that the jervia acts not only on 

lli« heflrt) but is also a powerful depressant to the vaso-motor nerve-centres. 

In frogs, as well as in the higher aninialsy pniscjucd with jer\*ia, there is a 

s^ery marked diminution and finally abolition of reflex activity ; and, as tho 

fUiicaoDS of neither peripheral nerved nor muscles are interfered wtth^ it ifl 

ident that the alkaloid is an intensely powerful spinal depressant. The 

ivulsitms are cerebral in their origin, as tlicy do not occur below the 

point of section when the spinal oord is divided.* Loct\lly, jervia is very 

My if al all irritant. 

The general symptoms induced by vcratroidia resemble those caused by it<i 
eongcneric alkaloid, but It is decidedly more irritating than the hitter, and 
alwajTB ifidueea vomiting, and tKT'asionully purging. In poisoning by it thcr<^ 
ftre in moat cases some muscular twitehlngs, and Bnally marked convulsions, 
but neither of these ♦trc so severe and bo repeated as in the case of viridia. 
Dettth takes place from asphyxia, due to paralysis of the respiratory muscles. 
U[>OD the spinal cord, the peripheral nerves, and the 'uuscles, veratroidia 
eta very much as does Jervia, being a decided spinal depressant. 
Tbe action of veratroidia upon the circulation is a very curious one. 
After a hypodermic injection of the poison the rapidity of the pulse and the 
artcriJil pressure are at first decidedly letisened. After a time, the puLse still 
peninining very slow, the individual heart-beats become endowed with a force 
p^uly beyond nonnal, and the arterial pressure becomes normal; then sud- 
denly the pulse-rate becomes very nipid, the individual cardiac beats losing 
uiueh of their extraordinary vigor, but the arterial pressure rising nearly 
fifly jicr cent, beyond its original position* 

When the alkaloid b thrown directly into a vein, these phenomena are 
iTit<ui«ifie<l and abbreviated. I bave seen the artcriid pressure fall to zero in 
thirty seconds, and in one and a quiirt^jr minutes rise U} 1(15 (111) nonnal) 
e4'«timelre«i. Tlie rise is not due t^ a direct action of the drug, hut to the 



• S<tiD« <»r Ihe oondu^ioni of my flr§t lureilij^iitifm {Amvriean J*iumal of the tHetiieal 
Sfi^H'f*^ 1S70J of this <injg were enljcj in quoaUun, bul I liavo in ui^ la«t piiper gone 
4»wr ibv wliufr gruuiid iifrtfcb. The ciirliLir «liNi^ti>:.«i>i»iT nuvy l>o rraiiid iti tho Pkitadclj^kut 
Mittiir^l Timem, VoIa, it. Mil Vt\* 



104 



srSTEMW REMEDIES. 



suddon ui^phjKb wTiicb it iDduces^ since it does not occur if free artlBcW 
respiration be maintained (Philadelphia Medical Tima^ vol. ir.). 

When artificial reflpiration ia kcp>t up, veratroidia steadily lessens both 
ai'torial pressure and pulse-rate When the par va^m haii been dividedi 
artificial respiratinn being maintained; veratroidia is powerless to reduce the 
|nilse-rate, and when the pulse-nite has been n^diiCLd bj the drug in the un- 
Injared animal, divis^^n of the par vagum is followed bj an enormous rise 
in the number of cardbc beats per minute. These facts certainly prove I hat 
veratroidia is a powerful stimulant to the inhibitory nerves of the heart. 
Moreover^ I have found that when the spinal cord is divided so as to paralyse 
the antagonists to the par vagum, a mtnutc dose of the poison (nnc*thirtioth 
of a grain) will at once pn>dacc diastolic arrest of the heart s action, but if 
the pneumogastries be now severed, and the repressive force thus taken off, 
the nJaied, seemiiit^ly dead viscus recommences its beat. The slitw pulse 
of mild veratruidia-poisoning becomes rapid when a large dose of the poison 
is injected. Further, after a large dose division of the pnemnogastrica hoa 
no effect upon pulse-rate, and the most intense galvanic current applied to 
tlie periphera] ends of the divided ner\*es is powerless to affect the viscus. 
Evidently, large doses of veratroidia paralyze the cardiac inhibitory appanituw, 
whilst small ones stimulate it intensely. The paralysis is certainly peripheral \ 
whether the stimulation is centric or peripheral has not as yet been deter- 
mined. ^Vhen cnurmous doses of venitroidia are thrr^wn directly on the 
heart by venous injection, they at once kill the cardiac muscle. Upon the 
TEBO-motor nervcfi veratroidia in mod?rute toxic amounts has no demonstruble 
influence* Br. F. Reigel {Pjiu^ers Archiv^ 1871, p. 409) has demonstrated 
that the rise of arterial pressure whi :h occurs in asphyxia is largely due to 
vaso-motor spasm. In viridia-poisoning asphyxia baa very little inffuence 
upon the arterial pressure, because the vaso-motor centres are paralyzed ; in 
veratroidia-poisoning the slightest intermission in the working of the bellows 
of the apparatus for artificial respiration is followed at once by an enormous 
rise of the mercury in the cardio meter, conclusive proof that the va so-motor 
centres are not seriously affected. This deduction 1 have experimcntjdly 
e<jrroborati?d by gulv auizatifm of a sensitive nerve: always, unless an enormous 
auKiuntof the alkaloid had been given^ tlie rise in the arterial pressure wa« 
marked and iumicdiate. In esti mating the physiological action of veratroidia 
it must be borne in mind that artificial respiration was maintained during the 
study of the action of the drug ou the heart and vaso*raotor centres ; tliat 
its influence on the respiratory centres is so intense as to overbulance its car- 
diac action, and, when the animal is left to itself, to cause death before any 
very decided influence has been exerted on the heart. The action of the 
alkaloid may, therefore, be summed up as follows : it is a powerful respira- 
tory poison, lessening at first the frcfjuency of the cardiac beat by stimulating 
the pneuii^ogastrics, but soon loi^ini: all control over tlie hearty owing to tlie 
powerful i flui'mvii which the induced asphyxia ex.ertfip 



CARDIAC SEDATIVES, 



Tlic n^in of veratniin viride, when compleUjly deprived of the alkaloids, is 

irly inert. It aeem^, however, to he irriLitiiig to the digestive orgnns, mid 
probiil>ly ai(JiJ tu the produetion of the vomiting occ4ifiIoned by full doBcs 
of the tlnig. 

Aa the action of the alkaloids of veratrum viride is very similar, and as 
tliey are the only active principles of the drng» it is very easy a priori to 
deCenube what the influence of the drug will bo. Sufl&ciently numerous 
experiiuuntH * have been perfonued with the crude drug, or its preparations, 
to diow that it acts upon the lower animals as upon man ; but it i^ not 
Pflcywry hero to do more than allude to them. When taken in small 
doses by man, veratrum viride first reduces the force without much lessening 
liie frequency of the pulse, but after a time the pulse falls very much in 
miiidity, sometimes, according to J>r. Norwood, even to thirty-five a minute, 

li* any exeition be made during this stage of depressionj the slow pulse will 
he suddenly converted into an exceedingly rapid one. The slow pulse is 
flometiities tDoderately full, hut is always Yory sofl and compressible ; the 
mpid pulao is exceedingly feeble and small, often thready, and may become 
imperceptible. Severe nausea and vomiting accompany or follow the reduo- 
tian of the pulse-rate. That the latter is not due to gastric disturbance is, 
Itovrerer, shown by the fact that it often precedes the stomachic symptoms, 
tuid may exist without them. Thus, Prof Percy states that he has seen the 
pube reduoed to thirty per minute without nausea being induoed. During 
the stage of depression there is always decided muscular weakness and 
rekxntion. 

ASitT a poisonous dose the symptoms above noted are increased in inten- 
and become very alarming. A running, almost imperceptible pulse, — 
I culd^ clammy skin, — intense nausea, and iueestiant att^^mpts at vomiting, or 
rotching, or hiccough, — absolute muscular prostration, — falntness,— vertigo^ 
— lass of vision^ and scmi-unconBciousness, make up the group of extreme 
Hjmptoms. Various observers also &pe4d£L of an excruciating praacordial pain ; 
but this I have not seen. 

From these symptoms, with what has already been said in regard to the 
alkaloids, it follows that veratrum viride is a powerful spinal and arterial 
depresMuit, exerting little or no direct iiiflueneo upon the cerebral centres. 
In full therapeutic doses it lowers the pulse-rate both by a direct action on 
the musc^le ( jervia) and by stimulating the inhibitory nerves (veratroidia); it 
diininishes tJie force of the he^rt-beat by a direct infiuence on the canliao 
nuiscle ( jen'ia), and prfiducos a gr'ueral vjtso-motor paralysis (jervia) more 
or less complete according to the .size of the duse.f Under its action the 

^ Sm MfMMittilj a T>ap«r Ky PmL 8. R* Pore)", TruHtactioHM of fA« AmtrUan MtUi^'tii 
M*0i*rtnlitfn. Rep rioted tta ^iun\>h[i>i, 1804. 

t Vrut. fv It. P«rr>" ftaU't tliul u diktutlon of the blotHl-reindi of the frog's welj nm{ 
bftl't wiag eaa be riadilj wotn hy the mtercsoopfl tu follow the ftdminititratioa of th« 



166 SYSTEMIC REMEDIES. 

functional activity of the skin is greatly increased ; bat, as this is a neces- 
sary result of the profound arterial depression, there is no reason for believing 
that the drug has any specific influence upon the perspiratory glands. In a 
similar manner the excretion of bile is often indirectly increased by veratrum 
viride, through the severe vomiting which it induces. 

American hellebore undoubtedly lowers animal temperature very decidedly, 
but whether directly or indirectly has not been determined. I have fre- 
quently seen it reduce the bodily heat, and M. Linou {Gazette Midicale (le 
S'rasbourfjf, quoted in the Bulletin TJUrapeutigue^ 1869, tome Ixxvi. p. 95) 
states that it docs so, but not so certainly as it lowers the pulse. Oulmont 
(^Bulletin Thirapeiitiqiie, 1868, tome Ixxiv. p. 153) asserts, as the results of 
his experiments, that in animals from half an hour to two hours after the 
administration of such doses as would produce violent symptoms without 
killing, the temperature fell 2®, 3®, or even 5° (C. ?), and remained at this 
point for twenty-four hours. 

Therapeutics. — With our present knowledge of the physiological action 
of veratrum viride, it is evident that there are only two rational indications 
for its use, namely, to reduce spinal action and to reduce arterial action. 
Owing to the very great effect veratrum viride has upon the circulation, and 
the numerous drugs which are purer spinal depressants, it is never called for 
to meet the first indication, and in practice should simply be used to lessen 
the force of the circulation. The use of the drug in typlwid fever and other 
adynamic diseases is simply an irrational and dangerous practice, founded 
upon an erroneous idea of the action of the remedy. 

Veratrum viride has been recommended in Tnania a potu ; and in cases of 
irritation of the bnun from drink, with strong bounding pulse, it may be of 
great service ; but in the true delirium tremens, with universal adynamia, it 
is a thoroughly improper remedy, capable of deepening the prostration into 
fatal exhaustion : indeed, I have known of death occurring in this disease from 
its use. 

When true sthenic arterial excitement is to be combated in any disease, 
except it be gastritis, veratrum viride may be employed as a prompt, thor- 
oughly efiicient, and at tlie same time very safe remedy, — ^very safe, since it 
is almost incapable of producing death in the robust adult, unless used with 
great recklessness and in repeated doses. In the early stages of stitenic pneu- 
monia it offers, I believe, the best known method of reducing the pulse-rate 
and the temperature, and of ameliorating the disease.* It is hardly neces- 
sary to mention other individual diseases in which veratrum viride may be 
employed to carry out the present indication. 

In peritonitis its tendency to cause vomiting is very much against its use, 
and, unless this action can be controlled, should interdict its employment. I 
desire, however, to call attention to its value in preventing inflammation after 

• Coni]>nre Oulmont, TiuUetxn Therapeuti*^ue, t. Ixxiv. p. 146, and MM. Zuber and H. 
Hirtz, Ibid., t. Ixxvi. p. 468. 



€A nOIA C SKDA TI VES. 



1G7 



fOvciQ aitdomiiud injurit^^ — indeed, aAer any seTere injury. Thus, I am 
^jQgnisiixil of tho case of a woman whose belly waa torn open by the horn of n 
bull ; the iih^lomina] walls were rent for ab<:)ut eix inches, and the ei^oid 
fl^iore of the cr^lnn cjime out and was dragfjed in the dirt. It wiia wiished, 
replaced, the wound sewed up, the patient restricled to low diet, and veratrum 
vtrtde ftdmioistered very carefully so as to keep the puL«c ni< depmssed as 
poasible and at the saiu^ lime to avoid vomit mg, to aid in which opium WM 
ilflD gtren. RecoveTy without a bad s} inptom resulted.* 

A» mi canetic, veratnim viride should never be employed. 

Ill chronic cardiac diseases it may beuHHl In precisely thf>se c^^es in which 
dlptAltii i» ccvntra-indicated^ — f./*., where there is excessive hypertrophy. 

Tlie contm-indicationi^ to the u^e of veratrum viride are cardiac weakDOM 
and the cxbtenoe of general adynamia. 

Toxioouioy. — Although venitruin viride is a remedy of grejit powoi, 
capable of protlucing the mof^t aliirming Hymptomsi yet I believe it to be the 
iiafest of all Uie cardiac depressants ; certainly it ia far le^ dangerous than 
ttocnute. Overdoses of it produce vomiting eo soon and so certainly that it Li 
•OOMwhat doubtful whether a robust adult could be killed by a single dose of 
any of ita ofltciual prcpurations, especially if prompt and judicious treatment 
were afforded. I huve several times known a teaspoonful of ita fluid extract 
lo be taken ; and Prof Percy cites recoveries after the ingestion of a tunibler- 
lU of the tincture; a(\er thirty grains of the retinoid; after two do!*es — a 
tsmUcrful each — of a syrup representing a pound of the root to the pint 
A frirblc child, eighteen months old, was killed by thirty -five drops of the 
ttiieture (Am. Jour. Fharm , 18G5); and a doubtful c^ise (»f fatal poisoning 
tci the adult is mentioned in M^d. Sur^. lirp., vol. xh, 372. 

1 have seen the most alarming symptoms result from large medicinal dose» 
repeated at abort intervals^ and have been iistonished at the rapidity with 
which they yielded to treatment; but Dr. J. D, Blake reports (Amencan 
Mimical Weekly^ No. 20, 1874) a death re^nulting from tho adnunistnition of 
between three and four drops of Norwood's tincture every two hours to a 
bsbe eleven months old. 

In ciuies of poiscming, vomiting should bo encouraged by large draughts of 
warm water until the stomach uj well wixshed out. Then the patient should 
be forocd to lie flat upon the back, with the head lower than the feet, and the 
effort* at vomiting should be restrained. If they cannot be checked, and 
if Uae prostration be severe, on no acccmnt should the patient be id lowed to 
rise up, but must be made to vomit into a towel. A full dose of Inudanum 
should be given by the rectum, and brandy or whisky be administered by the 
tEtotttii. I have noticed that spirits will sometime* be retained onlv when 
^ven undiJuted, and in such form will quiet the stomach at once. If the 
stomach refuse alcohol in any shape, the rec^tum should be made use of Am- 
monia may bo ejnployed as an adjuvant to alcohol, and in extreme cases 



♦ C«fitiiH alto Dr. C. 8. Bishop, Amtrican Journnt nf the ^hMtal Sehncetf Oct. 1861. 



il^iib 



1C8 



SYSTEMIC HEMEDtES, 



bLouM be iijjec'tecl hj^Kxiennically^ or even into a vein. The use of ext4*nia! 
heat 18 imporUiit, and mltd iitjuellatiutis, rubbinir with coanic towels, siimpiBm.^ 
etc., may bij usod to keep up the oxterual capilliLry circulation. 

Administration. — In administering vemtrum viride, it should always be 
borne in mind that it will do oo gond in acute diiteufle unless given in increaising 
doses until its physiolog^ic^l action i^ manifested. In almoat all cases voniitiDg 
U to be avoided aB far m po^tble. To do this, small C[uantttt»s of the drug 
eht»uld be given at short intervals, and carr<?«pondins^ doses of Undannm (five 
to ten drops) should be exhibited fifteen minuter before each done of the 
venitrum viride. An hour is generally the beat interval between the doaes. 
The drug should always be administered in the fonu of the fluid eaUract 
(^Extractum Veratn Viii'dig Flnkfum^ U.S.), doee, one to three dro[>e; or 
ot' the tincture {Tinctura Veratri IVnWM, — I to 2» U.S.), doso, three to 
six drops. A saturated tincture is somettmeH kept in the shops uuder the 
name of A^orwood^a tincture, 

Vboatrum Album, — In cases of human poisoning with veratrura album 
iho Bymptouis* have been — exeessive vomtting, generally aocompanied by 
severe ohdominal, and often o^Bophiigeal, pain, and followed by a veiy severe 
diarrhieii; intense prostrdtiou and muscular relaxation; very pronouneed 
reduction of the temperature and pulse^ the latter being sometimes rapid and 
almost imperceptible in the advanced stages, and finally becoming extinct; 
sunken eyes, contracted, anxious countenance, a cold skin clammy with pro- 
fuse perspiration, and other evidences of collapse. The mind remains clear 
until the last. A fatal result is very comiuon, and, when recovery occurs, 
the convalescence is usually protracted. 

The exact nature of the active principles of verntrum album is still in- 
volved in doubt. Felletier and Caveniuu thought that they found suptT- 
gallate of veratria in it. So far as I can make out from tiic authorities at 
my conmiand, Simonf claimB that there are three allcaloids in the veratrum 
album, — vtratria^ Uit^timt^ and j*nma ; and Dr. Mossel {Sur la VirtAit'ine^ 
Thdse, Paris, 1868) certainly indicates that mhadUita and barytina are tlie 
same. Very recently the subject has been elaborately inveatiguted by Clkas. 
L. Mitchell, who finds two alkaloids in the rhizome, one of which he denomi- 
nates jervia, the other veratrtfUmt. The resin, ViAun entirely freed from 
ftlkaloidii, is inert. In a number of experiments made separately by Mr. 
Mitchell, Dr. J. B. Haynes, and myself, veratralbia proved itself a most 
active poisnn, one-tenth of a grain killing a lai^e pigeon in four minutes, and 
one-twenlielh of a grain a dog of fourteen pounds weight in one hour The 
symptoms were nausea and vomitings with violent purging, if the animal 

• For oapoft oml jiaaljBia of BymptomSi we Dr. Pcugoet'B pnper in tho JVeie Vvrk Mfdicnt 
Rteord, It. 121, 1872. 
f I hu\e Dot bod accesi to Simoii'i original papori. 




CARDIAC SEDATIVES. 160 

li^ed aome time, salivation, muscular weakness passin; iiu<i pttralysis, eon* 
TiilsouAf jiod dtjdihj — from fiiiluro of rtjspimtion after motlema^ Uixio dosea, 
from caniiuc arrest aftor very l^irgo tm^. When the fiutid robult hud been 
alowlj produced^ iotenne hypcraaiaia of tho jut^^stinal mucouA m«jmbraue wais 
found after death. Veratndbiu appears to be very closely allied io both 
chf^uitcal and pUysioIogicul proper! titu to veratria. 

ARNIOffl rLORES-ARKICA PLOWEfiS. U.S, 
AENICiE RADIX-ARNIOA ROOT. U.B* 

Tlie flowers t>f the Aniica uionlaua, a pi.Teiiiiial cMtuposite, uiitive of 
NurtJieni Europe and A^ia, and Baid also to be found in the Northwestern 
United States. The yellow flowers have about fourteen striated ligulate 
Iridentata floretij in the ray^ twice as long as the dbk, which eouijist^ of 
numerous tubular floreU. The taste is bitterish and acrid. The rhizome ia 
alfio employed medicinally, but i;^ not reco*^niwid by the U, S. Phannacopteia. 
Two alkaloids, Cytxsin and Armcina^ are stated to have been found in the 
flowet9. The first of these \a believed to be identical with the alkaloid of 
ihn sccdA of the laburnura-tree {C^tUm Lalmrriam). 

PuYSlOLoaic.VL AcTioM. — Locally, arnica is stimulating, and, if in suf- 
iieut Btrength, decidedly irritating. Upon some 'skins the tincture act« even 
olclitly, rapidly developing an acute eczeniatous infliiinmutton of the upper 
dertoid layem, n» manifeat^Hl by hyperajinia, papulea, vesicles, excoriations, 
tsrogts, and scales in regular sequence (Dr. White, Button Medical and Sur* 
gical Journal f Jan. 1875). 

Tli.it the influence which the di'ug exerts upon the general system when 
Itcn internally is very decided is certain, but the exact nature of this 
iidlaence is at present unknown. Viborg (quoted by Sttl)6) a^nns that in 
hursGS and cows it causen increased action of the heart, flow of urine, and 
warmth of skin, followed by very decided g^ineral dcpn?8»ion. According to 
StUI^j the effects of moderate doses on man are fiimilar to t!io»e noted as 
uccarHng in the lower animals, — nameh\ increase of the cardiao action, of 
the reirf>irdtiou, of the temperature of the skin, and of the (K^rspiration and 
urine, — along with very decided symptoms of gastric irntation. I suj?|)ect 
that to the irritation of the stomach were largely due the symptoms men- 
tkmcd above. Certainly there is couiiiderable clinical evidence to show that 
ten dr«*i»s of the tincture every three or four hours act as a decided arterial 
0edatlve (Dr. C. C. Balding, London I^tncety Dec. 1870); arul the few and 
ODiitrndictory cases of p<iisnning by the drug rejiorted seem in a measure to 
Irciir out this view. Thu?*, in a woman, two cups of a hlrong infusion pro- 
duced violent giistro-lnte.Htinal irritation, as shown by vomiting and choleraic 
dlarrhcDJi, reduction uf the pulse to tiO, and finally collapse {Bidktin Th^rap. 
Ixxvl), In Barbier*s cat*e (<|uoted by StillL^), an infusion of eighty grains of 
tb«» flowers caused giddiness, and intense muscular weakness, with ^p^jsmodia 
■lO^reiiMSUta of tlie limbs. In another, not latali case {London Lancet^ Not. 



170 SYSTEMIC REMEDIES. 

1864), according to the statement of the patient, an ounce of the tincture 
did not produce any symptoms for eight hours, when approaching collapse, 
dilated, immovahle pupils, with a cold, dry skin, and a feeble fluttering pulse, 
rapidly supervened upon an intense epigastric pain, which was increased by 
pressure. 

Therapeutics. — In the present state of our knowledge, the internal use 
of arnica is absolutely experimental. Externally it is employed to a very 
great extent as a stimulant application in bruises and sprains, generally in 
the form of tincture ( Tinctura Amicss, Florum — 1 to 5, U. S. ; Tinctura 
Arnicst RadicU — 1 to 10, U. S.), which may be applied pure, but sometimes 
as fomentations of the flowers. Its ptoperty of occasionally producing intense 
dermal irritation should be borne in mind. An extract (^Extractum Amics^ 
Radicis^ U. S.) and a fluid extract (^Extractum Amicm Radicis Fluidum, 
IT. S.) are officinal. 

VERATRINA. U.S. 

This alkaloid is procured from the seeds of Veratrum sabadilla (Asagrsea 
officinalis). As found in commerce, it is almost always more or less impure, 
and occurs as a grayish-white powder of an intensely acrid taste, and pro- 
ducing, even in the minutest quantity, when smelled, frequently-repeated 
sneezing, which may continue for hours. It has when pure been considered 
uncrystallizable, but Merck has obtained it in rhombic prisms about half 
an inch in length, through the spontaneous evaporation of its alcoholic 
solution. It is very slightly soluble in boiling water, not at all in cold water; 
soluble in alcohol, freely so in ether, and still more so in dilute acids. 

Veratria dissolves in concentrated sulphuric acid, with the production of a 
yellow color, changing in five minutes into orange, then into blood-red, and 
in half an hour into a splendid carmine. Masing states that this test is 
very faint with 0.0026 of a grain. If some bromine be dropped into the 
freshly-prepared sulphuric acid solution, a beautiful purple results. A more 
delicate test than either of those yet noted is, according to Masing, that of 
Tn43p, which consists in warming the colorless solution of veratria in con- 
centrated muriatic acid, when a dark-red very persistent color is produced 
This test is said to afford very marked proof of the presence of 0.0026 of a 
grain of the alkaloid, and to be especially useful when the veratria is impure. 

Physiological Action. — Veratria is exceedingly irritating to any surface 
it may come in contact with, producing when given hypodermically or ender- 
mically severe pain, and when rubbed on the skin a feeling of warmth, fol- 
lowed by prickling, severe pain, numbness, and, if its use be persisted in, a 
marked redness. On the mucous membranes its action is even more decided. 
In the nostrils the minutest portion of it produces intense irritation, as shown 
by repeated sneezing and free discharge, which may be bloody. Upon the 
tongue a speck causes burning, with free salivation. 

When taken internally, in small doses, it produces slowing and weakening 



CARDIAC SEDATIVES. 



ITl 



of the poliie ; more freely administerod^ inJiciitiona of gttstro-inicsiinal irritit- 

tioa ; and m large doses it h folluwed by violent voinititig, serous purgin*;) 

()fWn with tiit43ii5e bumiug iu tlie mouth and throat, and general muscular 

teiikuea». No fktul case of poi80iiin<i; is on record '* but iu the experiments 

I itf Ksche on him^F a half-graiu of the acetate produced collapse^ with a pale, 

I »ld, wet akin, pmcbed feuturea, a rapid^ thready, irregular puliie, violent 

iTomiting, and marked museular tremblitJg^, Other observers liiivc noted 

[ more pronounced indications of convulsions ; and, according to Bardaley, 

wkn aLsorbcd through the skin, instead of purging it produces iu sjonie cases 

I Teay Tree diuresis. On the whole, the re«^emblauee between the symptoms 

siuduced in man and in the lower animals is, t^o far as we know, eouiplctc. 

Tlie plieaomena of veratria-poisoning in a mammal are violent muscular 

twitch iugs aad convulsions, which are often plainly excited by external irri- 

Unts, severe vomiting, generally but not always aecompatiied by purging, and 

^turbuDoe of motion, respiration, and circulation. The pulse is at first^ if 

the dos« t>e not too large, quickened and i^trcngthened, but iu a very short 

ufflc it beconiiss slower and weaker, and tiiially very frequent, thready, and 

I in^fular. There b early a marked loss of muscular power, even in the midst 

I of the couvulsiuns, and the latter may give way to the quiot of paralysis, or 

f maj continue up to death. 

Acoc»rtling to the researches of Claus (Journal of Anatomy, viii.) veratria 

|4D toxio dose8 causes first a slight fidl of temperature, then a rise to about 

ormaJ, imJ fiually a fall immediately before death. Sabadillia, on the con- 

pruducies a ri»e of temperature, followed only by a partial fall, so that 

*ily heat even at the moment of death is above normal. 

^ iVevost (Robin's Junmal de l Anatomic, 1868, t. v. p. 206) has, 1 

Very well di\ided the action of veratria in poisonous doses into three 

Bt, that of excitation or restlessness ; ^cond, that of convulsions; 

f of paralysis. It sliould, however, be understood that these may 

5€ doees be fiised uiXa} one, I Imve seen an animal suffer a eonvul- 

**"i or perhaps merely give a convulsive sli udder, and drop dead* 

' ^'^r death from a very large dose, the muscles are found to have lopt 

^^ less completely tlieir irritability, so that they either do not respond, 

^^ '^fH-*nd very feebly, to the strongest faradaic currents. That this is 

' ^ IL direct influence of the alkaloid upon them is proven by the fact, 

*^ iiot^hJ by Kiilliker ( Virchows^ Archiv, Bd. x. p. 257), but which I in 

^i>D ^ith other observers have cxperimentaUy confirmed, that if an artery 

*^^I beiWre poiaonlug, all the muscles supplied by that artei^ maintaiu 

*'*U*grity. 

** 'S**. QrQry«*m ffawpitai Htpnttt, 1870, vol. V., Dr* C. Pagut Blake roporta a. ««9q of 
^^ adXci Ibc ingeelioD it( n linimeui suppuitMl to contain ihreo grains of vcmtrmt 
"hing of the flkia wot % promiaoat symptom. 



172 SYSTEMIC REMEDIES. 

It ia evident that veratria is a muscle-poison ; but it has other powers, and 
the subject is best studied in detail, system by system. 

Central Nervous 5^#/cwi.-^Upon the cerebrum the action of veratria is 
not very marked. That the convulsions are not cerebral is shown by the fact, 
which I have frequently noted, that they are in no wise affected by division 
of the spinal cord. The spasms must be, therefore, either peripheral or 
spinal in origin. M. Prevost (Robin's Journal de rAnatomie, 1868, p. 
209) has found that convulsions will occur in the frog even when the spinal 
cord is destroyed, but that under these circumstances the convulsions are not 
spontaneous, but occur only when an irritation is applied to a part, and are 
limited to the part irritated. A fact analogous to this was noticed by 
E5lliker ( Virchow'i Archiv, Bd. x. p. 262, Exp. IX.) : in frogs whose 
nerves were paralyzed by woorari, the exhibition of veratria induced phe* 
nomena similar to those just noted. These facts, however, do not prove 
that the convulsions in the veratrizcd frog are not spinal, but only show 
that there is a state of excitation of the muscles. But M. Prevost furnishes 
the following direct proof that the cord in veratria-poisoning is not affected. 
The hind legs of a frog were separated from the rest of the body by a very 
tight ligature, so placed as not to include the lumbar nerves. Some veratria 
was then introduced into one of the fore 1^, and of course found its 
way into the spinal cord and the anterior portions of the body. Under 
these circumstances it is evident that the convulsions produced, if spinal, 
would affect the whole body, but if peripheral would be confined to the 
anterior part of the frog. It was found that the posterior legs were never 
affected , that whilst irritation of them caused most violent spasms in the 
anterior part of the body, only the normal reflex actions occurred in those 
muscles not reached by the poison. If this experiment be confirmed (and 
I see no intrinsic reason to doubt its accuracy), to Prevost belongs the credit 
of having proven that veratria has no action on the motor centres of the 
spinal cord. 

There is, however, an apparent opposition between the experiments of Pre- 
vost and those of Kolliker ( Virchow'a ArchiVy Bd. x. p. 261), The latter 
observer noted (Exp. VI.) that when the skull of the frog was opened and 
a ten per cent, alcoholic solution of veratria dropped on the cord, violent 
general tetanic convulsions were induced ; also (Exp. IV.) that when one 
crural artery and vein of a frog were tied and the veratria solution placed in 
the mouth, tetanus ensued, involving the protected limb, and continuing 
there afler it had ceased in the other members. I see no way of recon- 
ciling these experiments of Kolliker with those of Prevost except either 
by supposing that the latter are incorrectly observed, or, what seems more 
probable, that the poison in the former reached the protected parts by dif- 
^ion, although in less quantity than it did the other members : this would 
also explain tlie continuance of tetanus in the protected limb afler it had 
ceased elsewhere. 



CARDIAC SEDATIVES, 



173 



M» QutttnanD (Reuhert's ArcJuv/Ur Anafomie^ 1806) is in accord with 
Kulliker in his txpentnents^ for he s^tes that^ Dotwithstmidiug the iirtery 
of ft limb La tied, yet spasms occur in the leg during the cotivulBive stage of 
tettOria^potsoDbg : of course the "diffusion** theory would apply to tbb aa^ 
veil as to the ezperiiDeuts of KoHiker. 

Tht only conclusion to. ho dniwn from the evidence seems to me to be that 
il |tf«eut it ia uncertain whether verairia does or doea not act upon tho 
QUitCMr centres of the cord, 

lo regard to the action of the dnig upon the sensitive centres of the cord, 
Oftr knowledge is by nu means perfect. Anaesthesia of the posterior feet was 
Qodeod in the frogs exporimciitod upon hy Prevost in the manner dt^scrtbed ; 
titti when the circulation is cut off from the feet uf a frog, loss of sensibility 
always endues* 

Peripheral Nervtim System. — Tho study of the action of venitria upon 
ibc fieripheral motor apparatus evidently divides itself into a study of tho 
infliuoee upon the miBicles and the extreme nerve^ndings in themi and upon 
tlie ncrrc-trunks. 

TbLiro can he no doubt that voratria finally de«trop the contractile power 
of the niU5tcle itself, so that it fails to rcj?iHind to any irritation whatever, 
and scKin, becoming stiffs exhibits tlie acid reaction of post-mortem rigidity. 
Tbiia fer all recent observer* are in accord ; and I have frequently witnessed 
llie same phenomenon. Ki»lliker in some of his expcriuienta Hoc. cit) noiei 
lluit the muscle in the eai'ly stage of vcratria-poisoning responded inordi- 
nately to stimulL The study of this phenomenon has been especially made 
by Besold and Hiri ( Untrrstwh. Phtfuirtdtg. Ijithomt. Wiirzbvrr^^ L) by M. 
Prevoet,* and by Row bach {Pjlilijers Atchn\ xiii. p. Ol7j» When a muscle 
during the couvulsiye stage of voratria-poi^oning is momentarily stimulated, 
inatead of the usual momentary contraction a prolonged tctaTiic spa^m resnlts 
aod Usts som e seco n ils : t h i?; a pa.s m is i n d u ced by tb c si t <4 b lest i n* i ta ti o n . W li e n 
m nerra is irritated repeatedly within a s.hort time^ the tributary muscle lt>sefi 
tCa power of entering upon a ''^veratriii contraction/* but if left quiet for a time 
weoofTtm itaelf. There is therefore in veratria-pjisoning, preceding the stage 
jf muscular pandysis, a stage of muscular bypcr-excitability To thi.^ are due 
no doubt in great part, if not altogether, the amvulnions, Ti can scarcely \m 
donbied that it is the result of an action not up^n the nerve-en dinga, but 
upon the soroolcmma of the muscle,'!' That the muscular pandysLs is of 



* QuoUd bj lliL9ci»niin* 

t fivk aod Bfihm, in the di^oratQ paper alrDadj referred to, believe tfaiit they jirurtt 
tluit the prolongfttioa of th^ inuitcutAr coDtmctioni in rerfttria-poboDiQip ia due to a 
gTMklifr iolpntitj of (ht ch^mionl procefiios of the iiiuF«1e», and not to a di^lnj of the 
proeKM ef rettitution., A diacaa^ion of tbit point would inrolre that of uiuRouliLr pbysi- 
9i»gji and euLDut b« entered tato here. Tbe vrenJc point uf tbo urgiiuieDt mudu hy Pick 
aoii Bdhm unkj^j however, be puintt'd out, Uriiutitig itl] ihvir AssvrteU tucU, it in perfect!/ 
|M»Milile thfti grcAtcr intenftity of the obcmicikl pruecMCi ia aq ttj^tetf nut » cuute, of the 
^r»loa|;«d ooolra lions. 



174 i>rSTEMIC REMEDIES. 

siinilar nature would seem to be proven by the rapid changes which take 
place in the muscle after death, and by the fact, noted by Guttmann (^Retchert^t 
Archiv/Ur Anatomie^ 1866, p. 498), that whilst frogs apparently dead from 
nerve-poisons such as atropia, strychnia, and curari often recover themselves 
after a period of stupor, those poisoned with veratria never do. 

When a muscle is dead, galvanization of the nerve of course elicits no 
response ; but it is possible that a substance may be at the same time a nerve- 
poison and a muscle-poison. Veratria is both a muscle-poison and a nerve- 
poison. Kblliker denies this, but the experimental evidence brought forward 
by him amounts to almost nothing. Outtmann (Joe, cit) asserts that in his 
experiments, whenever irritation of a nerve failed to elicit a response, direct 
irritation of the muscle was always equally unavailing. Bezold and Hirt (Joe, 
cit.) experimented, with a full knowledge of Guttmann's work, with small and 
with large doses, and evidently with great care. They found (Joe, cit,, p. 90) 
that when a tmall dose is used there is at first a very marked increase in the 
irritability both of the nerve and of the muscle, so that, whether the current 
be applied directly to the muscle or indirectly through the nerve, contractions 
take place more readily than normal. After a time, both muscle and nerve 
lose their irritability, so that no contraction follows either the direct or the 
indirect stimulation. The process does not go on pari passu in the two 
organs. The irritability increases sooner and is sooner lost in the nerve than 
in the muscle, so that there is a time when galvanic irritation of the nerve 
fails to induce contraction, although the muscle still retains its functional 
power and reacts instantly to direct stimulation. Moreover, the upper or 
spinal end of the nerve dies first, so that at a certain stage irritation of the 
nerve-trunk close to its origin fails to induce contraction of the tributary 
muscle, although when applied lower down it elicits a response. This im- 
portant observation is confirmed by Fick and Bbhm (Arheiten aus dem 
Physiohg, Lahorat, der Wurzburger Ilochschule^ 1873, p. 147), and by J. 
Ott (^Toxicological Studies, Philada., 1874), and would seem to prove that 
veratria acts directly on the nerve-trunks. Fick, however, affirms that under 
these circumstances he has frequently proven the existence of the normal 
muscular galvanic currents in the seemingly dead nerve-trunks, and that 
therefore it is only the peripheral nerve-endings which are attacked by 
veratria. But it is difficult to reconcile this observation of Fick with some 
of those of Bezold and Hirt. At present, therefore, it must be considered 
undetermined whether it is the nerve-endings solely, or the whole peripheral 
nerves, which are affected by veratria. 

As already stated, the action of veratria upon the sensory centres is doubt- 
ful ; its influence upon the peripheral sensitive nerves has not, that I am 
aware of, been carefully worked out, but the effects of its local application to 
rli(! human skin seemingly show that it first strongly excites and then para* 
lyz(M them. 

Circulation. — After death from a large dose of veratria, the heart is soft, 



CARDIAC SEDATIVES, 



175 



dllatod, full ufblood^ and incapable of responding to galvanisni ; uc, the heartr 
muMcle t» dtmd. According to Bezold and Hirt {he. ciV.), after a smd) dnse 
liiere are ijuickciiing uf iha puke and ri^ of the blood -pressure, which Boun 
nsturu to iho normiil cundition ; whikt imnieiliate and persistent fall in the 
oumbor of the heart-beat*' and in the arterial pressure follows a large dose. 
If die vagi be divided previous to the poisoning, a large dose produces a tern- 
pumry increaae in the pulse ; and a stimulaiion of the distal end of tho cut 
tiervtti hy a current t-oo slight to be felt in the unpoisoned animal retard** 
rery markedly the beat. Fix»m these facta it foUowsj that in the iininjurKd 
auitual, after poisoning by veratria, there b an inhibitory retardutitm of the 
puke, and also an excitation of the peripheral ends of the vjjgi. That it is 
not iiiei-ely the peripheral inhibittiry appanitun which is affected mvws proved by 
lajecttn^ the alkaloid into the carotid, — /.«?., into the inhibitory centre, — when 
there happened an instantaneous ajid retnarkable retardation of tlie hearts 
bsatf which could only have been ciiUJscd by excitation of the inhibitory 
oeiitr«». Iq a later stage of the poisoning the strongest faradaie currenta 
applied to the pneumogastrics fail to affect the heart. It is, therefore, 
eTid«fUt that veratria first exalte and then destroys the functional activity of 
the par Tag:um, as of the spinal uerv^es. 

Aooordiug to the reseurches of Prof. S. Ringer, veratria acts directly upon 
the cardiae muscle m it does upon the skeletal muscles* Kauh excitation 
caas^es in the veratrizcd frog's heart a prolonged series of in€O'0rdiftnt<;d 
contractions; therefore a lessened regulation with an increased amount of 
Ibroo-generation (Archives of Med. ^ 1882, p. 21). 

When the heart is separated from the nerve-centres by section of the par 
*agum and of the spinal oordj Yeratria produces, according to Bezold and Hirt, 
at first increase in the pulse and blood -pressure, secondly, lowering of both 
to the mtniuiuni ; showing that it exerts upon the internal heart-ganglia, or 
npdn the hejirt-muscle, its peculiar action of first Btimuluting and allerwarda 
l^nilysmg functional activity. 

That the poison has a similar action upon the vaso-motor centres seems 
prtihable from the facts noted by Behold and Hirt: first, that injection into 
ibc carotid after section of the pneumogustrics causes immediate rise of the 
Uood-profivure ; second, if the mesenteric arteries have been previously bared, 
ihtiy ijan be seen to eon tract. This excitation is followed after a time by 
foflo-motor paralysb and dilatiUion of the vessels. 

lCe4ptra(ion. — ^Bezold and Hirt conclude, from the fact that aft«r section 
(bf the pneumogastrics even the smidlest doses of veratria cause retardation 
uf the respiration without previous Increase, that the alkaloid depresses im- 
mediately the centre of respiration In the medulla^ and finally kills it 

TiiEHAPEUTio Action. — The study of the physiological action of vera- 
tria shows that m rational th crape u tic use must be limited. As a heart- 
sedative, it ia much inferior to aconite and vcnttrum viride, for obvious 
B, and, although it has beeu used as such, it has not achieved much 



176 SYSTEMIC REMEDIES. 

reputation. When exhibited in full doees it is very apt to give rise to 
exceedingly disagreeable secondary symptoms, and has no advantage over 
the medicines just named. Some years ago it was employed in acute rhevf 
matism, having been recommended by Tumbull, Bardsley, Piedagnel, Trous- 
neau, and others ; but it is not so efficacious in this disease as other &r less 
dangerous remedies by which it has been superseded. The same is true of 
Its employment in dropsy; and I know of no condition which would justify 
its internal use. 

Bardsley originally employed it in neural^, especially when arising from 
cold. He used it both internally and externally. At present it is rarely 
employed except as a local application. My own success with it has not 
been very encouraging, but others of larger experience recommend that it 
be rubbed over the affected nerves in rheumatic neuralgia. 

As an external stimulant and rubefacient it is sometimes used with good 
effect in narcotic poisoning ; also in various spinal troubles as an irritant ap* 
plied to the spine, and to the skin of the paralyzed limbs, to aid in maintain- 
ing circulation ; but all these indications can, I think, be better met by other 
taeans. In regard to the dose of veratria for internal use, it should be borne 
in mind that one-sixteenth of a grain has produced the most alarming symp- 
toms (Taylor, Medical Jurisprudence^ 2d edition, London, 1873). 

An ointment ( Unguentum Veratrinse — 1 to 26.5, U. S.) and an olcnte 
{Oleatum Veratrinm — 1 to 50, U.S.) are officinal. 

AOONITUM. U.S. 

The Aconitum Nnpellus,'*' or monkshood, is a tall perennial, indigenous 
in Europe, and caltivated in this country for the sake of its spike of bine 
flowers. The leaves are three or foar inches in diameter, and cut almost to 
the base into three to seven thrce-lobcd, wedge-shaped divisions. 

The root, which is the only officinal portion, is from three to four inches 
long, very tapering, about three-quarters of an inch in diameter at the base. 
Its taste is bitterish, acrid, and after a little while benumbing, giving origin 
to intense tingling of the lips and mouth. It is to be distinguished from 
horseradish root, with which it has been fatally confounded, by its external 
brown color and its absence of odor when scraped. The whole plant is 
active and tastes like the root. 

In 1833 Geiger and Hesse discovered in aconite an alkaloid, Aconitia^ 
which is undoubtedly the active principle of the drug. This alkaloid is now 

* All of the (ipccies of the genus Aoonitum are more or lesg poisonous, although A. 
Kapollus in the only one officinnl. For a study of the comparative strength of the variout 
aconites, see Schroff, Journal f Mr Pharmacod^namikf 1857, p. 335. He arranges thorn as 
follows, commencing with the most virulent: A. /erox, A. Napel Ih», i^ith its varieties, 
neotnoutajiunif tnuricuntf and variahiUf A, Cammarutny A. paniculatHnif A. Anthura, The 
toxio properties of the A. Anthora were very weak. Lycocttmin is the alkaloid of A. lyooo* 
tonnm. For a physiological study of it by Dr. Ott, see Philad, Med, Timet, vl. p. 25. 



CARDIAC SEDATIVES, 



177 



tifficJnal. As prepared accoTding to the directions of the U. S. Phannacopceia, 
it is a yellowish-white jK^wder In comincrcc there are sevenil varieties of it, 
ouidr by different large manufaeturera : the German aconitia^ wliich is very 
iiopare, and, aceordiri^ to niisemanD, is less active than the extract; impiire 
E/itflUh aeonitia ; and the Bo-called EngU&h acotntia, prepared by MorsoD 
bud anid tu be chemically pure. The latter is a grayiish p«:)wder,* 

DuquesDcl (OompteS'RaidugjVot Ixxiii., 1864) first obtained the aconitia 
in the form of colorless, rhombic, tubular crystals, soluble in alcohol^ beDziDe, 
ether, and cjctromely so in cblorofurin, very slightly soluble in water, insolublo 
in glycerine. 

The salts of aconite are soluble, and from their solution the alkaloid is pre- 
cipitated by atkaliea in an amoqjhoiis stjite. That aconitia is the only active 
priueiplfi of the root would seem to follow from the experimenta of Hottot 
(Journal de Pk^Hiologie^ 18t>4). 

PBYSiaLooiCAL AcTiON. — When applied to a raw surface, or to the akin, 
looDlte, or its alkaJoid aconitia, act^ ua a local irritiint and narcotic, soon pro- 
ducing numbness, with tinghnj^, which may persist for a long time. When 
giTea in safficient dose internally, it is a violent poison, acting, so far as ia 
known, similarly upon all animals. 

If the dose be large, dirnth may be almost immediate, and, if the alkaloid 
be given hypodermically, may occur in less than a minute. In such cases 
I he rcduJt is apparently due to sudden panilysis of the heart-muscle, 

After moderate toxic dc»se3, the prominent spnptonia aj-e p^reat disturbance 

of the respiration, muscular we^ikneas, vaseular depression, and finally death, 

with or without convulisions. As I have seen the rabbit afler the injection 

I of ono-sixth or one-c^uarter grain of Morson's pure aconitia, the animal com- 

[ fiiences to jump vertically in a very peculiar manner^ and often to sw|ueal pite- 

loudly. The jumping soon grows less and less pc»werful, and finally is replaced 

j bj severe convulsions, during which the animal often lies prostrate ou ltd side* 

In the dog, however, the muscles have remained without a quiver during all 

* In 1357, ItUbMhmiLnn aonooiiCQd tb« presence \n mmnto qunntirj of a fe<^ond Alka- 
loid in the root of A«»aitum Napellui,— A'«/»e/6>ia, ScbroflF* {JitHrnTd pir Phatmac*nig* 
mnmikf t. .1) ootitd find no esuetitial i]ifr«rcnofl betw^'eti iU itirlion iind that of German 
ieonitia. T. and 11, Smith, of Kdin^^urgb, have found a third non poi»onotii alkaloid, 
de**i**ffa, whiob thcv thmk to hn prtitmlilj idoniica) wiLh narcoiinn; ixnd FVixck^ger asserts 
^at iber« are four lilkaloidi conttiincd in the genus Aeoititnm, nnmdy, ArouitiOf Ptttd* 
meoMitin^f Xapi^tlina, and Cystoma {Stfdfuhnm Yeitr-Hnok^ ISfll) and 1870). Itoceotlj Dr. 
C. A. Wright huK fiiimd that there arti thrm? iilkdhfUlj fn Aconitum Napeltui, ory^tallisable 
$oiiitia, a nrarlj in<»rt b»flc»/>iVrrt acnnftm, aod a thin! iilkalfud, iticapiiblc of ery»taUUing 

I nr farming erjrMiallt talkie mlt, wbtcrb is snld tu frm^uoDttj form the bulk uf cummorriaJ 

I •edDjUa. 



* Ff»fn wh'it SrhMir my* iit«onl the niAtctial b« luad In his cxp«iim«iits, It Is SYldsiil that ht bad 
bD pruul iUnI It VMS jr<»niilitt« nuiH^ltlna. 
i StOtm attd Kw^m Unv< 1 ' .;< aHy ittidf'oil tb« alkalrvlrl of Aoonltuin fi^ros under thu njims of 
uriil Unnil El ii«tHc'^'ii il* Actrfui rtnd (but ofsroiitiiA to h^n on^' uf •h'grcw, rtol 

iJua i it »,.• U... nr.M ^y-o {Archiv/ar Expfrim. PatfioU>ffie Mitd Pharmak.^ Bd, I., ItfT'J^ 

12 



178 



SrSTEMIC REMEDIES. 



Stages of ilte poisoning ; in the hoi^e Hurlj hii§ noticed eonvnlsions (S^. 
Thoit. Ilfjsp. Rt'porh^ v*)» The convulsions are an inconstant symptom, de- 
pendent upon peculiarities of the individual or species, as well us upon the 
nuiomit injected. Dilulatiuri id" the pupil very tretjuently cm^cuhs, if it be 
not indeed a constant phenomenon. 

Tlic symptoms which ai-e induced by smal] thcrapcutio doses of aconite in 
man aru reduction of the force and frequency of the circulation, a sonse of 
miLseular inertia and weakness, and a slight tingling lu the extremities or in 
the lip£$. If the dose administered be large, all these symptoms are mtenn- 
fied; the muscular weakness is extreme; the tingling is felt all over tbe 
body; the pulse is feeble, and reduced to thirty or forty per minute; tJie 
respirations are diminished ; giddiness and disordered vision may be maai- 
fested, espeeially when the erect posture is assumed. After three or four 
hours these symptoms gradually eubside. 

When a poisonous dose has been ingested, the first thing noticed in most 
cases is a burning or tiugling in the throat or in the extremities, soon spread- 
ing over the whole body. The pulse rapidly falls in frequency, and in a very 
little time becomes exceedingly weak, intermittent, irregular, and finally im- 
perceptible; the muscular strength is greatly reduced, and sometimes almoet 
entirely gone ; the respirations are shallow, feeble, irregular, and infrequent ; 
the general sensibility is very much benumbed, so that marked anaesthesia of 
the surface is present; the skin is bedewed with a cold sweat; the counte- 
nance is anxious, sunken, livid, and the eyes are often protruded, or are even 
gpoken of as glaring; the pupil is genei-ally dilated, but when there are no 
convulsions may be contracted ; gastric buining is sometimes complained of, 
and severe vomiting may be present, but the stomach is not rarely retentive. 
The intellect generally remains unaffected until very near the close, sometimes 
to the very moment of death.* In the collapse of the latter stages of aconite- 
poisoning the special senses may be lost, especially Uie sight. The voice is 
veiy generally extinguished. Convulsions occur in some cases, not in others ; 
and certainly in some instances, if not always, the patient is unoonscious during 
their continuance. Diplopia, or other disorder of vision, has been noted 
in some eases. Death may occur suddenly, especially direcH^ after some 
exertion on the part of the patient, from syncope. 

The symptoms* which aconite prod aces in man and in the lower anio 
are so entirely identical that the conclusions arrived at in regard to the lati 
may be accepted without reserve as applicable to the former. 

Orculadon. — The action of aconite upon the circulation is very decided. 
According to Dr. Acliscliammow (^Reicliei-t^g Archiv^ 1866, p. 255), in the 
frog a moderate toxic dose of aconitia produces at first a reduction in the 
number of the heart's pulsations, then an increase in the rapidity of its action, 
with very evident loss of power, and finally irregular systolic movenjentiL, with 



CARDIAC SEDATIVES. 



179 



very loog intervening pauses ending in diastolic arresL Dr. Rudolf Boh in 
BJid L. Wortmann (Arbeiten awJ fiem IVn/molfig. Laborat. der Wiirzburfffr 
MGchschuh^ 1873) liave substantliillv conGiTued tliose observationB. 

Id ike Ligbcr animuli^ the exhtbition of aconite in mifficicnt doses yields 

lilajf results. In the doj? and Ciit (Bohm and Wartmann, and m}^ own ei- 

^pcrimcDts) there is a stoafly sinkinj^ of the arterial pressure; in the rabbit, 

ftccordlng to B«>hni and Wartniann, tliis full m preceded by a brief rise. The 

fato of the heart a pulsations also undergoes reduction, and there is finally 

dttstolic arrest in these and other mammals. 

The method by which tbo aconite influences the heart \b not certainly 
•ettleii. Aocording to the experiments both of Bobm and of Wartmann, it 
produces a gradual paraJysia of the peripheral vagi, a constant increase of 
the tfitensity of a galvanic stimulation of the pneunaogastrio nerves being 
rec|utred to influence the heart as the poisoning deepens, until finally the 
ra^ entirely refuse to transmit any inhibitory impulse. 

In a isingle experiment, Auhscharuinow (p. 272) found that after section 
of the vagi in the early stage of aeonito-poisoning there was an immediate 
rise botli in the number of the cardiac pu!:<utions and in the arterial pressure. 
From theae data he argues that the Blowing of the pulse during the early 
stage of ocunite-poisoning is duo to stiinnlation of the inhibitory centres in 
the medulLi oblongata. Biihm and Wartmaiin (loc. cit., p, 2C(») repudiate this 
ooQclnsion, becauBe, according to their experience, the phenomena of aconite- 
poiflODing occur in the usual manner allcr section of the vagi, or in atropised 
aniniiJft. It is evident that there is no necessary contradiction in the asserted 
Ikcts of these observers, lu it is posssible that the Flowing of the pulse may be 
doe to two immediate canses, one having it« seat io the medulla oblon^ata^ 
the other in the heait. Although i\m explanation cannot be considered 
proven, it is probably correct. Prof Phijrjie confirms the ilatement of 
Bdhio and Wartmann, ihiit aconitine finally iinralyzes the periplieral vaj^us^ 
whilst Ivcwju agrees with Achscharumow that tliere is a primary rise of the 
pube when aconttia is given after section of tlie vagi^ but states that this 
rise is of very brief duration and b soon followed by the usual reduction 
(^Pratfcr Virrteljcihrs.^ Bd. cxxxi.). It is very certain that aconitia also 
influences directly the heart or its contained ganglia* for Ach.schariimow 
(i€te, eit.^ p. 262) has found that it acts upon the frog^s heart removed from 
the b<xJy, and Li^eois and Ilottot (Juumai de Phyaiolo^t'e, p. 520, 18fil) 
have observed the ordinHry cardiac pltenoniena of aconite-poi^oninj* pro- 
duced by the alkaloid placed directly upon the vi«tcus. BlVhm and Wart- 
mann have ulso noted that tn aconite-poiHoiiini; the furce of the individual 
beat is lessened. Ailer death the cardiac muscle fails entirely to respond 
to gnilvaiijc trritation, its contractility betog lost.^ 



• Oppoitd to mil thtfl ovirU^nco nrp the extr»orditmry and nt present inesi^nciibte ^tAta- 
m^Dtt 'tff Iftintcr Mfickentiti ^Pravtlltonrf, xxh 10U), Ihmt JutonUia has ao eOeot upnn the 
ki«ri, an<l if )i|i|ilie<i dircclly to it ituea aut ^criuu^l^ atTect iu jmUuLiuna. 



ilk 



180 SYSTEMIC REMEDIES. 

Our knowledge of the action of aconitia upon the va&o-motor nerves is 
not complete. Achscharumow, Dr. F. B. Nunneley (/Voc Royal Society, 
p. 46, 1870), and still more recently Dr. Mackenzie, have studied with the 
microscope the influence of injections of aconitia upon the vessels of the 
frog's web, but have been unable to detect any alteration of their calibre. 
The first observer has also found that afler division of the sympathetic iu 
the neck, galvanization of the peripheral end produces the usual phenomena, 
even in the most advanced stages of aconite-poisoning. These facts indicate 
very strongly that aconite does not affect the vaso-motor nerves, and this 
indication is confirmed by the experiments of Bohm and Wartmann, who 
found that when in aconite-poisoning a galvanic current was applied to the 
vaso-motor centres in the medulla, an immediate rise of arterial pressure 
took place. As stimulation of a sensitive nerve produced at such time no 
rise of arterial pressure, the conclusion would appear to be logical that 
aconitia, whilst not affecting the efferent vasomotor nerves or the vaso-motor 
centres, destroys the conducting power either of the afferent nerves or of the 
cord, so that in an animal under its influence no impulse can be transmitted 
from the periphery to the vaso-motor centres in the medulla. 

Nervous System, — Such diverse experimental results have been reached 
by different investigators that it is very difficult to draw any positive con- 
clusion from the evidence. Achscharumow concludes that the paralysis and 
loss of reflex activity induced depend upon the destruction of the conducting 
power of the peripheral motor nerves, because he has found that when a frog 
is poisoned after the abdominal aorta has been tied, reflex and voluntary 
activity is preserved in the hind legs long afler it has been lost in the ante- 
rior portion of the body ; and, at the same time, whilst the brachial nerves, 
as tested by galvanic stimulation, have lost their power of transmitting 
impulses, the protected ischiadic nerves have preserved their functional 
ability. The very recent experiments of Prof P. C. Plugge ( Virchotcs 
Arcliiv, Bd. Ixxxvii. p. 410) confirm these experiments of Achscharumow, 
showing, however, that it is the peripheral ends of the motor nerves which 
are affected, since, when in the frog's leg the lower portion had been pro- 
tected from the poison, galvanization of the nerve-trunk a considerable dis- 
tance above the point of protection caused response in the tributary muscles. 
This concurrence of testimony would seem to prove that aconitine paralyzes 
tJie pei'iplieral motor nerves. The testimony, however, to the contrary of 
this is strong. Bohm and Wartmann in many experiments with Merck *s 
aconitia found that both the nerves and muscles in poisoned animals preserve 
their normal excitability until death ; they also determined that tying all 
the structures of a limb except its nerve did not prevent the usual develop- 
ment of paralysis when the poison was exhibited. In the elaborate research 
of Lieireois and Ilottot, to be spoken of in detail directly, when all volun- 
tary reflex actions were lost, the motor nerves and muscles were still found 
excitable. Mackenzie and A. Guillaud {Arch, de Physiol,, 1875) also bear 



CARDIAC SEDATIVES. 



181 



testimony to ihe samo effect. The explanation of this conflict of teslimony 
i» not to be fuund, as ha« been suggested by C. Ewera (Arch. Exper, Path. 
«, I^harm,, L 1873), in the use of different species of frogs, because Plugge 
eioplojed various speciei^j nor is it in the eiiipluyment of different cura- 
mercial aconitiai*, bec;iuse Plugge experimonted with ull the varieties^ and 
foiidd them to vary in power, but not in ([tiality of action. Those observers 
wbo huve found leiist influence upon die luotar nerves ackriowled»i;e sume 
tii^hi effect, and that when aconitine is Iroypbt in contact with an exposed 
nerve it rapidly destroys its functional activity; also that after death in the 
Kcoijittz^ frog the nmtor nerves lose their irriti\hiliry more rapidly thun 
Donual (Lit^geois and Hottot, GuiMaud, 8. Rin^^orand 11. Murrell). Furlher, 
it ha& been noted that when in frogs the convuyoas are very tievere the 
motor nerves seem temjiorarily to lose their functional power from cxhuus- 
titin (Maekeniie). Mackenzie afErros {Practlt loner ^ xx. \M) that aconitiii 
has a primary stimulant effect upon the motor nerve, ant 1 cnuses at tirst a 
dkttnct augmentation in the irritabUity both of nerve and of muscle. 

According to Dr Li^geois and M, Hottot (he. cit,^ p. 533)^ in aeonite- 
poisoniog loss of sensibility occurs in the frog's legs siinultaneously with or 
cren before the disturbances of respiration, and long before the power of 
Tolunlary motion is lost, and even when the reflex activity is intact. This 
sensory paralysis, according to the experiments of the French invcsligatora 
just quoted, first appears in the hind legs of a frog poisoned witli aconitia, 
and has not its primary seat either in the peripheral nerves or in the spinal 
eord» for it was found that tying the aorta close to its uhdoiuinal bifurcation^ 
io as to prevent access of the blood — re., of the poison — to tJje posterior 
oeires, did not affect the development of the anicsihesia; furtlier, that closing 
tbe artery nearer its origin in such a way as to shut off the circulation to the 
oonl and spinal nerves, but to i\llow the passage of the blood to the cere* 
biTUO, did not cause sensory paralysis to come on more slowly than is normal 
in poiMining by aconite. 

Of course it is possible for the peripheral ends of the sensory nerves to be 
pandyxed either at the same time that the perceptive centre is, or aflerwards; 
ftnd of course, tlie centre being paralyzed, it becomes very difficult to deter- 
mine whether the periphery is or is not affected. Li^geo'is and Hottot assert 
thnt this paralysis of the centre occurs before any serious iuiplicatiou of the 
peripljeric nerves, because after aconitio anajsthesia had been produced 
atr)'ehnia was able to induce tetanus; aflerwards^ however, the extreme 
peripheric nerves became affected, so that irritation of the skin in the 
doubly- poisoned frog would not provoke con\HilsionB, even at a time when 
irritation of the trunk of a nerve would produce general reflex motor dis- 
turbance. At last galvanization of the nerve-trunk itself failed to induce 
resfionse. From these facta Li<?geom and Hottot deduce — very logically, I 
think — tlie conclusion that aconite induces ancesthesia by paralyring, first, 
the perceptive centres; secondly, the peripheral extremities of the norvesj 



182 



SrSTEMIC REMEDIES, 



thirdlj) the nerre-tninks theiuaclves. The obtetrers alluded to also ooii- 
firmed this eoucluaiou by other experiments than those already noticed. They 
found that akhout^h aconitia applied directly to a nerve-trunk paralyzes ita 
BenBihility^ yet when the yeius of a frog's 1^ are tied and the alkidoid m- 
jeeted into the artery lind allowed to permeate the tissues of the leg, the akin 
loses its sensibility long before tlie Tjerve is affected- 

In regard to motion, Liegeois and Hottot found that in a certain stage of 
aconite-puisoning the frog lies with his limbs extended, relaxed, and perfectly 
panilyzcil, and yet is capable of executing vigorous voluntary movemeiita and 
evinces nearly normaJ reflex activity. Tliey attribute this condition of ap- 
parent but not real motor paralysis to loss of Bensibility from paralysis of the 
perceptive centre, as the unpoisoned frog evinces the same phenomena aAer 
division of a)l the posterior spinal roots. After a time the reflex activity is 
also lost, the power of voluntary movement remaining. Li<!'*geois and Hottot 
believe that this loss of reflex mitivity is spinal ; but in their experiments 
upon the conjoint action of aconite and strychnia it wjv? found that at u eer- 
tain stage, when no amount of irritation of a nerve would induce convulsions, 
a slight direct irritation of the cord would cause violent strychnic spusnii^L 
This would seem to show that at least the earliegt abolition of the reflex 
activity was dun t-t) paralysis of the afferent nerv^e-fibres. 

In some particulars the researches of Ltegeuls and Hottot have been 
confirmed by the later studies of l)r. George Hunter I^Iuckenzie (Loiulon 
iVactitioner^ XX. p. 100)» The pe^si^!tence of voluntary movement after 
abolition of reflex actions, which was flrst noted by Bohoi and Wartmann, 
and afterwards by Lit^geois and Hottot, as well ws by Mackenzie, proves that 
at a certain stage of the poisoning, whibt the motor peithway from the brain 
along the anterior columns und the efferent nerves is open, either the sensory 
nerves or the receptive centres of tlie cord are parulysted. The experiments 
of Li^geoLs and Hottot upon the joint action of aoouitia and strychnia are 
also accordant with those of Mackenzie, for that observer found that when 
a nerve was protected from the poison by tying its supplying artery, irrita* 
tion of it caused reflex actions when the remainder of the frog's periphery 
was insensible ; also that there is a st«ge of poisoning in which irritation 
of the extreme peripheral nerves fails to induce reflex moveniouts, although 
such movements are called out by irritation of tlie sensory nerve-trunk ; 
later irritatiun of the trunk was piwerless, whilst irritation of the posterior 
columns of the cord still produced wide-sprestd movements. It must there- 
fore be considered proven thiit aconite pttra/i/::es the semmy nervfSj cot¥^ 
mencing al their peripheral emit ngif^ and tbat the loss of reflex activity is due, 
at least in great part, to such cause. 

Thoapp;in?nt contradiction between those investigators who have reached 
the conclusion just giveo and those who have found ihe motor nerves 
ospeeially affected (see p. 178) can, it seems to me, be reconciled only by 
the theory that aconttlne acts upon the peripheral ends both of tensorf/ and 




CARDIAC SEDATIVES. 



183 



of moior nerves ; wKich nerve is raoat severely affected may poe^iblj tlepeod 
upon the siao of Ihe dose employed, or, more probably^ upon the pbyt^icul 
ocmdltiou of the frog» The excesnive uutubut^sa and tinjiliiifr of the local 
ftud gencrul action of aconitiDC upon m^ni iadicatc that m the kifihcr 
aaumait it e^peciaU^ affecfa the sensory nerve endings. 

The eupposed action of iieonitia upon a higher perceptive centre is at 
pjrCBent very doubtful. S* Hinger and 11. Murrell (Journal of Physlohtfif^ 
i-, Noa 4 and 5) deny the accuracy of the delicate experiments of Ll6geois 
and Hottot. Curiously enough, Drs. Hiuger and T^Iurrell, whilst doubting 
tlie experimeuis of Li^'geoit^ and Hottot, accept the concluslous founded upon 
these assorted erroneous experiment!*, see mi ugly becuui?e I hey themselves 
have found that aeonitia causes aboliiion of reflex action more ntfiidly in 
brainless than in normal frogs. It is evident that even if this were invariably 
tho case it would in no way prove the eonclusions of Li^geois and Iluttot. 
Further, the experiments on brainless frogs were only three in number, and 
i& is perfectly possible that the rapid reflex palsy was simply the result of 
butmchian idiosyncnisie?. The only safe conolusion on the evidence is that 
the evidence dtjes not warrant any conclusion. 

It is evident that we hiive not exaet knowledge as to how aconite aflft^ctg 
the nerve-centres/ but the nervous phenomena of aconite-poisoning seem 
to ine explainable by the action of the drug upon the sensitive and motor 
BTves. 

Respiration, — The action of aconite upon the respiration is very decided. 
In mammals the respirations, under the influence of the drug, are slow, with 
i prokmgcd expiration following immediately upon the inspiration, A fter the 
cpiration there is a long puu^e. The whole breathing cycle resembles very 
much ihiit occurring after section of the vagi ; and, like the alteration in 
lithbg after this section, seems to be due at least in part to paralysis of 



* Experintt-ntj^ by MAckonzl^i on frogfl hiive jtolded apparently contrary rentitU to ihoso 
of Bdbu) nud WftfUurtnn a* to iho olfeoit arremo^Al of tlui intluenco uf Setschcrmw's eentr« 
apo<i the ol>^l in Jw^uoiUxeNii froga. The flifTorenoe prolmbfy depends upon difference in th« 
tliiMMi «uip1t»yod* Ilohm nod WurtiMuiiit UihUnotly ^Lutc thiil when minute doKi''4» of iicouttiii 
mro ciiipJf'jcd there ij n priintiry pcri^id of cxcitcnii^nt of Lh« ^ipiiiui ceutrci*. Mjivki'Usiiv 
h%m found tli<it [he (H»nvttl«ii»ns whiuli urc i^o j«tivare in iVog^t nfter flujail i|iiikiUittL«.s ul iicctiiitv 
mr« cLt«;fly «if »pin)il uri^in, but that the perif>hcra1 niat^r np|Jitratiifl shares tbe HituiuUtiun 
utth ihc •piii*l motor triw:t. M. (jui]Uu>l {he. cit., p* 7(U<j iilso iittirMsf thi» priuiiary stimu- 
tani »pinal a^aitm. If it ext^t iit nil in niummal?!, it U in Iheni ouutptctvly mii^keJ, Tho 
eontuUiofii! **>cn in lujoijite-jwi^oniug in mvae inanimnlw lire tofebrnl, not spinal, us I hiive 
eiponuivntivDy detcnuiuod thtO tliey d» not oeeor in tboM portloas of the body eeparated 
by flpiu»t ^t.'ction fttiin oercbriil intliienco. 

As Biihm &jtd Wartiiinnn found tbnt the roflex activity vrtit lo«t more rapidly than tlie 
P'lwer of vohintJvry movement, and thtit no increase of rcflcJt jiotivity occurii in the aco- 
nilixed tn>^ vrUtiu ihe curd i^i eut «o m to rek*u«e it frum'tlie infftienou of Set^chenow's 
f«lleit inhibitory ecotrcs, they draw the wncluMion Xh&i the acoukia Hi^t deprersc* tbe 
nflvv mftlvity of the Meni^ittve ifptnnl centres aud afterwartJU Chat of the motor fpinnl 
9ailr««i» tntil Iho cord i» completely parnlyicd. 




184 



SrSTEMIC REMEDIES, 



eensorj or afferent fibres. The koown influence of aconite opon the periph- 
eral afferent nerres in general suggests that the poison di«tur^>s respiration 
by paralyzing the peripheral afferent fibres of the vagi. Mackenzie states 
that in the aconiiiied animal section of the vagi produces no effect on the 
respiration; and Bolim and Wartmann (p. 127) affirm that aconite produces 
its usual effect after division of the nerves. It ia plain that even if the 
aconite does paralyze the peripheral afferent vagi, it must also act upon the 
respiratory centres^ since arrest of respiration could not be caused by afferent 
palsy* As the arrest occurs tu tlie frog be lore the motor nerves are affected 
by the poison » Ll^geois and Hottot believe that the disturbance is centric; 
and I think there can be no doubt that aconite h a direct drpteuani and 
pandf/sant of the refplratory centres. 

Close studies of the action of aconite upon the temperature in bcalthare 
wantim^'. Achscliarumow ftmnd in fatal poisoning a fall of about 3^ C.* 

Therapeutics. — Our knowledge of the physiologicaJ action of aconite, 
although imperfect, is Bufficient to show that there are only two or three 
indications to meet which the drug may be used. 

The first of these is to lower arterial action^ and often, with it, excess 
of temperature. For this purpose aconite is very valuable. I have never 
used it in those cases, such as pnetimtmia^ in which a sudden and very 
powerful effect is desired, simply because veratrum viride seemed to me safer, 
more readily controlled, and et|Ually effective. Aconite may, howeveTj be 
used with ver}^ good results in these cases^ and especially in such diseases 
as pen'ttmiti^j in which it is very important to avoid vomiting. My own 
experience with ic has been in fevers of a sthenic type not dependent upon 
flo de6p-seat«d a cause (as an example may be mentioned the febrile move- 
ments of severe, acute inumidar rheumatism) ^ and in the ephemera or irri- 
tative fevers of childhood : in Buch cases its influence for good is often very 
decided. In the early stages of scarlet fever and other exanthemata^ when 
not decidedly adynamic in type^ it is very usefuL In the reflex fever which 
sometimes follows the passage of the catheter or bougie (the eo-called urethral 
fever) it is very effideot.| 

In some cases of hypertrophic of (M hearty when the valves are perfect, or 



* MM, <irt'bivnl »tni Duqwejpual {L'tlmoH Phttrmt$ceutiqut, Aug^. 1871) bftv© couiniu- 
nicaied to the French Aciideiijy vamo dXperimenlA upim trOj^s with crj^mUtffizfti acnnitiit^ 
wbo»o reffutU arc so strikioglv difrvnint fmiu tboso uf other cxpcriniciitoni u^ to itidtcjile 
the oxiflt(?ni]e of hoidu fallacy ; [K>j^)<ib!v tb^ alkalolil ut>ci\ hy tb«u mn$ aot the fame fif Iho 
•mtirphoug ationiUn. Thpy found Id tbo frog, iift^r cuifiU doac« (^ niilligmmme) of their 
alkuluitl, thftt the heart oontiuiieii to beat ((tDudily and regul^irlj nfter nil fiQWcr orKpoutii- 
oeous or reflux movement hiiLd been lo^t, that icnsniion wns preserved as long &s anj power 
of motion exintC'r], und that the motor nerve-trunks were itfirtilyied. After Inri^o dofci 
(oBe miirigrtiuuue) they ob-^ervud ^utl^lcn mrrest of the heart's fiotion. 

t The following formula affords an excellent eombmatioii : ^ Tr. Mooit. md., gtt« i ; 
Bpi ether, nitrooi^f 5o ; Mist potaaa. citrat*, (|. b, ad f 51. E. — Besaertipooafiil every twc 
bour« for a. child three year* old. 



CARDIAC SEDATIVES, 



185 



wlieii, the valTes being diseased, the hypertrophy is greater than is ueeeasary, 
aoDiute is of use to control cardiac excitement When, however, there ij* 
dikUiilioii of the heart or any degenenitiun of the heart-muscle, it ia an 
eMeedingly dangerous remedy^ and h also at all times to be avoided if the 
hjpeft*x)phy be not excessive. 

A second indicatioD» which aconite mijiiht be used to fulfil, is to allay 
tpntm. As, however, its influence upon the motor centres and nerves is 
macb less than upon the S4^n»itive eentrcfl and nervea and upon the heart, 
the indication h better met by other remedies. 

A third indication, which it would Bcem from its known physiological 
■etioD that aconite should meet, is to relieve over-exeitatioji of th^i 9enfitiv€ 
menptt. Clinical experience has confirmed this. As lun<j; a;i;o u» 1S34, Dr. 
Tumbiill ( On (he Ft^panitum^ and Medical Employment of Acfmitiua by 
tAe SmUrmic Alvthoil^ London, 1834, — On (he Medical Proiierfteit of (lie 
Xaimal Order Ranunculficest^ London, 1835) called attention to the use ot 
the alkaloid in neuraltpa ; and his estimate of its value has been confimied 
by Dr. A, Fleming {^An Inquiry into the Phytioluffical and Medicinal I^'oper- 
tim of the Acomtam Napellus^ Ediiibui*gh, 1845) and by other obsenrerg. 

In cases of rheumatic neuralgia dependent upon an acute exposure tx> cold 
and attended with more or less febrile disturbance, in combination with other 
SQitable remedies aoonlto is ofleu of great fiervico. In chronic neuralyia^ 
laociated as it always is with a lowered systemic tone, the remedy is less 
efficient ; yet in some cases It seems to give relief Owing to its very marked 
lood benumbing influence, applied to the painful part it is sometimes very 
QSaliil. In my own experience, this local use of it has, however, very seldom 
heeu effective when, as in vnijrainc^ the pain is of centric rather than of 
peripheral origin. 

Given in full doses in the reflex vomiting of pregnancy ^ aconite is often 
advantageous, acting probably by benumbing the sensory reflex centres, or 
pooaibly the afferent periplieraJ nerves, I have noticed that relief lasts only 
00 long as decided constitutional effects from the drag are apparent. 

ToxicoLOOY.^ — Aconite is an ejtceedingly powerful poison, one-twelfth of 
a grain of the crystallized alkaloid being, according to Duquesnel, sufficient 
tij kill a rul^bit in a short time. Five grains of an extriiet and eighty 
minims of a tincture are Siiid t^) have caused death (Keichert, Fhilad, 
Med, Timrfty Nov. 1881, ji. 105). The symptoms usually come on ia 
a very few minutes. In the shortest case we have met with, death 
occurred in thirty minutes. The average time of death (Reiehert, loc, 
eit,) is three and a third hours: tlie longest recorded case being five and 
a half hours. 

The jHiculiar tingling is the only diagnostic symptom, but it is very char- 
acteristic The fijst iodicivtion for treatment is to evacuate the stomach and 
muh it weU out with the stomach-pump. Alcoholic stimulants shjuld be 
fbedj adminiatered, hot and conoentratcd, and the injection of ammonia into 



186 SYSTEMIC REMEDIES. 

the veinp may be practiced. Great care should be used to keep the patient 
absolutely quiet, upon the back, with the feet a little higher than the head. 

Recertly attention has been drawn to the employment of digitalis in 
aconite-poisoning. It was discovered by Dr. J. Milner Fothergill {Di^talis, 
London, 1871, p. 6) that the heart of the aconitized frog is visibly relieved 
by the use of digitalis. Even when all cardiac action had apparently ceased, 
digitalis had power to recall the systolic movements, until finally a return 
to the normal state was brought about. In a case reported in the British 
MedicalJotmial of December 11, 1872, recovery occurred after the ingestion 
of an ounce of Fleming's tincture of the root.* The patient, when first seen, 
was apparently dying. Twenty minims of the tincture of digitalis were 
hypodermieally injected, and after twenty minutes, the man having revived 
sufficiently to swallow, a fluidrachm of the tincture with ammonia and brandy 
was given him, and was repeated twice within the hour. Dr. C. G. Carleton 
(^BriL Med. Surg. Jour., Oct. 1879, 544) reports a case of recovery after 
the ingestion of 3 fluidrachms of the tincture in which 60 drops of tincture 
of digitalis were given hypodermieally. The evidence, though as yet scanty, 
seems to me strongly in favor of the use of digitalis in aconite-poisoning. 
In a successful case treated by Dr. Elliot (Lancet , 1878, ii. 917) nitrite of 
amyl freely inhaled seemed to do great good : a flnidounce of a concentrated 
aconite liniment was thought to have been taken. Ammonia injections were 
unsuccessful in a case reported in the Australian Med. Jour.y 1879, i. 283. 

Administration. — Aconite is never used in substance. The dose of th*5 
tincture of aconite ( Tinctura Aconiti — 1 to 2.5, U. S.) is one to five drops, 
repeated every one to three hours pro re nata^ its effects being always 
watched. Fleming's tincture is a stronger preparation (Jxss to Oj). 

The dose of the extract (^Extractum Aconiti, U.S.) is one-quarter to 
three-quarters of a grain ; of the abstract {Alstractum Aa/niti, U.S.), one 
grain ; of the fluid extract (Exfractum Aconiti Fluidum, U. S.), one to two 
minims. The tincture or the fluid extract of aconite is very frequently added 
to stimulating and anodyne liniments. 

The alkaloid (Aconitia) is not officinal, and, on account of its intense 
activity, should not be given internally ; and even its external use requires 
care. The ointment may be made of the strength of from two to ten grains 
to the drachm. 

AOIDUM HTDEOOYANIOUM-HYDEOOYAHIO AOID. 

Pure hydrocyanic acid is a colorless, transparent, volatile, inflammable 

liquid, giving rise to giddiness and headache when smelled, and having, it is 

said, a burning bitter taste. So poisonous is it that when inhaled it causes 

death, and it must be handled with the greatest caution : smelling and tasting 

* In Brit. Med. Join'n., 1877, i., i« a cuso of recovery from two Buidouncea of the British 
tincture. It seems to ine probable that the tincture was not of full strength. 



CAJWIAC SEDATIVES, 



187 



of li are excessively dangeraus proceedings. It is indeed an iinperaiive rule 
that no one should experiment with aiihydraus pnissie acid alone, or under 
any circumstances in summer, or in a wann roiim, or in an opartiiient wliose 
open windows and doors do not admit of a free draft of air. T!ie chemist 
BcheeJe.tlie discoverer of prussic acid, is believed to have been killed by the 
inliJLlation of the fumes of this material^ whose poisonous prnperties were 
first pointed out by the Berlin apothecary Schrader in 1803, The anhydrous 
add is soluble in water and alcohol, but is never kept in tlie shops^ and is 
Qot officinal 

Hydrocyanic acid of common medical parlance is the officinal Dilute N^dro- 
cyanic Acid (AcrDCTM Hydrocyamicum Dilutum, U.S.). a colorless, wateiy 
solution, containing two \^t cent, of the anhydrous acid. Its odor and taste 
are the familiar ones of peach-kernels and bitter almonds ; its reaction ia 
IkinUy acid. According to the directions of the 11. S, rhnrmaeopoeia, it is 
prepared by distilling a mixture of ferrocyaiiide of potassiLtm, tiulphurro acid» 
and water^ or by precipitating cyanide of silver from its watery solution with 
muritttio acid. With solution of nitrate of Milver added in slight excess, one 
hundred ^^rains of it produce a white precipitate, which, when washed with 
rater until the washings are tasteless, and dried at a tempeititui'e not exceed* 
; 21 2"^, weighs ten grains^ and is wholly soluble in boiling nitric acid. 
The precipitate in this case ia the cyanide of silver^ and the amount 
afforded shows that the liquid contains the officinal percentage of anliydmua 
prussie add. 

Aa hydrocyanic acid haa a great tendency to undergo spontiuieous de- 
composition, especially under the influence of light, it should be kept in 
well-stopped, dark-colored bottles, 

PUYSIOLOOICAL AcTlON. — In warm-hlooded animals, poisoning by hydro- 
cyanic acid divides it*?elf naturally into the acute and the subacute ; death oo* 
curring in the first in at furthest ten niinntes, in the second not at all, or else 
only after the lapse of a longer time than that noted, Afler a full dose of the 
strong anhydrous acid, the animal ga^ps once or twice, and then instantly falli 
in a tetauio or clonic convulsion, or else drops motionless and powerless upon 
I side. In either coAe, at once the signs of asphyxia manifest themselves, 
Eld grow more and more intense, until they end iu total arrest of respiration. 
I heart beats irregularly, often at first slowly and strongly, with intervalu 
suspension of movement, but always becoming weaker and more rapid in 
its action, until, after the breathing has ceased, its efforts gradually die away, 
li* the dose has been enonnous, the lieart and lungs may stop acting at ooee ; 
otherwise the cardiac pulsations may continue some minutes after the arrest 
of respiration. Ordinarily, three distinct stages are apparent : a first, very 
brief one, of difficult re8i)iration, slow cardiac action, and disturbed cere- 
bnition ; a eecond, convulsive stage, with dilated pupiis, violent ccjuvulsions, 
aucon^ioueonQflSy loud cnes, vomiting, oflen spasmodic urination and defecation) 



188 



SrSTEMIC REMEDIES. 



erections^ etc. ; & third psriodj of aspliyxia, collapse, and paralysis, sometlmefi 
hiterruptod by partial or even general spasTiis. 

The slow flirm of the poisioning follows the exHihition of the poison in an 
amount just sufficient to kllL After the log^tion of such a dose^ no phe- 
nomena are offered for some eeeonds; then the broithmg heeomes labored, 
and the pulse slow and full. The animal perhaps crieii out, and muscular 
tremblings invade the whole body, to give place, in a very short time, to 
clonic and tonic convulsions, which ccmtinue at inter\'als until the third stage, 
that of collapse, is developed. The convulsions are less violent and less fre- 
quent than those of the acute poisoning ; all the gyniptoiiLS noted as occurring 
during the second stage of r^pid cases are present in the corresponding jjeriod 
of the subacute poisonings although less violent and less intense in their mani^ 
festations. When the third stage is deVL"k)i)ed, the anaesthesia is marked, 
affecting 6r8t the hind legs, but finally spreading to sill parts of the body, and 
even being couiplete in the widely-dilat^id pupil Death finally resulta from 
failurtj of respiration. Recovery nmy occur even after the conjunctiva lias 
lost it« seusiljility ; the return to life by a Buhsidence of the symptoma ie 
usually rapid, so that generally in from one-half to three-quarters of an hour 
the animal will he eating as though nothing had happened. Coullon, Low- 
ever, noted pei^istciice of paralysis, in some cases, for days. 

In man, prnssic acid produces results closely parallel with tht>&e which it 
causes in the lower animiJs. The symptoms oonie on suddenly. In a rooroent 
or two the individual falls to the ground insensible and convulsed, the respi- 
rations arrested or occurring at long inter^'als, the eyes salient, the pupil 
dilated, the mouth covered with bloody froth. If the dose be sufficit?ntly 
large, death may occur in three or four minutes ; if lesa have been taken, 
deep insensibility, tetanic or clonic convulsions, dilated pupils^ a bloated 
countenance, cyanosed euiface, set jaws, and irregular respiration, eonstituf* 
tlio chief symptoms. The breathing is mostly convulsive, with deep, forcible 
expinitions, hut in some cases it has been stertorous. Death result* from 
asphyxia, Afl-cr small toxic but not lethal doses of prussio acid, giddineaa, 
lightness of the head, nauaea, a quick pulse^ and muscular weakness, are the 
chief symptoms. 

Action on Blood. — ^As early a^ 1814, Dr, P. B, Vieti (Medicin, Jahrh 
d, l\ k, Oesferrekh, Staatejij Bd. ii., 1814) called attention to the change 
of color that occurs in the venous blood of aninjsils poisoned with pruseic 
acid ; and his observations have been confinned by E. L. Schuharth (//c/m't 
Arcliiv/. Med Er/tfhrung, Berlin, 1824)>hy J. F. Sobemheim {Htnulbuch 
der Frakt. Ttrxicohgie, Berlin, 1838), and by Dr. Coze {Gazette Midicale 
de Pari\ 1849), In his Ler.om sur leg Subatanees toxifpteM^ p. 193 (Paris, 
1857), Claude Beniard rcAffirms the occurrence of these changes^ and fiirther 
states that if the animal die suddenly the blood in the veins and right heart 
is found of a bright arterial hue at the poat-mortem. Notwithstanding all 
this testimony, J. II. Bischoff ( Lkber Vergifiungeii nebst eimgen Ver$uchen 



CARDIAC SEDATIVES, 



an Thteren^ wdche mit Blmtsaure, Cf/ankalium und Artenik angestdU 
teurd^n^ Wicn, 1844) and immeroos other observers have found tbat aJ\^r 
dctUi troin pmssic acid, either in man or other mamniaJsi nothirig but dai'k 
veocms blood exists in the body. Of the correctness of this observation 
Ibtre can be no doubt. 

Prof, W. Prefer {Die Blamiiure^ Bonn, 1870) bfu* afforded by hb ex- 
periments an explanation of these apparently contradictory facts. He found 
tliAt directly aRer the exhibition of pruf^tc acid U\ a tnanimaJ tho blood 
becxnnes, even in the veins and in the right heart, of a brij^ht arterial hut% 
but that ai\er a time this color darkens into the blue of venous blood, and 
finally, even in the arteries and in the letl ventricle, only blofid of such char- 
acter is to be found. l)r, Carl Gaethgenf^ { Unppe'ScYlcr's Medtciniitch- 
chrtni^^he Utifenvchnru/eft, Berlin, 180l>, p. 324) has, irj a number of expcri^ 
luePts, confirmed thin, so it mast be accepted ns a fact. When an animal 
di«s stiddenly from cardiac paralysis, during the first stage of poisoning, this 
prnfMiTe arterialization may bo Ibitiid jifVr death, as mcntiunod by Claude 
Bernard; and, as Prcycr first noticed, in cold-blooded animals the bright 
color |>erBists for many hours. By sfwctroscopic examination Prof. Proyer 
(kpc^ n"/,, p. 95) found that the dark blood of prussic acid poisoning is abso- 
\au*\y or almost free from oxygon, showing only the absorption bands of 
deoaudlxed haemoglobin, whilst Gacthgens (loc. ciV,, p» 328) has discovered 
that the red venous bhxid of the first stage of the jwisoning shows very 
dearly the absorption bands of oxyhaamoglobin. The first question which 
ariaea at this juncture is as to the causes of these changes of the blood, lUt 
primary excessive arterialization, its seeondary excessive carbonization. Prof 
IJcippe-Seyler affirms (jl/<r(/it'/^H.hT/j-f:/i^miWttf Uhtermchnn^en.jt, 140, Berlin, 
18G7) that the appearance of red blood in tho veins is bec^jiuse the rod 
blood-corpuscles have l>ccn so acted upon by the pois*>n as to have lost their 
alulify of yielding up their oxygen in the capillaries. Dr. Carl Gaethgena 
{JUd.^ p. 325) has by an clabtirate scries of experiments shown tbat in the 
first stage of prussic acid poisoning much less than the norma] amount both 
of earlionio acid and of exhaled oxygen is eliminated. The lessened ex> 
halatioii of oxygen probably depends simply upon a lessened inlmlation of 
oxygen, owing to the disordered respiration, Tliat the lessened excretion 
of oarbotiio add is not due to the same cause, however, is shown by the foot, 
detenntned by Goethgcus (^c. ciV., p. 347), that the percentiige of the acid 
in the expired air is less than normal^ whilst that of oxygen is greater than 
normal. It is evident that if the lessened excretion of carbonic acid were 
prtniuced by the entrance into the lungs of an amount of air insufficient for 
the wants of the system, the expired air would (X)nlain more than its normal 
pn^portiun of carbonic acid and less than its normal amount of oxygon. 
The observed phenomena seem to me to prove that during tho first stage of 
prussic acid poisoning oxidation is arrested. They do not demonstrate, how* 
6ver| that the arrest ia due to a direct action of the poison upon tlie blood- 



ii^i^ 



190 



SrSTEMlC HEMEDtBS. 



ooipnsclcs. The probabilities of such occurretice are rendered very slight by 
the investigations of Gafith*;ens himself, for he found that when the experi- 
ments were prolonged from seventeen to forty-four minutes, much more than 
the nonnal amount of carbonic acid was exhaled, a feet in accord with the 
exceaaive carbonization of tbe blood known to take place in protracted hydro- 
cyanic acid poboning. As it seemB incredible that a subst^Lnce should one 
minute paralyze the ozonizing power of the blood-corpuscles and the next 
minute increaBe it, it is very impmbable tbat the super-arteriaUzation of the 
blood in the first stage of jirussic acid poisoning is due to a direct action of 
the poii^ni upon the red disk. 

Preyer \\m proven {he. cit., p. S5) that when to blood at the temperature 
of the body liydrocyanic acid is added, the spectrum after a time is altered 
and new ahsorptioti band?* appear. Tbese bands are due to the formation of 
a new compound by t!ie union of the liiemoglobin and the hydn>cyanic acid. 
This sul^tance, c^anoh^moghhin^ was first discovered by IIopi>c-Seyler ( Vir* 
chotd's Archw, Bd, xxxviii. p. 475), and has no ozonizing power whatever; 
to its rormatiun, no dt»ubt, is owing the loss of ozonizing |>ower by bhxMl to 
which hydrocyanic acid is added outside of the body, a phenomenon |>ointed 
out by Sehonbein* (Schmitlfs Jahrhiicher^ Bd, cxL, 18G8, p. Itil ), and 
indicated even earlier by tbe researcbes of Prof Harley (LomJon Phlhmph' 
teal Trail met km fi^ ISGS, p. 706). f Tlie latter observer found tlnit the blood 
taken out of tbe vtins of a subject forty-eight hours after death from pnissic 
acid poisoning, and thoroughly arterialized by shaking witli air, and then 
allowed to stand, yielded gas containing llt.SG parts of oxygen, 80.44 parts 
of nitrogen, and 0.0(> parts of carbonic acid. 

These facta at first slight seem to prove the theory of Hoppe-Seyler, to 
which indeed they no doubt gave origin. Preyer has s<hown {he. at., p. 95), 
however, that the dark blood of prussic acid poisoning has not lost its power 
of oxidization, for on being ehaken with the air it assumes tbe red arterial 
hue ; and Drs. LceonhL* and Meuriot {Archives G^neralrs^ t xi., 6c s^rie, 
p. 539) have determined that artificial respiration will produce the same 



* lu tbo fame tnomoir BcbrEuhdn calle Ktiealbn to tbe fact tbtil pruBBto aoid dcitroxi 
aliii) ibe uzonixkig power of living vugetnblea, i»oh oj roots, fuugi, clc» 

f AecordiDg to Br. E. Ray Lnnkefltet {Pjiiifjer^a Archive ISfiH, p. 4JJ2), wben blr>od il 
ibtkeo with OTnnogi'Q gnfl, nncl nllowoiil to *<tund for two or Ihrwe bourf, Hio ffKNatram* 
tsbangea arc exactly the sutne as oJTter similar treatment of hbiod witb CO. Tlie eom* 
pound of cyanogfD and b«i?mathi (Cj^lb) offers not only tbe identicat epectrum of 
CO,Ilb, but, like tbe JiiUer, it unjkflTected by roduciDg agenlg. After tbe blond standi 
ftwhile^ BGflording to Dr. E. Ki^y Liuikcster, tbe F|>ectrum of liydrocyanie acid (11. CN) 
be«omofl Ttsible in it, and tbe Cy^Ub undergooii oonfersioa into tbe cyauobtpmoglobin 
(Cy^llb) of Hoppe^Scyler. 

Any one d(^girolls of investigating thii Bubjeet more deeply thiui can be done in • work 
like) the prcuenf i^bould ootiault espetiialiy tbe pjiperi by Hoppe*Seyler, Virehuw'n Archiv^ 
Bd, xjcxviii.y and icattered through the Meftkmhch-chemiacht U*ii^9vchHnytn ; by HbHcj^ 
L0i*dvn Pkihtojthicai TramacHom, 18fl6, p. 706^ fttid by Preyer, PJfilg9r'9 AreMm^ 
p. 395, 




CARDIAC SEDATIVES, 



191 



IpBult ID ihe poisoned animal. MoreoTer, the epectroscope shows plainly 
lliat the kffiiDOglobin exists in the blood cither in its pure stJite ( Preycr, loc. 
ci'l-, p. 95), ar else as oxyhsenioglobin ( W. Lftschkcwitseh, RdcherC 9 Archiv^ 
p. 652, 1868; lliller and Wagner, Lftncet^ 1877, ii. p. 933)^ and that no 
cyanohtemoglubin is present* Tlie reaction between hytlrocyiinic and heemo- 
glabia is one reijuiring some time, and evidently does not oceiir in poisoning. 
On tlie whole, therefore, I think that the cliemical evi deuce clearly ehowg 
the falsity of the iheor}" that prusaio acid acta in the body directly upon the 
tf*d blood-eorpuselea, 

Preyer {loe. ciL, fweiter Theil, p* 88) has shown that the excessive oxy- 
genation and the subsequent excessive carbonization of the blood are not 
peculiar to hydrocyanic acid poisoning, but are ocjually present ai^er the 
exhibition of sulphuretted hydrogen, and oven after mechanical closure of 
Uie mouth and nose. It is possible that an increased arterial pressure, an 
incitased nij>idity of circulation, may cause the blood to pass too quickly 
U&rough the aipiUaries to aJlow tinje for the usual changes j but this has not 
been proven, and at present it niutst be aeknuwledged that we arc ignorant aa 
to the Immediate cause of the blood-changes in these cases. 

It is possible^ although seurcely prububle, that the changes in the color of 
the blood are due to alteration in the form of the corpuscles. According to 
Ernst Geinitz (Pjiu^era Archw/Ur d. ^.mmmU Phydohgie^ Bd. iii,, 1870, 
p» 46), outside of the body prussic aeiJ produces in the blood-corpuscles 
of the Ch>g, first, a shortening of the long and a lengthening of the shoH 
diameter, and conse<|uently a rounded funn, then granulations, and^ Enally^ a 
folution and setting free of the nucleus. In frogs poisoned with prussic acid 
t rounded form of the corpuscles was cotnmonly exhibited, and sometimes 
graoulaiions were present. M, Geinitz also found that the red disks of 
mammalLin blood, exposed to the vapor of hydrocyanic acid in the moist 
chamber of Strieker, become first somewhat asymmetrical, then mulberry- 
shaped, and finally undergo molecular deistruction. In poisoning of mammals, 
acxjording to the same investigator, the granular blood-corpuscles are commonly 
met with. Preyer (he, ciL^ CTreiter Theil, p. 91) confirms the observation of 
G«init3 so far as the action of the poison upon drawn blood is concerned, but 
both he and Hiinefeld (/?er ChemUmm m tier (hierlschen OrganUatiim^ 
Leipeic, 1840) assert that immediately ailer death from prussic acid the 
corpuscles ofier their usual characters. 

Whatever may be the oiuse of the changes in the blood, the experiments 
of Lewisson {ReicJiertt Archn\ 1870, p. 352) would appear to prove that 
the action of the poison on the nervous system is a direct one, and not due 
to the^ changes in the vital fiuid, for the observer mentioned found that 
prussic acid acted upon the bloodless *^salt frog*^ as upon the normal 
batrachian. 

Action on tha Heart. — The action of hydrocyanic acid upon the heart 
yarifis aooordlng to the dose. In sufficieut amount and concentration, it 



192 



SrSTEMIC REMEDIES, 



produces instantaneous diastolic arrest^ which is either permanent or re-oceois 
after a few slow feel>le beate (Preyer, ^>c. crV., p. 52^ and Drs, Lecorch^ and 
Meuriot, Archhrx Gininde*^ t. xi., 6e s^irie, p. 543). As early as 1626, 
Krimer fauod that prujssic acid placed directly upon the heart of the frc^ 
produces arre8t of it^ boat luid loos of its muscular irritability. Preyer has 
conliriued tliis, and it would seem to be proven that the cardiac arrest spoken 
of above Ls due to a direct action upon the heart-muscle or its contained 
ganglia^ yet that after cardiac death from prussic acid the heart responds to 
galvanism. 

The earditic r&sults of the exhibition of small non-toxic doses are^ aooordii|^H 
to Prejer, simply alowhig of the hearths action. ^^| 

Preyer and Laschkewit^ch agree as to the action of large, but not enormous^ 
dnses- At first there li^ a sudden prolonged diastolic arrest of the heart, 
followed by an augmentiitiou in the nipidity >if the cardiac actiou, and a^er 
bis a diminution of the rate, — to the normal number in cases of reooreay, 

cardiac stand-still in cases of death. Both Preyer* and Loiichkewitsch 
{RHch*rC» Archiv fiir Atiahnme^ 1868, p. U53) iound that after section 
of the vai^ci the primary diastolic arrest of the heart did not occur. The 
jecent investigations of Jos. Lazarski confirm the statements of Preyer as 
I the action upon the vagus. A complete inhibitory arrest of the heart 
was rarely achieved, yet slowing id' the pube was constantly produced by 
moderate doses of the poison in the normal animal^ but was prevented by 
previous section of the vagi, and was removed, when present, by division 
of the inhibitory nerves ( Wkn. M^l. Jahrb,^ 1881, 141 ), It would seem, 
therefore, proven that small doses of prusjsic acid simulate the cardiac 
inhilntory nermntB system. Bohm and Knie noted that large doses of the 
acid caused slowing of the pulse whether the vagi were cut or not (Archw 
fiir Exper. Path, nnd Therap., ii. 137), and in this have been confirmed 
by Lflziu'ski. This j^lowing would seem to be due to a direct action upon 
tlie mui^cle, as Lazarski found that the cardiac accelerator nerves are not 
paralysed. 

Modt^rate doHcs of prussie acid seem to produce a primaiy very brief but 
great rise in the arterial pressure, followed by a fall to or below the normal. 
This primary rise has been noticed by Biihm and Knie, by Wahl {/>« Fi 
et Efff'ctn Ilt/drncynnato ad Our at ton &m Attrib.^ Bonn, 1865), by Rosfrbach 
and Papitzky {Centralb. Med. Wisscm,^ 1877, p. 1140), and by Lazarski. It 
does not seem to be altogether the result of the asphyxia produced by the 
acid, as it is recorded by Bohm and Knie {Joe, tit, p. 14(i) as occurring 
when artificial respiration was U!*ed, and Lazarski has confirmed this. All 
observers agree tlmt it is followed, if the dose of the poison has been large 
enough, by a profound sinking of the arterial pressure. Lasarski f^und 



♦ Preyisr {Inc. oV.,p. 9.1) 1 
it J hjdtocyanlQ acid. 



I »1«0 noted the 



nbionce in ourarixpd animals noi 



large ' 
found j 

liltUllCil M 



VAIiDfAC SEDATIVES. 



m 



I fiat pilvflnization of a ^ensifcive nerve baa no effect at this time upon the 
tlootl-pre^iiref &o that we must cumskier that lijdrocyanic acid /)m/mn7^ 
tHmnlattM very hrujly the Vftsfj-molor f^sfeni directly or tudirrcflyj and 
nfierwnnU piiriilyzem it, 

Aclton on Rtspirathn. — Ae^jording t4> Preyer (7o<?- d"A, pp. 17* 18, ID), 

dmifig all tliret* stages of hydroeyauiu ucid poison ing the respirations are 

leanitiod in frequency, and during tlio hitt^^r monients of life the efforts at 

Wtthing are very distant, ai»d finally ceaLse before the arrest of cardiac 

owTtfincnt^., The observer just montioned fijund that, aHcr division of the 

^«gi, rn»rroally letlml doj^ea did not kill, and that when death was brought 

•wat l>y the exhibition of larger doses it was by cardiac arrest. From this he 

^nee# the conclusion that the prime respiratory action of the poison Ls upon 

tiit^>o?ipbcral end^ of the vagi. Dr. Preyer's experiments have been par- 

fiilljr oi>ijfirmed by Drs. Lecorch^ and Jleuriot (loc, cit.y p. 538) ; but Boehm 

««d ^Cnie {Archiv fiir Exper. PaiL und Tfierap.y Bd, ii* p. 135) have in a 

*enfc» f)f ejEperiments fouod that section of the va^s has no iniuenee upon 

^^ ^fespiralory action of the poison, and in this have been confirnied by 

***• X^aiiireki (foe. ciK.). Even if investigations had proven the eonrectncas 

^^ *^^cver*g experiments^ his conclusion could not be eonsldered established, 

"**'''* ^A»e we know so imperfectly the normal relations of the pneumogastrics 

^ ""^^iSpirHticin. Moreover, Prof. Joseph Jones (Xew York Medical Record^ 

^** ii p. 451>) found that whilst to kill an allifiator by the administration 

P*"**tiSKic ncid required a considerable lenj^th of time, its applieation to the 

i^CliLmlb produced within one minute a mos^t powerful expiration^ ending in 

anent contraction of the muscles of respiration and collapse of the 

<• We must^ it seems t^o me, at present consider that the respiratory 

<iniena of prussic acid poisoning are due to an influence exerted directly 

"^^^ the respiratory centre. 

-^^^Mwi on MuMcles and Nervet and AVrrc-c<?w;r«».— Dr. Kblliker (Vir- 
*™^*^«^*« Arclu'v^ Bd, X* p. 272) has found tliat in frogs dead of prusf^ic acid 
P**^*^Uininf: b<jth the nerve-trunks and the muHcles are unexcitable, or that the 
'P o^^ cs respond very feebly to direct Btlmiilation. This is in accord with the 
**r* ^JLTiments of Stannius i Arckiv fur Anatoime^ 1858, p, *J5), who fmnd 
^^^^- when strychnia and prussic acid were ji^ven together, the convulsions 
^^ *^»ally produced by the former pois^on were altogether absent, or preeeni 
^^^ b a slight degree. In order to determine whether the nerves are or 
*ol primarily affected, Kolliker experimented by tying the vcaselfl of the 
t\ then divi<ling ju8t below this point all the tissues except the nerve, 
ftdininisLcring pru>!siu acid by the mouth. In n number of such exj:>eri- 
it» he found tlmt always the nerve and muscles below the point of section 
iiiod their irritability, but that when the gidvanic or other stimuli were 
to the nerve higher np, they failed l4j elicit any response from the 
^^oifioned tributary muscles, — positive prtKjf ttiat the nerve-trunks are 
il^'ied by a direct a* ti*m of the drug. This !h seemingly opposed to the 




194 



srSTEMW HEMRDtES. 



cid tlian 



experiments of Stanniua (loc. cii,)^ who concluded that prussic acid applied 
locaUy t<j the nerves 1ms no effoct upon them. Stanniii^, boweveft compared 
tlie results of sonkiiig a nerve in water and in a weak solutioa (tliree to four 
per cent.) of pruasic acid, and water thus euiplojcd ia toxic to the nenre* 
trunka. KblUker used, in repeating the experiments of Stannius, neutral 
Bolutiona of phosphate of sodium, one containing, the other free from, hjfdro* 
cjanic acid, and found that the nerves in the poisoned liquid died much sooner 
than did those in the non-poisoned solution. 

The experimenta of KoUiker arc in a^eeraent with those of Sta 
that the muscle dies very much more quickly in the solution of the aci 
docs the nen e, losin;^^ itfl exeitahility in from seven to eight minutes. This 
rapid destruction uf muiicular irriudjility by the local application of pnissic 
acid w:ls, I believe, first noted by Coultun in 1819. Yet it h most probable 
that when given internally prussic acid acts almost as rapidly upon the nerve- 
trunkti aa upon the muscles, since Kolliker noted that in some c^^ises fi;'alvani- 
Eation of the nerve was incapable uf causing contractions in tlie tributaiy 
muscleri, although the latter responded feebly to direct stimuhuion. This 
fact has been experiment*illy corroborated by Funke {BencJktc iiher die Ver* 
hatffll tl. k. stichn. Gf'Mlhchafi iL WtH^eufich. zu Lf;ipzi</^ Bd. xi., ISjO, p, 28). 

Upon the peripheral sensitive nerves prussic acid probably, if in sufficient 
cunccntration, acta as a pjirulyzant; at leuiit KiiHiker {he. cit,^ p. 2B2) found 
that if tlie leg of a strychnis^ed frog, whowe heait had been cut out to prevent 
absoqjtioii, was put in a four per cent, solution of prussio acid, in a very abort 
time irritation of the immersed skin ceased to produce couvidsions. 

Frum the slowness with which, in Kolliker's experimeut**, the nerve-trunkf 
were affected in frogs poiiKjned by hydrocyanic acid, it seems probable that 
he is curreet In his conclusion that in these batracliians the poison firs?t para- 
lyzes the brain, and then the reflex centres of the spinal cord, and iilXtTwards 
the motor nerves. But I have not met with any experimental evidetioc in 
regard to the order in which prussie acid affects the nervous system. Ac- 
cording to Kiedrowski,* iia quoted by Preycr, in fix*gs it fir^t paralyzes the 
gray, then the white substance of the bralu, and the early disapi>eaTance of 
reflex movements is not due to spinid pidsy, but to deatructiou of the func* 
tional power of the peripheiid afferent nerves. Preyer also states that the 
conuluHions of Kiedrowski rested upon the following expcrinientully proven 
fact, which, if accurate, seemingly renders them logically inevitable. When 
a frog is poii«oned with prusaic acid, and afterwards with strychnia in properly- 
proportioned doses, there is a stage at which slight irritation of the afferent 



* I buve, unfortunatelj, been unahlti to obtiiiio ncceef i<* the original jfid^fi-r of £. de 
KiedrowcikL Ev«n Prcycr appcarf to know it cmJy in uiiftracU Aooording to bitn, U vrwi 
imbIi«liGd in IB5S, At BreiflaU:^ a« a diytftirtiLtioD, utidcr the fuDtiwlitg title: JJe tfmftMtfttm 
tj'p'rnmvt^tiit quibus quantam vim hnbrat acHtum /itftlajc^tiHieum in ucrvorum »*/ittettm crf«4ff»- 
tpUiaU atqtui in mmculoa tifHemati* verttbralia prohntitr. 



CARDIAC SKDATiVKS, 



iur> 



i»#rTe»n>ols eauBcs violeot general tetanic spasms, altliough tlie most iiiteijse 
pertpbenU trritallot) fails to elicit rasponse. 

It h a question of interest to decide as to tlie cause of the convulsions in 
poboniug by hydrocyanic acitl I have found that they do not occur after 
aeeiioii of the cord in parte below the point of section, and that they are 
tliercfore cerebral in origin : fur roasons detailed elsewhere (see p. 143), it is 
wmej probable that they are due to disturbed cerebral circulation, and this 
probttbiHtj is confirmed by an experiment of Laschkewitach {Rcichert'* 
Arrhw /tir Anatomte. 1868), who opened the thorax of a rabbit so as to 
expose the heart, maintained artificial respiration^ and administered prussic 
ftcid ; directly after arrest of the heart had conunenced, the convulsion came 
on. The earlier observation of Coze iCortipfeA-Rendm^ L xxviii., 1849, p, 
780) is also to the same effect, as he states that the oonvulsions did not 
•iccur until directly after the arrest of the circulation. In frogs poisoned 
with hydrocyanic acid, convulsions do not take place. Preyer states that 
after section of the vagi convulsions do not generally happen in mammals, 
but if artificial respiration be performed they come on (h/c. ctt.^ p, Gl>). 

TllERAPKimcs- — Our knowledge of the phyj*ii>l<igiciil action of pntasic 
acid does not lead to a belief in its wide applicability to the relief of disease, 
and I think clinical experience has demons>trated that it is of little value 
except in meeting three indications : first, tn ttlLitf coittjh ; second, to rth'fi?e 
iMTi/itfi'fH iff (lie gnatrk nerves ; third, tf/ alhti^ trritattm of the peripherul 
urttttttve nf'rve$. 

There appears to Im? in the profc^jswion u very widivsprcad belief in the 
power uf this remedy to allay cou^h ; at lisist it la very largely used f^»r this 
pttrpiisc in oju^li-mixtures, either itself or in the form of cyanide of potas- 
Kuiu. I hare employed it in a great number of cases in hospiud praetiee, 
mud ap[>arent]y with gocKi efl'wt, although, a?< It was always given in cond>tna- 
tion with such remedies as morjfhiaj it is difficult to say how much uf the 
mutt was due to it, I do not believe it can cfimpare with such narcotics aa 
opittin or hyoscyamus in its aVdity to fulfil the present indication 

There can be, on the other hand, no doubt as to the value of prussic acid 
to certain stomachic affections, especially neiTous vamitmg and yn»trn^^a* 
Whm the pain i.s accompanied by decided dyspeptic symptoms, the remedy will 
eometimes succeed, but more often fails. Even in the most favorable cases it 
dcK3s not always afford relief j and as the relier when it does occur is jmnnxliate, 
«ir At least is vcr)'' soon apparent, it is useless to persint long in the exhibition 
of the remedy. In tht^m* csises ita action is probably local, as it certainly is 
when the acid is enij>luyed to relieve itching in ptiinffo and other cutaneous 
di!*ea«ea. For tin?* J^u^IHJs^e it is used as a wash {i^>^i^ to fji in fji } ; but great 
eoFM must be taken to avoid constitutional effects, especially when there is 
any abnision of the skin. Very serious rej^nlls are said to have been caused 
by itj* al*5ir>qftton when carelessly used in skin-diseases* 

I'russic acid has boen commended as an arterial sedative; but it is evident 



196 SYSTEMIC REMEDIES. 

til at we possess numerous more efficient and far safer remedies of such 
character. 

Toxicology. — The symptoms of prussic acid poisoning have already been 
mentioned : those of most value from a diagnostic point of view are the 
sudden occurrence of unconsciousness ; the violent convulsions ; the general 
paralysis ; the peculiar character of the breathing, expiration being prolonged 
and forced ; and the rapid results. The odor of prussic acid upon the breath 
is very often, but by no means always, present "When distinct, it is, of course, 
of very great diagnostic value. Leaving out of sight the cyanides, the only 
poison with which prussic acid could well be clinically confounded is uitro- 
benzole. The distinction is of^en very difficult, large doses of the latter sub- 
stance killing almost as quickly as prussic acid, and inducing analogous 
symptoms. Caspar advises that after death the body be left open, exposed 
to the air, as the odor of prussic acid disappears rapidly, whilst that of the 
nitro-benzole is persistent. The diseases with which the poisoning may be 
confounded most readily are some forms of apoplexie foudroyanie^ and sudden 
failure of the hearths action. The diagnosis may, during life, be almost 
impossible. It has been asserted that stertorous breathing docs not occur 
in prussic acid poisoning ; but it has been present in several reported cases. 
(Sec Tayh/rs Principles and Practice of Medical Jurispi'xuhnce^ Philadel- 
phia, 1873, p. 363.) An autopsy, however, ought generally to enable the 
physician to determine whether the case has or has not been one of prussic 
acid iX)isoning, if the symptoms during life are known. 

The period at which death may occur after the ingestion of the poison is 
set down by Lonsdale at from one to fifty-five minutes ; but a case is reported 
in Guy 8 Hospital Reports^ 1868, p. 259, obsen^ed by Dr. Hilton Fa^j^e, in 
which the fatal result was put off for at least an hour and a quarter after the 
ingestion of hydrocyanic acid. After death the body often presents a livid sur- 
tiice, bloated countenance, fixed glassy eyes with dilated pupils, and clenched 
fingers ; sometimes it offers nothing worthy of note except excessive rigidity, 
and the face may be very pale. When opened, the odor of prussic acid is 
generally, but not always, emitted ; the mucous membrane of the stomach is 
very commonly found much congested, and the dark or cherry-colorcnl liquid 
blood usually everywhere fills up the veins. The heart is soft and flaccid. 

The treatment of poisoning by prussic acid is, unfortunately, as inefficient 
as it is simple. There is no known chemical or physiological antidote to it, 
the asserted antagonism of atropia having been disproven by the experiuicntB 
of Keen (^Proc. Phil. Acnd. Nat. Sci.y 1869) and of Boehm and Knie. 
The stomach should, if possible, be emptied, and the hypodermic use of 
atropia as a respiratory stimulant might be tried ; the inhalation of the 
vapors of ammonia, and the free exhibition of ammonia by the mouth and 
by injection into the veins, may be practiced. Artificial respiration has 
been found very successful by Prcyer, and by Boehm and Kiiio, in animals 
when poisoned by small doses of prussic acid, and should always be assidu- 



CARDIAC SEDATIVES. 



197 



^ph< 



^fiiettecil. Next to it in importance is the uso of tbe alternato cold 
d liot douche, about a half of a small buckctfiil of onid water and the sfimo 

ily of very hot (115*^ F.) water being daahed upon the chest in rapid 
n. 
Admikistration. — The doae of the officinal dilute pnissic acid is one to 

drops. 

le Cyantde 0/ Fbtamum (Potassii Cyanidum, U. S.) is prepared, 
according to the U. S, Phtirnrnt'opaoia, by heating together the ferro^yaoide 
of potaauum and the carbonate of potassium. It cjccure iu white, ainorphoua, 
ppsque maases, having the odor of prussie acid aud a taste of Biwilar charao- 
r, hut somewhat alkaline. It ia deliquescent) and readily eoiuble in water, 
^^beu the nitrate of silver is added to its solutiou, there falJs a precipitate of 
e c3ramde of silver, which is wholly soluble in finimonia. 
When tbe cpnide of potaBsium is taken into the stomach, the acids there 
presient convert it into prusslc acid, and the same change probahly occurs, 
ftltbough more slowly, even when the salt is injected directly into the blood- 
YoneU. The physiological, therapeutical, and loxicological properties of this 
Mli are similar to those of prussic acid.* Death, however, does not occur so 
■OCM) as when hydrocyanic acid has hiien taken, and insenstbiUty is sometimes 
not manifested for several minutes. Five grains of the Sidt have caused death 
several caaes. The therapeutic do^ is ouc-teuth to one-twelfth of a grain. 
The Qfanide 0/ Sifvtr (AfiOENTi Cyanidcm, U. S.) is a white insoluble 
powder, which is used solely for making prussic acid, 

Hyanogcii (Jas has been studied physiologically by Dr. B» Buuge i Arckv, 
PatK u, Phiirm*^ xii, 71)* He finds that it kills by paralyzing the 
ties of respiration, but is less powerful and strong in its influence than 
drocyanic acid, and causcj* only very feeble convulsions. 




VEGETABLE ACIDS. 
hough most of the oflicinal vegetable acids differ so much from the 
OiW substances considered in the present class as not to be poisonous except 
ill enormous doses, and although they are never used to produce a profound 
iprenioD upon the circulation, yet since they have, or at least are believed 
have, the power of lowering the furce of the cardiac niuvenienLs to snnie 
it, and since they are so commonly believed to have a tendency to de- 
animal lemfierature as to be Ui^ually spoken of as refngeranU^ the 
it soems to m$ a fitting position for their consideration. 



ACIDUM TARTAKTCUM-TARTAUIC ACID, IT,S. 
Tiuiftric acid occurs in large, hard, transi>urent, six-sided prisms, which 

* r<»i»Mtiing i« i<Liito(l to hiiir« uocurreiil frata tho iiihiiUaion iitthi} rii|iora of thv cVAtiide, 
■d, 10 )jbutog;rikjiljt;r«, fruia ihe nbatorptioo. thrt>ugh tbe huu'Jj {lit it, timi fftr, Mtd.-Ckin 




198 



SrsTEMiC HEMEDIKS. 




are pyro-electric and phosphorescent when rubbed id the dark, and are ncariy 
free from odor, but have a very aour taste, I a iho &hopa the acid is almoet i 
always kept in the form of powder. Tartaric aeid is the acid of the grape, | 
and occurs in gnipe-juice as u fu per tartrate of potassium. When the juice 
undergoes fernientjitiun and alcohol is developed, the acid salt, not hciii;^' sol- 
uble in the newly-fuiincd menstruum, precipitates, cf>Ilectiug m a dark maae 
in the wliie-easks, whence it is sent into eommeroe under the name of aryol 
or tartar. Out of this fiubslaace the acid is manufactured by treating with 
lime, 3^ as to form a tartrute of calcium, aTuI precipitating this new eom[)ouod 
in its watery solution by sulphuric acid, sulphate of calcium falling, tartaric 
acid remaining iJi solution. Tartaric acid is soluble in little more than half 
itii weight of hot water and less tluin it^i weight of cold water. It is distin- 
gxiished from all other acid.s by forming a crystalline precipitate (bitartrate) 
when added to a neutral solution of potassa. 

PuYsiOLOOiCAL AcTiON. — When appliL-d to a denuded surfiice, or insuffi- 
cient concentration to a nmcoui? nicmbrane, tartaric acid acts as a very decided 
irritant, and even upon the skin its saturated solution atler a time 
redness and burning. 

When the dmg is taken internally in sufficiently large doses, it acb 
an irritant jwison, causing violent o?mphagCid and gastric burning, Tomi^ 
and, it may be, fatal gaatro-enteritis. Upon animals it acta in hirge doses 
precist*ly as it does upon man. Thus, I^litsehcrlieh states that throe or four 
drachms suffice to kill a nihbit, the evident symptoms being great weakness 
of the heart's action, difficult and alow breathing, steadily-increasing pains, 
with slight ci>nvnlsious beR»re death. Acctirding to Devcrgie, it requires 
nearly half an ounce to kill a dog when given by the stomach ; but Pommer 
(<|tuvted by llusemann) asserts that one gi-amme (15,34 grains) injected into 
the crural vein of a dog will produce death. 

Tartaric acid is never n^ iutermftly l>y practitioners in such doses as to 
cxin^i any of the sympt^nns above detailed, inid it is evident that these symp- 
toms throw little light upon its iictinn in therapeutic doses, except to render 
it somewhat probable tliat tlie tendencies of the medicine are to lower cardiao 
action. Thb pr«^»bability is increased very ^ much by the experiments of 
Bobriek ( quoted by Husemainn, Die Pflanzemtoffe, p. 5til), who found that 
very large doses render the heart's action weaker and slower, 

A great deal of intercut to the therapeutist centres in the question m to 
what beeomes of the acid in the system. Unfurtunately, our knowledge in 
regard to this matter is t;^r from complete ; but the drug is probably partially 
burnt up in the body and partially eliminated by the kidneys, Wiihlor,* in 
his experiments, found it in the urine in the form of tartrate of calcium, 
whilst Buchheim* and Piotrowski* could find only a very smaU percentage 
of the ingested acid in the urine^ and conclude that it is nioatly deutroyed in 



• All thcae are quutcd by Uufiuiiiani}, Die PjlaiavH^to^i:, I have not »ei'ii the 




CARDIAC SEDATIVES. 



\n 



tbebody* Dr. Muoch {Archie des Vt^-eins/Ur Oemtin, Avhelten, 1863, p. 
ri70) finck that when tartaric acid or citric acid is given it mon appnars in 
tine urine* Br. H* Bence Jfjnea (,}feJtcul l^mes and Gaz*'tir. vol ix,, 1854, 
p^ 408| and I^cturet on Patholofjy and Therapentics^ Loudon, 1807) has 
Ibynd that both citric acid und tartaric acid cause a very great incrc^ase in the 
aotditj of the urine of persons taking them, and are apt abo to give rise to 
tbe preseoce of free tiric acid in the excretion. Unfortunately, Dr. Jones 
did not attempt to detenu i no whether the increased acidity was or was not 
dtu! to the presence of the vegetable acid id the urine. 

TuKHAPEUTios, — Tartaric acid is very rarely used in medicine, the citric 
mci ' ' nlwaya being proferred. It maVi however, be employed whenever 

it . 1 to Tender the urine acid, in duses of ten to twenty grains j but 

U k los9 valuable than the acid of the lemon. 

Toxroou>GY'. — There are, I believe, but three fatal cases of t^irtaric acid 
paisoning on record: one reported by Devergie (Ann. d' Htfffthne^ 1851, t. 
ii) ; one by Prof Taylor (Frinciplea and Practice of Medical Jurispru- 
date€f London, 1873, p, 230), in which death took place niue days after 
the ingestion of an ounce of the poison disi^olved in half a pint of water \ 
and one {Aftd, Ptru and Circtdar^ Nov. 1880) in which a half ounce of 
the acid was sttppotttd to have been taken. The treatment of tartaric acid 
pobonitig eonsisits in the free exhibition of magnesiti, of lime, of the carbo- 
Sftte of potassium or of sodium, or of any article, such as soap, containing 
AD adka}i in a suitable shape, which may be at hand. The after-treatment 
ii that of toxic gastro>enteritifi. 



ACIDUM CITRICUM— CITRIC ACID. IT. 8. 

Citric acid is the acid of lemon- and lime-juice, from which it is extracted 
by a process precisely similar to that employed in the manufacture of tartaric 
■cid. It tKJcurs in rhomhoidaJ prisma, which are sometimes very large, are 
nearly free from odor, but are possessed of a very sour, almost corrosiTe 
tefite, which, when the acid is in sufficiently weak solution, is quit^ pleasant. 
Citric acid is soluble in three-fourths of ita weight of cold water, half of its 
weight of boiling water, s«>lu}»Ie in alcohol, insoluble in ether. 

It is sometimes adulterated with tartaric acid, which may be readily de- 
tected by the addition of a strong neutral solution of earltonate of potassium 
to a strong solution of the suspected drug, when, if tartaric acid be present 
in any amount, a precipitate of the bitartrate is formed, 

Pbybiolooical Action. — ^Citrio acid in concentrated solution certainly 
aot« upon abraded surfaces and upon mucous membranes as an irritant, but, 
aooording to Mitscherlich, is less Lrrttant than tartaric acid, since its concen- 
trated solution has no action upon the sound skin. 

No case of poisoning by citric acid has occurred in man, that I iim aware 
of^ and Piotrowski (quoted by HtisemanD, Die PflanxcnAtoffe^ p» 561) took, 
to Atx hourR, thirty grammeSi an hour later fiileen grammes, and an hour 



200 SYSTEMIC REMEDIES. 

later thirty grammes, or nearly two ounces and a lialf in all, with the induc- 
tion of no more serious symptom than vomiting. It is, therefore, somewhat 
douhtful whether citric acid is capahio of causing death in man. This differ- 
ence in action between it and tartaric acid may depend upon the latter being 
so much the more irritant of the two ; upon the urinary secretion their 
action is probably similar. 

Therapeutics. — Citric acid is sometimes itself employed in medicine, 
but is almost exclusively used in the form of Lemon-juice (Succus Limonis), 
which some, it is true, have thought to be dependent upon citrate of potas- 
sium for much of its virtue, but which contains, as shown by the analysis 
of Prof H. Bence Jones {Medical Times and Gazette, vol. ix., 1854), in 
every ounce twenty-six or twenty-seven grains of free citric acid, and not 
two grains of the citrate of potassium. 

Lemon-juice has several v^ry distinct uses in medicine, all of them resting 
upon clinical rather than physiological data. The chief and most important 
of these is in the cure and prevention of scurvy. During the disease it 
should be drunk freely in the form of lemonade, three or four ounces of 
it being taken daily. As a prophylactic against the disease, lemon-juice is 
simply invaluable ; but it is absolutely necessary that it be of good quality. 
It may bo prepared for long voyages in one of two ways: first, boil the 
juice slightly, strain, allow to cool, pour into bottles up to their necks, fill 
the vacant space above with pure olive oil, cork tightly, and keep the bottle 
upright ; second, add ten per cent, of brandy, and bottle as before {Medical 
Times aiid Gazette, 1854, p. 635). Citric acid is of some value in scurvy, 
but is incomparably less active than lemon-juice. In acute rJieumatism, 
benefit may be derived from the free use of lemon-juice, as originally pro- 
posed by Dr. Rees, of London. One or two ounces of it may be given four 
or five times a day ; but it is certainly less efficacious than the alkalies. In 
catarrhal jaundice, and in habitual torpor of tlie liver, the free internal use 
of lemon-juice oflen aids in effecting a cure. In fevers, lemonade often 
affords a very refreshing and useful refrigerant drink. 

Administration. — Lemon-juice, when it can be had, should always be 
preferred to citric acid ; when only the latter is available, an artificial lemon- 
juice may be made by dissolving in a pint of water an ounce of the acid 
with which four drops of the oil of lemon have been well rubbed up. 

ACETUM— VINEGAR. 

The physical properties of vinegar are too well known to need description 
here. That best suited for medicinal use is in this country prepared from 
cider, and should have a trace of the taste of cider. It is sometimes adul- 
terated with sulphuric acid, which may be at once detected by boiling with 
chloride of calcium, which precipitates any free sulphuric acid as sulphate 
of calcium, without affecting the small proportion of soluble sulphates ex- 
isting in vinegar. Vinegar may be substituted for lemon-juice as the basis 



CARDIAC SEDATIVES, 



201 



of an iddoUtUB drink iu fever whon the Ienioii<-juice is nat to be* liud ; but 
iks an antutf^bufic it is certainly very much inferior to it, and has uot, thai 
I am aware of, been tried in rheumatism. 

Aeetus Acid (Acidum Aceticcm, U.S.) m a colorless liquid, having u 
pun^eDt odor, free from empyreunia, and an intensely acid, corrosive taste. 1 1 
•OOtains thirty-six {>er cent, of the roonobydrated acetic acid, and has a spe* 
«ific grarity of L047. Glacial or monohydratcd acetic acid is not ufficinaJ- 
It is a colorless lirjuid, crystallizing at 34*^ F,, and actively cscharotic,— in a 
measure, no doubt, owing to its properties of disisolving gelatine and gclati- 
nous iiMsue and of effecting a partial solution of albmninoas matters. Dilute 
Acetic Acid (AciDi'M Aceticcm Dilutum) is officinally prepared by ibe 
addition of seven parts of water to one part of acetic acid, and should bavi* 
tile sp. gr. 1.0U6, Acidmn Aceiictim Glaciale^ \],S.^ glacial or ahmlttte 
acetic acid^ b at 51P F. a crystalline solid. 

Dilute acetic acid, or its equivalent, vinegar, is a useful topical application 
in Tarioutt superficial iuflanimatiuns of the skin, such as ^^ sunburn,^' and iu 
tpraifui* Applied to the skin, it acts as a powerful stimulant and astringent, 
caHMJiif; con traction of the vessels and great whiteness. Diluted with two or 
lliree tixued its bulk of water, it is occasionally employed as an injection against 
feii#>ic?omt< ; but the infusion of quassia is preferable. 

Tlie ude of acetic acid as a caustic wilt be spoken of under the heading of 
EacKarotica. 

ToxicoLOOT. — Acetic acid in any of it» more concentrated forms is a 
oomiaive p<>ison, and death has been produced by it in at least one cajse 
(Urfila, Toxicuhi^ir, t, ii.). The symptoms resemble those caused by mineral 
acid(4, and the trejitmetjt is exactly similar, — neutralization by lui alkali or its 
carbonate, or by some substance, such as soap, containing an alkali* and the 
njceting of indications as they arise. 

Oxtilic Afitl (AciDt'M Oxalicum), although never u^d in medicine, 
has fio frequently caused death by its poisuiKius influ*nce as to merit 
Botioe here. Iu 1874 {Gaz, Mid., p. Old) Kabuteau announced that in 
oaajic add poisoning the nerves and muscles are not affected, and that 
therefore the acid acts upon the nerve-centres. Tbis has been confirmed 
bj the elaborate researches of i>r.s. It, Kubert and B, Kiissoer ( VirchotcB 
Arthiv^ Bd. Ixxviii. 109), who find that it paralyzes the respiratory, vaao* 
aotor, and other motor spinnt centres. Tbe add is eliminated by the kid- 
neys. As a poUon, oxalic acid figures in two forma : that of simple oxalic 
actdy and I hat of the acid oxalate of potamnm, or Malt of iorrei^ or euen- 
iial taU of Utnom, as it is variously termed in common parlance. The 
ayniptouid produced are a hot acrid t4iste experienced during the swallowing, 
a bumitig in the gullet, soon exLending to the atomaeh, intense abdomimd 
pain, vomiting of highly acid, greenish, blackish-brown or bloody mucus 
(rarely of arterial blood), collapse^ livid surface, cold skin, entire prostra- 
lioa of strength, «mall irregular pulse^ stupor^ unconsciousness, sometimea 



202 SYSTEMIC REMEDIES. 

convulsions (cases, Gux/'$ JSosp, RepartSy 1838, iii. ; Dublin ffosp. RepartSj 
1818, ii.), and finally death. In some cases the gastric symptoms are very 
prominent ; in others they are nearly wanting, and the chief manifestations 
are collapse and such nervous symptoms as almost complete general paraly- 
sis, numbness, and finally stupor ; indeed, the patient may suddenly fall 
unconscious immediately afler the ingestion of the poison (case, Guyn 
Hosp, Reports^ 1874). According to Taylor, the smallest quantity which 
is known to have caused death is one drachm. An ounce usually proves 
fatal, but has been recovered from. Ailer death the coats of the stomach 
are usually found softened and swollen, and sometimes perforated (case, 
Edinb, Med, Journ,, vii., July, 1861). Dr. Rabuteau (6raz. Mtd., 1874, 
p. 93) affirms that the blood is everywhere scarlet ; but this is certainly not 
always the case (case, Taylor, Mtd. Jurisprudence^ i. 224). Accordinj^ to 
Kobort and Kilssner, the urine during life contains some strongly reducing 
substance of unknown nature, oxalate crystals in abundance, and usually 
albumen and tube-casts. A pathognomonic post-mortem lesion is, accord- 
ing to the same investigators, the incrustation of the urinary tubules with 
crystals of oxalates. In poisoning by oxalic acid, the immediate adminis- 
tration of an antidote is of the utmost importance. As the oxalates of 
potassium and of sodium are poisonous, neither potash nor soda is avail- 
able ; but fortunately lime or chalk is a perfect antidote to oxalic acid, 
forming the excessively insoluble oxalate of calcium. As time is a matter 
of so much importance, very oflen it is best simply to scrape the whitewash 
off a wall, ceiling, fence, or wherever it may be at hand, rub it up hastily 
with water, and administer it freely. The afler-treatment is that of toxic 
gastro-enteritis. 




CLASS V.-AJ!rriSPASMODICS. 



Ondee the name of Anttupagmodics are grouped in this treatise a numbnr 
of mediciues genenJIy of very feeble powers^ but of frequent use. In ccrtam 
oondidoQfi uf the nervous system — conditions afisociatetl with wcaJcneas rather 
thaa with 8iiiij)le depression — the ucrve-ceiUres appear t/> be more susceptible 
lliaD IB noruial to externiil iTTif»rc8»ion8, as well us to those ini])ul5(?a which 
orij^DiUe in the tjerebnil centres themselves an J are connected wit!i the emo- 
tiOQiL As a result of tliis state, various sympt^iins ariee, of trifihig import, 
but often a|ij«ire«tly severe^ and always annoying. Such sjmptomsT in their 
SQildest furuif coiistituto the »tate of unrest known as nen>oittne8$ ; m their 
sonrarer type they may rise iu intensity up to the wildest oonvulsioo of hysteria, 
II is in this class of u fleet ions that the so-called antispasmodics are useful. 
Am the wndition which they relieve is always associated with weakness, tliey 
are often spoken of as '* nervous s^timuliinls." In regtird to most of them 
Uiere 10 but little evidence of their increasing power or functional activity 
when jopven to healthy individuals. Sonic of them act very slightly upon the 
circulation when given in very large do&cs, and a few when administered as 
finedy as possible induce slight cerebral Bymptonis, such as vertigo ; but, ex* 
O^rtifiig oimphor^ cafTein, and Hoffmanns Anodyne^ none are capable of pro- 
dllOiO^ serious poisoning. As any theory of the method in which t!ie hysteri- 
eal coDVulsioD originates — of its immediate causes and the mechanism of its 
production — would, with our present knowledge, be at best but an ingeniooa 
ipectthition. the safest plan in rcgartl to tlie action of drugs belonging to 
ilie class now under consideration is to accept the teachings of cliuicjil experi- 
mm ai to facta, and to avoid theorizing as to the way in which the results 
tre brought about. 

MOSOHUS-MTTSi:, U,S. 

A htglity odorous, unctuous substance, obtained from the glands situated 
juBt in front of the preputial orifice of the Mo«chus mosoliiierus, or mu»k- 
deer of Thibet. The geimine nmsk-sac is to be distinguished from imita- 
tiooe of it by the hairs being arranged conceDtrically around a minute orifice. 
As it iieeurs in commerce, musk is very greatly adulterated, 

FliyfiloLoaiCAL Action. — Musk appears to act upon the nenroua system 
tttziply as a mild stiiiiulant and antisptismodic, Ji>rg and Sundeliu have 
«fX|ieniiieuted with it upon healthy men with somewhat contradictory resulta, 

203 



204 SYSTEMIC REMEDIES, 

According to the first -named observer, twenty grains of it induce exhilaratioo 
without lassitude, but, according to the latter authority, may cause giddiness, 
drowsiness, and lassitude. Both observers noted a slight increase in the fre- 
quency of the pulse. It seems to me evident that the action of musk upon 
the organism is a very feeble and uncertain one. Yet there is considerable 
clinical evidence that when the nervous system is exhausted it is of service in 
calming restlessness and equalizing the disturbed balance of nervous power. 
Therapeutics. — Musk is at present very little used, but it is strongly 
recommended by some of the older writers in various spasmodic affections, 
especially in hysterical convulsions. In hiccough it has been considered a 
specific. In the delirium of low fevers it is sometimes valuable ; and it has 
been especially commended by Trousseau in the ataxic pneumonia of drunk- 
ards, when the nervous symptoms are out of proportion to the local disease. 
The dose of musk is from five to fifteen grains, which may be given sus- 
pended in mucilage. Tincture of Musk {Tinctura Moschi^ — 1 to 10, U.S.) 
is given in doses of one-half to two fluidrachms. 

Castoreum — Castor. — The preputial follicles of the beaver are pyriform 
sacs, occurring in pairs, and containing an unctuous material, — ^the castor. 
This is a substance allied to musk in its physical properties, and apparently 
also in its medicinal qualities. It is certainly less efficient, however, than 
musk, and Mr. Alexander {Fereiras Materia Medica^ American edition, 
1866, p. 949) is said to have taken a quarter of an ounce of it without 
having experienced any effect. It is employed in the same affections as 
musk, in doses of fifteen to sixty grains, suspended in mucilage. There is an 
officinal tincture, which is stronger in alcohol than in castor. 

VALERIANA-VALEEIAN. U.S. 

The root of the Valeriana officinalis, an herbaceous perennial of Great 
Britain. It consists of a short, yellowish- white rhizome, with numerous 
fibrous roots, of a bitter taste and peculiar odor. The active principle of 
valerian appears to be the oil of valerian, which, according to Pierlot, con- 
sists of a mixture of valerian camphene, valerian camphor, valerianic acid, 
resin, and water. 

Physiological Properties. — Upon cats valerian has a very extraor- 
dinary effect, attracting them strongly, and greatly exciting their sexual 
passions. It is possible that this action is suggestive, due rather to the re- 
semblance of the odor to that of the animals during sexual excitement, than 
to a direct action of the drug. Valerianic acid given to rabbits in large doses 
produces,, at first, a slight acceleration of the pulse, which, with the respira- 
tion, afterwards becomes less frequent than normal, and at the same time 
lassitude and muscular weakness are developed. Enormous doses kill rabbits 
somewhat suddenly, or produce Msl gastro-enteritis. 

Upon man, large doses (3ii to 3^v) are said to produce a feeling of warmth 



ANTISPASMODICS, 



205 



in tl»e stomach, and sometimes nuuBea, vomiting, and colicky pains. The 
pislae b gcoerallj slightly (juickened, and a sense of exhilaration i^ induced^ 
Bcoompanicd, however, by lt>rmication in the hands and feet. Very large 
Mmotinte cati^ a feeling of hc;ivi[ieii8^ and even of pain, in the head. 

TuERAFCCrrics. — Clinittil uxj^hcrieucc Iuvh demonstrated the value of valerian 
«8 a means of relief for the mildur forms of fuoctional disturbance dependent 
ttfxm A wtaik and over-excitable or an exhausted nervoua sjatem. In the 
HAte of unrest familiarly known as *" nervf^mneu^** by Boothing and quieting 
the {luljent, it will often indireetlj prueure sleep. 

In hjfMierta it has been the most frequently msed of niedleines, and iu action 
id oftttmes most liappj. 

It baa also been employed, but with more doubtful advantage^ in mania a 
poitty and in the tUlirium of ndt/unmic ftverts. In these etuies it is almost 
invariably conjoined with more powerful remedies, and it is very difficult to 
«Wide bow far it a&$ists in protmring the benoficiid result. 

AbJUXISTRATION. — The best pref*arat ions of valerian ure the Jim'd extract 
lEaetractum Valeriana FluUlurn^ U. S.)i dose, one fluidrachm ; and the 
ammoniated tincture {Tinctura Vaierianx Ammoniaia^ U.S.,^ — §it to Oj), 
dote, ooe to three fluidraehma. The dose of the infitsion is a wineglaaaful ; 
ibAl of the simple tinctuyc (^Tinctura Va/tnati^Cy U, S», — 3i^ to Ojj 18 one 
lo three fluidrachms* 

AcTDtTM VALimiANICtTM. — Valerianic Acid is an oily, colorless liquid, 
of a eaustio taste, and a strong odor, resembling, but differing from, that of 
▼ilefian. It is made by the action of chromic acid upon anjylic alcohol, 
hj a somewhat complicated process, and is employed fur the manuliicture 
of Vfitcrianate of Ammonium (Ammonii Vakrianag^ U. 8.), a white salt 
occurring in qundrnn^ulRr pliites, which efHoresce in a dry and deliquesce 
in A moiKt atmoi*phere, have the odor of vnlerianic acid and a sbiirp sweetish 
t»&t^ and are very sijliible in water and in alcoboL 

TflERAPECTlCfi, — This salt was introduced by M. P^ckt) of Paris, as a 
remedy for neuralgia* It has since been used very largely for ^wrvoui head* 
nefte and in hysteria. It appears to be about equivalent to valerian, but, 
unleM it be in nervous headaches, is less elBcicnt The dose of it is ten 
gmusi which id generally adminbtered in the form of an datir. 



ASAFCETIDA-ASSArETIBA. IT.S, 

An exudiition obtained by incising the living root of the Narthex Assa- 
f«Btida, an umbelliferous p!ant of Afghanistan, It mostly occurs in irregular 
opaque masses of a dull yellowish- or piiikish-brown, white when freshly 
broken, of a bitter acrid taste and a strong garlicky odor. Even this htmp 
iuttt/etida U largely comjK.^sed of tears agglutinated together; sometimes 
tlicae teant are distinct and separate, when they conBtituto the variety known 
aa ama/etida in (ears, Assafetida is composed chiefly of gum and resin, 



206 SrSTEMW REMEDIES. 

but its properties arc id great part due to the volatile oil, of which it con- 
tains from 3.5 to 4.5 per cent. 

Physioloqical Action. — When taken into the stomach, assafetida acts as 
a local stimulant and carminative, and on this account is in some parts of the 
East used as a condiment. The oil is without doubt absorbed. The evidence 
as to its action upon healthy men is both scanty and contradictory. Thus, 
whilst M. Pidoux took half an ounce in a single dose without perceptible 
effects other than to render his secretions horribly offensive for two days, 
Jorg and his disciples found that in twenty-grain doses it produced gastric 
uneasiness and pain with alvine dejections, increased the p\ilse-fi*equency and 
animal warmth, quickened the respiration, and caused headache, giddiness, 
and erotic excitement. 

Therapeutics. — Clinical experience has abundantly proven that assar 
fetida is one of the most efficient of the so-called antispasmodics, and may be 
given to fulfil the same indications as valerian in functional spasm, in hys- 
teria, and in nervousness. It differs from valerian in having a much more 
decided action upon the mucous membranes. It is an excellent carminative, 
and in the form of injection is constantly used for the relief of tympanitis. 
It also in small doses increases the appetite, and affords relief in the dys- 
pepsia, with flatulent colic and costiveness, of the aged or hysterical. As a 
stimulating expectorant and antispasmodic, it is useful in whooping-cough 
and in chronic catarrh. It is especially efficient in palliating the latter 
affection as occurring in old people, when the difficulty of breathing is parox- 
ysmally increased by spasm of the bronchial tubes. In infantile conmdsions 
and in severe infantile colic, assafetida enemata (f 3^i ^ f S^ ^f ^^^ milk) 
ore exceedingly useful and harmless. 

Administration. — The Pills of Assafetida (Pilulse AssafaJidm, U. S.) 
each contain three grains : from two to four may be given at once. 

The dose of the mixture or inilk of assafetida (^Mistura Assafoitidse, U. S., 
— 5" to Oj) is half to one fluidounee; for injections, one to three fluid- 
ounces ; that of the tincture {Tinctura Assafoetida, U.S., — Zu to Oj), half 
to one fluidrachm. The suppositories contiun the equivalent of forty mia 
iins of the tincture. Emplastrum Asa/ietidm, U. S., is used externally. 

OAMPHOEA-OAMPHOR. U.S. 
Camphor is obtained in China, Japan, Cochin China, the Sunda Islands, 
(^tc, by boiling the comminuted wood of the n)ot, stem, and branches of the 
Laurus Camphora, and skimming off the camphor as it rises to the surface 
of the water when cold. This camphor is then partially purified by subli- 
mation, and comes into commerce as crude camplior, which is in grains of a 
whitish or pinkish color, and is finally purified by sublimation with lime.* 

* A variety of camphor, as well as of camphor oil, yielded by the Dryobalanopi Caa- 
pbora, is very highly valued in the East, but does not reach this country. 



A N TISPA S MOD res. 



207 



Refined eafDpbor (or, as it ia cotuDionly called, camphor) occurs in diAs or 
betBlnphcrical bowMike trntisliicent masses, of a fibrrms orirranulnr fracture, 
1u tiiBte is hot and peculiar; its odor very strong and Lbaractcristic ; it is 
Tdlflitile. inflammable, tough, but readily pulverized on the addition of a few 
dn»p9 of alcohol ; melts at 347*^ F. ; Is soluble in one thousand piirta of cold 
WHtcr,* in one port of strong alcohol, and atiJl more soluble in chloroform ; 
tliniwn upon water, a granule of eampbor floats, and exhibits a rot^iry motion. 

By slow sublimation at ordinary temperatures, camphor can be made to 
2ryistnHizc in handsome hexagonal tabku. 

PjiVHiOLOOlCiiL Action. — Locally applied, camphor is a decided irritant, 
■bllOl^h when it is taken into the mouth a svmsc of coolness af\er a time is 
CVporienoed, due no doubt to the volatility of the drug : a precisely analogous 
phcDomenon occurs with some other volatile irritants, such as oil of pepper- 
mwLf 

Great dlfferenoes of opinion have prevailed in regard to the action of 
^Muphor upon mun, and it is scarcely doubtful that it acts differently upon 
Afiereut persons, or at least that doses which in some cause only exhilaration 
in others prLduce general depression. When a modenite do.ne (five to ten 
g;imt]ia) of canjplior is taken, a feeling of exhilaration is usually induced, a 
aetiM of comfort and quietness, cBpeeiatly marked in those previuusly sufler* 
Ii^ itvm ** nervousness f' the pulse may be somewhat accelerated, although 
h is undoubtedly not markedly afl'eeted in the majority of cases, and TrouB- 
ieio saw it fall ailer the ingestion of ten grains of the drug. After larger 
dtiset (twenty to thirty grains) the pulse is usually lowered in frequency, 
ftfid giddiness, with a feeling of lassitude, is produced, preceded, it may bo, 
by a whort period of exhihirative excitement. After poisonous doses (thirty 
iCf sixty grains) the syuiptoms, which are tolerably unif*>rm, are as follows : 
fiiintnesjj, headache, vertigo, confusion of ideas, burning pain in the stomach, 
delirium, violent convulsions, insensibility, apparent gcnoral paralyais; n 
ptdae genendlj small, but sometimes uceelenUed and sometimes lowered in 
iiumb<!r; n fikin cool, pale or livid, generally bedewed with sweat. Sudden 
unconM*iousneaB| with or without convulsions, ba£^ been in »ume instances the 
Emt nianifeiitation of the action of the poison, and, of course, in any indi- 
Tidual caiio many of the symptoms narrated above may be wanting.^ 

No death has occurred in the adult directly from camphor. A joung, 
eickly infant was killed by ten grains of it ; and a woman four months gone 

• By mbbisg tbo gam up with mognciia lo water, the liitler eftQ be mftd« ta tiik« up 
much more than one part tu on« tbouiaod. 

Y Fur phjr Biological acUon of V'tmphor-CgmM, •«« Arck* Experxm, FatK, und Tkerap,^ 
l»73, M. i. 

' t Omw, Edinhurffh Med, /c.H«in/, Mny, IS73; The Ciinic, March, T8r»j Wtttter M^di- 
amttcAr Pr^tt, 1874, p, 268 ; Bcrtnu KUtu »*"«<■**«*♦, Sept. 1873-74; frwut. Lnnd. Clitt. Soe^ 
1»7«, p. 27 i London Ltntett^ 187fl, li. 71 1 Brit, Med. Jouru^ F«b. 1876? »!■<» 1877, I. 607. 



L 



208 SYSTEMIC REMEDIES. 

in pregnancy, having taken three drachms of camphor, suffered the usual 
symptoms, followed by an abortion which proved fatal. 

Much contradictory evidence might be adduced as to the influence of cam- 
phor upon the genital organs. The truth evidently is that its action varies 
according to the dose and the idiosyncrasies of the patient In the great 
majority of instances, I think, camphor in moderate doses has no decided 
influence upon the sexual system ; at least I have seen many hundred such 
doses taken and have never yet seen any aphrodisiac effect. In some per- 
sons, however, full therapeutic doses are said to cause sexual excitement. 
In regard to very large doses, the testimony is quite uniform that if they 
exert any action it is to lessen the erotic feelings. 

Camphor acts upon articulates as a violent poison ; in birds, according to 
Menghini, it causes stupor or delirium with epileptiform seizures ; in mam- 
mals it produces symptoms similar to those seen in man, such as vomiting, 
violent convulsions, coma, and death, apparently from asphyxia. The con- 
vulsions must be of cerebral origin, as, according to the experiments of C. 
Weidemann (^Arch. Exp. Patlwl. und Therap., vi., p. 216), and of Hoffmann 
(quoted by Weidemann), they do not occur after section of the cord in por- 
tions of the body below the point of division. Whether they are the result 
of a direct action upon the cerebrum is not determined, but the other symp- 
toms produced by camphor indicate that the drug has a decided influence 
upon that organ. In frogs, Weidemann found that the convulsions are masked 
by a general paralysis, chiefly due to a depressant action upon the motor nerves; 
the spinal cord, however, also suffering in its functional activity, the muscles 
escaping. The action of toxic doses of camphor upon the circulation is de- 
cided. In the poisoned frog the cardiac beats become slow and powerful, and 
as Heubner found (Arch. Exper. Path, und T/i£rap., v., p. 427) the camphor 
was able to excite the heart when arrested by muscarin, it is probable that its 
action is upon, the heart itself The same investigator failed to get any rise 
of arterial pressure in rabbits ; but in the more extended researches of Weide- 
mann it was found that in the convulsive stage of camphor-poisoning there 
is a very marked rise of the arterial pressure, which is largely due to the 
convulsions and disturbance of breathing, as it is in a measure prevented by 
curarization and artificial respiration. Under these circumstances, however, 
sudden periodical elevations of all of the arterial pressure occur. The cause 
of this phenomenon is not obvious, as Weidemann affirms that it is prevented 
by section either of the cord or of the vagi. As, after section of the cord, 
toxic doses of camphor lessen the arterial pressure, it would seem probable 
that it is directly depressant to the heart. 

Camphor appears to be very much altered in its passage through the body. 
Exactly in what form it escapes is not determined, but the studies of Weide- 
mann seem to indicate its conversion into a glucoside-like body. 

Therapeutics. — Camphor is very largely used internally as an antispa£»- 
modic, to quiet restlessness and ^' nervousness.^^ It is also employed in certain 



A NTISPASMODWS. 



209 



flmfnfbl aSeciions soen tn iho^e persons who are c^pmalt^ ImLle to the con- 
dition of the Ticrvoas system jitst iiientioDod : tliui^, it h ofteti useful in 
ii»4TfOM4 hetiilftrhrn nnd Jt^xmcnorrhaa. Indeed, in tlic ktter disease^ eithei 
slofic or ciiuibtned with opium iu bad cmeSj it is a moat yaluabk' drug, but 
miut be ^ven freely* In diarrhoea not dependent upon infiammation, in 
chfdetinr^ and even to »ome extent in chokra, cixtnplior is a very efficient 
natuedy, allaying intestinal paiu and spa^m, and also eliocking intestinal secre- 
tion. It enters into a large proportion of the pttpular elmlcra-mixturcs. In 
ndjfnamw/fver» it haa been very greatly empluyed, but la of doubtful advan- 
ti^C^ : «tilU a gtXKl deal of testimony could be adduced in favor of its u^neful- 
na» in ausUiniiig the system in tlie low atages of these diseaj^e^s; and in 
UtfiTOtts rwsdessneas occurring at such time^ it is often very soothing. In 
tihHonmd Kxual excitement^ and in chonlee^ large doses of camphor very 
often appciir to act most happily. The drag has also been veiy tVequenlly 
exhibited in Tarious apasmodic affectionSj such as whiMqnn^-coufjh, cpilepi^y^ 
aitil even puerperid and iirychnic convuhmiSj but is, I believe, at present 
never so employed. In hy$trricnl convuhlons, a^ in other phenomena of the 
mm/t origin^ camphor is a useful antispasmodic. 

K&t^snially, camphor is much used In Uniments a^ a stimulant application 
Ibr imsiBfs^ tprauu^ etc* 

Administration. — Large doses (ten to fifteen grains) of camphor are 
best aJministered in emulsion, because when given in this way^ being yezy 
finely uubdivided, they create as little irritation as jK)ssib]e, and are rapidly 
^ibaorbed \ smaller doses may be given in pill. A 8 an antiKpasmGdic, the 
Camph&r Water (Aqua Camphorm, — 1 to 125, U.S.) is u.sually preferred; 
Its doae is half a Huidounce to two tiutdounces, but, when a decided effect is 
desired, the Spinl of Camphor {^SptHtus Oimphorm — ^1 to 10, U.S.) is 
preftirable : its d^jse is lialf a fluldrachm to a fluidrachm. For external uHe, 
the U, S, Pharmacopoeia recognizees the LitiimeniumCttniphoraE. (camphor one 
pMt, olive oil six parts) and the Limrtventum Suponisj or Soap Liniment^ — 
ft Sttld linltnent, y&^ popular by itself, or as the basis of more stimulating 
preporatiooB, 

Oleum Ca^wuokm. — Oil of Camphor is the volatile oil of the Cam- 
phora (»f!icinaruui. As it occurs in our market, it is a reddish or yellowish- 
brown li«{uid, having a strong odor of camphor, and a hot, camphoraceous 
ta*te. It contains camphor in solution, and is probably equivalent to it in 
p^ tl action, except that it i?^ locally more stimuladnir, and therefore 

pr ut intestinal disorders. The dose is five to ten drops. 

CA3IPH0RA MONOBROMATA. U. S, — MoHohromafetl Otntpftor, or Bro- 
maUti Otmphor, — With iodine and bromine camphor unites to furm eom- 
|Kiiindfl. According to Laurent^, hromcamjfhor occurs in red i»rthorhombio 
oryttiala, Theae when exposed to die air utidoriro rsipid spontaneous decom- 

u 



^ 



210 SYSTEMIC REMEDIES, 

position, but by heating in a closed vessel are resolved into hjdrobromio 
acid, and a compound in which one atom of hydrogen of the camphor has 
been replaced by bromine. This bromated camphor b a crystalline solid, or 
occurs in large acicular crystals several inches long. 

We have just sufficient knowledge to show that bromated camphor pos- 
sesses most interesting physiological powers, which ought to be thoroughly 
investigated. All this knowledge is derived from the veiy incomplete re- 
searches of Bourneville (Zc Progrhs Med., 1874, and The Practitioner^ 1874, 
also CompteS'RenduSj Aotit, 1875), of Lawson (7%c Practitioner, 1874 and 
'75), and of Pathault {Bromure de Camphor, Paris, 1875). In mammals it 
produces muscular weakness passing almost into paralysis, convulsions, reduc- 
tion of temperature, great decrease in the rate of the respiration and of the 
pulse, profound sleep or stupor, and finally death. The fall of temperature 
is most remarkable, amounting sometimes to over 30° Fahr.(!) (Bourne- 
ville, Practitioner, Aug. 1874, p. 119). It is at first rapid, but in fatal 
cases appears to be progressive. Bourneville states that the blood-vessels 
of the eyes and ears are diminished in calibre. He also found that the 
continuous use of the drug produces a very notable loss of flesh in rabbits 
and cats. 

Therapeutics. — Bromated camphor was first introduced by Prof. De- 
neffe (Presse Medicate Beige, 1871) as a nervous sedative, and as a useful 
antispasmodic, especially in delirium tremens. Its value in the latter dis- 
ease has been confirmed (a single case) by Dr. A. M'Lean Hamilton {New 
York MedicalJoumal, July, 1872), who also commends it highly in chordee. 
In hi/ateria it has been used by various physicians with different results, 
sometimes appearing to do good, in other cases failing (see Pathault) ; it 
has also been employed with some success by Dr. Wm. Hammond (A^. Y. 
Med, Jour., July, 1872) in the convulsive irritation of teething, and even 
in more serious convulsive diseases, such as epilepsy. The clinical evidence 
in its favor is, however, not very convincing, and Lawson has not found it 
very serviceable. In spermatorrhoea! have certainly seen much good from 
its use. It is taken with difficulty, and is apt to irritate the stomach. 
Bourneville proposes the following formula for hypodermic use, but Lawson 
states that it is so pungent that it cannot be employed: Bromated camphor, 
gr. xlv ; Alcohol, f 5ix ; Glycerin, f 5vss. The dose of the drug is five to 
ten grains, repeated as necessary. In Bourneville*s experiments twelve 
grains injected under the skin of a cat caused death in seventy-two hours. 

Carholated Camphor, — When fifteen grains of carbolic acid dissolved in 
an equal quantity of alcohol are rubbed up with thirty-five and a half grains 
of camphor, an oily, pale-yellow liquid with a feeble odor of camphor results. 
This does not mix with water or glycerin, but does with almond and olive oil. 
It has been proposed by Dr. Soulez as a non-irritant, antiseptic dressing for 
wounds (sec Amer, Joum, Med. Sci., July, 1877, or Loud. Med. Record, 
May, 1877). 



A NTISPASMODJCS. 



211 



80CCINUM— AMBER. 

Amber b a fossil resin fouud on the southern coasts of the Baltic and In 
cvtbf^r partions of the world. It i» not itn^lf officinal or ii>ed in inedicine, 
bm bjr dedtmctive distillutlou viold^ aii empyniumatic oil which i^ included 
ttt ibe Mdieriii Medicii list of the U.S. Pharmaeopoob. 

OLKUM 8UCCINI— OIL OF AMBER. XJ. S, 

Oil uf amber is an amber-colored liquid, of a hot taste, and a very t^trong, 
dtsa^n^cable odor. As kept in the shops it is said to be usually sophibti* 
oUed. It is a powerful local irritant, and has been used as a rubefacient to 
ebroiiio rkeamaii^m and similar disorders. It is also an efficient unti^^pas- 
naodic, and as such is used in h^^teria, in whfx/piugcovgh^ and in ut/utttilc 
cofuniZnoftf. lo the brouchitU of infante, with severe nervous sjiuptomSp 
Si wcU as in the two affections last naiucd^ it is very useful as a counter- 
trritaot and nerre-stiiuulant when diluted with from one to three parts of 
f>Uve oil and freely applied over the spine. In obetinato hkcou^h^ pven by 
the stoomehf it is probably^ next to musk, the most efficient remedy. Dose, 
ten to twenty drops, g:iven in emulsion. 

SPIRITUS ^THERIS COMPOSITDS^-COMPOUND SPIRIT OF 

ETHER. US. 

ftoffmant Anodi/ne consiiJts of aleobol a pint, ether h:ilf a pint, and ethe- 
reftl oil six fluidrachnis. It is a c^tlorie^, (nUaiuniabte lL«[uId, of an aromatic, 
mhcreal cwlor, and a burninp, sli^htly'swc^jtish ta^te. It^ sfHScific |jjavity is 
0.815. IlofTuian's Anmlync is sometimes offered for sale without the ethereal 
oiL Forty dropts of the genuine preparation will render a pint of wat4?r dis- 
tiDclIy milky; but if no oil of wine be pR»sent, milkiness will not occur. 
Stfutrtal oil (^Oleum jEthcreum^ U.S.) is a tranf^pareut, nearly colorless, 
volatile liquid, of a peculiar aromatic odor, and sharp, bitter ta.stc. Its 
ftpoctfio pravity is 0.91. It is heavy oil o/wine, prepared by the action of 
an excess of imlphuric acid on alcohol, and diluted with ec|ual partij of strong 
ecber. 

Tri KRAPEUTICS. — We have little or no knowledge in regard to the action 
of bt^vy oil of wine upon the syst<im. Clinical experience hiw shuwn tlmt 
lltiffinun*s Anodyne is more persistent in its effect.^ upon the nervous* system 
than an cfjuivalent amount of ether. It is a very efficient carujinative, and 
li aliMi a most useful antispasmodic in all the disorders for which iiueh reme- 
dial aro cmjiloyed, c^prvisilly when tliere i.s u tendency t*) failure (tf the irir- 
calalion, as in tvi/tvr/tii* tmi/iac itisease. The diisc is one ctr two Huidnu.hms. 
refteated in half an hour ur un hour if reriuired, and y:iven in csold water. 

HDMULUS-HOPS. U.S. 
Tbc strobiles of Humulus kpulus, or the hop-vine, cultivated in northern 



«itt 



212 SYSTEMIC REMEDIES. 

and middle Europe and in the United States. Hope are soft, greenish ood^Sy 
one or two inches in length, composed of tbin, leaf-like, imbricated scal^^v 
having a bitter taste and a heavj narcotic odor. At the bases of the scsil^* 
is a yellowish powder, officinal under the name of Lvpulinum. Litpulin is i«* 
minute grains, and contains, according to Payen, 2 per cent, of volatile €>iU 
10.30 per cent, of bitter principle, and 60 to 55 per cent of resin. Volatile 
oil of hops is yellowish, and has a strong odor of the drug, and an ac«^<* 
taste. The bitter principle has been obtained by Lermer in brilliant rhoml^^^ 
columns, of an acid reaction. 

Therapeutics. — Hops are a bitter tonic, and a very feeble narcotic, pr^>' 
ducing, when taken very freely, some heaviness, and perhaps sleep. Tk^y 
are especially useful as tonics in cases of nervous irritability requiring med^" 
cines of the class. In delirium tremens they are veiy largely used to quE<^* 
nervous irritability, to aid more powerful remedies in procuring sleep, and ^^ 
the same time to strengthen digestion. In priapism, in irritation of /A^ 
bladdery and in abnormal sexual excitement, hops have been exhibited wicb 
asserted benefit. They may be tried in large doses, but very oflen will fail- 
Externally, hops are employed in the form of poultice, and when fresb 
certainly seem to aid the heat and moisture in allaying pain. 

Administration. — The dose of the tincture (^Tiuctura Humuli — 1 *.<> 
5, U. S.) is half a fluidounce to three fluidounces. For a decided narcot ic5 
effect the practitioner may use either the oleoresin of Z/upnlin (^Oleoresiwm^M^ 
Lupidinxj U. S.), dose, ten minims to a fluidrachm, in pills if desired, o^ 
the Jluid extract {Extractum Lupulins^ Fluidum, U.S.), dose, half a fluid — 
drachm to two fluidrachms. 

A hop poultice is sometimes made by simply moistening with hot wat>^^ 
the hops contained in a gauze bag of the required size and shape. In 80i*»^3 
cases a mixture of the broken strobiles with an equal part of Indian mecv^ 
affords a more eligible preparation. 

LAOTUOAEIUM. U.8. 

The concrete juice of the Lactuca sativa,* or garden lettuce, occurs m t^^*' ^^ 
forms in our markets. The English variety is in small irregular pieces ab<^^*-^* 
the size of a pea ; the German, in masses of about an inch long and half ^^""^^ 
inch in thickness. The color varies from a dark reddish-brown to a li«^^^ ^^ 
yellowish-brown. The odor is faintly narcotic, the taste bitter. It 
tains a bitter, crystallizable principle, Lactucin, probably first discovered 
Aubergier, but especially investigated by Ludwig and Kromayer (-4 
Phann., cxi.). 

Therapeutics. — Lactucarium is certainly a very feeble drug. Bouch 
dat gave half an ounce to a dog, with merely negative results ; and ir 
number of trials made with it some years since I was unable to perceive tl 



* For case of reputed poisoning by Lactuca viro8a,8ee Schmidt** Jahrb,, Bd. 171, p. 1 



r*"^ 



ANTISPASMODICS. 



213 



■ it eierud anj influence* A very krge amount of teBtimouj exists to the 

■ aanw effect ; but, on the other hand, various ohservei-s have chdmcd that it 
H cierta 1 pocuJiar soothing, hypnotic influence, like to, but much less intense 
H Inni, tlmt of opium, and free from its disagreeable aftor-effects, such as de- 

■ |fw>ii, Daujea, coustipatiou, etc. It may be tliat the drug varies greatly 

■ WConUng to age, time and mode of preparation, etc. 

■ Ltctttcin has been expKirimeixtud wkh by FroHmiiller, who found it pro- 

■ ^JrtlQiiately lesB hypnotic than the crude drug (Dtut^ches Klinik, 1865). 
K Toe astjtlly as^i-^ned dose of lactucarium u thiity grains^ of ihajluid extract 

■ i^rodum Liicitwwu Fluid iim, U.S.) half a fluidrachm. Much larger 
I fiujjtities may be given with little effect. 

I OIMIOIFUGA-BLAOK SHAKEEOOT. U.S. 

■ rhe root of Cmiicifuga racemosii, au indi;^ouous herbaceous plant, growing 

*^iitniuitly in rich, shady woods, attaininj^ a height of six or seven feet, aud 

'^dily distinguished by its very largo multi compound heaves and it« huig- 

^faxiehed spikes of whitish polyandrous flowers, naked when oiwn. The root 

^Oiiaiats of a knotted head, with numerous fine, brittle rootlets ; the odor is 

*i*it^ the taste bitterish, sojntnvhat astringent and acrid. It has not yet been 

®t^nuiaed exactly upon what the activity of cimicifuga depends. Mr. Geo, 

H. lHaTis has found in it a volatile oil, which Prof. Geo. B. Wood thinks is 

^ry probably active, since the virtues of the drug deteriorate on keeping. 

The?r^ are also two resins in the root. 

I^ IIYSIOLOGICAL AcTiON. — Although ciniicifuga has been mofit extensively 

****^^^ by American practitioners since the publicatiou of the paper of Dr. Youug 

i^^^mtrican Jonrtud ijf tlu^ Medical Sciences, vol, ix.) in 1831, yet we have 

little accurate kuowledge as to its physiological action. Dr. Chapman 

'iiitiUM a/ TherapcHtici^ Uth od., vol. i.) affirms that in full doses it tumses 

•**^*^ ^ nausea, more or less relaxation of the surface, vertigo, tron»ors, and decided 

™* faction of the pulse; and Dr, N, S. Davia (D'ansttcfiom of th^ American 

^^^ml AMociati&H^ 1848, vol. i. p. .^51) dwells very strongly upon its seda- 

^ action. In full doses it certainly influences the cerebrum, producing 

headache and giddiness. Although In large doses it vomits, yet its 

. -^^^^ ictian is never violent, and it never causes more than relaxation of the 

^^^rek. Vorioos practitioners have asserted that it actji upon the respiratory 

^^•cona membrane. 

TMERAPErTlcs. — Cimicif\iga was originally proposed by Dr. Young as a 
^^lucdy in chrrea^ and since his time has I*cen very largely used in that 
2**ea»c by American practitioners. In simple choi-ca, such as exists in 
Idren, it* value is unquestionable. It must be given freely, and in most 
tlie consentaneous exhibition of iron and laxatives materially aids ia 
ng a cure. 

Ill ictite {njiammatorff rheutnatigm, eimiclfuga has been highly recom- 
^tended by Dr. Davis and other practitioners. I have soen it do good, but 






214 



SrSTEMJC RKMBDIES, 



it ia at prt^nt very rarely, if ever, used. In chrmnc bronchitU it b some- 
tinies eiijpktyed with beoefit, egpccially when the expectoration is free and 
ht!ctic existi^. 

ADMiNisTaATlON. — ^As cimicifuga deteriorates by keeping, the fresh dmg 
should always be used. The powder (dose, twenly grains) b preferred by 
soQJC practitioners; but I have found the officirjal yAr/r/ extract {ExtractHm 
Ctmici/ti(/x Fluidunif U. S.) very active in doses of from twenty minims 
to a JIuidriR-hm. The dose of the tincture {Tinctitra Cimici/u^g^ — 1 to 5, 
U, S.) b one to two fluidraulims, 

OAFFEA-OOrrEE, 
The seeds of the Caffea Arabica are such familiar objects that spaoe will not 
be here oceiqued with their de-^criptiun. It sliould be reiuembcred that cofTet 
contains, hasides Qiffetn^ an eujp) icumatic oil, whith has dctiiled effects upon 
the system. 

CAFPEINA. U.S. 

Caffeine occurs in long, suow^white, silky, opaque, odorless crystals, some- 
times conjoined into feathery crystals, of a feeble hitter taste. It ha« a neutral 
reaction, but unites with acids to form salts. It is soluble in 100 porta of 
water, ICO parts of abmilute alcohol, and 220 parts of ether. It was first 
discovered in coffw by Kunge (Schweiffff. Juum, Chem. Ph^$., xjuti,), in 1S20. 
In 1827, Oudry discovered a principle in tea which he called thcin^ which in 
1838 was proven by Mulder and C. Jobst to be identical with caffein. War- 
tiua, Stcnhouse, J. Attfield, and other cheiiiist* have also ehown that caffein 
la the active principle of Gaarmia (the fruit and leaves of the Panifima 
sorb a IS of Brazil), of M<iU or Pumfpuir/ tea (the leaves of the Hex Para- 
ifitak'usui)* and of the Kfjia nut of Africa ( Ctif^i aatminatn), IL M. Stutth 
(Journal of Applied Science^ Sept. 1S74) has also found it in Yaiipon (the 
leaves of our native Ilex Casame), 

riivsiOLoaiCAL Action. — Thestudj of the physiological action of caffein 
in relation to its tberapeutje use vmi be most conveniently made in two 
divisions, namely, the action of toxic and that of mmute doses. 

Ihxic DoKcs. — The influence of the alkaloid upon frogs has been studied 
by Alboi-8 (DfutuchcH Klhnk, 1 853, p. 370), Falck and Stuhlniann ( VirchotCM 
Archiv^ Bd. Sill p. 3(35), Mitscherlich (Der Cacao und die Chfjc(d*ide^ 
Berlin, 1859), I. Iloppe {UEcho MhL, 1858)^ Brill (Z>aj« Kajfdn, Innug. 

• Mafi t« used m South Aioorioa very largely aa a eubfitituto for tciu Acscording to ibw 
ftliftlysci of Dr. Pc^kdt, of Eio Janeiro, it cotitain^ 2,5 parts in a (bou^and of cafein | bat 
M. Byanon found 1.85 |ier cent, of lh« alkaloid {Bult, Thitfip., xuiiL). It i» iold jn two 
feirniDt mafi in Unf if prepared an onlLnary ti^a ie, and taken with sugar aud milk to 
taster; Mifif/ ht potrder la prfjpi^rcd by pouring upt»n the powdered niat6 boiling water, 
and flucking up thrutigb a ttii>o, the bu1bou§ und ut which is fumifhed with a fine tieroi 
or the powder t^ thrown into the bc>ilinj| waiter, and when the mixtnre reuomtnenccA boiiiD^ 
oold water is poured iatu it; this pr€vipitate« the puwdcrrj, and the infuKioa li takoa Glfittr, 




A NTISPASMQV tCS. 



215 






h^ 



Hju4;>arg, 1861), Oscar Joliaiinsen {Ueher die Wirkung chs Knffein^ 
'lias., Dorpatj 1860), und vsirluus otlter observers. The minimum futal 
dose is stated by Levcn {Arch, de Pht/md.^ 1S5S) bo be .015 gniiii in a frog 
of moderate eize. AccordiQg to the various observers, the chief symptoms in- 
dooed by poisonous doses in the batnichian iire inuBcular quietness and weak- 
noBS, with disturbance of respiration, succeeded by a stage of violent t«>tanic 
ooovnlsioRS, ending in general pamlysis and death hy asphyxia, the heart 
beating sifler the cessation of respiration, although evidently miieh affected. 
Johannaen denies that there are any tnie eonvulstonij produced in the irog 
by caffein, but merely a rigidity, muscular in it-s origin and very closely allied 
to that produced by heating a musele, i,e,^ to post-mortem rigidity, Pratt, 
bowever, previous to the publication of the paper of Johaniisen, had very 
dearly recognized the existence both of this muscular etiifness and of con* 
Tul^ns, and had pointed out the diflferenec between the latter and those of 
stzychiiia, differences which are the result of the peculiar condition of the 
uniflcles in thein-poisoning. He says, " At the commencement there is the 
ttSual rapid action and abrupt contraction of the muscles; but as the phe- 
Domena go on, the muscles soem to act sluggishly, refjuiring quite an interval 
io contraJi*t and relax, . . . the spinal cord having to deal with muscfos already 
Qch Contracted by the loeal action of the poison on their fibres.'' ^loreover, 
Leven {he, cil.j p, 182) destroyed entirely the lower third of the spinal cord In 
a frog, and administered cafi*ein, when the characteristic convulsions appeared 
in the upper two-thirds of the animal, but not in the lower third. 

Fratt included all the tissues of a frog, except the spine^ in a tight liga* 
tare just above the bifurcation of the aorta, and administered theia, when 
the anterior le^ became very stiff, and had also occasional severe convulsions, 
in which the hind legs participated, although between the paroxysms they 
were perfectly relaxed. He also noted in a number of experiments that the 
bind legs became very rigid, but not convulsed, after the lower portion of the 
spina] cord had been removed and the animal poisoned. 

Buehheim and Eisenmenger (quoted by Sehmiedeberg) have recently cor- 
roborated the muscular changes noted by Johannscn, but insist, with Pratt, 
llbat there are also true nervous convulsions. O. Schmiedebcrg (Ardnu /Hr 
*xp^tm. PnthoL und Phnm\.^ Bd. ii*) believes that he has reconciled these 
differences of observations by finding that the alkaloid act« much more power- 
fully upon the muscles of liana temporaria than upon those of H. pHt-ulenta; 
that a dose of caffein which causes intense general muscular st illness in 
e foniicr produceia in Ihe latter only true convulsions, the eon\Til8ions in 
tempuntriii being prevented or m[ifiked by the disorder of the ujuseles. It 
to nie established by the whole evidence that in the frog caffein pHnluces 
nervous convulsions and muscular rigidity. The convulsions are prfibn- 
ilj spinal, since Pratt found that destruction of the spine pre vented their 
jjment^ but that removal of the cerebrum had no eflfect* The rigidity is 
ftduit of a direct uction of the caffein upon the muscles, since, as Johiiiinsen 



216 SYSTEMIC REMEDIES. 

first pointed out, it spreads from muscle to muscle, as the hypodermically- 
injected poison diffuses itself and is never developed in a leg whose muscles 
are protected by tying the artery. Moreover, in Voit's experiments the 
rigidity was developed as usual after the nerve of the leg had been severed. 

In birds poisoned with caffein, the symptoms (Brill, he, cit,^ p. 66) are 
irregular movements, apparently to some extent due to cerebral disturbance, 
increased rapidity and irregularity of respiration, spasmodic tremblings, and 
tetanic and clonic convulsions, with paralytic phenomena. In mammals the 
results of the toxajmia, as noted by various observers,* are restlessness, hur- 
ried respiration, at first a slight lowering and afterwards a decided elevation 
of temperaturef (Alex. Bennett), uiui?cular weakness, tetanic and clonic con- 
vulsions, increasinggeneral paresis, and finally death, apparently from paralytic 
arrest of respiration. There is still a good deal of uncertainty as to the 
nature of the convulsions ; but Amory in some not very conclusive experi- 
ments found that they did not occur below the point at which he had divided the 
cord. If this result be correct, the convulsions must be cerebral ; but con- 
firmation is lacking. Uspensky (^Reicherfs Archiv, 1868, p. 526) has found 
that forced artificial respiration in great measure suspends the convulsions.^ 

Nervous Si/stem. — There is no evidence that caffein exerts a very marked 
influence upon the cerebrum of the frog, or even of some of the lower mam- 
mals, unless the convulsions induced by it are believed to be the result of 
some such action. In certain of the higher animals, such as the cat, it often 
produces a condition of almost frantic cerebral excitement. Upon the spinal 
cord the poison probably acts decidedly ; but as to the nature of this action 
we are as yet greatly in doubt. The reflex function of the cord is probably 
increased in the earlier stages of the poisoning and diminished in the latter 
stages ; although I have met with no carefnlly-conducted experiments actually 
proving this. Alex. Bennett has brought forward the theory (loc. ciif., and 
British MtdiculJovmal^ 1874) that caffein paralyzes the posterior columns of 
the cord without affecting the anterior columns ; but his evidence appeiirs to 
me insufiicicnt to prove his conclusions. He grounds his belief chiefly on 
finding that in poisoned frogs and rabbits galvanization of the posterior 
columns of the exposed cord produced either no muscular contractions or 

• Leven {Archivet de Pht/fiologief 1868; Amorj {Boston Medical and Surgical Journatf 
I., 1868); Pratt (/6iU,ii., 1868); Alex. Bennett {Edinburgh MedicalJoumaly Oct, 1873). 

f Attention has recently been called, especially by Prof. Binz, to the effects of caffein 
upon animal temperature. He states that minute doses have no effect upon the bodily 
temperature; doses just enough to produce slight toxic symptoms cause a rise of 0.6° C. ; 
excessive doses an elevation of 1® to \.b° C, the maximum being reached in one to two 
hours ; doses which rapidly kill hare very little effect upon the temperature {Arch, Exptr, 
Path, M. Therap., ix. 31). 

X In an elaborate series of experiments, Dr. Bennett {British Medical Journal, 1874) 
found that the minimum fatal dose of the poison for the cat and the rabbit was a little 
orer a grain for the pound, five and a half grains being required for a five-pound animal. 



A NTlSPASsMODICS. 



21i 



iDBty sucL as were Tciy much more feeble than thoee provoked by galvmiim. 
tloii of the posterior columns. 

The motor nerves appear not to be affected, since AJex. Bennett has round 
that after death from thein they retain thetr normal susceptibility, and Pratt 
surmundctJ one crural nerve of a frog with a pa^te '* of theln and water," 
and irriuted the spinal cord, when both legs responded with uuifarci alacrity, 
Bennett aldo tied the crural artery of a frog, poisoned it with the alkaloid, 
ftnd found tliat irritation of the cord produced etjtially active conCractionB in 
the two le^rs. Upon the sensory ner\*ea it h affirmed that the poison acts 
more decidedly ; but careful exj»erimenti§ are Btlll wanting to prove this. Tho 
chief evidence is furnished by Pratt, who found that when the lefl sciatio 
nerre of a belieaded frog was surrounded by a paste of thein and water, after 
ten minutes irritation of the right foot produced reflex movements, whilst 
irrit&tian of the lell foot failed to elicit any response. 

Mutailar %<^^m.— When the isolated muscle of a frog is thrown into s 
ooe per cent, or even weaker solution of caffcin, it becomes in from two to 
ikree minutes contracted, swollen, round, stiff, and unable to respond to the 
galmanie ourrent. It has been proven that rigor mortis is due to a coagulation 
of the myosin of muscles;* and it ii* probable, but not proven, that the 
dlange wrought by catfetn is of guch nature. That it is purely muscular la 
ahown by the experiments of Pratt and Voit, already quoted, in conjunction 
irith one in which Pratt found that when an iaoktod muscle was soaked io a 
solution of eurari until the nerves were killed, and then thrown into a sola- 
ticm of caffein, the usual rigidity was developed, Johannsen {foe. ciV., p, 22) 
states that when a muscle under the niicrosc^ope is touched with caffein, its 
fikres can be seen to contract half their length. 

Circulation, — Caffein undoubtedly exerts an influence upon the hearty 
^though the viscus in animals poisoned by the drug continues io beat afler 
the cessation of respiration. According to Voit (quoted by Brill), in the frog 
the rapidity of the c^diac pulsation is at first increased, hut the pulsations soon 
beoome slower and slower, and are aecompanied by irregularity of rhythin j 
the heajt fijially oeasing to act, but still responding to stimuli at a time when 
the voluntary muaoles are absolutely dead. Upon the heart of the mammal 
the poison probably acts precisely as it does upon that of the fix>g : in tho 
fint ftagee of the toxaQmia the pulse-rate is very greatly increajaed) as, ao- 
cordiog to Leven, is also the arterial pressure. The action of the poison ia 
probably directly upon the cardiac muscle or its contiiined pinglia, for Jo* 
haoDflcu found that the cut-out heart of the IVog^ when placed in the si>lution 
of caffein, acted very much as the viscus does in the poisoned batrachian. 
Mriregver, Leven (ioe, cif,, p. 184) divided the pneumogastries and sympa^ 
tlietice, and, as he assertg^ istilat^ed rhe begirt from the f^pinal cord, and, on 
idminidtering caffein, found that both the arteriid pressure and the rate of 



218 SYSTEMIC REMEDIES. 

the cardiac pulsations were increased. In regard to the action of the drug 
on the vaso-motor nerves we have no definite knowledge. 

On man toxic doses of caffein would probably act as they do upon the 
lower animals, the cerebral excitement being more prominent in th'^ same 
proportion as the human brain is more developed than the animal cerebrum ; 
but, so far as I know, there is no recorded case of acute poisoning by caffein. 

Effects of Therapeutic Doses, — The peculiar wakefulness, the increased 
mental activity, and the often nervous restlessness which are induced by strong 
coffee are familiar phenomena to almost every one. They are without doubt 
largely, but are not altogether, due to the caffein contained in the beverage. 
By doses of two or three grains of the alkaloid a very similar state of body 
and mind is induced. Lehmann found that eight grains of caffein produced 
increased frequency of the pulse, very frequent urination, tremulousness, 
excited mental action, passing into a form of delirium, with confusion of 
thought, visions, and finally a deep sleep. The largest amount that I have 
met with as having been taken by man (twelve grains) was ingested by Dr. 
Pratt (loc, cit,). About two hours afler the dose had been swallowed, intense 
physical restlessness and a very uneasy condition of the mind were developed; 
very marked general muscular tremulousness soon followed, and the mental 
anxiety increased. After this passed off, there was obstinate sleeplessness, 
with active and persistent thinking, and frequent urination. The increase of 
brain-power which has been noticed by various observers afler caffein, as well 
as afler coffee, tea, guarana, and all the allied crude drugs, is undoubtedly 
real, and must be due to a direct stimulant action exerted upon the cerebrum. 
The experiments made upon animals with toxic doses indicate very strongly 
that the physical restlessness and tremulousness are due to spinal stimulation 
and are the counterpart of the convulsions which toxic doses produce. 

It appears to me that the cerebral stimulation of caffein differs from that 
of opium in that it affects the reasoning faculties at least as profoundly 
as it does the imagination. Coffee prepares for active work both mental and 
physical, opium rather for the reveries and dreams of the poet. 

The enormous use made by mankind of substances containing caffein m- 
dicates that in some way it is directly of service in the wear and tear of daily 
life. It is not probable that any of the caffein is assimilated, but it is thonglu 
by some authorities to check very greatly the elimination of nitrogen, or, 
in other words, lessen the waste of tissue. The subject was laboriously 
investigated by Julius Lehmann in 1853, and by F. "W. Bocker in 1854, and 
earlier. Dr. Lehmann found that the exhibition of six grains of caffein daily, 
the regulated diet being uniform, diminished the elimination of urea from 
twelve to twenty per cent. Upon experimenting with the empyreumatic oil 
of coffee he found that it lessened even to a proportionately greater extent 
the elimination of urea, and also acted very powerfully in producing sleep- 
lessness, so that the favorite beverage is by no means dependent upon its 
contained caffein for all of its activity. Dr. Bocker published his researches 



PISPASMODICS. 




tin 18-40 {Brjtrii0€sur ITeiJknnt1e^ Bd, i.), but I have never seen 

net of the article, other than the stiit<?ment that he found that the 

' drug oiuses diminished elimtnation of urea* His investigation of the effect 

of tea was most elaborate and laborious {Archh der Vtrtlnn /tir Geinems, 

At^^iienM. J^rdenotr^ d. Wmm, Ilet'lkumk^ Bd. i. p. 213). He analyzed 

I fmoeSt the urine, and the products of respiration, and found, a similar diet 

; nmiutaincd, that the t-ea did not affect scniiiblj the elimination of car- 

I'boiuo acid from the lunga, but did very decidedly diminiiih the excretion of 

; area, aud also of nitrogenous matters in the faeces. He then tried abstaining 

&om food for periods of thirty-six hours^ with and without the use of tea, 

frith ri'&uka perfectly in accord with those just st4ited. The results obtained 

by various experimenters are sinirulurly at di^icord. Henri Iloppe (^Deutsdie^ 

Kh'nik, 1857), in experiments upon a dog, tound that coffre diminishes very 

lllightlj the urea elimiuation, but greatly increases the output of carbonic 

lieid. In regard to urea^ llabuteau »nd liLs pupil Kurastrriliade, working 

lirith coffee upon men and dogs, obtained resultsS similar to those of BDeker 

l(C^mp^ Rcndti^ 1870, Ixxi. 42t5, 73^}, as did also Hammond in this 

try. On the other hand, C. 0. Lehniunn (LehrL d, Ph^siol^tg. Chcmie^ 

J., Leipsic, 1812), Voit {Wniersiichuii<^en^ Munich, 18(il)}, and Hour 

{Arch* Phyniolog, Norm, et FafL, 1874, i. 5^*2} found that caffein or 

i aensibly increase the elimination oC urea^ or, in those accustoniod to 

r<iai]y use of coffee, have no influence. 

Id the present state of the evidence a positive conclusion can sca.rcely bo 

reached, but I ajn strongly inclined to believe that the hiibitual use of mod- 

ente amouutu of tea or coffee has pracrically no effect upon tissue-waste. 

ITllEBAPEtrxrcs.' — The use of caffein i\& a remedial agent in disease ia very 
limiced, whibt its employment in health as an article of diet is the daily 
pimctioe of a great part of the race. The chief indication in disease which 
<mr kDOwledgc of the physiological action of the drug establishes its fitness 
to meet, is as a cerebral stimulant; for this purpose it is of^n used in 
Iterf&ta headaches and in opimn-pouoning. The first of these disorders it 
0ometimc8 relieves in a marvellous manner, but more often it fails to ac- 
OotDpUsb good. To predict in any case what its influence will be, in the 
prBsent state of our clinical knowledgep is impossible ; but the remedy may 
thrtys be tried in safety in the dose of two grains, takeo when the paroxysm 
IS coming on, and repeated once in forty minutes if necessary. Vct}^ strong 
L coffee \a ahnust always administered in unlimited rjuan titles in op ium-poisi fi- 
ling, but, so far as 1 know, Dr. J. Hughes Bennett {British Med. Juurn„ 
1874, p. 697) has made the only attempt to establish by exact experiments 
be asserted antagonism of cuffein and opium. That observer found that 
If the exhibition of from four to four and a half grains of caffein would Siive 
proportioD of cats poisoned with the previously-ascertained minimum lethal 
I (1 ir gr.) of morphia. Several of the cats which had thus been saved 
tibed some days afterwards to one and Beven-eighths grains of morphia. 



220 SYSTEMIC REMEDIES, 

The caffein was powerless to save animals to which larger doses of the nar— 
ootio had heeo given : so that it is fair to conclude that caffein b within 
narrow limits antagonistic to the narcotic ulkaloid. The statements of Prof. 
Oahler (^BuU, TfUrap-^ zciii. 523) that the citrate of caffein is a powerful 
diuretic have received strong confirmation (see Lond, Practifioner, xxii., 
xxiv., XXV.). It may be used in cardiac drops^y and in chronic Bngh£$ 
disease in doses of three grains every three or five hours. In doses of five 
grains I have seen it cause some cardiac distress. In acute Bright' s dis- 
ease, it should be employed with caution, if at alL It is said that most of 
the salts of caffeine are decomposed in the presence of water, and are, there- 
fore, ineligible for hypodermic use ; the double bencoate of sodium and caffeine 
has been proposed as moderately stable and free from irritant properties. 
M. Tanret also states that the solution can readily be made extemporaneously 
by dissolving the caffeine in a solution of benzoate or salicylate of sodium 
(Lond. Med. Record, 1882, p. 48). 



CLASS vi-a:nalgesics. 



Iff the gIqss Analgeixa, in this work, are placed tboae drugs whose chief 
clinical use is id the relief of pain. Of course the Anm$(heHc$ might also be 
diBGnacd under thia headtn*;, but^ && they make a very marked group of tliem- 
Mlnee, thej are best considered ns a separate doss. The only drug, besides 
opium, which seeins worthy of a place in the present divisioUp is eannabis 
iodtca. 

OPIUM. U.S. 

The inspissated juice of the unripe capsules of the Papaver somniferum, 
or poppy. It is obtained by incising the capsules with a small, t^harp knife, 
«Dd twenty-four hours afterwards scraping off the exuded juice with a blunt 
blade. Opium is produced in various part^ of the world, — chiefly in Turkey, 
Aata Minor, Persia, and India, but also to a very slight extent in England, 
Oenaatiy, and the United States, Our market b almost exclusively supplied 
fn^m AMa Minor, with the variety known as Smyrna or Tttrhy Opium, 
This nccnre in masses from tbe f^izc of the fist to that of a chiUFs head^ 
irregularly globular, more or less flattened, covered externally with tho cap- 
sules of a si^efiea of Hum ex t»r dockj hard externally, softer and of a reddish- 
brown c5olor within, and of a strung narcotic <jdor and taste. 

Smyrna opium is at tirne^ variously adulterated with gum, licorice, and 
other aubstances. Such specimens are said generally to want the Rumex 
e^eulee. A rough but pretty fair test of the purity of opium ia per- 
formed by drawing a piece of it across a sheet of white papt?r, D' it be 
much adulterated, tho mark will be continuous^ — not interrupted, as it should 
be. Often tlie black color, the adhesive oonsistency, and the sweetish ta^te 
will also betray the nature of the sample. 

On exposure to the air, opium becomes hard and brittle, and is readily 
reduced to a powder of a yellowish-brown <^lor. It yields to water, alcohol, 
and diluted acids, forming dark -brown solutions. Ether does not extract all 
of ilrt medicinal principles. It is a very complex body^ contuining the alka- 
loids morphia, oodeia, narceia, narcotina, thebaia, papaverina^ porpbyroxia, 
eryptopia, meconia, opiania, paiumorphia, besides meconic, thebotactie, and 
aalphuHc acids, extractive matter, gunvj glucose, fixed oili?, a volatile odorous 
pnncipie, and other substances of no importance. In regard to the propor- 
tions of the more important principles, Messrs. Smith of Edinburgh obtained 

221 



\ 



99*> 



SrSTEMIC REMEDIES. 




from 100 parts of fine opium 10 parta of morphia, 6 of narcotina, 1 a^^- 
papaveriiia^ 0.15 of tliebaiaj 0.03 of codeia, 0,01 of meconia^ 0.02 of ni 
and 4 of mecoiiic bjciJ {Pharm, Jounu ami TranM.^ October, 18G5, p* 183 
Good opium should yield from nine to fourteen per cent, of morphia. 

As mecouic atdd strikea a blood-red color with a persaltof irouj the latte::^^ 
aflbrds a ready, although not decisive^ test for opium and the meoonatea. 

pHYSiOLOorcAL ACTION. — WhcD opium is taken in such dose as to pn 
duce its mildest physiological effects^ it exerts a quieting influence, inducin^^ 

a peculiar dreau*y condition, — very generally a feeling of himfm^ance^ 

during whieli images and ideas float before the mind, and by their endless 
and effortless repetition shorteo the time, which seems to lose itself in re^^ 
It is commonly asserted that there is a stage of the action of opium in whicb^ 
the activity of the mental faculties is cxalled, TJiis may be so in aom» 
persons, and especially in those who have accustomed themselves to the U8^ 
of the drug as a stimulant ; but my experience is that in those who do jkc^ 
habitually take opium true Uicntal power is^ during all the stages of thft^ 
action of the di-ug^ diminii^hed rather than increased* The state induced 16 
rather the fabled calm of the lotus-eater than the energetic activity of pro- 
duction. Even in those who are accustomed to the use of opium as an aid 
to work, I think it is the imagination rather than the reasoning faculUes 
which is excited by it* After a length of time, varying according to the 
idiosyncrasies of the patient and the dose of the drug, the condition which 
bus been noted gradutiily passes into sleep, — either light and dreamful, or 
natural, or heavy and deepening into stupor, according to the amount of the 
drug ingested. On awakening, the patient may return at once to his normal 
condition, hut very oHien he experiences a state of depression, as shown by 
languor, a little beaiiache, nausea, or even vomiting, which may last for some 
hours. 

Aflcr very large doses, the first stage of the action of opium is very short, 
or it may be entirely wanting, sleep coming on almost at once. Thus, I have 
seen deep coma produced in three minut-es by a hypodermic injection of 
morphia. The s^iiiptoms of the second stage of opium-poisoning closely 
rcacnible those of congestion of the brain \ the pupils are strongly contracted 
the face more or less suffused, often deeply cyanosod ; the pulse full, alow 
and strong j the skin genemlly dry and warm ; the respiration slow and deepi 
and, it may be, stertorous ; unconsciousness is apparently complete, but very 
generally the snlvject can be aroused by violent shaking or by shouting in hi» 
ear, but relapses at once when letl:. to himself. When the patient is aroused, 
the re»Hpi rat ions become more rd]>id, and tbe skin of\en regains almost at oncse 
its normal color. Death very rarely occurs during this second fitage of opium- 
poisoning. When the symptj^tms do not gradually ameliorate, the third stage, 
that of prostration, is develoj>ed. The conia is now profound, and to arouse 
the patient may be impo.^sible; the pupils are absolutely contraet^sdj or, aB 
death approaches, are widely dilated ; the respirations lU'e distaotj alow, feeble. 



ANALGESICS. 



223 



intl imperfect^ mid often interrupted by intervals of death-like (juiet ; the 
count45tiatioc is at once pallid and cjanosed ; the puUe grows more and more 
rapid tind mure and more feeble; the skin is cold and moist, finally covered 
with a diinmiy aweat, Even jet the imticiit may recover: if he do so, the 
K rtitajTi to life is most graduid ; if he do not, death occurs generally by failure 
™ 3f the rcspinition, but aniid an almost complete extinguishment of the vital 
fttnetioDfu 

AJtlioagh the sjinptoms which have been narrated are those naually pro- 

^c^ by opium, yet in certain individuab the drug provokes quite different 

pheiiuiuena. One of the most common of these departures from the ordinary 

^ course i»f symptoms is an excc»i?*ive de|>ression following the sleep produced 

■ by moderate doses of tlie medicine* This stiite is seen, so far as my expe- 

■ netioe gii>c«, most usually in females of weak, nervous organ badon, such as 

■ tre peculiiirly liable to attacks of neuralgia. The symptoms aie a feeling of 
K veaJkue^B and prostration, of\en ace<:»njpanied by chilliness, dull headache, and 
■g^ddLijcss, but e*pecially marked by intense nausea and frequent vomiting. 
■\ ery frequently the latter does not occur so long as absolute rest in the 
■lionatcmtid position is maintained : indeed, im almost diagnostic sign of this 
H|^pot.iuii may be found in the fact that tire stomach is quiet so long as the 
^pK^»t keeps the head upon the ] billow, but the distress occurs at once upon 
^f******^ tip. In some cases this condition of depression even replaces the 
^P*^*~*iiiil second stage^ so thiit npiunj, instead of inducing quiet sleep, will 
^rt>x-«jke alarming depression and vomiting, either with or without drowsiness, 

^ hiji^Q^ ,j^;3«j^ l^YQ been reported in which onc*fourth of a gniin, or a somewhat 
^P'^^^Xer quantity, of morphia, hypoderniically injected, hiis been fijllowed at 
W^^^^^^ by fifyncope, with struggling for breath, and upparently imminent or even 
*^^^^^^^nt death.* A rarer idiosyncrasy exists in those persons who are ren- 
^^'■^^d by opium very delirious, it m*»y be even wildly so. In certain eases 
^ ^^pittm- poisoning, partial or complete couvulsiuns have occuiTed amidst the 
BP^^^^e usQj*! phenomena* (Cases, Brtt, Med. Jmirn.^ 1876, ii., p, 496 ; Pacific 
^E^^^. and Sur(f, Jonrn,^ July, 1876.) 

^^^^CZ)pium at first sight appears to act so differently upon the lower animals 

""**^»j it docs upon man, that it seems necessary to discuss this action by itself. 

In 1826, Charvet (Pern'ras Mutcna Medica^ vol. Ih p. 1035, Thiladel- 

*^^a, 1854) found that opium acta upon all classes of aninnilsj inducing in 

^^ invcrttbrata weakness or paralysis df the contractile t issue j with gradual 

* * siting and death ; in fishes, a weakened paralytic condition of the muscular 

^^"^rm, associated with eonvulsions; in birds and mammals, pardlysia, oon- 

^^Viljiions, and stupor. These researches have been recently much extended, 

* Mt in considering them I shall confine myself to the vertcbrata. 



* See Report of the Cotumitt^e on the HjpotliTtnic Method of Injection, Afcdieo* 
'^yikimryical Tran$Qctwn§f rol* L ,* s«e olfio Medical Time* and (Ja»tit€f 1S6^, catCfl reported 
^j Mr. Bntine »nd by Mr. Rob«rtf* 



224 SYSTEMIC REMEDIES, 

When one or two grains of opium are injected undei the skin of a frog 
(KoUiker, Virchow's Archiv, Bd. x. p. 248 ; J. F. H. Albers, Vtrchow'n 
Archivj Bd. xxvi. p. 229), in from six to ten minutes a condition of excita- 
bility is induced, so that the least touch produces violent tetanic oonTulsionB, 
which, a little later, also occur without obvious cause. Afler a time, these 
convulsions gradually give way to a deepening paralysis. The breathing, 
previously disturbed, becomes more and more shallow and imperfect, and 
finally is suspended. Morphia acts, apparently, on frogs in the same manner 
as opium : at least Drs. Kichard Grsoheidlen ( Untersuchungen aus dem 
Physiolog, Lahoratormm in WUrzburg^ Bd. iii. p. 15) and W. Baxt (/2ei- 
chert^s Archiv/Ur Anatomie^ 1869, p. 128) have found that in large doses it 
induces the counterpart of the series of phenomena just described. The 
latter observer noted, however, that when a minute dose (15.25 milli- 
grammes) was employed, immediately following the injection came a brief 
period of disquietude ; one minute afterwards the frog returned to its nor- 
mal state, in from six to ten minutes suffered a diminution of excitabili^. 
and in from twelve to fifteen minutes fell into a stupor which continued from 
four to ten hours. Aft^r awakening, the reflex excitability seemed greater 
than normal.'*' 

According to Kolliker, the opium-convulsions take place after the cord has 
been divided below the medulla, or even as low down as the third vertebra. 
In a single experiment, tetanus did not occur aft«r division of the cord at 
the fifth vertebra ; but the quietness was probably simply due to exhaustion, 
as the frog had already been poisoned for a length of time and had suffered 
section of the medulla and of the cord below the medulla. These facts 
seem to prove that the convulsions are reflex and of spinal origin. The 
convulsive movements which are present late in the poisoning would appear 
to be of peripheral origin : at least, in Albers's experiments {loc. cit.) they 
occurred in limbs whose nerves had been previously cut so as to sever all 
connection with the nerve-centres. Further, both Kolliker and Albers assert 
that some of the convulsions are epileptiform, — i.e,, of cerebral origin. 
Further, Dr. S. Meihuizen (Arch./. Phy$iolog.y vii., 1873) states that the 
convulsions occur at a time when mechanical irritation fails to induce any 
response. If these experimental results be correct, opium apparently induces 
in the frog three kinds of convulsions, of which those of reflex origin are 
probably the chief 

Kolliker, from his investigations, concluded that opium does not act upon 
the peripheral nerves of frogs ; but the recent very elaborate and apparently 
accurate experiments of R. Gscheidlen ( Untersuchungen aus dem Fhysiohg. 
Laboratorium in WUrzhurgj zweiter Theil, 1869, p. 1) have shown that 



* Dr. S. MGihuisen affirms {loc. eit.) that this inoreased reflex activity is only towards 
ehemioal and not towards mcohanioal irritation. This is, however, opposed by such a 
mans of experimental evidence that I think it must be Incorreot. 



ANALGESICS. 



225 




morpbui 10 smaU doses increuea the exaitabilhj of the motor nerves and 
ftlierwiirdii depresses them ; after large dosea the period of excitation m short, 
(hal of depression soon coming on ; and atler enonnous do^s diminution of 
ftraeckmal activity ia at once matiifestcd. Both Gseheldlen and Kulliker 
iigny> that neither the contractile power uf the museles nor the excitability 
of ihe motor nerves b destroyed by opium or moq>liia, although Albers 
' Virchow'i ArchWj Bdt atxvi,) asserts that both are extingiiishcHl. Gscheidlen 
Btion to this disrtfn"e<?tneiit, and states that he has verified his own 
lily lTef|iient experimentation with eoomious doses of the alkaloid. 
KxfMinmeritA upon the sensory nerves are always unsatisfactory , but 
en (Joe cit.^ p. 17), employing the method of Pfliiger^ found that 
\ locally applied intensifies and protracte the excitability of an afferent 
f in cases of gtrycbnic poisoning,* 
A^ already stated, the opium^convulgions of the fioer are chiefly due to an 
OBieltiltioQ of the reflex centres of the cord, Gscheidlen Inia confii-med this 
by direct experiment, and baa also proven that in the latter stages, when the 
atoter functions are depressed, the paralysis in largely of spinal origin, the 
reiez activity of the cord being greatly lessened. 

Our knowledge of the action of morphia upon the nervous system of the 
frof^ may be summed op as follows : 

Morphia in minute, non-toxio doaes causes sleep, followed by augmentation 
of reflex »cti\ity ; in large, toxic doses it produces violent convulsions, fol- 
lowed by paralysis. The etmvulsions are ehiefly spinal, and duo to a height- 
ened spinal activity, but are to some extent probably, also, of cerebral 
Otigtn, and later in the attack arise from a dii'eet action of the alkaloid 
Wpoik the muscle or the nerve-en dings therein ; the paralysis is caused by 
H depreenon of tiie cord and a diminution of the conducting power in the 

Dr. 8. Weir Mitchell has shown (Americafi J&urtuil of the Medical 
9, Jan. 1SG9, and Jan. 187(>) tbiit birds, as represente<] by pigeons, 
■8, and ducks, are very insusceptible to the toxic action of opium and 
\1M chief derivative, morphia. It appears to be impossible to kill a pigeoD 
bj opium given by the mouth, and of morphia from eight to fifleen grains 
mre nHjuired to produce a fatal rusuk ; but when given hypotlemiically from 
two to three grains of the alkaloid suffice. Tliese results have been in great 
meamire confirmed by Dr. B. W. Kiehardsfjn, and are no doubt accurate. 
Tbe symptoms induced liave been very uniform : they are nnsieadiness, 
UiafBd breathing, increjw^ing signs of a|)Tiam, vnahcred pupils, and, finally, 
f^envrml eonvulsiotis and death* No true hypnotic effect has bceu observed, 
but a curious and very great rise of tempera lure just before death was noted 




• fcrhapt it ii appropriate here lo call aittciition to » paper bj Diott and ViDtachg^a 
(fyUgtr'a Arch., Bd. Ifl), m which it is attempted to bo cxporimrntiiDy ihowa that 
■Mrphla lnoreaii««, eaJTein leAtcMiJi, ami iiTculiol fml Maeoi and then iDurco^cB the iimn 
T«i|Btn»(I bjr til* nttfowa ijitem for tbc rpco^oitioa of a peripbcral irrltiition^ 

n 



220 



SrSTEMIC REMEDIES. 



ID Doe case. As Flourens affirms that a single grain of the aqueous extract 
uf opium will throw a itparrcw into a profound stupor, it can scarcely be 
allowed as proven that the drug acts upon all birds as upon those experi- 
mented with by Dr Mitchell 

Upon do*;a moqihia act^ verv much as upon man.* In vtry \\vM\y cases^ 
if not in the majority, eight to ten grains of the alkaloid injected into a dog 
of moderate size will cause deep sleep, amounting to txima, so that tlie 
animal will remain in any position in which he may be placed. The lengih 
and drpth of thb sleep are, of courao, proportionate to the dose : when al 
all pnjtbund, it is accompanied by marked insensibility to pinching and other 
forms of externa! irritiition. A repetition of irritation , and ej^peelally a 
sudden loud noise or shaking, will^ however, arouse the animal^ precisely as 
in man. Indeed, sometinics the dog, even when comatosCj seems more than 
normally seuaitive to sudden iitiise, trembling and starting in an almost eon- 
Tulsive manner. Afler awaking^ the dog shows unml<itakable signs of nervoos 
and ppychieal depresffloUp In walking, the hind legs are dragged, as tboagh 
Bemi-pai'dysEed ; the eyes are haggard ; the uatiLrally brave animid cowers in 
a corner or seeks to hide himself, no longer recognhdng his master, and does 
not return to his natural condition for mimy hours. After smaller dosea the 
eifectis are proportionately less intense. It has been shown hy Harley that 
in gome dogs, precisely as in some people, morphia fails to exert its usud 
hypnotic action, but produces great depression, as evineed by faintness, pro- 
longed nausea, and retehing, interrupted only by intervals of dreamy delirious 
somnolency. 

In the horse (Harley, he, ciV.),two or even three grains of morphia hypo- 
derm ically injected produce sometimes a slight drowsiness, sometimes no 
perceptible effect. Doses of from four to six grains cause great restleasness 
and accelerated pulse. The mouth is moist, tJie temperature of the skin and 
its secretion increased; the animid paws continimlly, and treads about in 
his stall with an ahnoet rhythm icid movement. After twelve gndns, Harley 
noliced in some eases very great excitement^ as shown by marked increase 
in the rapidity of the heart's action, by muscular rigidity and tremors, by 
the animal walking rapidly to and fro, slobbering and sweating profusely. 
In anothi^r horse, after an iuimcdiate strong erection of the penis and oo|W- 
oua euiiiftiion of semen, heavy sleep came on, interrupted after the third hour 
by the usual symptoms of excitement. Thirty-six grains of the acetate 
cuuBed in a powerful hunter deep comatose sleep, oommeocing in fifteen 
minuter and lasting for three hours, when it was replaced by intense rest- 
Jefisnesa and severe deUrium, continuing for seven hours. During this dme 
the auiuial was perfectly blind. 



♦ Uarlej, Tht Old VeffttahU AVwrofiej, p. lOT, London, ISfl^j Cl*ade Bcrnitrd, Arekivt^ 
Glnfrnlft p. 4.17* Vol, lt.| 6tb setiei, 18ft4; J. J. Re«te, Am^ricnn Jmtruai of tU HWiea/ 
Scieneef, *!*», tS7l. 



ANALGESICS. 



227 



Harbier^s previous experiments upon ihe liorsc (quoted by Prof. Stil!^*) 
had yielded resnlta similar to those of Hark^y. He used larger doses, 
and found that four draelims of tlic arjueou^ extract of opium produced 
viol*!nt tTemblings, apparent iimeusibility to external irritunte, couvulsioQR 
wtthuut coma, and death. One hundred graiug of the acetate of morphia 
killetl a horec bj convulsioES in three hours. 

In the mousej according to the experiments of Harley, the first eiTect of 
an iiijeetion of from one- twentieth to one-twelilh of a grain of morphia is a 
totiic cramivUke contraction of the muscles, especially of the trunk, of such 
diaracter that periods of forced rest alteniate with a slow, laborious creeps 
wbich seems to originate not in the limbs but in the trunk it^lf. There is 
in this state no tendency to somoolency, but, on the contrary, an abnormal 
•enativeness to loud sounds, which cause the mouse to resume for a moment 
•ctive ninning roovementa. The breathing is irregular, the pulse accelerated, 
and finally stupor develops itself, and coma deepens Into death by apnoea ; or, 
I jtherwise, reeovciy, preceded by convulsive movements of Uio hinder part 
ijf ihe body, is gradually brought about. 

In reviewing the action of morphia upon the lower aninials, it beeomea 
fcry evident that whilst we arc not in a fH:(gition to exf>)ain all of the gymp- 
lomSy yet two classes of phenomena are everywhere discernible, — i.e.^ the 
ipiiiil and the cerebral, — and that tlie higher in the scale of life any given 
animal may be, the more marked are the brain-symptoms. These cerebral 
|>bcnomena are mostly sleep and atupor; but, as is well known, in some 
htiiiiut] individusils morphia acts as a delirifacient ; and it seems very prob- 
^ttle that the peculiar robtlessnesa of the horse under the influence of the 
CBkaloid U due to delirium, and not to spinal excitement. 

When looked at in this manner, it seems to me that morphia dms not act 
BO differently as Is generiilly believed upon the lower animals iind upon man. 
The immensely hi^^ber cerebral organization of the latter, with the immensely 
greater sensittveuees which it involves, makes the man con-cspondinglv more 
•OBceptiblc to the cerebral acti*»n of the drug : henee not only is he affected 
by much gmiiller doses of the alkuluid than are the luwer animals, but as the 
nplDal symptoms are triumphatit in the frog because its spinal syt^tem is 
inaitly more developed than its cerebral, so in man the cerebral symptoms 
mask the 8j>inal because in him the brain is more developed than the cord. 
The two creatures — man and the frog— occupy the two extremes of the 
series; between them is probEibly to bo found every gradntion,* 

Tlie action of opium upon dogs and rabbits is sufficiently close to that 
upon man to enable us to reason from ex|>eriments upon the foiiuer us to the 



• A cuHoui eorrobomtion of tbu viewi eiprewcicl in the parn^p^ph i* found in the fol- 
owitig pentcnco taken from AUhauji (lh'*e'i»e4 «/ the Nerrnn* Sif»tem^ Xtsw V«»rk, 1878, 
p« IZ'^) : '* In infaata, bonev^er, and t^lm in the luwer rncefl of mankinU, a* in nt*gro«i And 
M»lMyf| oooYulffiooi aro ubtarved after it« [opium] ingeetioo." 



i 



228 SYSTEMIC REMEDIES. 

influence of the alkaloid upon the circulation and respiration in the latter. 
Indeed, so fkr as these functions are concerned, morphia appears to act 
identically in hoth instances. 

Action on Circulation, — In man, the circulatory phenomena are a slight 
primary evanescent acceleration of the pulse-rate (see Nothnagel, Handlmeh 
der Arznmmittellehre, Berlin, 1870, p. 8), succeeded hy slowing and increased 
folness and force of the pulse, which is followed by a return to the normal 
pulse, or a great increase of rapidity and loss of strength during the third 
stage. K. Gscheidlen has found in rabbits and dogs after the injection 
of morphia, first an increase in the pulse-rate, then a decrease, and finally 
return to the normal pul»e, or else increased rapidity. Sphygmographic 
studies of the effects of small doses of morphia have been made with 
various results by several observers; undoubtedly, in some individuals, 
therapeutic amounts of the alkaloid depress sensibly the circulation, but in 
agreement with Riegel and Priesendorffer, it can scarcely be doubted that 
therapeutic doses have no sensible effect upon the circulation in the ordinary 
man (see Deutsches ArchiVy Bd. xxv. p. 48). 

The slow, full pulse of the second stage of opium -poisoning is due to an 
action of the drug upon the inhibitory cardiac nerves, as may also possibly 
be in some manner the increased arterial pressure; for Gscheidlen (/be 
eit.j p. 45) has experimentally demonstrated that after section of the vagi 
morphia is powerless to lower the pulse, and also that division of the nerves 
during the second stage of morphia-poisoning is followed by an extraordinary 
rise in the pulse-rate. That the peripheral ends of the vagi are stimulated 
was proven by the fact that cardiac arrest took place when the distal ends of 
the cut nerve were more feebly irritated than would suffice to affect the un- 
poisoned animal ; that also the inhibitory cerebral centres are stimulated was 
demonstrated by the instantaneous very great fall of the pulse-rate, amounting 
in some cases to one-half in less than half a minute, which ensued upon the 
injection of a large dose of the alkaloid into the carotid, — i.e., into the brain 
and the inhibitory centres. The rapid, feeble pulse of the third stage of 
opium-poisoning Gscheidlen found to be due, at least in a measure, to paraly- 
sis of the peripheral vagi ; for at such time stimulation of the peripheral 
end of the cut nerve was powerless to affect the heart 

The experiments of Gscheidlen also indicate that morphia exerts first a 
stimulating, then a depressing, influence upon the intracardiac motor ganglia, 
since, after isolation of the viscus by section of the cord, sympathetic, and 
pneumogastrics, life being sustained by artificial respiration, a large dose of 
morphia induced a momentary increase in the number of the cardiac contrac- 
tions, followed by a marked decrease, and finally extinguishment, of the same. 

The question of the action of morphia upon the vaso-motor system is of 
great interest, but cannot at present be fully answered. Gschekilcn believes 
that it first stimulates and then depresses it, and asserts that after the injec- 
tion of a large dose the arterioles in the mesentery can be seen to contract, 



ANALGESICS. 



229 



Md hi&c (tliird stiige) to dilate. The objections to this sort of evidence are 

fufficicDtJj stated elsewhere in this book ; and tbe rise of arterial pressure, 

wii itr:|] be alftO adduces as an iirgurnent^ may he accounted for without calling 

apt^Tk the aid of tbe voso-mutijr nerves. While, therefure, it is probable 

tWc. morphia does exert the tnfluetice he claims for it, tlie question must be 

ttill considered as sitbjndlce: that the voso-motor system is not paralyzed 

ei^eti in extrtmU, is shown by Gacheldlen's experimeut Hoc. cit.^ p. 52), in 

wliioli electrical stimulation of the cord at such time induced immediate rise 

af tlie irteriaJ pressure. The action of morphia upon the brain is certainly 

iDcl.^ pendent of any action on the vessel s."*" 

^%ction on Rtspiration. — Death occurs from opium, in the great majority 

of causes, by failure of the respiration ; and that such failure is due to a direct 

acticn of the poison upon the respiratory centres in the medulla, is proven 

bjT ^t fiict that morphia affects the breathing of dogs and rabbits whose 

i^iiBjogastrics have been cut, ai? nmch as it does those whose nerves ore 

tilts (Gscheidlen, he. ciL, p. 64). 

Action on PupiL — Since morphia locally applied does not affect the pupil, 

foUows that its constitution id action upon the latter is through the nerve- 

trta. It is probable^ but has not, that I am aware of, been experimentally 

•▼eu, tltat tbe contraction of the pupil is due to a stinmlation of the oculo- 

n»otor nerve-centres, and that the dilatation of the pupil, as death approaches, 

due to a paralysis of the same. Indeed, it cannot well be otlierwlsc ; for 

the primary contraction were due to paralysis of the sympathetic^ the 

•®<?ondarv wide dilatation would be impossible j the dilating force — t.e., the 

^^patbctic— having been withdrawn, the pupil would not widely expand 

eveD if the contracting force^ — i.e,^ the oculo-motor — were paralyswid. 

I^ biids (Dr. S. Weir Mitchell, !oc, ciL) the pupil is not affected; in horses 

^^ »A widely dilated (Dr. Harley, he. cit,) ; and in dogs it dilates before con- 

^B^eting (|)r. Reese, loc. ciL, apparently cunfirmod by Experiment number 

f •ight^ Harley, loc. cit.y p. 109), or s^jmetimcs remains unchanged (Harley, 

F *«c. oi>,, p. Ill), At present these anomalies cannot be explained. 

^timinatum Actifm on Kidneys and Infesfines. — The exact fate of 

"^^rphia m the system is uncertaiiL Varir^us chemittts have failed to find 

*^ iri the urine of persons or onimids poisoned by it, but it seems to me 

^^taljlialied that it is at least in part elimiuHted with that secretion, as it 

^»« tjiiHMi detected by Dr. llilger (Gscheidlen, loc, ciV., p. 32), Bouchfirdat 

^^'^t.miilt'i JiihrbUch^r, Bd. cxx.), Lctbrt (Joum. de Ckimie^ Bd. xi.), and 

^»mtnn ( BeUra^e, etc., Inavff, Dtioert., Dorpat, 1868). Although Prof. 

'tiilcy i Micro- Vhemhtri^, 50 Ji) stata^ that the leats relied upon by Bun- 

dat are not decij^ive, it is probable thai t be tourlusioUcS reiithcd in tl^o t'bdxi- 

^^ Pts^areh of W. EHaason are correct {Bt-itrtii/^. z. Lrhrc den Sifyc/iJiofA 



^OBftilt Binii Arek. Sxper, Pathol, %md Pharm.f vL^ p. 310; Vulpian, X>evu»« mhf 



^•^nr, V(t*o-M**te%irf 11., p. l&O. 



230 SYSTEMIC REMEDIES. 

Alorphtnsj Inaug. Dissert^ Konigsberg, 1882). They are, that when bi^ 
amounts are ingested morphine appears freely in the urine, but that after 
small doses it cannot be found, although a substance is present giving some 
of the reactions of morphia, from which it is a deriyative. The theory that 
morphia b burnt up in the blood has been advocated by those who have 
failed to find it in the urine (see E. Landsberg, PJliigers Archtv, 1880, 
413), and there is reason for believing that it and other alkaloids are to 
some extent destroyed in the liver. The amount of the uripary secretion 
is said to be sometimes increased by morphia ; but more generally it is 
diminished. Retention, which after a full dose of opium is not rare, de- 
pends upon the blunting of the sensibility of the bladder. In a series 
of examinations S. Fubini found that morphine, codeine, narceine, narcotinc, 
and thebaine each increase the excretion of urea in man : upon the lower 
animals their action seemed to vary greatly (^Hoffmann und Schtcalbe 
Jdhresher.y 1883, 219). It is stated that in habitual opium-eaters morphine 
occurs in the urine not longer than seven days afler the cessation of the habit 
(Land. Med. Record, 1877, p. 92). 

Peristaltic movements, according to the experiments of Prof. Nothnagel 
{Archiv f. Path. Anat., Izxxix. p. 2), are diminished by small doses of 
morphine, but increased by toxic doses. The first effect is evidently due to 
stimulation of the inhibitory nervous apparatus, and the second to paralysis 
of the same : it is probable that it is the centre which is affected. The 
experiment which Prof. Nothnagel brings forward as evincing a peripheral 
action is certainly not pertinent. 

Upon the digestive tract opium exerts a very marked influence, checking 
secretion and causing constipation, acting in these respects more efficiently 
than does morphia. 

Therapeutics. — The chief indications for the use of opium are con- 
sidered below, seriatim. Nearly all of them flow evidently from the known 
physiological action of the drug ; others, however, although established by 
clinical experience, and undeniable, are not so plain in their philosophy. 

1. To relieve pain. As an analgesic, opium is without a rival in the ma- 
teria medica, except it be the ansesthetics. It is used to allay pain arising 
from any cause whatever, except acute inflammation of the brain, and is 
preferred to the ansesthetics whenever the pain has any permanency. In 
painful spasm it is especially usefiil, as it seems very frequently to quiet the 
motor as well as the sensory disturbance. 

2. To produce sleep. Sleeplessness occurring in acute disease, and not 
dependent upon cerebral inflammation, may very frequently be relieved by 
opium. While it is often necessary to use the drug freely in such affections 
as delirium tremens, care should be exercised not to overwhelm the nerve- 
centres by enormous doses. In habitual sleeplessness great caution must be 
used in the employment of opium, not so much on account of the disturb- 
ance of digestion which it is liable to cause, as for fear of producing the 



ANALGESICS. 



231 



** opium liabit," Chloral is perhaps a more generally applicable hjpnotio 
tlian opium. Be tb^ however^ as it nr^y^ I have found tbe com lii oat inn of 
morphia and chloral singularly cfticient. In low fevers, wdynnmie deliritUQ 
ofteo cocxi^ with sleeplessness, and is then best met by opium. 

3. To alioy irritation. In various forms of nervous erethism, opium is 
most Taluable ; but when tbe afieetion i^ at all chronic, the dangers of the 
opium habit should not be lost sight of. On the other hand, in acute cases, 
as m tlie excitement which so frequently attends hmmaptyini^ the drug should 
be used freely. In many ciLses of diseaae^ opium is serviceable by sustaining 
iIm vptem againiit an irritation for the time being irremediable, by blunting 
die sensibilides. Id this way it is useful in the advanced stages of mialfpoXj 
mud in various surgical affectionsj in which it also does good by allaying pain. 
In Tarious local irritations, opium is contioually employed, as in the coiir 
caused by undigested food; in bronchitinj it is thus used t-o quiet cough. 

By aUuying irritation and pain, opium affords relief in most eafie« of in* 
flammation ; but in certain varieties of the affcetion it seems to do much 
more than this, exertiog, in some way at present difficult to explain, a life* 
aaTing iufluenoc. In peritonitU^ after due depletion ^ or in cases not requiring 
depletion, it should always be exhibited in large doses at regular intervals, in 
sach a way as to keep the patient in a state of decided narcotism. 

In severe acute vomiting^ opium is one of the most reliable remedies. It 
IB best used in the form of suppositories. Although, by checking secretion 
Hid peristalsis, opium usually catues constipation, yet when obstruction of tbe 
howdi is produced by spaam due to ao irritation or inflammation^ by relieving 
fhm latter the drug will sometimes act tis a most efficient laxative. 

4. To check exceMtive fecreium. For this purpose opium is very kingelj 
employed in diarrfuzas^ and is very efficient cither alone or in combination 
with various remedies. In enteritis and in dysenter^f^ although no less fro- 
qneotJy used than in diarrhcea, it is of service rather as an antiphlogistic and 
miiJi%ei(ic than by checking secretion. In diahetm iftsipidus^ the combinafion 
of it and gsdlic acid is, I think^ tbe most generally successful remedy. 

In true saccbarine diabetes^ opium is of very great value in many cases, 
ofien ameliorating the symptoms, atid^ in conjunction with restricUd diet, 
MHiietlmea even effecting a cure. Of course, however, like all other known 
remedies in this disease, it most frequently acts simply as a ptdliative. Ac- 
cording to Br. Pavcy (Medical Times and Gazette^ June, 1869, p. 641), it 
affecta tbe quanUty of the urine before diminishing the sugar in it 

In severe mercurial pt^aliam^ opium often seems to check the discharge, 
hut certainly is not nearly so powerful fn this regard as atropia. 

5. To support (he system. Opium appears in low fevers, and in various 
protracted adynamic illnesses, to afford actual support to the system in some 
way not as yet made out. This is especially the case when, from any reason^ 
sufficient food to keep up life cannot be taken or retained. 

6. Ai a sudor ijk. Dr. A. Loom is (^New York Med. Record^ 1873) praises 



232 SYSTEMIC REMEDIES. 

very highly the use of hypodermic injections of moiphia in ctcute urssmia. 
He states that the drug must be given in sufficient quantity to control the 
convulsions, which it does most happily, at the same time producing profuse 
diuresis. Dr. Morrison Fiset {New York Med. Record, July, 1874) and Dr. 
Dain (American Med, Journal, July, 1874) confirm this. In some instances 
the remedy has seemed to act very happily, but in one or two cases at the 
Philadelphia Hospital its exhibition was shortly followed by death in ooma. 
In the form of Dover's powder, opium is very largely used when it is desired 
to produce sweating, as in the early stages of a "general cold," or other forms 
of muscular rheumatism. With its use should generally be conjoined such 
measures as " soaking the feet," covering warm in bed, and the free drinking 
of hot lemonade or hot teas. 

Toxicology. — Sufficient has already been said concerning the course and 
symptoms, of poisoning by opium in ordinary cases.* Sometimes in adults 
trismus and other convulsive manifestations are added to, or in a measure 
replace, the usual phenomena, and in children the drug appears at times to 
overpower the nerve-centres at once, so that the second stage is very much 
shortened or aborted, and symptoms of collapse, with unconsciousness, are 
developed very rapidly. The positive diagnosis of opium-poisoning from the 
symptoms alone is often impossible.f In some cases of congestion of the 
brain, or of apoplexy, or of urscmia, the phenomena are identical with those 
sometimes seen in opium-poisoning. I have thought that inequality of the 
pupils is proof that a case is not one of narcotbm ; but Prof. Taylor ha& 
recorded an instance of opium-poisoning in which it occurred (^Manual of 
Medical Jurisprudence, 7th Am. ed., 1873, p. 205). 

The indications in the treatment of poisoning by opium are : first, to 
evacuate the stomach ; second, to maintain respiration ; third, to keep up the 
circulation when failing. The first indication may be met in two difierent 
ways : by an emetic, and by the stomach-pump or tube used as a siphon. 
There is oflen in narcotic poisoning great difficulty in getting an emetic to 
act, owing to the obtunding of the sensibility of the nervous system by the 
drug. For this and other reasons, so palpable as not to need mentioning, a 
prompt stimulant emetic should be used ; antimony, on account of its depress- 
ing influence, should always be avoided. Mustard JUmr is almost always to 
be had at once, and is very efficient. A heaped tablespooniul stirred up in a 
tumblerful of warm water should be exhibited as soon as possible, and, if it 
fail to act in fifteen minutes, should be repeated ; then a powder of thirty 
* grains each of sulphate of zinc and ipecacuanha may be given, to be repeated 
once or twice, at iuter\'al8 of fifteen or twenty minutes. Large draughts of 
warm water should be administered in the intervals, and also between the 

* Fur discuHsion of eflfect on nursling and foetus when morphia is given to mother, 8e« 
Awer. Jouni. Oh»t., 1877. 
t See Philadefjihia Med. Tiwcf, vol. iii., 593 ; also Dr. Wilks, Mtd. Timet and Gaz., 1863. 



ANALOESICS. 



235 



I, BO as tlioroughlj to wash out the stomticli. The stomach- 
pQUip^ ta of no value when tho solid drug has hcen ingested, but, if at hand^ 
18 pniWabla to emetics when a fluid preparation has been taken^ because of 
the prompCocsa of it« reaulta. 

To maintain respiration is the ultimate object of all the measures which 
warn ommnonl^ undertaken for the purpose of arousing the system in opium- 
poiioiiiQ^, UnconsciousDcsa in itself is of no moment^ but as it deepens 
the sensibility of ilie respimtory c^jntres grows hi*s, and cunse<|ucntly the 
involuntar)^ breathing is less rapidly or les^ perfectly performed. More than 
tlua, when at all awake ^ a patient suffering from opium-poisoning can be made 
to aupplement the almost suspended automatic breatliiug by voluntjiry respi- 
mtioD J and every eflbrt to induce him to do tliis should be used. It is oflen 
siirpcising how an apparently unconscious man can be made to breathe by a 
fsommand shouted in his ear. To keep a patient awidte^ w^alking, flagellationa 
with small, Jine twigs^ shakings shouting, and various other methods which 
BUJ silggest themselves, should be practiced. Care should always bo exer- 
cned not to carry these useful measures unneccjssarily far, and perhaps add 
pliysical exhaustion to the natural prostration of the third stage, I desire 
adeo to call e«pcci;d attention to strong faradaic currents as a means of causing 
patn, and therefore of rousing the patient, without leaving the bruises and 
Mwmeai which often result from the severe flagellations practiced. 

The cold douche affords an excellent method of rousing the patient and 
ftt the same time of especidly ^timuLiting respiration. The simplest method 
of application is to support the head and shouldenj of a patient stripped to 
the wmst over a common wash-tub, and to dash the water over the chest and 
hmd* The eifeot is much greater if ice-cold water and water a little hotter 
than the hand will bear {115*' F.) be used in (juick succoi^sion. In the way 
of drugs, there are only three substances worthy of mention. Very strong 
iuAisions of coffee or of green tea have been long used in opium-poboning, 
tnd recent scientific studies (Britijih Mr^d. Journ.^ 1874, ii. G9S, G99) have 
ihowTi that in animals doses of morphia otherwise lethal may be successfully 
C90<ithated by thein or caffein ; atropia, as a respiratory stimolaut, is of the 
greateet value in opium-poisoning when there is evident failure of respiration 
(for diacussioa of its use, see tho article on Atropia) j and alcohol is to be 
etupluycd in the stage of depression to susuin the arterial eystem.*!" 

Whenever life is in evidetit danger from the insufficiency of natural res- 
pirmtiun, the use of artificial respiration should not be postponed, hut should 



• Tli« Mtpi^ft Bhtmarh^fintny mnj l»e «st«mponxe<l hy hoy one. It wtififit!* ^imjily of ^n 
latlbir-mblmr i«b« tlir«« au^J a hnlf to four and n h»lf ftfet in leujjth* of pruper c»Iibre, 
mimh t» pMti'*! intw the ft^jmaeh. Th&i:xternnJ end being elevated, nkt&r U poun^d iota 
it uatll the aturttn^'h it full; tbrn, without thi> tube bving allowed to empt/ iUolf, tha 
•Ktemal i>Dd U dropped* whrn, of couraLS tbc dovr of vrulcr U Tf^verscd. 

f V«j-{out dru|^ bnvcr been etnted to b^ aiitagiitiiglic io opitiiu nod cMes of recovery 
f«port«il. Vrratium tinde, CUeinnati Lancet and Clinic, 1879, iii, 4o8; Si. Lnuit Med* 
^»d Snfj. Jmt'%nt 1ST», utxvil, 60l. AeomU, Jfeie York Med. Hecord, 1S8U, viii. 



234 SYSTEMIC REMEDIES. 

be practised to supplement nature, and should be maintained so long as there 
is any hope. Life has undoubtedly been saved in this way. A case is 
reported (JV. Y. Med, Jaum,, June, 1880) in which a baby, who had taken 
one-third grain of morphia, was rescued by artificial respiration kept up, off 
and on, for twenty-four hours. In some cases excess of bronchial mucus 
seems to be of serious import. Under such circumstances good might be 
achieved by placing the patient in an inverted position {Brit, Med, Joum., 
1871, ii. 374). 

Opium-poisoning usually has no sequelae ; but a case in which amaurosis 
was produced is reported in Schmidt's Jahrbiicher, Bd. clvii. p. 74. 

In regard to the amount of opium which will cuuse death, the smallest fatal 
dose on record is a sixth of a grain of morphia in the adult (Dr. Buskirk, 
Washington Post^ Jan. 30, 1878).* According to Dr. A. Calkins {Quart, 
Joum, Psychol, Med., 18G8, vol. ii., 739), four grainsf of crude opium placed 
in the ear have caused death ; also four grains by the mouth in more than one 
case. According to the authority just quoted, out of twenty-nine reported 
cases in which a fluidounce of laudanum was taken, nine died. The maximum 
doses from which recovery has occurred without emesis are fifty-five grains of 
the solid opium and six ounces of laudanum. In a babe a day old, one minim 
of laudanum (E. Smith, Lancet, 1854), and in one aged nine months, a few 
drops of paregoric (Wood, Bast, Med, Surg, Joum., 1858), have proved fatal. 
Death of an adult female has been attributed, with doubtful accuracy, to 
thirty grains of Dover's powder, given iu divided doses {Chicago Med, 
Joum. and Exam,, July, 1882). 

Administration. — Whenever it is desired to produce very decided 
narcotism by the use of repeated doses of opium, the drug should alu>ays 
he given in liquid form, since opium pills sometimes become very hard and 
undergo solution so slowly that they may accumulate in the alimentary 
canaL On the other hand, in diarrhoeas, or in sickness of the stomach, old 
opium pills are thought by some to act better than more soluble forms of the 
ing. 

Many persons cannot take opium on account of the very great seconUary 
nausea and depression which it produces. It has been supposed that these 
disagreeable after-effects are due to the narcotina in opium ; but this can 
hardly be, seeing that they often follow the use of the pure alkaloid, morphia. 
The deodorized tincture of opium agrees with some individuals better than 
any other preparation of the drug ; and, as first pointed out by Dr. Da Costa, 
by giving a drachm of the bromide of potassium with twenty-five drops of it, 
the after-effects of the narcotic are often entirely avoided. In many neural^c 

* A number of cases are now on record in which death has been produced in the adult 
by the hypodermic use of from one-sixth to one-half grain of morphia. Consult Afedicth- 
Chir, TraM,f vol. i.; Chicago Med. Examiner, May, 1878; Quar, Joum. Pnycholog. Med., 
1868, vol. ii. p. 739. 

t Taken from Journal de Chimie, 1831. Assuredly there is a mistake in this case. 



ANALGESICS. 



235 



women tiie knowledge of this fact is an inestimable boon ; in others tlie im- 
plesaant jsymptoms are not averted by the bromide. 

Children always bear opium very badly, and to them only the weaker 
Uquid preparations t^hould be ^^vcn. Dover's powder should espoeially be 
Avoided. It is probable that in its manufacture on the large scale the 
iogredienU are Rimctimi'S not thoroughly mixed : at least I have seen case« 
in which the symptoms caused by it were seemingly so out of proportion to 
tbe doee as to suggest that more than the officinal amount of opium wad 
preset 

In acute vrnnitrng fit)m any cause, in d^seittery^ in afrawywi^, and other 
Irntations of the nrino-genital organs, great advantage is oflen to be gained 
^m the use of opium by the rectum. SuppoHitories made out of the extract 
(^, » to i), or euemata of laudanum (gtL jjlx to xl), may he used in these 
aises. The latter should be made by adding the narcotic to a tablespoonful 
of starch-water. 

The dose of opium for an adult is from one to two grains ; for a child 
• year old, on e-tw en ty- fourth of a grain. The U, S. Pharmacopoeia directs 
that opium in its normal motst condition .should contain uot less than nine 
per cent, of morphine^ and that dried ptjivdtred opium (^Opii Ptdth^ U. S.), 
out of wluih the preparations are made, should contain from twelve to sixteen 
per cent of the alkaloid. 

The solid officinal prt'paratiun« of opium are — the denarcotlztd opimyi 
^Opiurn Dr narcotist till m^ U.S.), Opium deprived by the action of ether of 
its narcotina, dose, one to two grains; pilh of opium {Pihdm Opiiy D»S.), 
eontui fling one grain each; watery tx^rac/ (^Exlractum Opiiy U. S,), twice 
the strength of opium, 

Parrgoric (^Tinctura Opii Campharata^ U. S,) has in every fluidouuce 
two grains of opium, befiides benzoie add, oil of an be, and camphor, and, 
in coDt«equeDce of the last ingredicut, is more constipating than the other 
preparations of opium, and hence is preferred in diarrhcea- mixtures. It is 
also much used in cough -mixtures. Dose, fji to f.^i. The oiher liquid 
prtparations all now represent ten per cent, of powdered opium by weight, 
and may be given in doses of ten to tifteen minims. The deodorized tinc- 
ture ( Tittctura Opii Deodoraia, U- S.) contains no narcotina, and nnno of 
the odorous principle of opium. It therefore is less apt to cause nausea 
than are the other prcpara lions. Its drop almost equals the minim in .size. 
The other preparations are — Tindura Opii^ U»S.| or Laudanum (one 
hundred drops to the fluidrachm) ; Tinctura Opii AcetiUa, U, 8», or Ace- 
tatfd Tiitctttre (formerly gr. xlviil to f^i) ; Vitittm Opii, U.S., or St/den- 
ham' 9 Jjtiudanum (ff>rroerly 5i ty f5i ) J Acefimt Opii^ U. S., or Black Drop 
(fonoerly gr, Uxv to V^\), 



236 SYSTEMIC REMEDIES. 

MORPHINA* U.S. 

This alkaloid occurs in minute, colorless, shining crystals, according to 
Guy melting at 330° F. and subliming at 340^ F. ; insoluble in cold and 
almost so in boiling water ; only slightly soluble in cold alcohol and ether ; 
freely soluble in boiling alcohol and in the fixed and volatile oils. 

The following are some of the most sensitive and characteristic tests. In 
a solution of the alkaloid in concentrated sulphuric acid, which has boen 
allowed to stand from ten to twelve hours, or has been heated for half an 
hour to 100*^ C. or momentarily to 150® C. and allowed to cool, the faint- 
reddish violet changes at the point of contact to a deep-blue violet upon the 
addition of dilute nitric acid or of a crystal of saltpetre. Morphia with 
concentrated sulphuric acid makes a colorless solution, which on strong 
heating becomes red, violet, dirty green. With concentrated nitric acid it 
makes a red color, and finally a yellowish solution. With the neutral chlo- 
ride of iron morphia strikes a blue color, perceptible only when the test 
contains one part of the alkaloid in six hundred. Less characteristic, but 
much more sensitive, is the iodine test, with which, according to Husemaon, 
one-ten-thousandth part of morphia can be recognized. Iodic acid, in the 
form of a mixture of iodate of potassium and sulphuric acid, is to be added to 
the suspected solution. K morphia be present, iodine will be set free, and 
can be recognized by the starch test. 

The Acetate (Morphine Aoetas), Sulphate (Morphine Sulphas), 
and Ej/drochlorate or Muriate of Morphine (MoRPHlN^ Hydroculoras) 
are all officinal. The first is a white powder; the last two occur snow-white 
in feathery crystals. They are all soluble in water, and are of a bitter 
taste. 

Therapeutics. — The salts of morphia differ in their therapeutic value 
from opium chiefly in that they act with less power as sudorifics and in 
checking secretion in the bowels, and consequently constipating. The small- 
ness of their dose and their perfect solubility fit them for hypodermic use. 
Almost the only purpose for which they are used in this way is to relieve 
pain. The advantages of the method are the quickness of the rcsulta and 
the increased power of relieving suffering which the remedy seems to acquire. 
In cases of severe pain, hypodermics are invaluable ; but it must be bonie in 
mind that sometimes they cause most unpleasant symptoms. I have sufu 
very alarming results from the injection of one-sixth of a grain, and half 
a grain has produced death. In females, unless very robust, the maximum 
dose should be one-eighth of a grain ; in men, one-sixth to one-quarter. The 
dose of a salt of morphia corresponding to a grain of opium is one-quarter 
of a jrrain. The dose of the formerly officinal solution {Liquor Morjthist 
Sulphatis, U.S. 1870, — gr. i to fji) is one to three dracbms. Magendie$ 

* For Bpeetrum aDa'jsis of morphia, seo Neva York Medical Journal, 1874. 



ANALGESICS, 



2a7 



SoimHim of Morphia contains sixteen graiiiB t4> the fluidouncc : it is not offici- 
bal, aad should not be kept in the apothecaries' shops. The Syppogitoriei 
( Sttpponitfna Morphist^ U. S.) contain each half a grain of morphia, 

NARCEIN. 

Tilts alkaloid, which is not officinal, was discovered by Pellctier in 1832. 
" II crystalliies out of it« watery, alcoliolic, and dilute acid solutions in long, 
wbit^i four-«ided, rhombic prinms, or in bunched niai^scs of fine aciculiir 
crystftls, odorless, and of a taste at first bitterish, but later styptic.*' (Pel- 
letter, Hease^ Winckler — Husemann, Die PjfamenstoffeS) According to 
Pellcilier, it is soluble in 375 parts of water at 13'' C. ; ac<x)rding to Hesse, 
SQ 12S5 pftfts at 12® C, ; whilst Dr, S. Weir Mitchell fouiid that a i^pecimeu 
pfepmt^ by Merck dissolved in 1000 parts^ one prepared by Powers & 
W * 11 in 4000 partii, and one of unknown EurofXian manufacture in 
of dintillcd wator at G0° F, Its saturated solution in boiling 



wmier on enoling filU with crystjila. Concentrated nitric acid dissolves nar- 
cein with a yellow color, and the solution on l>eing heated gives off reddish 
ftUDiis; iodine makes with it a blulnh-black mass, which forms a colorleaa 
•olutiiin in boiling water, but on cooHni; iseparat^^s; with concentrated sul- 
pfaunc at;id narcein stTikos a brown color, and finally makes a clear yellow 
aolutiou (Husemann). 

PavgloLooiCAL AcTlox,— According to Bixxt {lietclwrl'i Archiv, 1869, 
p* 126), three kit four centigrammes (0,40 to 0.62 gr.) of narcein, when 
iftjc^cted Into a frog, produce, in from ten to fifteen minutes, a scmi-comatoae 
ccMidttir»n, in which the batrachian makes no resistance or eifort wlien laid 
Upon his back or in other unnatural p«>sition. The respimtion and circula- 
Ckm are not diftturbetl. The fK)g C4Ui he arouBed by strong irritation; and 
when awake seems perfe<!tly conscious. In three to six hours he cornea out 
af bis lethargic condition appurcutly unaffected, Albers ( VircItoic$ Archw, 
Tol. xxvL) found that one j»rain produces in the frog sleep, refiex and i*pontu* 
IM01I9 oonvuJsiona, and, afber seventy- four hours, death. According to Ort, 
the OQDTdsions are chiefly spinal, the inut^cles uli^o being afiected. Br. S. Weir 
Mitchidl {Amer. Joitm, MeJ. iSW., Jan. 1870) found nine grains of the alka- 
Icnd to have very little effect upon pigeons, causing only wbnormal quietness. In 
Baxts ex|>t*riroent8 upon rabbits and guinea-pigs, fifteen centigrammes (2.3 
1^.) had no perceptible influence ; and on dogs Dr. B, Kersch (Schmidfs JcJit' 
hUchrr^ Bd. cxli. p. 15), and tilso Dr Hurley ( The Old Vegetable NeuroticM^ 
p, 143), found moderate doses (26 etgr. Kersch) equally inert. In a mouae 
(Dftriey) one-half grain caused tranfjuil sleep, with, afler a time, tremors, 
ffom which the animal recovered, to be taken Buddenly, some hours later, 
with fatiU convulsions. At the post-mortem the tubules of the kidneys were 
found completely choked up with the alkaloid, which bad crystallized in 
them and produt*ed a mechanical suppression of urine, to which di?ath waa 
pTQibftbly due. Schroff (quoted by iUbuteau), Froumiiller {Schmidt'^ Jahr* 



238 SYSTEMIC REMEDIES. 

hilcher, Bd. cxli. p. 15), Harley, Mitchell, and Da Costa {Pennsylvania 
Hospital Reports^ 1868), have found naroein to act very feebly upon man. 
Harley gave one grain hypodermically, Da Costa two and one-half grains 
by the mouth, and Mitchell took five graini^ himself, with the result of only 
causing some headache ; and Fronmiiller has exhibited as much as twenty 
grains with equally negative results. 

These investigations are in close concord, and seemingly conclusive ; and 
the study of Dr. Da Costa upon man was very full and exhaustive. They are 
opposed by a number of seemingly equally conclusive investigations made by 
various French and German observers. Much of the interest that has been 
manifested in the alkaloid arose from the assertion of Claude Bernard in 
1864 {Archives GirUraUsj 6e s^r., t. iv. p. 459), that it is the most pleasant 
and certain hypnotic of any of the opium alkaloids. He experimented upon 
dogs, guinea-pigs, rats, pigeons, sparrows, and frogs, and in all of them there 
was produced deep sleep, closely resembling natural sleep, with benumbed but 
not destroyed sensibility. The irritability of the morphia-sleep was want- 
ing, and no secondary depression followed. Seven to eight centigrammes 
(1.65 gr.) was sufficient to throw a dog into the profoundcst slumber. As 
early as 1852, Lecomte (Husemann, Die PJlanzenstoffej p. 176) had affirmed 
that 0.1 grm. (1.53 gr.) of narcein thrown into the jugular vein of a dog would 
produce deep sleep, and very recently Kabuteau has confirmed the results of 
Bernard. Further, Behier {Bulletin Thdrap., t. Ixvii.), Debout (/iirf.), A. 
Eulenburg {Schmidt's Jahrbucher, Aug. and Oct. 1866), Lin6 (Journal de 
Phamiacie et de Chimie^ 4e s6r., t. iii.), also assert as the result of ex- 
perience that narcein, in doses of one-half grain to a grain, produces in man 
pleasant, persistent sleep. Rabuteau {he, cit.) also agrees with this, except 
in placing the dose somewhat higher, — viz., at from ten to twenty centi- 
grammes (1.53 to 3.06 gr.). Oetinger {Das Narcein als Arzneimittel, Diss. 
Inaug., Tubingen, 1866) also asserts that decidedly larger doses of narcein 
than of morphia are required to obtain any action. 

As seemingly these opposing results are all true, the only possible expla- 
nation is that different substances were used by the different sets of observers 
under the one name. As the greatest care was practiced by Harley and 
Mitchell in obtaining the alkaloid pure, and as Claude Bernard states ex- 
pressly that the substance used by him was soluble in twenty parts of wat^r, 
it is most probable that the former observers really had, and that Bernard did 
not have, the narcein of Pelletier. 

It is, at any rate, a very plain deduction from the above facts that, if it 
be so difficult — nay, impossible — to obtain in commerce a uniform reliable 
narcein, it is not proper to use it as a medicine. 

CODEINA. U.S. 

Albers found that one grain of the muriate of codeine would produce in the 
frog, twenty minutes after its injection, tetanic cramps, alternating with con- 



ANALGESICS, 



2aa 



Tuluoiis: eTidentljr refleXf stoce the slightest touch would call them forth* 
AHer a time the conynlstve ezcitemcDt grew less and less ; the fore feet lost 
Uidr scsmitivcncss first, hut finally a puroxysm couM bo longer be provoked 
hy toueblug the hind feet* The piipUa at this time were widely dilated. 
I>Mith occurred hy failure of re«pi ratio n, the heart contiouing to beat a quarter 
of an hour after the extitiguishmeiit of all other movements. In Woldemar 
BiLxts {Hcicfwrt's Archiu^ 1SC*J, p. 125) expcrimeuta, three ceritigrammea 
(^0.45 gr.) produced in the frog deep sleep, lasting three or Rmr hours. On 
awakiug, the frog seemed more sensitive than natural to external irrita- 
lioa. Six oeotigrammee produced sleep more quickly, aiid fallowing the 
drep aleep a stage of excessive sensitiveness, din-irii; which external irritation 
produced repeated cramp-like contractions. JL Waehs ((juoted by Huae- 
tnanUf Die Pjlatizemttoffe^ p. lt>3) observed phenomena Bimilar to those de- 
tailed by Albers, but noted a peculiarity of gait in the frog preceding the 
convulsive stage, owing apparently to disturbance in the innervatiitn of the 
addactora. Wachs \m found that .010 gramme (0,15 gr.) produced in the 
pigeon only increased rate of respiration and sleepiness, whilst larger fatal 
doMB oaiised restlessness, inahillty t4) stand, moveineiits backward and in a 
ctrole, disturbance of respinititm with giispingj cramps of single mascles, and 
finally convulsions, mostly clonic, fref|uently repeated, and followed by an 
adynamic condition, termiiiuted hy sudden death. In Br. 8. Weir ^litchelfs 
experiments (yimer. Jouni, MitL Sci., Jiin, 1870, p. 26), seven grains pro- 
duced violent non-tetanic convulhjons, ending fatally in one minute; aud one 
p^jn caused similar symptoms, tcrmintUing fatally in eigltt minutes. Dr. Ott 
(^Ofvtm AUcttlouh) found that the convulsions in the frog are spinal, but 
ihat the muscles are affected, 

Aooordiiig to Husemann {loc, cit., p. 133), Kunkel, in 1833^ from his ex- 
periments arrived at results similar to the recent ones of Bernard, The latter 
obaerver found that five centigrammes (.075 gr.) prc:)duced in dogs a sleep 
fiunthir to, but not so profound iis, that of morphia, with less benumbing of 
sensation, and not followed hy any sjntpioms of depression. 

The^ results have been called in question hy Harley, and it seems most 
probable that Claude Bernard used something more than codeine in his ex- 
perfmenta. Certainly Harley found that one to two grains of the alkaloid 
prodtioed in the dog dbturhance of respiration, languor, and convulaive 
twitehings, but no sleep. Moreover, Husemann states that, af\er fatal doaes, 
Waohs observed similar symptoms in the dog and in the rabbit, us follows; 
lulling of the head; trembling, spasmodiu movements of the eyes and lipSj 
mrely trismus, movements in a circle and backwards, weakness of the legs, 
with hurried respiration and pnjmineuce of the eyeballs as prodromes ; later 
in the poisoning there were severe convulfjituja, atler one or many paroxysms 
of which great weakness developed, ending in death. B^rnay, in experiments 
npon dogs, cats, and rabblu, found that the convulsions were the mo^c promi- 
nent iymptom (Z^ la Cudeifu^ Paris, 1877}« Falck affirms {Deiiischei 



240 



STSTEMW REMEDIES. 



Kliniky 1870) that there are two fonus of poisoning produced by ccmI^,— 
the one tetanic and the other eoporific, — correspoadiog apparently to the 
diflftireut r<)sulta of various observers.* 

Ab tt hypnotic in miin, codeia has been used by Magondie, Bcrth^S, Aran, 
K rebel ^ IloLs-siier^ Robiijuct^ and others, aonie of whom assert that the sleep 
produced by it la followed by nausea or other symptoms of doprcspiion, whilst 
others deny this. It does not seem necessary to discuss in detail the researcbei 
of the authonties alluded to, but it may bo well to give the results of one or 
two of these observers more in fulL 

lM>iquet in a series of ejtperiments found that doses of 0.01 to 0.03 
gramme (.15 to .46 gr.) produced a feeling of contentment, calmed nervous- 
nesSj and induced refreshing sleep, whilst 0.1 to 0.2 gramme (1.53 to 3.07 
gr.) caused deep sleep, followed by nausea and vomiting; 0.1 gramme (1.53 
gr.) cnused in children very alarming symptoms. Harley has found in a 
number of experiments that^ given by the mouth , codeia is a very uncertain 
and fe'ble hypnotic, four grains produeing simply accelerated pulse, con- 
tracted pupils, and some giddiness, followed by nausea and vomiting. When 
the drug is given subcutaneously, " somnolency,** he states, " is a more promi- 
nent effect, but only occurs in certain individuals.'* His hypodermic dose tB 
one to two grains. On the other band, Dnorzak and Ileiurich found tbftt 
codeia in doses of 0.1 granune caused gastric uneasiness and pain, some sali* 
vation, nausea, hcat^ and feeling of weight in the head, some coniiision of 
thought, very marked reductinn of the pulse-rate, and very marked tremon 
affeciing the whole body ; and Mitvhell took five grains of the alkaloid with- 
out inducing other effects than a rise of twenty per minute in the pulse-rate, 
nauBea, slight giddiness, and a sense of heaviness about the liead. Dr. A. 8. 
MjTtle reeurds (Britijih Afedkaf Journal ^ 1874, i. 478) a «ise of severe poi- 
soning by four grains of ccideia prepared by the Jleasrs. Smith of Edinburgh* 
There was first vascular excitement and exhilaration, then depression with 
great anxiety, nnusea and vomiting, pale, cool, clammy skin, slight contnio- 
tion of pupil, and sleeplessness, with slight delirium. 

It is very evident that these various observers have not had the 8ai^|| 
principle. In my own experience oodeia, prepared by Powers & Weightmiap^ 
has failed to act in grain doses as a hypnotic. There are no reasons for 
believing that it has any advantaires of niorphiii, whilst its uncertainty is 
very great, I have found it of some value in one-lialf grain doses in quiet- 
ing bronchial irritation. 

The remaining active principles of opium being objects of physiological 
rather than of clinical interest, I shall allude only to their physiological actions. 



* From whni ho aivjB on p, 220, Li is probable tbnt Falek tiMd Iwo prepnr^iioni of 
oodeia, — wne rrnnie in hia owu livboratory, the other obtnined from Merek. U U aat 
pomible to dutermme from his text whctliur this bad anything to do with the diflerant 
reioltfl bis obtaiQiid. 




ANALGESICS, 



241 



Xarcoitna. — Although in Dr. Albers's eKperiment (Joe. etf,^ p. 244) one 
grain of nurcotina proved fat^il to a frog without the production of convul- 
aians, yet (ho united tci#timony of Claude Bernard (he. c*V,, p. UVl), of Baxt 
(Joe. cit., f, 124), of Ilabuteau (foe. cit.^ p. 206), of Mitcholi (foe. ciV., p. 23), 
mud of Ott (foe. ctV.), ahow that in the lower animals this alkaloid produces, 
whea giirvn in sufficiently large dose^ actiTO spinal convulsions. la saudl 
dam (ooe-half gnun) it causes, according to Albere and to Bait, in frogs 
« oemj-eotuatoee eXute, In lanrcr d* ifc ( 1 ,2 trrains) tJie last ob^rver found it 
to indtioe in the fitunc bntrachian vary decided c^invulsions, siniihu" to those 
oC iDorpbtA-p<iiBonmg, Dn MiteheU states that from two to three grains 
IWINiace violent and Mu\ convulsions in the pigeon. Claude Bcrnnrd ranks 
oafootina nboTG morfdiia and codoiii, next to papaverina, as a c*>nvuLsiint in 
the lower suiiuiols. Yet Orfila found thirty grains necessary to kill a dog, 
mud Baxi hiia given about two grains to rabbits and to guinea-pigs without 
im^dncing nay symptoms. 

Man is oo inqre sensitive to narcotina than the lower animals, if indeed 
lie be 80 senmtive. Twenty and thirty grains of it have frequently been 
UikeB without effect, and doses of one hundred and twenty grains are said to 
btTe been exhibited with no greater result. 

Thrhtua^ or Faramorpkia. — Magendie^ Orfila, Albers, Baxt, Claude Ber- 
nard, F. W. Muller {Du$ Thef^nia, Diss. Inaug., Marburg, 18(58), Harley, 
Frai»«*r. Mitchell, Rabuteau^ and other observers^ all agree as to the very great 
flinularity between the action of thcbaia and tbat of strychnia, Falok 
(^Dettifcket KJtniky 1809) divided the general symptoms produced by the 
poiBon ID mammals into three stages : the prodromal period, in which there 
wm restleamesfi, combined with a d<^ire to creep into corners, urination, 
inereMed frequency of respiration, and mme stiffness of the leg j the second 
stage, in which there were violent strychnic c^nvukions, greatly interfering 
with respiration, and somctiuipa producing cyanosis j the third period, in 
which there was paralytic muscular weakness, with apparent death, ending, 
afler a time, in real death. The third stage was usually momentary, and 
to me to have been merely the dying, which occunntd when the animal 
exhausted and cyanosed by the convulsions. A notable symptom of 
tltehaia-poi^ning is the incrcraiiie of bodily teniperature, which Falck found 
to amount to from l^ to 3*^ C. On pigeons (Falck and Ott) thcbaia acta 
•^ it|>c>n mammals;, and in frog?^ it produreB the munt violent tetunic spasms 
The ooDVulsiooa are undoubtedly .spinal, as they occur after section of the 
flHTical oord. 

The only detailed study of the physiological action of thebriia 3^et made ia 
that of J. Ott (Boston Med tad and Stinjictd Journal^ April, 1875), who 
foand that the alkaloid does not directly affect the motor or sensory nerves or 
tJie rtriftted muscles. The same observer also determined that thcbaia exerts 
0*^1 inHttcnce on the inhibitory cardiac ncrvea, but docs increase the arterial 
»ro by stimulating tho va4>i>-motor centres, and probably also by stimu* 

\n 



242 SYSTEMIC REMEDIES. 

lating the intra-cardiao ganglia. Tbebaia is undoubtedly an exceedingly 
active poison. According to Albers, less than half a grain will cause violent 
tetanus in a frog, and in Ott*s experiments .011 gr. produced very decided 
symptoms in the same animal. Harley found two grains sufficient to kill a 
bitch, and in Falck's experiments a grain and a half injected hypodermically 
killed a dog in ten minutes. The alkaloid must act upon man as upon the 
lower animals ; yet Fronmiiller (Klinische Studien der Narh. Arznetmittel^ 
Erlangcn, 1869) affirms that he has given it in as high as six-grain doses 
without producing any symptoms, and that Prof Leidesdorff (^Wiener 
Med. Wochenschrijl, No. 34, 1868) had had similar results. Rabuteau 
is said to have taken 1.5 gr. without decided symptoms. On the other 
hand, Eulenburg found one four-hundredth of a grain to cause increased 
respiration, pulse-rate, and temperature, with sometimes wide dilatation of 
the pupil (quoted by Ott). It seems impossible to avoid the conviction that 
the drug used by Fronmiiller must have been either very impure or else 
not thebain at all. Husemann (*4rc/i. Exper, Path, vnd TTierap., ix. 422) 
has found chloral strongly antidotal to toxic doses of thebain. 

Papaverina. — A great deal of discrepancy exists among observers as to 
the physiological action of papaverina, obviously dependent upon variations 
in the purity of the specimens which they have used. Schrofif and Hoffmann 
believe it to be inert in man, since the latter observer took about seven grains 
without any effect being induced. 

Albcrs and Claude Bernard claim that on animals it acts as a convulsant 
resembling thebaia ; whilst Baxt asserts that in frogs it produces profound 
sleep, with great slowing of the heart's beat, but without tetanus, and that it 
even acts as an antitetanic in the poisoning of codeia and of morphia. He also 
finds that rabbits and guinea-pigs bear enormous doses of it. Kubuteau says 
two to three centigrammes produce violent convulsions in the frog, but twenty- 
five centigrammes in the dog cause no symptoms ; yet in Baxt's experiments 
four to ten centigrammes served to cause profound coma in the latter animal. 
Ott affirms it is both narcotic and convulsant, and produces a condition of the 
muscles similar to that caused by veratria. These statements arc irreconcil- 
able, and no opinion can be arrived at until new researches, prefaced by a 
rigid chemical study of the alkaloid used, are entered upon. 

Laudantd, discovered by Hesse (^Annalen der Chemie und Fharmacie, 
viii.. Supplement. Bd., p. 272), has been elaborately investigated by Prof. 
Falck, of Marburg* (Deutsche Klinik, 1874, p. 298). He finds that there 
are three stages of its poisoning : first, hurried respirations, pupils con- 
tracted or dilated, muscular twitchings and convulsive tremblings ; second, 
convulsions closely resembling those of strychnia-poisoning ; third, adynamia, 

* The following is the minimum fatal dofic of alkaloids for rabbits, per kilogramme 
(2 lb. 5i drm.) of weight, as determined by Falck: strychnia, 0.0006 gramme : thebaia, 
0.0120 grm.j laudania, .0250 grm. ; hydrocotamia, 0.1600 grm.; morphia, 0.7200 grm. 



AN^iLOESfCS. 



243 



ippcu^Qt death, and finally death from fttilnre of respiration, the heart bfMni? 
ihe last part of the body to die. 

/*orpAyn«m, according to Albers^ nets upon the frog aa the most power* 
fttV of ili the convulsant opinni nlkaloida. Buxt {ioc. ct't.^y, 123) found it in 
4cMSof two to three milUgmmmcs (.030 to .045 graia) to throw the frog 
into « ^emi-comutoso conditiun, followed in fi!\eeu to twenty nnnutes by 
DK»t violunt convulsiivc excitement. In sparrowa one milligramme (.015 
|f^}} and in pigeons a larger dose, produced violent tremor^i lasting ten 
^ fifteen minutes, and followed by a stute of eemi-conia* In guiju-a-pigs 
^€0 to twenty millignimmea (J 5 to .30 gr. ), and in rabbits a one-fourth to 
w>e4hjrd larger dose, caused violent tetanic cramps; larger doses prf>dueed 
•pwiilj fatal convulsions. Acctjrdinz to Seliroff, 1.5 grains are without 
kfinueuoe upon man. 

Cryptopia^ according to Hurley, causes in dogs wild delinmii, with dilated 
jJBpila, fvHowed by tel^ioic spasms. In the mousi*. small dums produce some 
odiriofiii excitement, followed by Bouinoleiicy ; while krgc dtjses cause heavy 
•w»P, Had death from failure of the respiration. In the more detailed inves- 
ugation of Immanuel Mujik ( Wirknn^ tfti( Crt/pfoptu^ Inaug. Diss., Berlin, 
l^i_) tt w:is found that the convulwiun;* did not occur when artificial respi- 
"•udO was performed, and are, therefore, probibly i»ot spinal. The death 
^^ piHweded by loss of reflex excitability from spinal depressiouj and was 
due t<fc respiratory paraly3is. Enormous doses alsti killed the cardiac muscle. 
•A S^^Wi and a half injected beueath the skin by Harley caused in sfjme per- 
■W» iatense drowsiness; in others, very alight nymptoina. According to 
^' C^tt^ it is narcotic, exciting and then depressing the motor spintd centreS| 
ptmly ting spioal sensory centres, lesseuiog fuuctionul activity of the motor 
l*^^€5ts, and lowering heart-action by un influence on its muscle. 

^^Kifmia^ according to Alhers (i(K, c«V., p* 248), produces in (0.045 grm.) 

ftog mild tremors, lessening of Hcnsiition, and finully death. On the 

>eif animal.^ its poisonous action is n<tt very great. Ortila injected 0,06 

(0.9 gr.) into the jugular vein of a dog, without eflect. Harley gave 

^mius hypodermicttlly to the s;ime animal, with no further result than a 

*lc5 ibtjormal (|uietnes8» According to the Siune observers, subcutaneous 

U*>ct,ionsof fourteen gruina have no effect on the horse, but one*aixth of a 

**w pnxluces very decided hypnotism in the mouse. On man, Dablanc 

(iV«<ir»4. CkntraMut, 18:J2), Schroff (.Vt'ci/cm. Juhrh,, 1S70), Frunmiiller 

r. ""^^*'^ *SViiiAV/i A^ttrcot. Arzneten), and Harley have found meeonia, when 

?^*in by the mouth, inert in doses varying fioui one to eighteen grains. 

Uarltj*^ however, claims that in doses of oue to two grains given h^-poder- 

^b' it acts upon nnin as u very excellent Iiypnotic ; but Fronmuller ha.«* 

^t«xl nearly two grains, with entirely negative results, 

jJ^'/rocotarHia, — The physiological action of this alkaloid has been in- 

^*^ui4jd by F. A. Falck (London Mfdkal Rrcfml^ i. 21 8 J. Ho finds it 

Actively poisonous to rabbits than is morphia. In some of his experi- 



244 SYSTEMIC REMEDIES. 

mcnts it produced tetanic convulsions, in others coma and stupor. In frogiB 

the symptoms were always tetanic. 

In regard to the action of Pseudomorphia and Opiania we hare littJe or 
no knowledge. Sertumer, the discoverer of Meconic Acid (quoted bj Al- 
bers), found it in his experiments to be actively poisonous ; but Sommering 
and Albers have come to an opposite conclusion. Large doses (one to two 
grains) do, however, affect frogs, although slowly, inducing a stupor-like con- 
dition, with convulsions. 

OAIWABIS IKDIOA-INDIAU OANNABIS-HTDIAN HEMP. U.S. 
CANNABIS AMERIOANA-AMEBIOAN CANNABIS. U.S. 
Under the respective names which head this article, the U. S. Pharmacopceia 
recognizes the dried tops of the Cannabis sativa, or common hemp plant, as 
it grows in India and in our own country. 

EXTRACTUM CANNABIS INDICT — EXTRACT OP INDIAN 
HEMP. U.S. 

The alcoholic extract of Indian hemp is a blackish, resinous extract, of a 
decided narcotic odor and a peculiar taste. In the East, hemp and its educts 
are used as narcotic stimulants. Gunjah is the dried plant as sold in the 
bazaars of Calcutta for smoking. Churrus is the resinous exudation with 
the epidermis, etc., scraped off the leaves. Hashish is an Arabian prepara- 
tion of the drug. The resin, which represents the activity of hemp, is 
sometimes known as Cannahin. It is best obtained by precipitating the 
saturated tincture with water containing an alkali. Hemp also contains a 
trace of volatile oil. 

Physiological Action. — When given in full doses, cannabis indica 
produces a feeling of exhilaration, with a condition of reverie, and a train 
of mental and nervous phenomena which varies very much according to the 
temperament or idiosyncrasies of the subject, and very probably also, to 
some extent, according to the nature of his surroundings. The sensations 
are generally spoken of as very pleasurable ; often beautiful visions float 
before the eyes, and a sense of ecstasy fills the whole being ; sometimes the 
venereal appetites are greatly excited ; sometimes loud laughter, constant 
giggling, and other indications of mirth are present. Some years since, in 
experimenting with an extract made from the American plant, I took a very 
large dose, and described the result as follows (^Proceed. Amer, Philosophy 
Soc, 1869, vol. xi. p. 226): 

" About half-past four p.m., September 23, 1 took most of the extract. 

No immediate symptoms were produced. About seven p.m. a professional 

call was requested, and, forgetting all about the hemp, I went out and saw 

jiy patieiit. Whilst writing the prescription, I became perfectly oblivious 

^ vent on writing, without any check to or devia- 

d acta connected with the process, at 



ANALGESICS. 



245 



. llaat I am aware of. When the r<3cipe was finished, I suddenly recoU 
lected where I was, and^ looking up^ saw my patient sitting quietly hefom 
SIS. The oonvietion was irresistible thut I had sat tlius many minutes, per- 
lu^ hours, and direcUy the idea fksteDed itself that the hemp hod com< 
wtmoimd to act, and bad thrown me into a trance-like statti of considorable 
dmmdoDi during which I had been stupidly sitting before my wonderin«r 
I hastily arose and apologized for remaining so long, but was 
i I had only been a very few minntes. About seven and a half p.m. 
I fvttuued home, I waa by thiii time quite excited, and the feeling of 
hilftritj noiw rapidly tnereaaed. It was not a sensuous feeliTig, in the ordi- 
umxj meaning *if the term; it was not merely an intellectual i^xritation ; it 
w«a a sort of lien-ttrc^ — the very oppusiite to mfi/cuV, It did not uiime 
firom without ; it was not eonnected with any po^on or sense. It was simply 
m Ibeling of inner joyousn(^8 ; the heart seemed buoyant beyond all trouble ; 
the whole 5\n*tem felt as though all gcns« of fatigue were forever banishe*! ; 
tht mind gladly ran riot, free coastatJtly to leap frijui one idea to another, 
apparently unbound from its ordinary laws. I wjjs disposed to laugh ; to 
make ooiaic gestures ; one very frequently recurrent timcy was to imitate 
with the arms the motions of a 6iidler, and with the lips the tune he was 
Rip|>oeed to be playing. There was nothing like wild deliriumj nor any l-allu- 
climlioiia that I remember. At no time had I any visions, or at least any 
tlial I can now call to mind ; but a j>erson who vnxs with me at thnt time 
•tales that once I raised my head and exclamied^ ' Uh, the mountains! the 
mcmntains 1* Whilst I was performing the various antics already alluded to, 
I koew very well I was acting cxcetjdingly foolishly, but could not control 
tayvelH I think it was about eight o'clock when I began to have a feeling 
of numbness in my limb^, al§o a sense of general uneasiness and unrest, and 
m fbor le^ I had taken an overdose. I now constantly walked about the 
booflO ; toy skin to myself was warm^ in fact my whole surface felt flushed ; 
my tnouth and throat were very dry ; my Ig^ put on a strange, foreign 
ibdUtig, as though they were not a part of my body, I counted my pulse 
mid fuund it one hundred and twenty, quite full and strong. A foreboding, 
ma ttudciined, horrible fear, as of impending death, now commenced to creep 
ciT«r m« ; in Ituste I sent for medical aid. The curious sc^nsations in my 
Hmba inerenaed. My legs felt as though they were waxen pillars beneath 
me, I remember feeling them wtth my hand and finding them^as I thouglit 
At Imat, very firm, the muscles all in a state of tonic contraction. About 
m^i o'clock I began to have marked ^ spells/ — periods when ail connection 
wiiniiiH to be severed between the external world and myself I might be 
mid to hare been unconscious during these times, in so far that I wa:* ob- 
Itrtutis to all external objects^ but on coming out of one, it wa£ not a blank, 
draamlaift void upon which I looked back, a mere empty space, but rather a 
perbd of active but aimless life. I do not think there was any connected 
lIuMigkt in them ; they seemed simply wild reveries, without any binding 



246 SYSTEMIC REMEDIES. 

cord, — each a mere chaos of disjointed ideas. The mind seemed freed from 
all its ordinary laws of association, so that it passed from idea to idea, as it 
were, perfectly at random. The duration of these spells to me was very 
great, although they really lasted but from a few seconds to a minute or two. 
Indeed, I now entirely lost my power of measuring time. Seconds seemed 
hours ; minutes seemed days ; hours seemed infinite. Still I wa^ perfectly 
conscious during the intermissions between the paroxysms. I would look at 
my watch, and then after an hour or two, as I thought, would look again 
and find that scarcely five minutes had elapsed. I would gaze at its face in 
deep disgust, the minute-hand seemingly motionless, as though graven in the 
face itself; the laggard second-hand moving slowly, so slowly. It appeared 
a hopeless task to watch during its whole infinite round of a minute, and 
always would I give up in despair before the sixty seconds had elapsed. 
Occasionally, when my mind was most lucid, there was in it a sort of duplex 
action in regard to the duration of time. I would think to myself. It has 
been so long since a certain event, — an hour, for example, since the doctor 
came ; and then reason would say, No, it has been only a few minutes ; your 
thoughts or feelings are caused by the hemp. Nevertheless, I was not able 
to shake ofi" this sense of the almost indefinite prolongation of time, even for 
a minute. The paroxysms already alluded to were not accompanied with 
muscular relaxation. About a quarter before nine o'clock, I was standing 
at the door, anxiously watching for the doctor, and when the spells would 
come on I would remain standing, leaning slightly, perhaps, agunst the 
doorway. After awhile I saw a man approaching, whom I took to be the 
doctor. The sounds of his steps told me he was walking very rapidly, and 
he was under a gas-lamp, not more than one-fourth of a square distant, yet 
he appeared a vast distance away, and a corresponding time approaching. 
This was the only occasion in which I noticed an exaggeration of distance ; 
in the room it was not perceptible. My extremities now began to grow 
cold, and I went into the house. I do not remember further, until I was 
aroused by the doctor shaking or calling me. Then intellection seemed 
pretty good. I narrated what I had done and suffered, and told the doctor 
my opinion was that an emetic was indicated, both to remove any of the 
extract still remaining in my stomach, and also to arouse the nervous system. 
I further suggested our going into the office, as more suitable than the par- 
lor, where we then were. There was at this time a very marked sense of 
numbness in my limbs, and what the doctor said was a hard pinch produced 
no pain. When I attempted to walk up-stairs, my legs seemed as though 
their lower halves were made of lead. Afler this there were no new symp- 
toms, only an intensifying of those already mentioned. The periods of 
unconsciousness became at once longer and more frequent, and during their 
absence intellection was more imperfect, although when thoroughly roused I 
thought I reasoned and judged clearly. The oppressive feeling of impending 
death became more intense. It was horrible. Each paroxysm would seem 




ANALOESICS. 



247 



to bare b<M2n the longest I Had suffered ; na I came out of it, a voice s^med 
congtAutiy sayingi * You are getting worse ; your paroxysms are growing 
longer and deeper ; they will ovonimster yon ; you will die/ A srrnso of 
per^MQal antagonism between my will-power und niyself, as affected by tlio 
drug, grew very strong. I felt as though my only chance was to struggle 
against these puroxysmSt — that I must conwtantly arouse myself by an effort 
of will ; and that effort was made with infinite toil and pain. I felt as if 
aome evil i?[>irit had control of the whole of me except the will-power, and 
waa iQ determine*! conflict with that, the Uist citadel of my being. I have 
never experienced anything like the fearful sense of almost hopeletya atiguisb 
ttod utter weariness which was upon me. Once or twice during a partaysm 
I bad what might be called nightrinare sensations; I felt myself mounting 
upwards, expanding, dilating, dissolving into the wide confines of spaeei 
overirlielraed by a horrible, rending, unutt4?rab!e despair. Then, with tre- 
uieudous effort » I seemed to shake this off, and to start up with the shudder- 
wig thought. Next time you will not be able to throw tlijs ofl^ and what 
thea ? Under the influence of an emetic I vomited freely, without namtea, 
■^ '^^ithout much reUef About midnight, at the suggestion of the doutors, 
t tetxt up-stalrs to bed. My legs and feet seemed so heavy I could scarcely 
*Oire them, and it was as much as I could do to walk with help* I have no 
"Mol lection whatever of being undressed, but am told I went immediatelj to 
weep, Wbcn I awoke, early in the morning, my mind was at first clear, but 
*Da. £ew minutes the paroxysms, similar to those of the evening, came an 
>gtici,aDd recurred at more or less brief intervals until lute in the aflernoon. 
All of the day there was marked anfcsthesia of the skin. At no time were 
'iic»"'« any aphrodisiac feelings pro^luced. There was a marked increase of 
the ij^rinary secretion. There were no afler-effecls, such as nausea, headaehe, 
or constipation of the bowels/' 

Tlie sense of prolongation of time which I experienced was to me verjf 
Wtt^^jbible, but is not uncHimnmn in these cases. It is evidently due to the 
^bnxudiae rapidity of the succession of ideas. The mind, without doubt, 
^^P*^**«tires time by the duration of its owu processes, and when an infinitude 
^^f i«Jeiys arise before it in the time usually occupied by a few, time becomes 
lattuit^ily prolonged to the mind. It is a lifetime in the minute. A very 
•^^^'■^^iion mental phenomenon, not yet mentioned, is a condition of double 
'^*''*®*^oasncss, a sense of having two existences, of being at the same time 
ones^Jl* and somebody else. 

'*'* dome ca^es Indian hemp produces, in addition t^ or even in the place 

* ^Hq ^niptom already spoken of, marked disturbances of motility. Convul- 

'** Have been noticed by Dr. Lawrie (Stiflt^'^ T kerapeatics^ vol. i* p. 772), 

'ociil sj»a.smA, with saliiam ccinvulf^iuiis, by Dr. F. II. Brown. According to 

O'Sbaughncisy, the induction of cutjdo^Ksy i« not rare among the Uinduos. 

^^atevcr may be the symptoms of the first stage, sooner or lat43r, if the 

l>c du^cieiit, drowsiness csomcs on* Gcnenilly, before it is marked, par- 




248 



SrsTEMiC REMEDIES, 



tkl aniBJitliestii, ofleix with partial logs of strengtb, 19 manifested, especially m 
the lower Hmks. The pupils are dilat^nl, the pulse is quickeued, aud fiaallj 
the subject fidls into a heu^-y sleep, out of which he generally awakes hungry, 
without any of the wret4:hed gastric senaatiuna or the malaii^e felt after &q 
opiate, Cunfuslon of tliought, however, miiy poi-sist for some hour«. Can- 
nabifl exertj* no constipating iofluctico upon the bowels, and appears to ia- 
creafle, rather than decreu^, the excretion of the kidneys. 

Therapeutics. — Leaving out of i^iglit the employment of the medicbe 
by olienLats, heuip has been used in this country chiefly for the 7'c/*«?/'o/*^atk, 
but also to some extent aa a ht^pnotic. As an analgesic, it is very much inferior 
to opiura, but may be tried when the latter is fijr any reason contra- indiisited. 
In full doses, in neuralgic pains, it eertiiiuly often gives relief. It hikj been 
very largely omjiloyed to induce euthanasia in the advanced stages of phthitiij 
and con&ttitutes, it is said, a popular nostrum t-mployed fur that pnipose. In 
f^tamtSj Indian licmp hus been used quite largely, and until within a abort 
time was, after opium, one of the few known drugs of service. Dr. Roemer 
{J^t. LfjitU Medical and Siirgical Jounutiy p, 363, 1873) baa eolleetod 
thirty-five cases, with twenty-one Toooverios and fourteen deaths. 

Administjiation. — The action of the preptu-ations of Indian hemp j^H 
exceedingly variable, in some cases small doses producing alarming efi'ecta,|^| 
other instances the remedy seeming almost entirely powerless. There ap- 
pears to be a very great difference in the susceptibility of persons to its influ- 
6Doe; but thb cannot explain the wide variance of the clinical results obtained 
by its use- A large proportion of the extracts upon the market must be 
inert. Possibly the crude drug undergoes det-erioration during \i& long sea- 
voyage from India ; at least I have had extract carefully made from genuine 
Indian hemp and offering all the physical cbamctera of good extract, yet eo- 
ttreiy inert in doses of many grains, I have seen an eighth of a grain of an 
English extract produce in a susceptible woman decided intoxication. So far 
as my present knowledtre goes, although the foreign oxtractfl of hemp are 
often ineflicient, they are much niOTe reliable than the American. The only 
way of udminist43ring hemp with satisfaction at present is for the practitiooer 
to try vai-ious samples until he gets an active one, and then, being suppliod 
with thisj utid having kmrncd its proper dose by cllnictd experiment, to depend 
solely upon it. Hemp is not a dangerous drug j even the largest doses of its 
active preparations, altbough causing most alarming symptoms, do not compro- 
mise life. No case of acute poisoning by it terminating fatally has, that 1 am 
aware of, been reported. There is an officinal tincture ( TtHCfura Cunnabii 
Jndic^, U.S.), the dose of which is thirty minims. The dose of ih^Jlmd 
extract {^Extractam Gminahis ladicm Fluidum, U.S.) IB one minim. 




CLASS Vn-MYDRIATIOS. 



Ix the present group are considered three medicines^ — belladimna, byoscy- 
ftxnttfl^ and stramonium, — whose preparations, vhen given internally or applied 
k*callj to the cye^ dilate the papil, or, in other words, produce mydriasis, and 
whoae action upon the system appears to be almost tdentieal. 

BELLADONiri: FOLIA-BELLADONNA LEAF, U.S. 
BELLADONNJE EADIX-BELLADOKNA ROOT, U,8, 
The leaves and root of Atropa belladonna, an herbaoetma perennial, a native 
of Europe, but (niltivale<l in thi« country, and attuiniitg a heij^ht of some 
tkree feet The oval, pointed, entire, smooth, uneqii;!! leaves are in pairs, on 
m ikhoit ftx)tstalk. The bell -shaped, axillary, pendent flowers are of a dull 
reddiah color, Tlie glubular berry m about three quarters of an inch in 
dhuzietery deep purple, with a viulet^ colored juice, and adherent, green calyx. 
Tlwj dried leaves have a faint narcotic odor, and a sweetish, sub- acrid, slightly 
DBtiaeous taste. The dried eyUudrieal branched root is from one to Bcvend 
inches iti dtameter, much longer, tibruus, extenially reddish brown, internally 
whitish, tdmciftt odorleea^ with a very feeble sweetish taste. 

ATROPINA. IT.S, 

The sole active principle of belladonna, discovered by Mein in 1831 and 
iDdependently by Geiger and Hease in 1833^ occurs in silky prismatic and 
mcicular, oAen aggregated crystals, of a bitter, burning taste, without odor, 
#c>luble in three hundred parts of cold nnd fifty-eight of boiling water, forty 
of benxole, thirty of ether, tliree of chloroform, and eight of alcohol. It 
is iDost abandant in the root, and, according to M,Lefort (V Union MMicale^ 
Nov* 187 1)» in that of young planU. Cyanogen gas pojised through ite alco- 
holic solution makes a deep-red ( H interbeycr). The most reliable test is 
the physiological one,— 1**«., the production of mydriasis in a rabbit or a cat I 
by ih© hx-al application to the eye. It bus been found in all the tissues of 
poiH>ncd individuals, but always exists in greatest abundance, and b mos*t 
easily dcmonstrat^^d, In the urine.'*' 

POYsiouxiiCAL ACTIO.V. — When the smallest physiological dose of atropia 
is administered to man, the only symptom induced is dryness of the throat 
and mouth, and possibly K)roc disorder of vision. When a little lar^t 

• Fur A ehfmico-|»bjrffiologiciil Btudj of tropin and other derivativ«a from fttropU, le* 
Aftkiv R^jttr, PatkoL, Bd, ?., 465. 

240 



250 



SYSTEMIC REMEDIES, 



amount ia given, tliis dryness ia more intense, and is associated with reJn 
of the fauces, dilated pupils, disordered vision, and possibij diplopin. 
pulse is sometimes at first rendered less fre<]ueut^ but this decrease is very 
transient, atid certainly in many cases cannot be demonstrated at all. Often 
from the first, certainly after a short time in all cases, the heart's beats, aft^er 
n large dose of the alkaloid, become excessively rapid, the pulse rising to one 
hundred and twenty, or even one hundred and sixty ; and in a little while a 
pet-uliar bright- red flush ajipears on the face and neck, and may spreiul over 
the whole body. As I have seen this, it lacks the puuctations of the msh of 
scarlet fever, and is only in very severe cases fullowed by desquamation. 

Early in the course of the symptoms of at ropi a- poisoning there is very 
often forcible expulsion of urine, and erections of the penis may occur; bttt 
afterwards there is very generally, Harley says always (^Old Vrpetabfe Xcvh 
roiics^ p. 207 )t retention of urine. With the symptoms above enumerated, 
intellection may remain perfect ; but there are generally some lightness of 
head, giddiness, and confusion of thought, as well as a staggering gnit and 
restlessness. Occasionally, even with dti«cs which may be called medicioiil| 
there are spectral illusions. Prowsincsa is not a general or at all character- 
istic symptom: if present, it is apparently always produced indirectly, as 
by the removal of some cause of previous wakefulness. When a decidedly 
poisonous amount of belladonna or its alkaloid has been taken^ all the symp- 
toms already noted are intensified, and to them is added a peculiar talkative, 
wakeful delirium, in which the patient lives in a world of his own, engrossed 
by the specti-es and visions which throng him, and eorapletel}^ oblivious to the 
surrounding realities. Thus, I have seen a lady remain for a long time 
stooping and holding fmt to the bed-post, to wliich she talked in the most 
voluble manner, as though it were an intelligent living entity. Sometimes this 
delirium is wild, and the patient almost uncontrollably violent. After a 
time, sleep may come on, and on waking from this complete consclunsaoM 
may be regained, or the symptoms may gradually subside. After a very 
large do&e has been taken, severe convulsions may appear in a very short 
time, and persist, with or without furious maninetd delirium, until near death. 
Sooner or later, however, the delirium su brides into stupor, and the convul- 
sions into paralysis ; and when the dose has been enormouSj and especially 
when the alkaloid itself has been taken, stupor, with great muscular relaxa- 
tion, may occur very early. Lividity of the face, and evident imf»erfect 
aeration of the blood, are not seen in atropia-poisoniog, except in the stag© 
of most imminent peril Death is preceded by marked failure both of the 
heart's action and of the respiratory forces. In most casci?, I think, it is 
actually brought about by asphyxia.* Post-mortem examinations have shown 
in fatal ctises congestion of the lungs, oft^n with ecchymoses,aud a similar state 

^ 8ee a cubg reported by 6. W. GrotB, American Journal of ih% Mtdiml Svimen, 1809* 
p. 401^ M a strikiDg instanoo* 





MrDntATJCS. 



261 



of the membraDefi and even subistance of the brain and cord. According U> 
M, Lcmattre,* coDgestiuii of the retina is an almost characteristic lesion of 
Atropia-poisoning. 

Upon the lower aotmals belladonna to a great extent acts as upon man^ 
although iU influence is nmch less powerful in them, and very much larger 
t\oei*sA ane re»juircd. Seeming differences of action are in must coses simply 
apparent, not ival. Thus^ in the dog, as in man^ the pulse-rate is very 
graidy increased by atropi^, whilst m the rabbit it is not. As will he shown 
bewnftcr, tJie rise of the pulse-rate in the former is largely due to paralysis of 
the piir rngum. Now^ atropia paralyzes the par vagum iu the rabbit aa much 
as in the ^o^,^ but in the nibbit pneuniogustric paridysis, by section or other- 
e, is oeirer fuUowed by a rise of the pulse-rate at all comparable to that 
under similar circumstances in the dog. Evidently the action of the 
drug is identical in the two cases, although the symptoms are different la 
Uieir sensitiveness to atropia animals differ very much, and, as a general rule, 
kerbivora are less susceptible than curnivora. Thus, the rabbit may be fed 
for days entirely upon belladonna-leaves without injury, and many grains of 
»ttt)pia are necessary to kill him. Birds — at least pigeons — I have found 
will often recover after the hypodcnnic injection of two grains of atropia, 
nod three grains by the mouth did not prove fatal. A very curious and at 
pir«aent Inexplicable fact, which I have repeatedly verifled, is that the pupils 
iu pigeons eanoot be dilated bj the use of belladonna. 

The close study of the physiological action of atropia can only be made 
(lyHietu by system, and I shall now consider the subject under such headings. 

Action on the drculcUvty S^ntetn.f — In the dog and in the rabbit small 
doses of atropia cause an increased frequency of the pulse, with rise of the 
aTl42rial pressure. If, however, larger amounts of the alkaloid are used, and 
especially if the poison is thrown immediately into the venous circulation, 
tbero is an immediate fall of the bloi)d-presaure, although the pulse increases 
as before, Bezold and Bloebaum ( Ueber die pht/nioiof^i^chen Wirkttn^^en dei 
Schwe/el-Atrojuns^ in Unfern/ch. aiis d. Pht^niolug. Laboratory in Wiirzl/urg^ 
Helt L) state that the dose of atropia can be so gradtiated as to produce at 
fint a temporary rise of the arterial pressure, followed in a short time by 

In atropinized animals, as is stated both by Besold and Bloebaum (Joe. eit,^ 
p. 33) ttiid by Meuriot (Z>e la Mifhode phr/sioIogiqiLe en HUrapeutique et de 
§eM ApplicaiionM d t Ktude de la lielladont\ Paris, 18G8, p. 73), and as I 



* Quoted hy Tardicu, Sur V Empoi^tmnenv^nt^ P&ria, 1867j p« 762. 

f K kmf fiApi^r upon CAlftbur beiui aod atnj|jia ho* been publinhad hj Rotibaeh uid 
Ft^htkh { Verhiindimtgtn d, WUrtburfjer Phift. Med, Gr»rH»ehn/i, 1873), in which result! 
loUJIjr ml ir»riiit]c« wUb tbueo of »U other ob«ervcr8, antl manj of ihem ai lot&lly at viiri« 
Mioe Willi general pbj^nitilugicat lawi, hare bceu rcaehcd, SpiM?e oanDot be ffpiir«d for t 
CMrUtetiin of tbii pnpcr, and the reader h Tvfvrred tu the tiiomoir itflctt nbt^tracLird ( London 
Utfi. JUt.t i-) »n<i to the critique of llnrniirok {Arrhiv Ej^pttim^ PathuL Thcrajj.f ii. 307). 
9m mim Pkarmtthili^y. Unt* ikpA., Bd. 1. Ilefl S and 4* 



252 



SFSTEMIC REMEDIES, 



have frequently eeen, section of the vagi is not fulluwed by any increase at 

the heart*8 atitionj and galvtitiimtion of the oon^o is incapable of ii)6ueDdn}r 
the viscus. It follows that atrupiii iu toxic doses paralyzes either the truuk 
or peripheral filmiiente of the nerve^ and, aa Bea&old and Bloebaum believe, 
most probably the latter. The oheervers just alluded to have found that if 
atrc»pia be injected into the etirolid so as to reach the jtneuiiiogastrie cerures 
before the periphery, there is an iDStantarieoas fall in the mte of tlie lieart'g 
beat, — an iDdicaliou that upon the cardiac inhibitory centres atropia acts us 
a direct stioiulant, precisely as it does on the gplnal cord, the reason thai the 
action is not more nwuiife«t under ordinary cireunistancea being the incapacity 
of the paralyzed va^s to transmit the central impulse. This asserted stimu- 
lation* of the inhibitory centre, if it be correct, accounta very beautifully 
for the primary briel' slowing of the pulse stated to occur in some cahttt of 
afcropia-poisoning. (See StilU's Thettj^mitlc*^ voL i, p. 725. MitchelK Keen, 
and l^iorehouse found It in about one-third of the cases ailer large bypiMJeiiiiic 
injections; Da Costa in a larger proportion, Amer. Jour. Med, Scmicti^ 
July J 1SG5 ; Miss Mary Putnam in some cases, ^^eto rork Mtdictil Rvct/rd^ 
18730 

When, by the division of the spinal cord and vagi, the heart is isolated 
from the nerv^e- centres and the vaao-motor nerves are paralyzed, Bezold and 
Bloebaum have found that atropia, in minute as well us in large amount, 
lessens at once the arterial pressure* Botkin ( Vivchow^ Archii\ xxiv., l8(J2j 
Btftteii tliat when atropia is applied to the heart of the frog it at onee dimin* 
ifihes, and finally arrests, its action, which ciinnot be re-excited by galvanic 
or other stlnmli ; and Bczoid and Bloebaum {loc. ci'/,, p. 48) have found 
that the game thing occurs when an overwhelming do«*e of the alkaloid Is 
injected into the jugular vein of a mammuL From these facts it follows 
that upon tlie heart it^e// atropia acli as a direct deprestaiU poUoti^ but for 
this in£uence to be apparent a very large amount of the alkaloid must be 
used. 

From what has already been said, it is evident that the inereaao of the 
pulse seen in atropia-poisoning is in a measure due to a pai-alysis of the car- 
diac inhibitory nerves ; but that this is not the onl}* cause is shown by the 
fact noticed by Li?mattre {^ArclUveM Ginirales^ August, 18b5) and oonfirmed 
by my own experiments, that ufler section of the par vagum atropia still 
causes an increase in the rapidity of the heart's action. Further, Bea^ld 
and Bloebaum have found (Zbc. ctV., p« 54) thiut when the thoraao sym- 



* The cxpeHtneiiti und oonduEione of Ro9»biieli and FrohHoh oonflrm the existence of 
thia Btimuliiiinj^ luiiioa of atropia on the tohibitary eentret, but oaanot be r«<>«ire<i m 
correct^ for reiuona alreodj given, llaraaok {Arekiv fUr £xpar* PatknU wwrf Theraj^rit, 
iu 328) fiudfl that the miiiiitest doio of atropia inorea«ei ih« rftpidity of tb« hcitrt frtUr 
ititiiul&tiou of iU inbibltorj oontrei by muEwarin and ooiiie(|u«nt sluwiug of iU bcftt, 
Thif iloe« uot, howevori prove tbat atropia bai no aetioD oo tho iahibitory oeotrei* 
Furtlier iuvestigatioD is Qooetiaarj for a positive oocclusioa. 



MYDRIATICS. 



88S 



pfttKirtic 19 galvatiiaed, even after large doees of fttropia^ the heart is very 
eensibtj affected. From tlicso fact* it is obvious that atropia acts on the 
OHdiac accelerator nerve-centreji^ or po^bly nerves, a» a Mtiniiilant, and, 
imlcie it be ia lethal dosca, does not deMrotf the cxcitabiliti/ of these nerves. 

The relation of belladgnna to the vaso-mofor nervous system is of such 
prBeticd importance that it deserves the closest study. Brown-S<'quard says 
positively that the drug has the power of exciting the muscular fibres of the 
lU-tcHolcs; but, as he nowhere detidls the reiisona for this opinion, I think 
litde weight is to be attached to his stjiteincnt. In 1857, WTharton Jones, 
of England (Medical Ttmes and Gazette, p. 28, 1857), annonnoed the faol 
(oonfirmed by Lemattre, loe. cit,^ p. 52) that if atropia be dropped upon 
the web of a frog*s foot, under the microscope the vesaels can be seen to 
cootiact* Dr. Hayden (Dnhlin Quarterly, Aug. 1863) in repeating these 
experiments found that, if the skin were cut just above the foot, no oon 
traction occun"c<l, and concluded that the phenomenon was purely reflex. 
Mcuriot {loc. ei>,, p. 39) has obtained in some cases, hut not invarijibly, the 
results of tlie last observer. He has, however, discovered that if the nerves 
of the leg be divided, no contmction ever takes place. Atropia is an irritant, 
and it is evident that the contrnction caused by it« local application is simply, 
as Hayden believed, a reflex phenomenon, precisely similar to that wliich 
occurs on the application of any chemical or mechanical irritant. The ex- 
periments of Wharton Jones, upon which so much has been ba.'jed, must, 
therefore, be eliminated from the evidence on the question. The problem 
mik be 8olved only by studying the effects of the remedy administered so as 
lO act on the part solely through the circulation, Mcuriot, us the result of 
such studies on the frog's web, has concluded that there is in the first stages 
^f the poisoning a very slight contraction of the veaaels, amounting to nothing 
toore than increase of their tonicity ; never to any decided lessening of their 
Itiinen. Dr. Harley (Tft^ Ohl Vvgeinhh Neurottoi, London, 1801), p, 220) 
has witnessed a more decided contrai'tiim of the vessels. 1 have tried the 
experiment several timc», but obtained no decided results. On the other 
hand, Bezold and Bloebaum (loc. cit.^ p. 50 ) have made similar experiments 
upon the ear and mesentery of the rabbit, and have never been able to detect 
any contraction of the vessels, and consequently deny its existence. In these 
expenments it was not possible to use the microscope, — which detracts greatly 
from their value. 

The evidence derived from direct observation of the capillaries seems to 
nie to be, ou tlie whole, decidedly in favor of their contraction by minute 
doBOB of belladonna. I do not think, however, that much weight is to be 
atlaelied to evidence of this nature. The alterations in the calibre of the 
feneh) are so slight as to leave great play for the imagination of the observer, 
— ft source of fallacy which probabfy accounts f<>r the different results ob- 
Cauiod by different investigatoi"8. Jluch more decisive proof is however, 
obtainable from a study of the arterial preasure. I have found that afler 



254 SYSTEMIC REMEDIES. 

section of the vagi atropia still has the power of raising vorj materiallj the 
arterial pressure. As atropia docs not augment the force of the individual 
cardiac beat, and as the increase in the number of the cardiac pulsadona 
caused by it after section of the vagi is comparatively slight, it is exceed- 
ingly probable that the rise of arterial pressure just spoken of is due to a 
contraction of the small vessels. This logical conclusion becomes almost a 
certainty when it is further known that after division of the cord, and con- 
sequent separation of the vessels from their vaso-motor centres, atropia is 
powerless to produce rise of arterial pressure, a fact vouched for by Bczold 
and Bloebaum, and which I can confirm from my own experiments (^Amer. 
Jour, Med. Sci^ April, 1873). To this cumulative evidence must be added 
the experimental fact noted by Bezold and Bloebaum, that when a small 
dose of atropia \s injected into the carotid artery — t.c, into the vaso-motor 
centres — there is an instantaneous rise of blood-pressure.* 

Viewing all these facts together, I am forced to give assent to the propo 
sition that atropia, in not too large amount, is a sttmulant to the va$o-motar 
centres; a conclusion in harmony with the action of the drug on all the other 
motor centres. All observers agree that in the advanced stage of atropia- 
poisoning, after the blood-pressure has commenced to fall, there is dilatation 
of the capillaries. It seems most probable that this is duo to a direct action 
of the poison on the muscular fibres in the coats of the vessels ; for when 
directly applied to the web of the frog's foot, atropia, after a time, produces 
an evidently paralytic dilatation ; and Bczold and Bloebaum have found that 
the arterial muscular coats in atropia-poisoning finally lose their irritability, 
but that 80 long as they retain it, galvanic stimulation of a sympathetic nerve 
does not fail to induce contraction in the tributary vessels. 

Action upon the Nervous Si/sfem. — The delirium which is so characteristic 
of atropia-poisoning shows that it has especial relations with the cerebral 
cortex. Prof. Albertoni has made a series of experiments to determine 
whether it inhibits or affects the motor powers of the cortex. He finds that 
neither the single large dose nor the repeated continuous dose has any power 
in [irevcnting the epileptic seizure resulting in dogs from the stimulation of 
the motor zone of the cortex : enormous toxic doses seem only to render 
the response slower and less vivid {^Arch. Exper, Path, und Tlierap., xv. 
p. 265). 

In 18G2, Dr. S. Botkin ( Virchow's Archiv, Bd. xxiv. p. 85) found that 
when the vessels of a frog's leg were tied and the animal poisoned with 
atropia, whilst paralysis developed itself in the ordinary way in the un- 
injured leg, the injured leg preserved its motility. He also discovered that 
the nerve of the leg whose artery had been tied transmitted a forcible im- 
pulse to its tributary muscles under the stimulus of a galvanic current much 

* It is proper to state that Bezold and Bloebaum attribute this rise to psychical dis- 
turbanoe^ without, however, as it teems to me, good reason. 



MrDRJATWS. 



255 



w^ikeor than could elicit the faintest response from the nerve of the opposite 
stdo. He ooncluded, very logically, that atropia acts as a paralyzant to the 
motor oenre-trunks themselvea, and also, since motion jKjraktod in the pro- 
tected leg after it was completely lost in its fellows^ thai this in tine nee of the 
drag was exerted upon the motor trunks before the spinal centres* These 
experiments have been c<:>nfirmed l»y Lemattre (loc* cjV,, p. 411), by Bezold 
and Blocbaum (loc* cif,, p. 20), by Mcuriot (he, mt.j p. 90), and by Fraser 
«iid others, who have proven that atropiR, if in sufl5cient dose, has the power 
of dtitrtt^ing the cxci/ahilif^ of the vjferf^nt or mutor nervt Jihreg, but that 
it mast be in very Urge quantity, so that in mammals death may be caused 
by the ulkAbid and yet a notable amount of functional power be retained by 
ike motor nerves. BezoKl and Bloc^baumj whose elaborate experiments are 
especially commendable, affirm that very rarely have they been able totally 
to destroy by atropia the functional power of the motor nerves, and also 
hmve ^lown that both tlie neiTe-steni and the peripheral intra- muscular 
nerve-endings are affected. All the experimenters agree that no stage of 
super-excitability preceding that of depression can be disoovered. 

Prof. Tbos. R. Fraser discovered in 1869 ( Ttani. Rtn/. Soc. Sdinb., xxv. 
450) that if a frog receive an inject ion of iibuut onetlunisnndth psirt of its 
weight of atropia, a condition of perfect paralysis and abolition of reflex 
action comes on after a time, and lasts Irom two to four days, to be suc- 
ceeded by a tetanic stage, with violent convulsions and excessive excitability 
of the reflex centres. The eunvulMons of this stage have been shown by 
Fraser to bo spinal^ occurring after section of the cord in all prts of the 
bodjp Dr. Fraser found (Exp. 59, p. 481) that when he protected the hind 
legs by tying the aorta at its bifurcation, tetanus appeared m them at a time 
when tlie anterior legs were completely paralyzed and the bruchiul nerves 
were noable to respond to the galvanic stimulation. Again, he was able to 
produce symptoms closely analogous to those caused by atrojaa by injecting 
siiiiultaneoualy two poisons, — oue a stinriilant to tlie cord, the other a para- 
Ijxant of the nerve-truuks. Tiieae facts would seem to prove that during 
the paralytic stage of the action of atropia a convulsant condition of the 
oord is masked by a paralyzed state of tho efferent nerves. This conclusion 
14, however, invalidated by certain tacts observed by Fraser, auu especially 
by the recent researches of Utnger and Murrell. Thus, in some of Fraser 's 
experiments the paralysis was at no time sufficient to musk a tetanus ; in 
exp«rimcntg of all three observers the tetanus did not develop at once in 
parts IQ which the nerve-trunks were protected by cutting off their blood- 
supply; contrary to the observation of Fraser, in a number of experiments 
performed by Ringer and Murrell, after the aorta had becu tied tetanus de- 
vehipod no earlier in the protected than in the unprotected leg. In some of the 
experiments of Ringer and Murrell the paralyzant effect of the poi^ou passed 
off — voluntary and reflex action returning — -before the supervention of the 
telSDtis. These facts seem to show that the paralysis aa well as the tetanus 



256 SYSTEMIC REMEDIES. 

are due to an action upon the centres, the drug so acting upon the spinal 
cord as first to abolish and then intensify its reflex actiyitj. The explana- 
tion of this singular action cannot at present he considered as established. 
Drs. Hinger and Murrell believe that both the paralysis and the tetanus are 
due to a depressant action. The theory is that the normal cord has a power 
of resisting impulses received from (he periphery, and especially of preventing 
their wide propagation among the spinal centres. During the first stage of 
the atropia-poisoning it is supposed that the motor portions of the cord are so 
paralyzed as to be unable to form or propagate any motor impulse, and hence 
the general paralysis. Later on, however, the motor cells have so far re- 
covered themselves as to be able to generate impulses freely, although the 
resistive power of the cord is still in abeyance. Consequently a peripheral 
impulse plays, as it were, at will, up and down the spinal cord, and instead 
of giving rise to a simple reflex action, gives origin to a series of reflex 
movements, involving all the muscles, and constituting a tetanic convulsion. 

The experiments of Lemattre (loc. ciL) indicate that belladonna exerts 
a similar paralyzant and convulsant action in mammals, and Dr. Eraser's 
investigation confirms this. It would seem, however, that in mammals the 
convulsant action comes on more rapidly, and is less protracted, and that the 
paralyzant action is also less intense, than in the frog ; so that whilst the 
batrachian poisoned by atropia is in the beginning paralyzed and afterwards 
convulsed, the mammal suffers from convulsions and reflex spasms early in 
the poisoning, and oflen exhibits evidences all through of the excited reflex 
activity. The difference in the action of non-fatal doses of atropia upon 
the frog and upon the mammal is graphically expressed by the diagrams on 
the following page, which are copied from the paper of Dr. Fraser. 

Fig. 1 represents an experiment made upon a dog : in it the curve of 
paralysis, op, p„ leaves the line of normality, AB, before the curve of 
spinal stimulation, the first symptoms being those of paralysis. As the curve 
of op, p, never reaches the line of complete paralysis, CD, the paralytic 
action is not sufficiently great, in the height of the poison, to prevent the 
manifestation of the considerable spinal stimulant action. 

Fio. 1. 





Fig. 2 expreflsee the results of an experiment upon a frog : in it, although 



MYDRIATICS, 



ibl 



tlifire was some spinal stimuknt action, as evinced by the curve 8^, s,, ^^ a,^, 
anil ftltheiiigh the panilytic curve p^^ p^^^ p^^,, p^^, p^ neyer reachea the Hne of 
©ompbtc jmrnlyaw, CD, yet it is manifest that the paralytic action of th« 
dru{> thnnitrliout the experiment ma^iks aod covers up tho convulsive influence. 

It is very certain that id man atropia exerts this double influence ; for the 
tsorirrl^ of poisi^ning ca«is are at once the records of convulsions and of 
panily^i?^. It would Beem that early profound pariilysii occurs when a 
very large dose of the poison has been taken in its concentrated alkaloidal 
condition, and eonsefiuently Liib been iTipidly absorbed and suddenly pre- 
eipitatod upon the nervous 8ystem. 

In the ejtperinients of Botkiii, made by tying the vessels of the frog's legs, 
wm described on page 236, the investigator found that although for a time 
irriution of the f(X)t of the pcrFectly panilyzed leg would cause spasms in the 
Opposite limb whose nerve was protected, yet later in the poisonings although 
irritation of the foot of t!ie protect<Hl leg caused movements in that leg^ no 
iffhilion of the opposite poiwued foot wus able t<) induce any response what* 
mvt on either aide. From this he drew the inevitable conclusion that, whilst 
atropia [kanilytes first the motor nervca, yet later it actB al^ on the afferent 
••nrcp. The very beautiful ejcperiment^ of Dr, Fraser, already rjuoted, cer- 
tainly show that the afferent ner\-es enjoy a comparative immunity from the 
influence of atn^pia in large doses. For when one leg of a frog was pro- 
tected by tying the erund artery during the period of general paralysis, any 
irritation c»f the poisoned leg would produce immediate reflex convidsions in 
lh# unpoisoned extremity , — a demonstration that whilst the functions of the 
iiflitfeMt or motor nerves were sui^pended wherever the poison reached, the 
aflmot nerves retained more or less of their activity. This of course eon- 
irmn a portion of the experiments and conclusions of Br>tkin, and does noi 
AapfTcive that atropia acts to some extent upon the afferent nerves; for a very 
Ibcblft impulse reachiog the cord in its excited condition would cause reflex 
movements, Beiold and Bloebaum (Joe, cit., p. 20) have iuva'^ti gated this 
aubjcct by exposing the sciatic nen^es of a strychnized frog, immersing them 
lor a portion of their course, the one in a solution of atropia, the other in a 
aolution of the phosphate of sodium, and then testing the effect of the applica- 
tion of stimuli in Cjiusing reflex movements. The result was not very satis- 
&ctory, so uumy sources of fallacy arising — sources not necessary here to 
point out — as to vitiate greatly the experiments. They certainly found, 
bovereft that the nerve-trunk prescr\'ed for some time its power of trans- 
mitting impuUe even when immersed in a two-and-adialf per cent. sr4ution 
of the alkaloid. Beiold and Bluebaum (p. 201 also repeated the expcrimcotfl 
^ Botkin, Bul)8tantially c«:>nfirming them, but showing that very large doset 
am necoiSMry to affect seriously the conducting po Wei's of the afferent ner^'ea. 

The following experiments of Mcuriot {loc. cit,^ p. 1*5) prove concltisively 
thai atropia does influence the afferent ncn'ea. He found that if a frog be 
bound tightly around the body so as to interrupt the circulation, and then 

17 



258 SYSTEMIC REMEDIES. 

be poisoned by atropia in the front part of its body, at first irritations in any 
part give rise to general spasms, but after a time in order to get any move- 
ments of the hind legs it is necessary to apply an irritant to them. Ag^n, 
tho hinder parts of a frog were so bound by ligatures as to cut off on the one 
side all communication except by the nerves, and on the other to leave free 
the nerve and the vessels. A strong injection of atropia was then given, 
and when the moment came that irritation of the periphery of the leg whose 
circulation was free would no longer cause reflex spasms, the artery of this 
leg also was tied, so that both legs, the one atropinized, the other not, were 
now connected with the body of the frog only by their nerves. Strychnia 
was given hypodermically, and it was found that, whilst irritation of the 
atropinized leg had no effect, stimulation of the non-atropinized leg gave rise 
to general convulsions. The whole present evidence shows that atropia 
depresses the afferent nerves^ but much more feebly than it does the efferent 
nerves. Miss Mary Putnam (iV. Y, Med, Rec., 1873) asserts that if the 
general tissue of the frog's limb be tied, the vessels and nerves being left 
intact, so as to prevent diffusion of the poison through the cellular tissue, 
the sensitive nerves are alone affected by atropia. As no details of experi- 
ments are given, the matter rests simply upon the assertion of Miss Putnam. 
It is very difficult to imagine why a nerve should be affected differently by 
a poison when reaching it by different routes, and equally difficult to con- 
ceive how the poison should reach more effectively the motor than the sen- 
sitive nerves by diffusion. Further, it is also almost as unreasonable to 
believe that any perceptible diffusion through the cellular tissue should occur 
when the seat of injection is in a distant part of the body. Taking together 
the facts that Miss Putnam's assertion is unsupported by detailed experi- 
ments, is exceedingly improbable, and is seemingly opposed to an enormous 
mass of experimentation by some of the most experienced and able inves- 
tigators who have ever lived, it seems to me that it cannot be accepted. It 
is probable that atropia acts upon the peripheral filaments of the nerves more 
quickly than upon the main trunks ; this is corroborated by Miss Putnam, who 
states that she has seen galvanization of a sciatic nerve cause indications of 
pain in an atropinized animal when the peripheral sensation was already lost. 

There can be no doubt that in the higher animals atropia acts upon the 
cerebrum as it does in man, producing the same peculiar delirious intoxication 
often ending in stupor. It is not necessary to discuss this matter further, 
except to remark that belladonna is not a hypnotic. The fact that the 
exhibition of a remedy is followed by sleep in disease is no proof that the 
remedy is in a proper sense a hypnotic. No one would give oyster soup such 
a cognomen, yet in certain exhausted wakeful states of the system such food 
may bring back sound sleep. If belladonna ever acts as a hypnotic, it is in 
this indirect way, by removing some cause of abnormal wakefulness. It can 
never be relied on, like opium, to induce sleep. 

Action on the Voluntary Muscles. — The voluntary muscles escape un- 



MTDRUTICS. 



259 



oafAed in atrapia-poisooing. It Ia true tliat Lc^mattre has shown that the 
eontmelility of a striated muscle may be deatmycd by soaking it in a very 
concentrated solution of the ii!tc;tloi(l ; but l*mg before any auch action can 
taice place in life the animal is killed; consequently after death from bella- 
dmiiH the contractility of the voluntary muiicles is found unimpaired, 

Acitun on the Ahdomiiutl Canal. — On the non-strint<^d muscles the ai. tion 
t>f the drug is pronouncedj but its exact nature is ujicertain* Meuriot gtatea 
(/flc Cf7,, p. 112) that if the belly of au animal p^^isoned by atropia be opened, 
Vm intestines wilJ be found undei'going violent contntctlona, and that bella- 
I wjifia la a powerful excitiint of the non-striated muscles* On the other hand, 
fBvsolJgnd Blocbauni affirru that they have experimonted upon the intestine^?, 
^fludder, at4jnis, and ureters, and that in aJl eases there is a state of marked 
Mion from atropia, and that, whether a small or a large dose be used {loe» 
^^. 65), there are produced muscular cjuietiiess and relaxation in all these 
-evidences of sedation not preceded by any stage of excitement, and 
lys accompanied by lessening of the elect ro-nuisculur sensibility, They 
further, that by the use of sufficient doses absolute muscular paralysis 
tr\%e onjans alluded to is induced, so that the strongest faradaic currents 
unable to cause any motion. P. Keuchel (Dffs Atrfqnn nnd der Hern- 
tn^mmTtn^ Inaog. Piss., Dorpat, 1868) has made a most elaborate scries 
experiments to determine the effect of atropia upon the inhibitory fibres 
tite splanchnic nen^e. It has been shown by Pfliiger that galvanization 
of tte peripheral ends of the di.ided spilanchnics causes immediate arrest of 
pe peristaltic iutcstinal movements, and, although the subject has not been 
lately workini out, it is almost certain that some of the splanchnic fibres 
lie inhibitory nerves of the inte^stiual coats. Keuchel has found that 
fen when doses of atropia so small iis not to affect distinctly the motor 
"'^s are <?iven, galvanization of t!ic aplanchnics fails to inHucnec the intca- 
**^, whose vermicular movements arc still active, and therefore that atro- 
pandyzes the peripheral inhibitory intestinal apparatus precisely as it docs 
^^^ of the heart. There is, of ctiurse, a seeming disagreement between 
^*^9e researches and those of JTeuriot and of Btizold and Bloebaum ; but it 
■^ pt*«jbahle that both arc correct. It appears certain that, in full doses, atro- 
^^^ punvlyaes the smooth muscular fibres of the intcatiue, bladder, etc., and it 
^^■^y btJ tliai in any dose it depresses their activity directly, but that, by para- 
^^T^n^ mi>re f|uickly the inhibitory apparatus, it sometimes places the intes- 
t^iuul luuscular coat in such a position that it will respond more vigorously 
^ttu iiurmal to external stimuli. If this be so, it is evident that there is 
"•cfgrd in the results of all these investigatiotiSj for Keuchel used only 
'^'Uidl diises (.075 gr. in a rabbit). 
^''^»Vi.« (yn the Rijipirtiton/ St/stem. — It has already been stated that in 
arj i»iii;i[l Jijaes of atropia do not affect the respiration, whereas large doses 
'^'•"iitc iL The same is true in animals ; tind the acceleration bikes place 
'^iien the vagi have been previously divided, — a proof that it is due to 




260 SYSTEMIC REMEDIES. 

a direct stimulation of the respiratory centres in the medulla. (Bezold and 
Bloebaum, loc, cit,, p. 59.) When very large fatal doses are administered, 
there is evidently also a paraljrsis of that portion of the peripheral pneumo- 
gastric nerve which is connected with the function of respiration ; for if in 
an animal su£fering only from a moderate dose the par vagnm be cut, respi- 
ration is profoundly affected, but when the alkaloid has been more freely 
given, no marked influence is exerted upon the expiratory rhythm by section 
of the pncumogastrics. As death approaches in belladonna-poisoning, the 
blood, which has preserved its normal coloration, may become very dark, and 
the patient may at last die of asphyxia, — probably not entirely from failure 
of the centres themselves, but also, in part, from the loss of frinctional power 
in the respiratory nerves. 

Action on the Glandular System. — One of the earliest and most notable 
effects of medicinal doses of atropia is dryness of the mouth, due to sup- 
pression of the secretions of the mucous and salivary glands. The action 
of the alkaloid upon the skin is similar. It can scarcely be doubted that 
this arrest of secretion is nervous; and the experiments of Kcuchel indicate 
that it is due to an action upon the peripheral nerve-filaments. As was first 
discovered by Schiff,* section of the chorda tympani is followed by arrest 
of secretion of the submaxillary gland, and galvanization of the peripheral 
end produces a greatly increased flow of saliva. In Keuchcrs experiments 
these phenomena occurred in the unpoisoned animal, but when atropia had 
been exhibited, galvanization of the peripheral chorda tympani was power- 
less to excite secretion, — proof that the peripheral end of the nerve was 
pamlyzcd. 

Elimination. — When atropia is exhibited medicinally it probably all eft* 
capes from the body through the urine ; and even afler poisonous doses the 
amount eliminated through other channels must be almost infinitely smalL 

Action on Secretion, — After small doses of atropia the urine is increased. 
— sometimes, according to Harley, doubled. I am confident, however, that 
this increase varies very much, and is not always marked. After very large 
toxic doses the urine may be at first increased, but is usually lessened very 
early, and in the later stages may be entirely suppressed.f Meuriot states 
that the secretion of urine rises and falls in atropia-poisoning with the arte- 
rial pressure. The experiments of Harley upon men {loc. cit,^ p. 214) would 
appear to show that medicinal doses of atropia decidedly increase the solids 
of the urine, slightly the urea and uric acid, very markedly the phosphates 
and the sulphates. 

In regard to the secretions of the alimentary canal, the action of atropia is 

• See Physiology of Man— NerTOUi System, by Prof. A. Flint, Jr., New York, 1S73, 
p. 158. 

t See poison-oase reported by Dr. Gross {loc. ctf.), also cases of Dr. Morer {AnnaUt d€ 
la SoeiM dn Midtcine de Gaud^ 1873). 



MFDRIA TICS, 



mi 



ttjy im«>certain. It has been a matter of traditiorml and clinical belief that 
thcT ^^^ra incnjaaed, and Harlej gives some experiments whicb he claims 
cTimtooralc this ; Meuriot, on the other hand, stiitos that they are lessened. 
I cannot hidj however, any experimentg that Si^etn to nie at all decisive ; and 
tlinWa^ evidence certainly indicatfift that the alimentary secretions, if affected 
BiftlU «L^ hi creased. 

,\rif€m nn Trmperature. — In moderate doses atropia causes a pronounced 

fievio tt'Uijicrature, but in very large decidedly toxic amounts it lessens ani- 

IBlilheMt Thus, in the dog, Meuriot has obtained an augmentation of from 

I* io 3* C, and Dtim^ril, Demanjuay, and Leeomte* of 4^ C. In fata] 

j^jtsing; of the same animal, these obicrvcrs have noticed u fall respectively 

i»f S^° jiiid of 3".^^ In man, Meuriot, in the nm of medicinal doses, has 

oSwiTVfd the temperature to rise i** to 1^°^ and Eulenburg* }° to -j*^°*t 

HuWy has seen in man an elevation of 1° F, As |)ointed out by Meuriot, 

tlie rite and fall of temperature probably correspond to the rij*e and fiJl of 

tho blood-prcasure. 

SHmmniy, — From what hits been already stated, it is evident that the 
Mtkiu of atrupia in tlierupeutic and in toxic donees is in a sense r|uite dif- 

Id full niedieinal doses it produces a sort of febrile state, with dryness of 
ili<? mouth, increased rnpidity and foree of the circulation, f|uickened rc*tpi- 
ta**on, elevation of temperature, and st?eretion of febrile urine. The nipidity 
of 'li« hrart'a action is due to piiralysis of the periphei-al inhibitory nerve 
lod to stimalation of the accelerator nerves ; the increased arterial pressure, 
til iht! incrnaseil cardiac action, together with the general eontniction of the 
opukrics, the result of excitation of the vai*o-motor centres. The npinal 
wd ii unt sensibly affected by these doses } the motor, and probably to a 
oacn \es^ degree the sensory perijiheral nerves, suffer lessc^ning of functional 
"^^>ty, although the influence of therapeutic doses of atropia upon tlicm 
*** k Very slight. If the dose be sufficiently large, the cerebrum is thrown 
■**o » contlition of mild delirium, resembling also that of fever. 

«nef decidedly tuxic doac^t of atropia, the bhwd-pressure fiills, from dilata* 
Bon t>f the capillaries, owing to the paralysis of their muscular coats, and from 
■•'set laming of the heart- muscle. The tcmp4initure also fid Is ; the muscular 
P^UciQ ia relaxed, and sensation h imjmired, from the paresis of the motor 
' •^Oawry nerves respectively j yet convulsions may now occur fr<im the 



''^r 



"^-«etiirity of the reflex centres, the predominance of paralysis or of con- 
^Us varying with tlie dose, as the depressing or stimulating influence is 
I piwerful. Delirium precedes stupor, which in turn precedes death, 
kjxia, caused by failing trunkal nerve-functions, or very rarely from 
^^}>«, caused by failure of the cardiac mudcle. 

^ ^ ^"^ lljjurrp nrr probftbljr nil of thctn Centigrade, though it ii not itmted by Metin'oii 




262 



SrSTEMIC REMEDIES. 



Local Action. — It is evident tliat wbea Mladonna is applied I 
must act locaJly as a paral^zaot, no doubt overpowering tile capillary walla, 
tho sensitivtj and mutor nervtjs, and even muscular aud glandular cell-action j 
fur, except in the e^ise uf the latter, eacpurimental evidence has already been 
brought forward to prove that, locally and freely applied, belladonna is a 
sedative poUon, aud clinical cvideiico points very strongly to ItM exerting , 
a siuiilar iiiflaenct; upon gland-cella. A, Zellcr ( Vtrchov/i Arch,^ Ixvi.* p* 
384 ) UiLS found that a one per cent. Rolution of atrupia brought in contact 
with the blood, outside of the body^ has a decided influence in arresting the 
moveinenis of the corpuscles. 

Action on the Et/e, — Atropia pWal in the eye, or given iuterrjallVi dilates ' 
the pupil of all animals except birds. Aecompauying this mydriasis are 
paralysis of accommodation and a lessened intraocular pressure. In re^rd 
to the latter, the subject is so intricate that I must refer the reader to the 
treatises of specialists*^ 

Befure dtscusaiojr briefly the action of atropia upon the pupil, the fact that 
a recent American female writer has reasserted the old theory that the move- 
meuts of the iris are due to erectile tissue^ or, Id other words ^ to its blood- ! 
vessels, seems to render necessary a few words as to tlie real motile power of 
the part. In the flrst place, it is an indisputable anatomical fact that the 
Iris is largely composed of muscular fibres, and it is a simple common-sense 
deduction that the muscular fibres are there for the purpose of causing mo- 
tion, especially since, in many animalsj it can be readily demonstrated that 
whilst some of these fibres are circular, others are radiating, so that by por- 
tion they become antagonistic. The paper of Dr. Arlt (Archtv/ur Opft-- 
thdmohgte^ 18G9) seems to me vei-j" decisive. In a very elaborate series of 
experiments it was (Viund that when the upper cervical giuiglion was stimulated 
the pupil dilated long before any iuftueucc upon the vessels was detected, 
and that on cessation of the stimulation the pupil became natural lonjz before 
the spasm of the vessels yielded ; to my mind a proof that the ganglion has 
fibres other than vnso-motor, — fibres which control the muscular actions of the , 
iris J aud are more sensitive than the vaso-motor filaments ; aud^ seoondiirilj, a 
proof that the movements of the ixis are not due to movements of the blood- 
vessels, 8paee cjmnot be aiforded in the present work for a further discus 
sion of this subject. The reader is respectfully referred for further iiiformar 
tion to books on the physiology of the eye, and especially to Engelhardt*8 
paper, Bekriige zur Leitre vcm ilea Bewegungen der Iris {l/ntersuchuugtn 
aim dem phi/stolog, LaboraCorium in WUrzl/urg, zweiter Theil.) 

In considering the action of belladonna upon the eye, it is necessary to 
view separately its influence when applied locally and when given internally; 
and I shall consider these in the order in which they here stand. 



• See cBpeiJLalty Drr intraocutare Druck uftd die InnervatiQHt- VtrkUUnuu dvr Sruu V< 
Pjof. Dn Stdiwftg vuD Cadoa. H'jea, ISGS. 




Ml'DIilATWS, 



263 



It Buiy be fiist asserted tbat the diladition induced by the ]o<?al applieatioQ 
uf Ldladonna or of lis principles is a nervous phenoiiicnoD, and not due to a 
dim^ct iu!tiou of the drug upon the rauscular fibres of the iris ; for as all of 
thisH;, both the radiating and ih*i circular, are oF the mmc nature (fwrn- 
Birrated in niatntuals)} their antagonism is simply due to pcisition ; and it 
^^etufi inconceivable that mere position should affect the relations between a 
ittut^le and a drug. Moreover, deciMive proof is afford*^ by the cxpcriinente 
of Bernstein and Doi^iel, who fourjd that whilst galvanic irritation of the 
octilo-motor nerve was unable to eiiuso contraction of the pupil in the atm- 
ptnixcd eye, yet when the electrodes were applied to the eyes in such a way 
as to affect directly the iris, contraction occurred, — plienomena only cjtplain- 
able by the theory that the nerve-endings were paralyzed, whilst the muscle 
wn^ uiuiffcfted. Of the truth of thb observation there can be no <loubt, as 
;t has Iweri confirmed by Dr. G* Engelhardt {llntersuch. aus dcm pht/molo^, 
Lafjorat, in Wurzburg^ Theil ii. p. 321), 

Hie statement first made by Wharton Jones {Medical Times and (hizettfy 
1857)j that the reason atropin does not dilate tlic pupils of birds is tliat their 
irtdes have no radiating fibres, has been diwproven by the beautiful anatomical 
Tcaearches of Alex. Ivanoff and Alex, RoUett (Art^hiv fiir Opht halm f dope ^ 
ToL XV* p. l)j confirmed by Johannes Diegel (^Mnx Schnltzes ArcJiiv fur 
MieroiCfjp, Anat., Bd, vi. Hea i., 1870). Although Prof Bonders {The 
Accommodation and Rf/ntctiou af (hf. Eiff^ S)d. Soo. ed., p. 584) siiy^ that 
ibe pupillary action of atropia '* Ia slight in birds, in whom it was formerly 
Of erlooked^" in my own experiments the mogt thorough application of very 
strong solations to the eyes of pigeons him had no distinct effect* In pre- 
vioaa editions of this bouk I ventured the surmise that the lack of action 
of atropia upon the irides of birds might be due to the muscle being of the 
etriatod type. According to the experiments of Szpilman and Luchsingcr, 
this supposition iscorrtH't, In the cesophaguis of the bird the muiicle is non- 
Mriftted^and atropia paralyzes it ; in the oe^uphagus of the rabbit the nmacle 
IS Btnatcd, and atropia has no action ; in the cat a portion of the uestvpiiagus 
baa aniooth muscular fibres, a part striated, and the former is paralyzwl^ the 
hitter onaffected, by the alkaloid (Arch./, d. Ges. Phi/sioi., xxvi. 4VA\}, 

The dilatation of the pupil by the local application of atropia* is certainly 
independent of any nerve-centres farther back than the ciliary ganglion* 
This is proven by the following facts : Claude Bernard (Phi/siolo^k e( Patlm- 
logie. du St/sttfne Nervevx^ Paris, voL ii. p. 212) and Loniuttre (lac, at,) both 
haTti found that atropia-mytlriasis occurs in animals after sectiotj of the oculo- 
motor, and I have seen it in cases of complete oculo-motor paralysis in man> 
It also takes place after se<;tion of the trigeminus or of the cervical sympa- 
thetic, or of both of these nerves, as is shown by the testimony of uumertius 



9 OootmMion of tbe pupil before dttatation DOiiced in dogi (Reei«) and rabt>it» (Rott- 
«0i| FrfiliHdi), ji probcibl^ cuii««tl rcfloxljr bj ifHtaat nctiao of the atropia. 



mam 



264 SYSTEMIC REMEDIES. 

observers and by my own experiments. In man, I have seen it afler paral- 
ysis of the sympathetic (^Philadelphia Med. Times, vol. i. p. 290). Not only 
is the dilatation of the pupil by the local application of atropia independent 
of the central nervous system, but also of the ciliary ganglion, and it is there- 
fore due to an action exerted directly upon the nerve-endings in the iris. 
The experiments of Bernstein and DogicI, confirmed by Engelhardt, already 
quoted, arc in themselves almost enough to establish the truth of this propo- 
sition. More direct evidence is not, huwever, wanting. Thus, Viciordt* has 
found that atropia locally applied still causes mydriasis afler the removal of 
the ciliary ganglion. Prof. I. HOppe (Die Nerventmrknngen der Heiimittel, 
licipsic, 185G, zweiter Hefl, p. 179) has discovered, and Y. Valentin ( Ver- 
such einer 'physiohgischen Pathohgie der Nerven, Leipsio, 1864, zweite Ab- 
theilung, p. 368) has confirmed, that in the eye of the frog removed from 
the body atropia will produce dilatation of the pupil. According to Borelli 
(Edinburgh Medical Journal^ Nov. 1871), mydriasis is produced by the 
alkaloid when applied to the eye of a man just dead. Lastly, the presence 
of the alkaloid in the humors of the atropinized eye has been proven by 
numerous observers, among whom may be mentioned Lemattre (loc, cit., 
p. 55) and Prof. Donders ( Tlie Accommodation and Refraction of the Eye, 
Syd. Soc. ed., p. 588), who have found that the liquids removed from such 
an eye are capable of causing dilatation of the pupil of another eye. 

It having been demonstrated that the mydriasis of the atropinized eye is 
the result of an action upon the peripheral nerve-fibres, the question arises. 
Are the ends of the oculo-motor, the contractor of the pupil, paralyzed, or are 
the ends of the sympathetic, the dilator, stimulated, or is there a double influ- 
ence, both of these actions occurring ? Both Donders (loc, cit.y p. 589)t and 
Stellwag von Carion (loc. cit.^ p. 92) insist that the paralysis of accommodation 
is proof of paralysis of the oculo-motor nerve, and it seems to me they do so 
with truth. However this may be, there is abundant direct proof that the 
oculo-motor fibres are paralyzed, since the experiment of GrUnhagen, show- 
ing that galvanization of the exposed oculo-motor nerve does not affect the 
atropinized pupil, confirmed by Engelhardt (loc. cit., p. 321), and by Boss- 
bach and Frohlich (Phamiak. l/ntersuchungen, Wiirzburg, i., p. 6). 

In artificial mydriasis there is, then, undoubtedly peripheral palsy of the 
oculo-motor. The question arises. Is there also stimulation of the dilating 
nerve ? The evidence as to this is not so positive, but to my mind indicates 
very strongly that there is such an action. Clinical experience certainly 
shows that the dilatation produced by a mydriatic is not merely a passive 
movement of relaxation, but is active, capable of tearing up inflammatory 
adhesions even when of some firmness. Again, the dilatation that occurs 

* Un fortunately y the only notice I have seen of this capital experiment is in Hermann's 
" Orundrif der PhifiiolugU." No reference is given, and I have been unable to find the 
original paper. 

f Seo also Von Graefe, Deutuchev KUnikf 1861. 



MVDmATICS. 



205 



ftiUr tlie ptmljsb of the ocidcKiuotor Dcrve in man and afW its destruction 
b ttt ttimis is Dot at all equal to that produced by atropia, and^ indeed^ can be 
largely increatit'd by the uction of the dru<r ; further, iu the eye sopanited 
cfttirely froiu the nerve-centres (see iil>i>ve) litropin jitill eiiuisois a wide dilatu* 
tioa; fads which neceasitiUe the beUef either that the alkaloid act^ upon the 
inrmfiotlietic fibrillae, or thut the peripheral fibres of a nerve are in them* 
a^lres nerve-centres, acting upon the umsele of themselves even when fecpu- 
vated tbai their centres- 

II lijus been urged against the view here taken that even the widest arti- 
fidai iii)driasis is increased by galvanization of the sympathetic. De Ruiter 
«l*tcs the eontrary; but, since Grunhagen, Ilirsehmunn, and Engelhardt 
•eparattfly affinn us the result of personal experiment the correctness of the 
MBerted fact^ it must be accepted. Gnmtint: its truth, I do not think it war- 
^*nta tfie deduction, since it is very conceivable that an agent may excite the 
petipli^raJ filaments of a nerve very greatly, and yet not to that point that 
thej are hutipable of further excitation, 

la djuduAion, the action of atropia applied to the eye may be summed 

'^I* w follows ; the mydriasis is the result of a direct influence upon the 

P*Ftphcnil nerve-fibres, those of t!ie oculo-motor being certainly paralyzed, 

'noa* of the syrnpathetic and its ally the trigeminus being probably excited. 

^^ '^e^rd to the constitutional action of atropia, it is evident that when 

"**^ afltiilyicl is admini«t<ired internally there are only four possible ways in 

hicU it ean cause mydriasis, and thiit these are as follows: L By acting 

j^Jofie On the sympathetic centres, as a stimulant. 2. By acting alone on the 

f^o-iHutor centres, as a paralyzant. 3, By conibining these actions. 4. 

y bciijg earned to the eye, and acting as tliough locally applied. 

"^Utijurs are greatly at variance in their conclusions : thus, Harley ( The 

^ ^ *t^ctubie Neurotics) and Hay den (Ditblm Quarterly Journaf, August, 

^*^) may be cited as in favor of the first view, and Badge ( UthfT die Be- 

^**nff (ler Iruiy 1855), Braun (^Archrv /iir Ophthalmolo^e^ Bd. v. Abth. 

*)» a^(i Hiraohmann (^Zur Lthre wm tL durck Arztmmiffdf etc., Rrichert's 

^^^tAtf^ 1863) as favoring the st^cund. Neither the first nor the second 

±W ig^ however, tenable : the first, because of a fact which has been assert^ed 

* 'Authorities and which I have experimentally corroborated» namely, that 

*^pi» given hypodormically causes dilatation of the pupil after section both 

^tc trigeminus and of the sympathetic in the neck ; the second, fur the 

>ii that after section of the oeulit-motur in animals, or after complete 

^**^ysig of tlie oculu-mot<>r in man, the mydriasis is much less than that of 

-^^•^^pin-pcnso ni ii g. 

^t^ repird to the third view, I have noticed that the dilatation of tJie pupil 
[itrifier the constitutional action of the alkaloid after aectii»u of the cervicrol 
I "3 tojiuthetic is still greater than that which is normally produced by oculo- 
pliiocor paridysis. At my solicitation, Ur. T. G. Morton, of this city, out 
k» the optic nerve in a rabbit and divided all the structures about iL 



2G6 SYSTEMIC REMEDIES. 

The pupil contracted very much at the time ; the cornea waa not sensitive, 
hut recovered its sensitiveness in part after some days. Atropia given hypo- 
dermically dilated the eye very markedly, hut not nearly to the extent of 
the other eye. If in this experiment all the ciliary nerves were really cut, 
the proof is conclusive that the mydriasis is not of centric origin ; the reason 
that the pupil did not dilate so freely as the other being the strong contract- 
ing influence it was under, and the great reduction in the amount of blood. 
I.e., the amount of atropia, entering the eye, owing to the division of the 
blood-vessels. 

An experiment of Lemattre, if it be accurate, is also conclusive in proving 
that the action of the mydriatics upon the pupil, even when administered 
internally, is a peripheral one. He succeeded in producing mydriasis in 
normal eyes by placing in them aqueous humors taken from dogs poisoned 
with atropia, and even from a foetus whose dam had been killed by the 
alkaloid. Donders, however (Joe. cit, p. 589), failed to get the dilatation ; 
and two or three experiments have yielded me the same negative result It 
requires no elaborate argument to prove that in this case a negative result 
does not overpower a previous positive one : still, the experiments of Le- 
mattre need confirmation. In the Pennsylvania Hospital, under the care of 
Dr. Morton, not long since I saw a man who had been wounded by a rail- 
road accident in such a way that the whole of the temporal bone anterior to 
the petrous portion was thrust into the side of the head ; there was complete 
paralysis of the facial, of the trigeminus, and of the oculo-motor, as could 
be readily demonstrated upon the man, who lived some months, finally dying 
suddenly of abscess of the brain. The carotid canal was so pressed upon 
that the sympathetic, which passed upwards through it to the eye, must have 
also been paralyzed. The eye was, as proven by the autopsy, separated from 
all connection with the nerve-centres, and yet when atropia was given hypo- 
dermically the pupil dilated. The proof seemed complete that the mydriasis 
was owing to a peripheral action. 

Our knowledge of the action of atropia upon the pupil may be summed 
up as follows: Atropia applied locally causes mydriasis by paralyzing the 
peripheral ends of the oculo-motor nerve, and probably by stimulating the 
peripheral ends of the sympathetic. Atropia given internally almost cer- 
tainly causes mydriasis, not by influencing the nerve-centres, but by being 
carried in the blood to the eye itself, and there acting precisely as when 
applied locally. 

Therapeutics. — The results of clinical experience are in strict accord 
with what is known of the physiological action of belladonna. The chief 
indication for its use is to relax spasm. In the case of voluntary muscles its 
powers are comparatively feeble, except when it is thrown directly into the 
muscle affected. In this manner Dr. S. Weir Mitchell {Injuries of Nerves^ 
Philadelphia, 1872, p. 258) has obtained very marked relief in the fearful 
spasms following nerve-wounds, and Dr. J. M. Da Costa in rheumatic spasm 



MrDRlA TJCS. 



2tJT 



4Cj [\mm§Ufm nia Hotpital ReporU^ 1868). Tlie beocfit dcrivcMl in ihi^i way 
» vvidvotlj due to the depressing effoct of the drug upoD the terminal nerve- 
^krafot^ with which it comes in direct conmut, and to a certain extent aJsa 
miu the muscle iu>clf. When given by the mouthy so small an amount of ih^ 
^meciy reaches the diseased part as scarcely to afiect it, and very little or no 
rtJief fnUtiws. As hiw been previcniiily aht»wn, tbt; mm-i^trlated luuHctcs are 
lunre nffectcd thtm the striuted by belladonna, and eUnieiilly the drag b found 
to he even more efficacious in ^pamn of the luvolnntari/ than of the voluntary 
miij*t*Jes: in auch cases it is oflen of value used mtt^rnally. It must be thus 
ailminiittcrcd to lead colic ^ — iu simple spasmodic colic, — in itpajtmodic dt/s- 
mtnorrfuma^ — in ipaHnwdic coimtrtction of the l/owcin with obstinate con- 
itipatioii^ — io lar^ngismu* gtiidulus, — in ner&ms congh, — iu asthma, — in 
kiixoH^h^ — in whoopifig-cftughy — in which, aa originally advised by Breton* 
oefto, it luis be«m largely used, and is one of the best known remedies ; also, 
rrcn tti the spasms accompanying passage ot rtnal and htliajy calculi, where 
of course it often fails. Wherever it is possible, however, it should be used 
locally in spaam of the involuntary a^ well ua of the voluntary muscles. 
Thtia, in Mpairm of the urvikra, the ointment should be rubbed in dung the 
canal; iu rigid on uteri, the extract should be applied directly to the oe ; in 
aUhma^ belladonna should be inhahid, either by means of the ei^^rette or 
of the atomiiuition of a decoction of the leiives ; in spasm of the sphincter 
atai fnymjUture or other cause, it should be applied directly to the part by 
poultice or ointment. 

It is, no doubt, by relaxing spasm, or ratlicr by lessening irritability, that 

belladonna acts in that fi>rm of inmntinence of urine which is seen generally 

ia children. It has been taught that this affection is due to a relaxation of 

the Bphiucter, but undoubtedly in the great majority of cases itn real cauie 

is an irriuibility of the bladder it^elf^ so that spaijmixlic contraction occttra 

tmder the stimulus of a small portion of urine. A common result of the 

ingestion of a large dose of belladonna is a paralytic retention of urinci duo 

110 doubt to tlie local action of the atropia in the urine upon the bladder. It 

is needles to point out more in detail how the indications in ineoutinenco 

lire met. In these cases the drug mn.st be given in as large doses as the 

iiyalein wUl bear, and the impression should be maintained for weeks. 

l7ftiiaUy the dose has to be steadily inereaj^ed. Under the pre^^eut indication 

also probably belongs the use of the remedy in cou^h'ptttiofi. In doses of 

«iue-<|uarter to one-half grain of the extract, added to a laxative pill, belladonna 

is of great ftervice, and sometimes used alone will cure chronic constipation. 

It appears to be of most value iu subjects of rigid tone ; in feeble, relaxed 

people^ strychnia is preferable. 

To relieve Fain. — Physiologically viewed, atropia should bo of little value 
for this purfKtse ; and I think elinicid evidence bears thiij out. Dr. ^litehetl 
btt had probably the best o|>jK>rtuuitfes ever afforded for testing this, and he 
tays decidedly tliat it is of little use in severe suffering. My own experience 



208 SYSTEMIC REMEDIES. 

is to the same effect. There is, however, considerable evidence of its value 
in neuralgia^ but it is chiefly as to its efficiency when bjected immediately 
in the neighborhood of a painful nerve, or applied as inunction over its 
course when superficial. In large quantity, belladonna certainly affects the 
afferent nerves, and, used as above, may readily relieve pain. It is veiy 
probable also that at times it cures neuralgia by modifying the circulation in 
the affected part. Though these things be so, yet belladonna is almost im- 
measurably below opium as an analgesic. In some forms of neural^ with 
spasm it is of service by a double action. 

To impress the Heart and Blood- Vessels, — Under the idea of its contract- 
ing the blood-vessels, belladonna has been highly conmiended by Dr. Harley 
(he. cit,) in jyneumonia, acute nephritis, and various other acute diseases. I 
have had no experience with it in these affections, but the published accounts 
do not seem to me to indicate that it is of equal value with other remedies 
or combinations of remedies. In chronic albuminous nephritis I have tried 
it, as reconmiended by Dr. Harley (^c. cit.), but have failed to derive any 
advantage from it. In ordinary sore throcU, it does good by acting upon 
the blood-vessels, and by relaxing the pharyngeal muscles. It may possibly 
be of use given before the adminbtration of chloroform, to prevent cardiac 
inhibitory arrest. (See Brit. Med., 1880, ii. 620.) 

As a stimulant to the circulation, belladonna has probably not been em- 
ployed as much as it ought. Dr. Graves, however, commends it especially 
when the pupil is contracted in typhus fever, and it has been used with 
asserted advantage in erysipelas, scarlet fever, etc I think this use of 
belladonna offers a very inviting field for therapeutic investigation. 

To arrest Secretion. — Arresting secretion of the salivary glands by para- 
lyzing the extreme branches of the chorda tympani has already been shown 
to be a physiological action of belladonna, and it follows from this that the 
drug should be useful in ptyalism. 1 have tried it in several cases of fn«r- 
curial salivation, and found that it arrests almost at once the discharge of 
saliva, and seemingly facilitates greatly the return to health. In colliquative 
sweats it was originally recommended by Prof. Da Costa (Phila. Med. 7\meh, 
Feb. 15, 1871), and I have found it of very great service. A full dose of 
belladonna extract, or one-sixtieth to one-eightieth of a grain of atropia used 
hypodcrmically, at bedtime, will very frequently prevent the usual niyht- 
sweat. In colliquative diarrhcea it has been recommended by M. Delpagb, 
and very probably will be found of service. 

Employment in Poisoning. — It is stated that as far back as 1570 it was 
asbertcd that opium and belladonna are, in their influence upon the system, 
antagonistic. In the early part of the present century their employment as 
coun:er- poisons was again brought prominently before the profession ; but, 
although a few scattered earlier records of their use as such exist in medical 
literature, it was not until the paper of Dr. Wm. F. Norris appeared {Amer- 
ican Journal of the Medical Sciences, Oct 1862) that general attention wa» 



MYDRIATICS. 



2Gd 



Attmotod to the Bubjeot Since this publication, very nianj cases of the nm 

ci the one mediciue in poisoning by the other Lave been published. The 

eppcmte acdoDfl of belladonna and of opium up<ju iho pupib no doubt first 

soggoetcd tho klea of their untiigonisni; but in the li^ht uf recent atperi- 

moDts tbeee appai^otly i*f)p<iBite effects upon the eye cannot be constden;d &» 

prtiniig «ny antagonism between tlie drugs, aince it ta almost certjitn that the 

dOittation ta due to a peripheric and the contraction to a centric influcuoo. 

In au investigation by Dr. J. Hughes Bennett (^nV. MtfJ. JoMn*,» 1874» 547). 

iwentjKine rabbits received what previouis exyieriuientation hud sht»wn to be 

a fatal dose of meoonate of morphia (10 graing), and afren^ards ^ulphiitc of 

atropifl ; aix reoo?ered ; and of these six, four souie weeks iif>erwarda were ki)lud 

by a di ISO of 10 grains ttf ihe morphia suH. Eleven rubhits received a do^e 

of iuiphato of atropia (Ij to 2 grains), and afterwards 10 grains of the 

mooonate uf nior(jhia ; aovcn recovered, and some weeks aftem^ards the 

mooouatc of morphia (10 grains) lieing given, four of them succumbed to 

it Again* two dinis received the fatal dose of meconate of morphia (2t 

gndus/, and affcrwiLrds sulphate of atropia, and recovered, only to die some 

days afWrwards fmm the effects of a second two-and*ii-quartcr grain dt>8e 

nf the opium Sidt, Theje experiments certainly warrant the conclusion of 

Dr. Bennett that atropia is physiologically antagonistic to morphia within a 

limited area^ and that it exerts in dogs and rabbits a 1 eneficial influence in 

optuiii'poi£N.ining. Dr* Corona has experimentally reached €oncliision» very 

aimihir to those of IJenoelt {Lontlon Afffi. AVcon/, 1877, p. 341 ). What I 

affinncHl tn the first editiun of this work, namely, that our present knowledge 

of tlic physiulogieal action of tlie two drugs renders anything like complete 

latagouiFm very improbable, is stil] as true as it is obvious. 

T^Hien the subject in hand is looked at from its clinical aspect, the con- 

clo&ton of Dr, Bennett is confirmed. To tabulate and dif^cusa the reported 

tustag of opium- or belladonna-fHjisoning in which the oounter-nareotie baa 

been uped would require very many pages, and I tlierefore can only state my 

opiDiiai that theiMJ records es5tabli»h the thenqieutic value of atropia in o|miui- 

]ioiscinitig; but this does not indicate, much less prove, complete antagonism 

between the two drugs. No one would qu*?Htion the value of alcohol in eer- 

tain iftagess or eonditrous of opiiim-poisciuing, and yet no one would claim that 

opium and alcohol are in any sense antagonistic. In opilum-poisoiiinL', death 

oocum chiefly through fiiilure of the respiration* Atropia is the only known 

drug which exerts a decidtnily stimulating effect upon the respiratory eentrea. 

It is evident that in advanced stages of opium-pioisoning this proprty roo* 

dor« atropia an invaluable remedy. In protracted opium -narcosie the eardiao 

and vasi>-raotor actions of atropia are of service ; but it should never be for* 

gotten tlmt tho main inftuenee for good is upon the respiratory centres,'*' The 



• In lltt! 6i|t«riaie»ti of Uetibcwli and Anorbiich it wax found tbut Atropm |)rut|»c«d very 
doelilfttl vfTeLtU iijK^D the cii>:iitrv(ioii ami rt)q>'ir»Uua cur^'os uf ilug« |Kji«uacil wUt} o)duiJ)« 



hi 



270 SYSTEMIC REMEDIES. 

first improvement from atropia in these cases is nsoally increased frequency 
of respiration ; and as the breathing becomes less embarrassed the other 
symptoms ameliorate, largely because of the increased aeration of the blood. 

The double nature of profound opium-narcosis must not he lost sight of: 
the blood is saturated with carbonic acid almost to the dead-line, and mucb 
of the unconsciousness, much of the failing circulation, much even of the 
embarrassed respiration, is due to the presence of the gas. As soon as the 
system is in a measure relieved of this load, it begins to rebound ; emetics 
act, consciousness returns to some extent, the circulation frees itself, and the 
road leading towards health is entered upon. It is a matter of the gravest 
practical importance to decide when, how, and in what quantities the mydri 
atic should be employed. The exhibition of belladonna should, I think, 
commence so soon as there is decided failure of the respiration. The stomach 
is so paralyzed in the narcosis that it -is uncertain how fast absorption will 
take place in the viscus ; and the drug should always be given hypodermic- 
ally, in the form of the alkaloid if possible. The first injection of atropia 
should be of such size that it could not possibly do harm, and one-fortieth 
of a grain is in most instances a fair commencing dose. Very generally 
several repetitions of this are necessary, and the delicate practical point is to 
decide how often these repetitions shall be indulged in. 

I think that very frequently too much atropia is given, and believe that 
often a great deal of firmness is required in these cases not to use it too 
freely, especially since reliance is generally placed upon the pupils as a guide. 
They arc, however, a very unsafe guide, as is apparent when it is remembered 
that whilst opium contracts them by influencing the nerve-centres, atropia 
probably dilates them by acting on the peripheral nerves. It must not be 
forgotten that in doses of sufficient magnitude atropia paralyzes the nerve- 
trunks, and may thus increase the danger. A cardinal principle should, 
therefore, be to give no more of the mydriatic than is absolutely necessary. 
One-fortieth or one-sixtieth of a grain may be injected every fifteen, twenty, 
or thirty minutes, as the urgency of the symptoms may demand. The 
judgment should be formed from a bird's-eye view of the whole case, fresh 
atropia not being given so long as the respiration and other symptoms are 
undergoing araeliomtion, but the dose being renewed so soon as any tendency 
to a relapse is manifested. Thus, if under the influence of atropia in a case 
the respirations had risen from four to eight per minute, I would not use the 
counter-poison agdin until there was manifested a tendency for the respira- 
tions to grow less frequent, or unless for a long period there had been no 
improvement. 

Atropia is useful in other poisonings than that of opium. It has been 
especially commended as an antidote to poisonou$ fungi.* 

• Consult The Doctor, 1874; Brit. Med. Journ,, ii. 1874; Arch, Phyefol. Xormale, 1877, 
p. 831. 



MYDRIA TICS. 



271 



Am a Local Srdafive, — Locally and freely applied, belladonna is a acdative ; 

and, I believe, to gkndular as well as to luuseukir and nen'ous tissues. Id 

this Wiijf it is ofti»n very useful in various local inflaranjatioim. In the farm 

of a pla^r it frequently appears to do good in palpitaiiom of tlie heart. It« 

use locally in spasms and neunilgia has heeu eufficicntly dwelt on. In mia- 

tttu, or when it is desired to dry up the secretion of milk, its loi^td upplica- 

boD to the breast is often very effiottcious. Whenever belladonnti is used 

wKsally, ia order to get its good effects it must be employed freely. At the 

*Miie timCt it should bo remeuihered that a number of cases of poisoning by 

Its ejttcn)nl use have been reported (ilfedicai Timet and Gazette^ Nov. 1856 ; 

*^lso I/ondon Fkamiaceutical Journal^ 1871). In children it must be used 

With very great caution ; in adults, with a reasonable amount of care, its ex- 

^nial use is safe, provided directloas be given to have it washed off so soon as 

•**J affection of the eight or dryness of the throat is induced. 

Having myself no practical knowledge of diseases of the eye, Br. Wm. F, 
-^orrisj Clinicid Professor of Piscascs of the Eye in the University of Pcnn* 
^Ivania, at my recjuest, has prepared the following section : 

The Um of Atropia in Bisraneft nf tlw E^e, — ^Piire atropia, from its slight 

*>mDility in water, is only applieable where we desire a moderate effect; the 

^fiipliate^ however, can be disscdved in water in any desired proportion, and, 

taerefore, is generally employed. When a fuur-gniin solution of this salt is 

Wpped into the conjunctival sac of a healthy and emmetropic eye, we find 

that iti iih<jut fifteen minutes tlie pupil commences to dilate, and that this 

Jilatutiun rapidly increases, till in from twenty-five to thirty-five minutes it 

ha* uttaiued its majLimum. The power of accommodation, and consequent 

Uility to read fine print, does not show any marked decrease till twenty-five 

liiiut^'shave elapsed, when the near point commences rapidly to recede from 

the eye, antil in an hour and a half to an hour and forty minutes the power 

*5i a^-^coumiodation is completely annulled, and only objects over twenty feet 

uistsmt from the eye, or those pre.senting practically parallel rays, can b^ 

Ifaiifitinctly seen. On the second day after the application the power of acoom- 

^HiodutioD begins to return, and increases rapidly up to the sixth day, but is 

^piBiially [lot fully regained till from ten to fourteen days ; the pnpil remains 

With but little change till the third day, when it rapidly contracts, hut has not 

KXmy regained its normal state till eleven or twelve days have cliipsed.* The 
l»jcirimic action of the drug b far more marked from a moderately strong 
pi^oa applied to tlie conjunctiva than from its internal use, even when it 
** l>©cn pushed to the production of symptoms of poisoning. Thus applied, 
'*trtjj on the intraocular nerves and ganglia ; and it hiis been proved by 
-oAs juid Bonders that when the afjueous humor of riu animal is drawn off 



■Mbii 



^ftu^fi 



"or lituore dctaikvi difcasfioD of tbU subject, eee Dni\drr§*» Anomatitt o/ R€/r9€Hom 
-^ *T<:timinodatittHf p. 584, New Sydeabiun Society, 1884. 




272 SYSTEMIC REMEDIES, 

and collected after its application, it contains a sufficient amount of the drug to 
cause dilatation of the eye of another animal when applied to it. These experi- 
ments have been abundantly confirmed by later observers, and the rapidity 
of its action appears to depend on the thickness of the cornea and the age 
of the subject selected for the experiment. It will be apparent from the 
foregoing statements that the use of a strong solution of atropia is not to be 
undertaken without due consideration, inasmuch as it is likely to debar the 
patient from any satisfactory use of the eyes for a period of from five to ten 
days. It is, however, invaluable, from its annihilation of the accommodation, 
where we wish to determine with accuracy the reiraction of the eye, and is 
daily used for this purpose in cases of hypermetropia where the patients find it 
im])08sible to relax their accommodation, in astigmatism where it is necessary 
to determine the exact difference between the two principal meridians of the 
cornea, and in the rare cases of myopia associated with spasm of the ciliary 
muscle. To obtain this complete paralysis of the accommodation, a few 
drops of a four-grain solution should be dropped in the eye, and this repeated 
after an interval of five minutes. Tlie patient will be ready for examination 
one and a half hours subsequently. In the vast majority of crises it is entirely 
unnecessary to dilate the pupil to obtain a satisfactory view of the ftindus 
with the ophthalmoscope ; but where this becomes necessary we can often use 
with advantage a solution of one-twentieth grain in an ounce of water ; a 
drop or two of this will dilate the pupil, without, however, rendering it abso- 
lutely immovable, and with scarcely any interference with the accommodation ; 
on the next day the pupil is much smaller, and on the third day no trace of 
its action remains. In cases of suspected cataract the pupil should always be 
dilated ; otherwise we may readily fail to discover the lesion, which frequently 
first manifests itself in a few faint strisB shooting out from the periphery of 
the lens. Moreover, it affords us a valuable prognostic point as to the 
probable success of any operation where the cataract is ripe ; for where the 
iris fails to dilate ad maximum, we may be sure that it is more prone to take 
on inflammatory action, and more liable to be pressed on by any cortical matter 
which may remain behind in the eye. Daily experience shows that after the 
evacuation of the aqueous humor in the operation for cataract, the iris will 
contract in spite of any previous use of atropia ; but as soon as by the closing 
of the wound the humor reaccumulates and the anterior chamber is re-estab- 
lished, the atropia resumes its sway. It is most useful in all inflammations 
of the cornea. In phlyctenular keratitis, by its local anscsthetic action on the 
branches of the trigeminus, it diminishes the photophobia and blepharospasm, 
and seems to mitigate the intensity of the inflammation by its influence in 
contracting the ciliary vessels, thus diminishing the supply of nutritive ma- 
terial carried to the cornea. Where an ulcer has perforated the central region 
of the cornea, and a prolapse of the iris has ensued, the energetic use of 
atropia often enables the radiating fibres of the iris to detach it from the 
cornea as soon as the opening has been plugged by lymph, and the anterior 



MFDRIATtCS. 



273 



¥ 



¥ 



fbfT restored^ tiius preventing tlie formation of anterior synechiso. Mao- 
keuxic long ago called attention to the '* liealing and anodyne** efftxit of 
atfojiui in aloers of the cornea occurririi; in the ophthalmia of new-born 
childrun. — n fact since universally recoi^iiizcd, and which holds good c^iually in 
tbe ulwrs resulting from other forms of purulent conjunctivitia. It is held by 
many writers that part at least of this beneficial action ia to be ascribed to ita 
dinjinatioti of intraocular tension.* In cases of iritis a Btrong suluti«L)n ot 
•tropia should at the outset he applied repeatedly nt short intervals until we 
h»ve obtained a fiill dilatation of the pupil, and substequently sufficiently 
"ft« to maintain the iris in this condition. We thns place the uifiamed 
U»ue at re»t, diminish its blood-^ipply, and prevent the formation of poste- 
nor STnechiac, which constitute so frcqncnt a caiise of the recurrence of thia 
dis*»a»c by their meehanically-irritating effect: putting a strain on the irin in 
itscTery motion, hindering that variation in the diameter of the pujal which 
^(irmallT takes place with every change of convergence and with every varia- 
*^on of the intensity of light. Bloreover, extensive synechire where the iris 
*s pbatered down to the anterior capsule by lar^je patches of lymph tend to 
produce cataract, by interfering with the nutrition of t!ie lens. Where the 
*y»?chiie are narrow and tongue-fihaped, they may often be torn through by 
*^ >etion, even afV^r the lapste of years. 

•^Iropia acts more powerfully in iritis after the abstraction of blood^f and 
"*^ioiially, where there is much exudation, falls to produce iU effect till 
^*^ the constitutional effect of mercury has been obtained. In smne indi- 
rjuiiabi the instillation of a strong solution of atropia, by its rapid passage 
iflrtiug^i file tear-passages into the nOvSe and throat, produces symptnms of 
"'pit bclbdonna-poiwning, — viz., flushed face, rapid pulse, dryness of the 
""^t, slight dysphagia ; but this may usually be diminiMhed or prevented 

pw^ling the tlmmt with water, by compressing the canaliculi, or by cvert- 
'S the lower punctum lachrynianim. In some individuals it produces a 
^^otisly- Irritant action on the conjunctiva, known as atropine conjunctivitis; 

*s sometimes rjuit-e severe, calling furth dmost ei-yslpelatous symptoms, 



^%iftl fttroptct dimltiifibei intrttocular prcMuro haelnoeTi asserted bj Gmefe, Cocpiai.Bnd 

^^y jf^orid authorUicv ; und & r(»feronce to any mAniinl of diwii?«59 of the eye will fhow 

'*' >t. Ik ||,q accepted doctrine iprith moat clinkal ofaBervcrfl of the prciunt day. Oiber 

^^fat.^ tiitbnriiiea, each ils Dondent aud Slellwuf^p doubt it? ability to produco nny such 

Cfrt»fnly it fail? to reduce intraoculor prcFBure in ciww of glaucomii* Numeroui 

'!*•• to decide the question by physiofogical experinieut bare been rnadc by Henscn 

*»lpki'rf» We^er» Adamiuk, Grunbft^i?n» Dor, <?to. Th<* reitilta vary, however, eon- 

ff^^ljlj, ainonsr thcmielTCf. Tbof»e with the manomrtcr nrc opm to tbe oltjpction that 

*'U t fij)g „p(j^ tbe eyeball for its introduction quite changes the conditions of intra- 

I^PfMnfu nnd eircfilation, and that rery alight inovemeut of the loftrument or eye* 

"•'"ahdMes the rctulta ; while thono with the tenometer arc nlflo unnati? factory, 

'^^ a« w« have yet failed to obtain any reliable Instrtiment for measuring intm- 

•**'kni»le, #>rW*i#e» nf the Eyr, p. 63T, London, 1S54. Graefe, Arekie fUr Ophtkai- 



■ * v«L li. port 2, p* 20V (nutc)* 



1^ 



274 SYSTEMIC REMEDIES. 

at other times bringing out a crop of granuladons. This is owing to idiosyn- 
crasy, and will then happen with perfectly neutral solutions. It should in 
such cases be discontinued, and the conjunctivitis which it has called forth 
combated by weak solutions of alum and sulphate of zinc or other mild 
astringent. We find, too, in some cases of iritis, especially those occurring 
in rheumatic patients with posterior synechias due to repeated previous at- 
tacks, that we not only fail to dilate the pupil, but that atropia acts as an 
irritant to the eye. We are then obliged to give up its use, and resort to the 
application of dry warmth and appropriate constitutional remedies. Atropia 
will occasionally, in cases of chronic glaucoma, precipitate an acute attack, 
and is, therefore, to be used with due consideration in this disease.'*' 

A great deal has been written about the value of belladonna as a prophy- 
lactic in scarlatina^ and authorities differ very much. For a discussion of 
the subject I must refer the reader to the treatises of Dr. Geo. B. Wood, of 
Dr. Stills, of Dr. Waring, etc. I have never had a decisive opportunity of 
testing the matter, but have no faith in the efficacy of the remedy. It ought 
to be tried further, however. The plan practiced has been to dissolve two 
grains of the extract in a fiuidounce of water, and give two drops daily to a 
child a year old, adding one drop for every year in older children up to twelve 
years. 

Toxicology. — Sufficient has already been said about the general symp- 
toms of belladonna-poisoning. Those which are characteristic are the dry- 
ness of the throat, the increased frequency of breathing, the dilated pupils, 
the red efflorescence on the skin, the rapid pulse, the active talkative delirium, 
sometimes convulsions, all ending in abolition of function, as shown by stu- 
por, rapid feeble pulse, cold extremities, and paralysis. If the urine of a 
patient suffering from belladonna-poisoning be dropped into the eye of the 
cat or rabbit, it will dilate the pupil ; and the diagnostician may avail him- 
self of this test in any doubtful case. Dr. Morel (^Annates de la SocUU de 
Medecuie de Gand, 1873) calls attention to a sort of laryngitis produced 
by poisonous doses of belladonna, and characterized by pain in the larynx, 
roughness of voice, and the expectoration of minute, pearly, tough pellets. 
It was present in the advanced stages of two cases of poisoning under his care. 

The minimum fatal doses of the preparations of belladonna are scarcely 
known. An enema representing eighty grains of the root has produced death 
in five hours (^Casper's Woclienschri/t, Feb. 1845) ; but, on the other hand, 
recovery has occurred after the ingestion of three drachms of the extract 
(Taylor's Principles and Practice of MedicalJurispmdence, London, 1873, 
p. 432). A tenth, or even a twentieth, of a grain of atropia will often pro- 
duce alarming symptoms ; yet Dr. Chambers reports {Lancet^ 1864) recovery 

• Oruefc, Archie J'Ur Ophthntmufuyie, vol. xiv. 2, 117. H. Dcrbjr, Traits. Amer, Opktkul 
Soc., p .^5, 1868. Wells, Vitem^canf the Kife, p. 517 (2d Amer. oil.). 



MYDRTATICS, 



275 



in A cKUd four years old who had taken about two teaspoon fuls of a solution 
eomtsiiiiing a grain of the alkidoid in half nn ounce. 

Ailer death from belladurinay no charuvtenHtic Ifisiofis are to be fc>UTid, 

In the treatment of bolladunna-p{>isoriing, the first indication k to prevent 
the abeorptloD of anj more of the poison. For this pnrpo&e emetics oh the 
slomaeh-pttmp should be used. Tlie same difficuhies are to be met and the 
fluno measures adopted as in upiiiut-nLUx-u.>^i.s ; itnd, aM> in «>piiiin'pui8cmin;L; it '\^ 
well to exhibit tannic ucid freely, bee^iuse it forms with the alkaloids sfdts 
vhich are soluble witli difficulty^ so should vegetable astringents be *;iven 
when mn orerdose of belladonna has been ingested. After the stomaeh biia 
bocti eracuatedf symptoms must be met as tliey ari^e. During the iii'^t leb- 
rilc stage I would not hesitate to use cold bathings; and the raodentte use 
of tartar emetic, or other sedative, is perhaps justifiable. The value of opium 
in belladonna-poisoning has not, T think, been detenuined, and its use should 
only be tentative, although gixid is to be expected frt^m its judicious employ- 
ment. In poisoning by a mj^driatic, in order to keep up the respiration and 
the cirnilatloti during the stage of failure of ftineti<m the same meastirea 
rfinuld be employed as in opium-poi.soniiig. External stiumlation by heat 
and by mustanl, flsigellations, etc., artilieial respimti<>n, and especially the use 
of the ttlternute cold and but douche, should nil be pnictioed as necassary, 
Phjaostigma and jaborandi appear to be somewhat antagonistic to atropia 
within certain limits, and jaboraodi hns been used io atropia-poisoninj; 
{Lti/ieetj 1876j i-, p, 34*]), As this subject ctin best be elucidated after 
the discuasioD of the action of the respective drugs, the reader is referred for 
fiiriher ioformatioo to the articles upon Calabar bean and jabonitidi; After 
to(xie doses of belladonna, there is vury generally complete retention of urine j 
•fid as this secretion cootaitts the greater part of the ingested poison, and 
■i reabsorption in the bladder is at lesist conceivable^ the catheter should be 
vaed early. 

Admiki ST RATION. — Belladonna is never used internally in subatanoe. All 
the preparations of the U. S. lliarmacopeoia except two (designated below) 
are made from the leaves. They are the tincture ( Ttnctura Beiiadonnx — 1 
to $-66, U.S.), dose, ten to thirty drops; the alcoholic extract {^Extractum 
BeUadonnm AlcohoUcum, U.S.), dose, one-eighth to onehalf a grain; the 
flmd eaciracl of the root {Extractum Belladonnm Flmdum^ U.8.), dose, 
one to two minims; and i\\e plaster ( Emplaittrum Belliulonnm)^ which rcp- 
r(*cntj« in Htrength its weight of helkdonna root. The aU/ract (Altstractitm 
Btlhulonnm^ U. S,) represents twice itJ! weight of root, dose, one grain. The 
ftilphftte of atropine {Atropiiux Sulphuf. U.S.) ^ most commonly used, on 
account of its aolubility in water. One-sixtieth of a grain of atrupia or lU 
ialt^ given hypodermicidly, will generally produce s^light dryness of the throat 
or other indications of its constitutional action. Where rapidity of action 
U required, this is the best method of admruiiitcring belladonna. 

HjftirQhromate of Homatropine, — Homatropine ts an alkaloid artificially 



276 SYSTEMIC REMEDIES. 

produced from atropia, the bydrobromate of which is preferred for practical 
use OD accouDt of its being stable and not hygroscopic. It is said to pro- 
duce, when taken internally, symptoms similar to those caused by atropia, 
except that it slows the pulse, — an qhservation which needs confirmation. 
Dr. Wm. Macintosh ( Unpublished Inaug. Diss,^ University of Pennsylvania, 
1883) has found that, like atropia, it causes in the frog first paralysis with 
abolition of reflex action, followed, if the dose has not been too large, by 
tetanus : in the first period the conducting power of the motor nerves was 
much depressed : tying an artery was found to prevent the development of 
paralysis in the protected leg : the pneumogastrics were peripherally paralyzed. 
If a solution of the alkaloid (gr. iv-f 5i) be put in the eye, the pupil usually 
begins to dilate in fifteen minutes, and the efiect passes off in as many hours. 
As a paralyzer of accommodation the salt is too feeble for advantageous use ; 
but when it is desired merely to examine the fundus oculi, the fugaciousnesd 
of its action makes it a valuable mydriatic. 

STEAMONII FOLIA-STEAMONIUM LEAVES. U.S. 
STEAMONII SEMEN-STEAMONITJM SEED. U.S. 

The leaves and seeds respectively of the Datura Stramonium, or James- 
town Weed, a coarse, bushy, annual herb, three or four feet high, growing in 
waste places both in this country and in Great Britain, and readily distin- 
guished by its large, funnel-shaped, whitish, fetid flowers, and its quadrivalve 
spinescent capsules. The leaves are large, smooth, ovate, irregularly sinuate, 
with large acute teeth. The seeds are small, brownish-black, reniform, with 
a feebly-bitterish narcotic taste. The active principle v^ an alkaloid dis- 
covered by Geiger and Hesse, and named Daturine, but which, according 
to Ladenburg, is a mixture of atropine and hyoscyamine. 

Physiological Action. — The physiological evidence as to the identity 
of daturia and atropia is in strict accord with the chemical proof. The 
symptoms of poisoning by stramonium differ in no respect from those of 
belladonna-poisoning, although Laurent {^De V Hyosa/amine et de la Daturine, 
Th^se, Paris, p. 22, 1870) asserts that irregularity of the heart's action is 
more marked under the influence of stramonium. The same accelerated 
pulse, the same elevation of temperature, the same wild delirium, the same 
increased frequency of respiration, the same widely-dilated pupils, the sauic 
red efflorescence on the skin, the same restlessness or convulsions, occur in 
both cases, and, when the dose has been sufficiently large, end alike in abo- 
lition of the functions of circulation, respiration, and innervation : stupor, 
general paralysis, weak, rapid, thready pulse, threatened asphyxia, consti- 
tuting the phenomena of the closing scene in poisoning from either narcotic 

The most careful minute investigation of the physiological action of daturia 
which I have met with is that of Charles Laurent, already quoted. In his 
experiments that observer found that under the microscope the capillaries 
of the frog's web could be seen to contract after the application of daturia, 



MYDRIATICS. 



277 



eireD vihcn tlic ncires of the limb had been previously severed, and after the 
h^*|MKlermte iujectron of the alkaloid ; that the pulse-rate and arterial tension 
wer« kith augmetJtetJ by smalt dost^i uf thti poisun, but tluit by large doscfl 
tlie art«ria] tension Wiuj diminished, although the pulse was still increased in 
lriM]ucncy ; that when the heart was completely separated froiu all connection 
with the wnrnd nerroua ByiStem, daturia reduced the uuniber of its beats ; 
timt resptmtiun is aoeelerated by the alkaloid, even after section of the 
poemnogastriL-s ; that by moderate doses of the alkaloid the conducting 
|iower neither of the sensory nor of the motor nerves i^ destroyed; that the 
muscQlar eontraetility is not affected ; that small doses increase, large ones 
diiniDtsh, iutesUual peristalsis. Klaborate discussion of these facts seems 
otiDoocssary. It is seemingly demonstrated, from both a chemical and a 
phrsiulogical point of view, that daturia and cUropia are identiaiL 

Th ErtAPEUTlcs. — Stramonium may be used to meet precisely the same 
indications as belladonna. It has boon especially employed in spaHmodio 
asfhma^ chiefly in the form of cigarettes made by rolling up the dried leaves. 
These are often very efficient when there is no organic disease ; but theb 
use t«<iuire8 some caution, as very alarming symptoms, if not fatal results, 
luiTC been produced by them. In the form of cataplasms, stramonium leaves 
mee often applied with advantage to painful local inJiammaUonSj inJiaTned 
JUmorrhoidgj etc. 

Adwikistration. — The officinal preparations of stnimonium are all made 
fri>tu the 6e*!ds. They are the rxtract (^Exfntrfum Stfitmonii\ U.S.), dose, 
ooe-fottrth lo one-half a grain ; the tinchtm {Ttnvtum Stramonii — 1 to 10, 
U. S.)t dose, ten to twenty minims; and ihejfuid rxfntct (Exlractum Stt'ti- 
moini Flmdum^ U. S.), dnsi', one to two minims. 

ToXICOLOOr. — Accidental poisoning, espocially of children, by t-tnuiio- 
oiutn, Ln very common* In nil points, a.n regard.^ both symptoms and treat- 
suetit, strnmonium- and belladonna-poisoning are alike. 

HY080YAMI FOLIA-HYOSOYAMUS LEAVES. U.S. 
HjCMcyaiuus niger is a ooarse herbaeeous biennial, indigenous in England, 
ADd naturalized in the Northern United Stales. The leaves, which aloUA 
mfe officinal, are large, oblong-ovnte, deeply sinuared, and very hairy. In 
18!2l Poscbier aououneed the existence of an alkaloid in hyoscyamus, but 
il was not until 1833 that Geiger and H«'sse succeeded in obtiiining it pure. 
Aocordtng to Geiger^ when slowly crystallized, lltjtutcytunia occurs in trans- 
pttfont needles, and io star-.Hhaped or bushy ciusters of crystals* According 
ta the recent ret*earclics of Ladenburir» li}Oi!^cyamuH contains two alkaloids : 
onm is crystaUizabk% b:is the ^^ame ehemieul formula as atropine, !tad cun- 
sttioles the cri/»t<illn*e ht/oxe^ttmiHC of commerce, and its sulphate is the 
Jiiff4M:^ammst Stdphan of the U.S. Pharmacopoeia; the other is umorphous, 
COdMiitutcs the amorphous htfoicy amine of commerce, and^ although having 



^^^ 



278 SrSTEMIC REMEDIES, 

the same chemical formula as h joscjamine, is diverse from it ; to it Laden- 
burg gives the name of hyoscine. 

Physiological Action. — Hjoscjamia has a very similar, if not iden- 
tical, action with atropia. Schroff'*' asserts that it is decidedly more powerful 
than atropia, so far at least as concerns its local action on the pupiL On 
the other hand, Lemattre (^Archives GiniraleSj 1865) has found atropia 
much the more active of the two. It is, however, scarcely doubtful that the 
latter observer had an impure hyo&cyamia, and it seems to me that it cannot 
be at present considered as determined that there is any marked difference in 
the mydriatic activity of the two drugs. Both Schroff and Dullenberg have 
noticed in man, as the result of the ingestion of hyoscyamus, dryness of the 
throat and mouth, brief sinking of the pulse-rate, followed by increased fre- 
quency, mydriasis, giddiness, muscular weakness, and insecurity of gait. The 
experiments of Schroff, of Laurent, and especially of Harley ( The Old Vege- 
table Neurotics), indicate that hyoscyamus is much more of a hypnotic than 
is belladonna. Yet Barley's recorded observations would seem to show that, 
in some individuals, hyoscyamus induces insomnia. According to Harley, 
the primary sinking of the pulse is much more marked afler hyoscyamus 
than after its sister-narcotic. Laurent (i>e Vlfyoscyamine et dela DaturiM, 
p. 15) affirms that the delirium caused by hyoscyamus is calm, whilst that 
by atropia is furious ; but on page 19 of his book is recorded a case of hen- 
bane-poisoning in which the delirium was " furious." Schroff ( Wochenhlatt 
der Zeitscknfl der GeselUch. der Aerzte zu Wien, 1865) asserted that pneu- 
monia is a constant and even characteristic lesion of hyoscyamus-poisonmg 
in the rabbit ; but Lemattre (loc, cit.) has never seen more than little scat- 
tered points of hyperasmia ; and in Laurent's experience even these have 
always been absent. 

In the elaborate research of Laurent it was found that the capillaries of 
the frog's web contracted afler the local application of hyoscyamia, even 
when the nerves had been previously severed, and also afler the hypodermic 
use of the poison ; that small doses augmented both the pulse-rate and the 
arterial tension, whilst large doses increased the former and diminished the 
latter ; that the direct application of the alkaloid to the heart produced a 
rapid diminution of the number of its beats ; that moderate doses increased 
the rapidity of respiration even aflor section of the pneumogastrics ; that upon 
the nervous system, the muscles, and the intestines, the action of hyoscyamia 
was the same as that of daturia. The more important of these conclusions 
were also experimentally arrived at by Heilman (^Beitrdge zur Kenntniss der 
j)hysiol. Wirkungen des Hyoscgamins, etc., Jena, 1873). Dr. R. Gnauck 
i'ound ( Verhandl. d, Phydolog, Geselhch. zu Berlin , Aug. 1881) thjit hyos- 
cyamine agrees with atropia in its action upon the vagus and heart-muscle, 
but is less powerful and persistent in its influence, and also acts as a powel^ 

* Quoted by HusemaDo, Die PJlatutrntatoffe, p. i74» 



MYDRIATICS, 



279 



All Bopori6c : It farther appeared espcciallj to dilate tlie intemd abdouuoal 
▼rwnffli 

Tbe dboovcty of Ladeixbur^ shows that phjaiological studies should be 

^kiadc wttli the isolated alkaluidM, Dr. J. (.. Shaw (Jonrn, JVen?, and Ment 

^1^^, ¥11 p. 27) has recently partially studied cryst^ilHzed and presumably 

^^Bve hjo^cjaiuia^ and fouud that it affects tlic system of voluotary uioveiijeDt 

mnd the circulation, iiieluding the heart, and the vaso-motor gyisteiu exactly 

ma alropia does. In a single experiment the respiration did not seem to he 

aflecled fu$ by atropia; but this is cotitnt dieted by results arrived at by pre- 

Kious experimenters, and needs confirmadon. Upon man DnShaw belie veSj 
9 do many alicnistja^ that byo&cyamia acts as a soporific. He alsij atMei that 
ii is lew powerful m a mydriatic than atropia, and diminishes the rei^piratory 
rale. It must be remembered that these studies have been made upon 

Klanatics; before the conciusions can be accepted as establinhcd, much more 
eUborate experimental rescarclies are oecefisary, aUo studies upon normal 
individuals, and especially contracting studies made with atropia and byos* 
cyamta uf^oo mauiaes ; by the use of alternate doses upon the same indi* 
fidual any diflference of action of the two drugs could readily be detected. 
It should also be remembered that in bis studies upon normal men Dr 
[Riehtcr noted no tendency to sleep (Neuroloffische Centralb., r. U'J4). Ac- 
cording to Dn U* Gnauck (^CeniralO. Med, Wiasem.^ 1S81, p* 801 }j hyoncitte 
is ten times as active as hyoscyamine, has a very powerful iufluence in pro- 
I ducing sleep, and reduces the pulse-rate ; mydriasis is sometime^^ hut not 
ftlways, produced. If these observations are correct, byoseine must act very 
.differently from atropine, and it becomes a question for study how fur effeotn 
hitherto obuined from hyoseyamine have been due to coherent hyosetne, 
hydriodate of hyoscine is cryslallizable, and may be selected for use. 
ftuck gives the maximum doge of hyoseyamine as 0.02 grm. ; of byoseiiid 
as 0.002 grm. Like atropia^ hyoscyamia is eliminated by the urine. 

TuERAPKUTics. — Hyoscyamus may be used to fulfil any of the indica- 
tions for which belladonna is employed. Clinical experience appears in a 
measure to bear out the assertions of various authorities as to the superiority 
of byoi^cyamui* as a hypnotic. It has been much employed by alienists in 
various forms of delirious insanity ( Weit Ridh^ Lim, As^l, Med, litporU^ 
Y, ; Lotuhn PrcLciitwuer^ xvil p. 17 ; xx. p. 85; Lancet^ 1871*, ii. ; ^f^ 
ehive* o/ Med,f 1880). Many of them claim that hyoscyamia has a very 
especial calmative cfieet. The diagnosis and treatment of the poisoning are 
identical with those of belladonna. 

The preparations are tlie alcoholic extract {EjUracturn Ilt/oseyamt Alco^ 

holictwi^ U. S.,— dried leaves ), doso^ one to three grains^ and the tiuctnrt 

{Titictura H^oicyami — dried leaves 1 to C,G$, U.S.), do«e, half a fluid- 

I dmchm to two fluidrachms. Commercial hi/oicyamia was formerly very im- 

[ptirer and a i^rain has been given with impunity; but one^fortieCh of a gr»io 

' the pure alkaloid has produced violent poisoning ILancei^ 1879| i. 474)* 



CLASS TnX-AN^STHETIOS. 



The term Ansuthetics is here employed as the name of a group of volatilt 
substances, whose vapor has the power of producing loss of consciousness, 
preceded by or accompanied with loss of sensibility and diminished muscular 
action. The medicinal properties of these substances are largely due to their 
volatility, by virtue of which they are very rapidly absorbed and almost as 
rapidly eliminated by the mucous membrane of the lungs. As a consequence 
of this, their action is very easily controlled. That they are taken into the 
blood, and thereby reach all portions of the system, has been abundantly 
proven by recent investigations.* 

The action of the anadsthetics certainly is upon the nerve-centres. Thus, 
Bernard has shown (loc, cit.) that a ligature so placed as to cut off all circula- 
tion from the posterior part of the frog does not prevent the production of 
abolition of sensation, voluntary motion, and reflex action in the hind legs 
when an anaesthetic is injected into the anterior part of the body. 

Many of the theories which have been suggested to explain the production 
of anoBsthesia are so groundless that it seems unnecessary to discuss them 
here. All that are worthy of consideration may, I think, be arranged in 
four groups, as follows : 1st, those which assert that the symptoms are pro- 
duced by a partial arrest of oxidation ; 2d, those which look upon anaes- 
thesia as due to precedent physical changes in the blood ; 3d, those which 
assert that anaesthesia, like sleep, is due to cerebral anaemia; 4th, those 
which teach that the various agents employed act directly upon the various 
organs and tissues concerned, — including in this group the recently-pro- 
pounded theory of Bernard that anaesthesia is produced by a semi-coagulation 
of the nervous protoplasm.f 

As the theories of the last group are the most natural, the burden of 
proof rests upon the supporters of the other theories. All the proofs of the 
first two groups as yet brought forward amount to no more than as follows: 
that in asphyxia the symptoms are similar to those of anaesthesia ; that in 
profound anaesthesia there is an evident lessening of oxidation ; and that 
some anaesthetics probably produce changes in the blood. 

The objections to regarding these facts as proving the truth of the theories 
alluded to are very grave. Thus, it is very well ascertained that the symp- 

• See etpeoiallj 0. Sohmiedeberg, Inaugnral Di§9ertntton, Dorpat, 1867, Arckiv it ffeil- 
hHHde, riiLp 1867; Claude Bernard, La^ont fur leu Anetth^mitfHeM^ Parif. 1875. 
f For itadvof tiM ooa^lation theory, tee GeMtralblatt Med, Witt,, 1877, p. 6U9. 




ANJESTHETICS, 



281 



tmA of aspliyxiii are only anflJogous to those of anaestheaia, not identical^* 

iftd indeed that miicsthesitt as caiiiitid by different agents offers Jiffereot phe- 

ttonieim ; ftk)^ tliere is no proof whutever that the lessened oxidation and the 

i»lu* Kl-ehungcs which iire believed to oeour when ana^Hthetica are employed are 

cuttses of the nervous symptoms, and not simply coincident phenomena. It 

must hi iijaisted on, therefore, that these theories have never been proven. 

Aloreover, positive proof of their ineorrectneaa is not wanting. Thus, m 

'■^^^^rd to ihe theory of arrest of oxidation, there are substances, such as 

tiitj-it^j of aniyl, which lessen oxidation very remarkably (Richardson, Medi- 

*^«/ Tma and Gazette^ p. 180, 18ti8), but are not anaosthetics ; and an ex- 

^^as cf oxygen in the air does not lessen the rapidity with which unsBi^thesia 

ia in<Juced.| The Ansesthetica Commiltee of the British M4.'d, Association 

^^i[3tM,T. Anat. and Phtfs., xiii. 224) also found that during cldondorin nar- 

^*>sis there was an actual increiise in the elimination of carbonic acid. lu 

^egaxd to the bloodthcories, Ludimar Hermann {Rewhert's Archiv /Ur 

^-tix^jimk, 1866, p. 27) calls attention to the fact that the aoieisthetics 

-prtxiuce the same general symptoms in the infusoria, which have no red 

^luod. 118 in mammals; luid LewissonJ has shown that they influence the 

• •o-ealled **fla]t frogs,*' which wntain Uttle or no blood, prec^iscly as they do 

^hi^ liomial frog, from which the conclusion is inevitable that they do not 

*wect the frog by altering the nature of the blood or by inducing asphyxia, 

^ '■'^giird to cerebral anaemia, it appears to be estiiblished that it occurs la 

»; and recently Claude Bernard (/(*c. cit,^ p. 122j has shown thiit during 

*^ peri<Dd of excitement preceding anaosthesia there is cerebral congestion, 

during the angesthesia ccrebml anaemia. Cessation of function normally 

ills in amemia of the organ, and the anaemia of sleep and ami^sthegia is, 

^ probability, an effect, not a amse, of suspended eerobratiun. In the 

^^o^ it has been abundantly proven that abstjlute auiemia of the uerve-oentrea 

^'^^^^ Hot suspend their functions, and that on the bloodless cerebrum chloro- 

^nu exerts its m*ual influence. The only theury at all eompiiiible with our 

P*^^»ent knowledge is that aniesthesia is in most cases due to a difL-ct action, 

fp<^ii the cortex cerebri and other nerve-centres, of the agent inducing it. 

Tile action uf the anoesthetic upon the nerve-structure is probably a purely 
>*2il one, But by nu means all authorities acknowledge this* Many^ if 
^t nil, of the anaesthetics have the power of dissolving the red corpuscle^t : 
*** LuiJimar Hermann {HeichrrVB Archit) fUr Anafomie, 18l»il) has pointed 
*^ la (Kiessiblc connection between this and anaesthesia. He states thai 
*e^M^fj,i^ which constitutes Uie stroniaof the red blood-disks, is an importani 
inst^Uutnt of the nerve-centres. As death would necessarily occur betine 
^^ l>rotagon could be dissolved out of the nerve-centres, — ^c, licfore it could 
« <i*Jiolved out of the red corpuscles, — it is evident that no extetisive de- 
®«*ttotion of the hitter bodies can occur from the action of an anajsthetic and 



Pthc 



®^» Rcpfirt of Cblorofurm Committ««, Mtdieo-Ckirur^, 7^aii#,, toI* xltiiL p, 329. 
^ ^^ifL, |». 335. X S©e Ckii^rut for further detail*. 




282 SYSTEMIC REMEDIES. 

the patient survive. Bile-acids also dissolve protagon, and Hermann states 
that some experiments he has made seem to indicate that they have anaes- 
thetic properties. Before, however, the ingenious theory of Hermann can 
be considered proven, further investigations must be made. The recent 
coagulation theory of Bernard rests almost solely upon the asserted but 
doubtful fact that ansosthetics applied in sufficient concentration coagulate 
albuminous substances, and appears to me such a pure assumption that 
its discussion at length is beyond the plan of the present work. 

In 1848 {Archives Gin6rales^ 2e s^r., t. xvi., 1848), Dum^^ril and Demar- 
quay showed that during anaesthesia there is a reduction of temperature. 
This has been confirmed by Bouisson ( Traiti tfUoriqiie et pratique de hi 
Mithode an^sthistque, Paris, 1850) and by Sulzynski {Ueber die des Alho- 
hoh, Cldoroforrtis und Aetliers Einjluss auf den thierischen Organismiut^ 
Inaug. Dissertation, Dorpat, 1865) ; and Scheinson (Archiv des Hei/kundeSy 
1869) has demonstrated that there is no increase in the giving out of heat 
by the body during anaesthesia, and consequently that the anaesthetics lessen 
the production of animal heat, no doubt, like alcohol, by checking tissue- 
metamorphosis. 

The action of anaesthetics may be modified by the injection of narcotics. 
Morphia given hypodermically about half an hour before the exhibition of 
the anaesthetic is said to have a deoided effect in prolonging the anaesthesia. 
Chloral administered shortly before etherization certainly causes the first stages 
of the latter to be much quieter than usual, and also prolongs the narcosb.* 

The chief purposes for which anaesthetics are used are to relieve pain and 
to relax spasm. To meet the first indication they are employed by surgeons 
especially ; but they are also exceedingly valuable in cases of suffering from 
disease. It must be borne in mind that their action is very transitory, and 
is accompanied by more or less disturbance of the general system, and that 
consequently they are to be employed only when the pain is exceedingly severe 
and transient. To relieve pain, anaesthetics are used with great propriety 
during child-birth. In natural labor it is not commonly necessary to produce 
complete anaesthesia. When the full effect of either ether or chloroform is 
induced, there is almost always a weakening, and very often an abolition, of 
the uterine contractions. The anaesthetic should be administered in such 
quantities as to relieve the pain without decidedly interfering with the mus- 
cular spasm. In some cases this can be done, in others it is impracticable. 
I have obtained very advantageous results in some cases by suspending the 
pains for about half an hour by means of ether, and then entirely withdraw- 
ing the anaesthetic. By this treatment the weak, painful, ineffectual efforts 
of a worn-out, nervous patient may often be converted into regular, success- 

* Mr. Bonwill has proposed rapid breathing a^ a means of produoing slight ansosthesia 
in casrs of minor surgery. The putiont is required to breathe very rapidly for from three 
to fiv^c minutes, when a condition of partial loss of consoiousnoss, probably dependent upon 
disturbance of the cerebral circulation, is induced. (See Philn. Med. Timet, vi., p. 2C5.) 



ANjESTilhTiCS, 



283 



ftal patna. I think that Uie risk of poMt-partum herntirrhugt is materially 
UM^reued Uy iituBsthetics, and therefore hsvhitiially give jifl^r their u^e twa 
dmeltmsuf the fluid extract of or^ot, sis mm\ ui* the perinouiu \i& well diatondcd 
bj tlie chilli s head, Arncstiielii's are fretjuciitly used in HurL':ery fur the pur- 
pOM of rchixing spasm, a» in cases of tlulocatton^ /ler/iiVi, etc. Ixk modieiiie, 
llicj Iwvc* been employed in various forms of convuMuiu^ aud arts especially 
YidujiLile in severe hytttertcal convuhknit^ in puerperal ecUtmpttia^ and in apinal 
ec^rti/tfiV/f(tf ; in epiltpistf^ they are very rarely called for; in in/audk convul' 
wion*y they may be sparingly Ui^ed when die C4Jtivul»ioii iti^lt Threatens life* 
In Taiiuii^ Mpasnut of excretory duds or canah^ and esp<?eially during the 
pttflttge of cttictili, they act very favorably, both by relieving jtain and by pro- 
<Hlciog relaxation. In anthma^ and in gpasmodic ulricture of tlie a-^ophngus, 
ma m all other cases of oft-repcated s|)ti£ni, they should be ad ministered only 
to meet tempomry indications, as their habitual use is deleterious. 



iriTBOGEN MONOXIBE-NITEOUS OXIDE. (NO-N,0.) 

Nitrous ajiide is a colorless, almost id odorous gas, of a sweetish taste* It 
im a very active supporter of combustion. Water absorbs nearly its own bulk 
of it. It id made by the distillation of the nitrate of ammonium, which 
reaolvee itself into the gas and water. Thus, NO^NH^ = N,0 + 20^0. The 
wcM>d>cut on the opposite page represents the best apparatus,* and the rulea 
Appended thereto embody all the necessary inHtnictioDs for the production 
of the gas- As they are very coricis<e, they should be followed to the letter. 

The various effects of increasing heat upon nitrate of ammonia are : At 226*^ 
F. it fiises perfectly ; at 302^ F. it emits white fumes, condensiag in drops j 
at 347° F. it effervesces slij^htly ; at 350^ F, it bolls without decomposition ; 
at 437® F, it effervesces rapidly ; at 460*^ F, it Le^ns to evolve gas ; at 
482^ F. it evolves gas in abundance ; above 500*^ F- nitric oxide is g^ivcn off. 

To determine the tein|>erature^ thermometers have been prepared which 
maj be pasi^ed throup;h the cork and itito the retort, marking tlie following 
degrees: 22G°, 35G% 4G0°, 482^, DOO^* F. 

To obtain the largest amount of gas, the nitrate should first be melted in 
the retort at a temperature just sufficient (226'^ to 2*50*^ F.). When melu^, 
ibe heat may be at once carried up to the point of decomposition, 460^ F. 
If a gmdually-iDcreasing heat is used aflcr the Bait is melted, a portion of it 
wiM sublime unchanged until the teuiperature reaches 460^ F. The heat 
abould never be alli»wed lo rise above 482*^ F., tor beyond that noxious 
products are generated. After the gns has begun to come over briskly, the 
appearance of copious white fumes in the retort is an indication that the 
hemi IS too great. The nearer the heat can be kept at the point ueccBsiu*y 
to generate nitrous oxide, the purer will be the gas. — Dr. Jas, W. Wliite, 
Dtutal Materia Medica, Philadelphia, 18C8, 



28i 



SYSTEMIC REMEDIES. 



AH&r the gtis haa oommenced to come over freely, it is generally 
leaseu tire RDiount of lieiit applioil to the sand-bath. The ^aa should 
allowed to stand over wat^r for a few huui-s before using. It inipro^ 
rather than deteriorates by age, and m a pi"oj>crly-constnicted gaaometer m 
be kept for many weeks, especially if the water between the holder and ■ 
ceiver of the gasometer be coveretl with a thin film of oil, so as to prove 
its yielding to the air the gas which it absorbs, until saturated. In man 
facturing the gns, whenever the alkalinity of the potash solution in thej 
No. 2 h lessened, all the washing-jars should be emptied and refilled. 




AK.XSTUE1ICS. 






plJhfio Uj« bolder in a levtl pofilion. imd fiJI it with water to within an inob or two 
oC t^l»^s^w edge of the La.jn>r riiu. Open all the spigots, &9{tcoifttlj thf one io the top of 
%\k^ T"«e«iirer, imd gently eink it into the wuter; then cloao tbo spij^ot \n t\x<^ top of rho 
f.^^^^i'^-er And thst on the upper etjgo of the holder, and arnuit^o tbu weights thi%t ure at^ 
f ^fc^ l-m^g^ toihe rftoeiver. Nexi put pure water into the jar«, — No. 1 iwo-thimlfl full; No*. 2 
art*^ 3 witbiD one utd a biilf inchos of the top. Into jar No. 2 pnt a stick of eauteio | 

^rru|« the }*r» in line, ftiid connect them by tabing as fhown in the cot. The tabe I 
f^roia tji« r^ort mast connect with the hm<j pipe of jar No. 1, and io OQ* Alwayi be sure J 
^Kmt thd Inng pipe of cncb jar b next tho retort. When properly Hfrangcd* a curront of f 
^Xt l»lvwn tuio Ihe tnbo intended to connect with the retort will cause the water to bubblo 
Ia jan No9, 2 and o, and, the spigot to v^hii'h No. 3 i^ attuehcd being open, the receiver 
^rlU begin to riiie, ■ 

Put iflto the retort tbo quantity of ammonia intended to be oscd (1 pound will make I 
•i>otit AO g&U<»ni of giw). Connect the long pipe of the first jur to tbo retort by rubber 
tabing, no tbiit the condensed steam may run into it. Now apply the beat tjtailmtUi^, and 
««*a*rA the process, being careful not to ovr^rheot the ammonia, whiob will be known by its ^ 
^ioJent boiling, instead of the gcntio bul>bling which indicates the proper temperature. 
^«> not inaikegas faster than 30 galloiis per hour. 

^o husmt tbould be thnt off before the ammonia is qaite all dcoompofed, in order to 
armd lirr^itjng ehe retort; and when the gnj has ceased to eome oreri the rotort should j 
*** **»*eounocted from the tabing, and the reoeiring spigot olosed. 

" will 1,^ understood that the first Jar is merely to receive the drip j the use of the water« 
ciiQpljr to keep the jar cool. Some reeommiind placing thiA jar into a bucket of cold 
*at«r* 

^'*^ ibhftling-tiibe ts attaebed to the spigot at the top of the holder. 

Tb© ritgift«f indioatea the number of gallons of gas In tbo bolder, ai well as the quantity 
Uihml^^ 

*ni«a itator in jars Nos. 1 and 3 should be changed ercry timu the gas is made; that in 
tlwiat noo9 a month, when frei»b caustic potash jthouM bci added. The watur in the 



Md*r 



will keep sweet a year or longer if gae i^ made fre4|ueutly. 



1 

I 

1 



**nTsiOLOaiCAL Action. — Although nitroua oxide hag been used eDor- 
^*^Uslj as an anaBsthctic, and many fiapors liavo l>een written upon it, yet 

*^ kiiowlediKJ uf its phvsiolojHcal action is dun to three or four ubs*.'ri^ors. 

Qc?!! pure nitrous oxide *p}}^ is inhaled fVir from half a minute to three 

^''iutes^ insensibility i» prnduced, preceded in many eases hy decided ovi- 

**<^acea of excitement. Some persons under itii influence will sink quietly 

*^y into unconsciousness, but others will become bilarious, erotic, or pug- 
^<iioi3a, and be restrained only by force. During the stage of anEestheaia _ 

^^ patient presents the appeiirances of asphyxia, I 

-tt is probable tbat the par-alysii* of function invades the dififercnt portiona 
^' t.lii; oervons system in tbc same order as docs that cjiuscd by ether; but 
^^ Have no positive knowledge upon the subject. A single experiment of ■ 
^^»*- ^iiinry (New Vark Medical Jouruftl^ Aug. 1870) indicates that upon 
^Oe conducting power of the motor nerves nitrons oxide exerts very little or 
^^ influence. No studies whatever have been made of tlie condition of tbe 
^'ircu Ijifum before ansBsthesia m produced. But if, as is almost certiun, the 
^tiae^^tln-i^iji ig only an asphyxia, the well-known circnlat^jry phenomena of 
' "At stale ought to be present. Confirmation of thia haa been afforded by, 



286 SYSTEMIC REMEDIES. 

Dr. Amory, who, by means of a cerebrometer set into the skull of the dog, 
found that during the period of unconsciousness the cerebral pulsations are 
very decidedly lessened, and finally abolished, altboui>h the cerebral pressure 
is increased. This would seem to prove that the capillary cerebral circulation 
is checked and finally an'ested, but that the amount of blood in the cerebrum 
is not lessened. 

It is well established that the gas is not capable of yielding its oxygen so 
as to support life. A taper will bum in it, it is true, but its decomposition 
IP due to the high heat, and at the temperature of the body the compound 
is a stable one. MM. Jolyet and T. Blanche have found {Archives de Phy- 
tioloffie, July, 1873) that seeds will not germinate in it, and that animals 
(frogs, sparrows, guinea-pigs, rabbits) live no longer in an atmosphere of 
pure nitrous oxide than in one of nitrogen. Even Dr. Colton, who main- 
tains the absurdity that nitrous oxide produces hyperoxygenation of the 
blood, states ( I7ie Pht/siolo^cal Action of Nitrous Oxide Gas, Philadel- 
phia, 1871) that in an atmosphere of the gas a mouse will live only ftt)m 
thirty to sixty seconds, a pigeon one to two minutes, a kitten one to two 
minutes, a frog thirty to sixty minutes, — all dying of asphyxia. 

The French observers above named affirm that nitrous oxide has no effect 
upon the system ; that the phenomena induced are simply due to deprivation 
of oxygen. The series of facts which they have experimentally proven, and 
upon which their conclusions are based, are: 1. An animal lives no longer in 
nitrous oxide than in nitrogen ; 2. Auscsthesia occurs at the time that the 
blood of an animal becomes black ; 3. Animals breathing an air containing 
sixty to eighty per cent, of nitrous oxide, and twenty to forty per cent of 
oxygen, are unaffected ; 4. The analysis of the blood of two dogs yielded 
the following results : 

No. 1. Conscious. No. 2. Unconseions. 



Carbonic acid ... 46 per cent 
Nitrous oxide ... 29 per cent. 
Oxygen 19.7 per cent 



Carbonic acid . . . 3G.6 per cent 
Nitrous oxide . . .34.6 per cent 
Oxygen 3.3 per cent 



and other analyses showed that the coma was not developed until the oxygen 
in the blood was reduced to three or four per cent It is evident that if 
the above analyses are, as from their reports they appear to be, reliable, the 
anajsthcsia is not due to the presence of carbonic acid in the liquor sanguinis, 
since nearly ten per cent, more of that gas was present in the blood of the 
conscious (No. 1) than in that of the unconscious dog (No. 2), and also that 
it is more rational to believe the decrease in the oxygen, rather than the 
slight increase in the amount of the nitrous oxide, made the difference 
between consciousness and unconsciousness. 

In this connection the very careful experiments of Dr. Amory aro 
interesting. He found that during nitrous oxide naroosis the amoantof 



ANESTHETICS. 



287 




konie acid exhaled from the lungs is only two-thirda of tliat eliminated before 
B&c inWIntionf And that immediately after the recovery of consciouaneas lew 
HM une-third the normn) amount of carbonic acid is ^verv off. 
^Pphts certainly is corroborative of the conclusiona of the Frcncli observerSi 
vlilcli have also received confirmation from the experiments of Mr, Elihu 
frbonidon {PhiUtdelphia Medical Time$, November 15, 1873), who f(»imd 
lliat animals in an atmosphere of hydrogen and of nitrogen, and also in 
Tacm>, suffered symptoms precisely similar to those caused by the inhalation 
of pui^ nitrous oxide ; alao, that in man the inhalation of pure nitrogen 
causes the symptoms of nitrous oxide nareoais, except that the sense of 
hiliimtion is absent; finally, that nitrogen, hydrogen, and nitrous oxide, 
well its 11 vacuum, arc rendered capable of supporting life if a proportion 
oxygen approaching that existing in common air be introduced. 
le evidunce so fur cited would seem to show that nitrous oxide produoee 
hetjia by causing as}thYxiu ; but the phenomena of mechanical a»- 
ibyxia are diflferent from those caused by the gas. In the experiments of 
rL-huber (quoted by Lyman, Arttjicial Anmsthesia^ New York, 1881, p. 
315) th« circulation was iuund to be very differently affected by meehanical 
asphyxia and the iahaljition of nitrouis oxide. Prof. Paul Bertj of Paris, 
believing that the production or non^production of an£csthei)ia by nitrous 
oxide depends upon its tension in the blood, devised an apparatus by 
BMaDS of which the patient cuuld have administered to him nitrous oxide 
ga% mixed with an etjual amount of oxygen, under a pressure of at least 
two atmr^pheres. The result is said to be very satisfactory, and the method 
to be at present extensively used in Paris, The objections to it are the expen- 
uvcness and cumbrousness of the apparatus. It is plain that the method 
in which nitrous oxide acts cannot as yet be considered as positively deter* 
mined, and that the subject offers a very good field for research. 

Thkrapeutics,^ — As an amesthetic, nitrous oxide is chiefly valuable when 
lort, minor operations are lo be perfurmed. The rapidity with wliifh insen- 
llibility is induced, and with which it disappenrs, eomhtnes with the general 
ibionoe of after-effects to enhance the popularity of the gas. When, how» 
€ver, an operation requiring scmie little time for its performance i8 intended, 
ler is far preferable. Nitrous oxide lias been administered lo many thou- 
of persons, and until recently no deaths at all attributable to it have 
Oecnirred. Three have, however, heen reported within a short time. In one 
of tliese {Dental CotrfioSj editorial^ June, 1872) it is d^iubtful whether the 
gas had anything to do with the fatal result, or, indec^d, whether it was really 
administered. In the other instance ( /fnV. Journ, Dent. Set., Feb. 1873), 
death from a^phyiia, apparently induced by nitrons oxide, occurred in a 
healthy man. In the third, death is asserted to have been produced by 
iyucopc (Brit. Med. Joum.^ i., 1877, p. 460). 

Nitrous oxide is best administered from an india-rubber bag, which should 
ooobdo at least eight gallons. The mouth-pieee should always be made with 



238 SYSTEMIC REMEDIES. 

two valves, sor that the expired gas will be thrown out into the air, and not 
back into the bag. 

ETHEB-ETHTL OXIDE. (C,H,0-C,H,oO.) 
Ether is a colorless, very volatile liquid, obtained by the dehydration of 
alcohol by sulphuric acid. It is very inflammable, as is also its vapor, which 
is two and a half times heavier than air. It is freely soluble in alcohol, and 
is itself a powerful solvent. Its odor is strong and peculiar ; its taste hot. 
Its specific gravity, when pure, is 0.713, and its boiling-point 95° F. It is 
ofiicinal in two forms. 

-^TiiER — Ether. U. S. — ^This ether contains a large percentage of alco- 
hol, and has a specific gravity of 0.750. When shaken with an equal bulk 
of water, it loses from one-fiflh to one-fourth of its volume. A test-tube full 
of it held in the closed hand should be^n to hoil on the addition of a piece 
of broken glass. Any specimen which does not conform to these require 
ments probably contains an overplus of alcohol or of water. 

^TH£R FoRTiOR — STRONGER Ether. U.S. — ^This ether should have a 
specific gravity of 0.728, should not lose more than one-eighth of its volume* 
when shaken with an equal bulk of water, and in a test-tube held in the 
closed hand should hoil vigorously on the addition of broken glass. 

Physiological Action. — The first effects of ether when inhaled are 
burning in the fauces and a feeling of strangulation, both due to the local 
impression of the irritant vapor. The first indications of its systemic action 
are a sense of exhilaration and a lightness in the head, associated with a 
roaring or buzzing in the ears. These are soon succeeded by a feeling of 
the immediate surroundings being afar off", and this soon fades into semi- 
unconsciousness, with visions and illusions. These are of various characters, 
and arc often accompanied by a species of delirium. Some patients weep, 
others laugh ; some shout, some pray, some rave, and some become exceed- 
ingly pugnacious. In rare instances, the dreams become erotic ; and cases 
arc on record in which there were distinct evidences of the occurrence of a 
complete venereal orgasm. In this stage, the patient in most cases may be 
more or less perfectly aroused. There is rarely sufficient anaesthesia for 
practical purposes before the period of complete unconsciousness. 

The second stage of ether-narcosis may be considered to commence with 
the complete loss of consciousness. In most cases, some degree of muscular 
rigidity is at first still present, but soon passes off*, and the patient lies relaxed 
and quiet, with slow, regular, automatic respiration. The occurrence of 
stertorous respiration, due to a paresis of the muscles of the palate, shows 
that the stage of miuoiilir panljas ia bdng reached. It should, except in 
veiyiiffaai teiriliidntWBlof the anaesthetic. 



ANjESTHETICS, 



289 



The fnoe durinf^ ethemation is reddisli ; miirked pallor and lividity are re* 

ip^fciivolj importiint indications of fiiilure of tlwj licart's action and failure 

of rcAph-aiion. Tlie stago of excitemeTit ^onendlj lasis only a few minutes, 

but iu sooie cases is prolonged, and in iien'ous women may pass into a violent 

5t of hysterics^ which soon jiclAs, however, to a persistent u»e of the anaBs* 

thetic The pulse is qwiekened and increased in force by other, and it will 

often roaintain itself during a prolonged oarcosis. If the vapor of ether 

he taken in a concentriitcd f<»rm« there is upusiUy in the beginning a UToment 

ary arrwt of respiration aceoiupunied by a deeidud sense of suffocation, evi- 

dentljthe result of the irritant action of the vapor upon the upper air-pasHogea. 

So sooi) a£ ihiJ* has paxstMi off the respimtions are usually accelerated as well 

^^ tltvjiencil ; but as the stage of atioisthesia is reached they become fcilowcr, 

*ntl, if the iah«1ation of the ether be peraisted in^ they grow not only njoro 

ftncl more distant, but also more and more shallow, until they are gradually 

^3ttiij»itiishe<i. The roppiratory phenomena seem to be the Biuue m the lower 

msimniuliii as in man. It was noticed by Krat^climer (Sifziui^h. Wiener Aktni.^ 

187*), Abth. It.) that in the rabbit ether, when inhaled llirough the nose, 

produces at first a momenlary arrewt of respiratiou in expiration. He also 

found that aoclioo of the vagi did not prevent this arrest^ but thai section of 

^ne IrijTfmini did; also that the arrest never occurred when the ether was given 

ihpootrli a tnichettl fistuhu This would appear to show that the phenonjenon 

^^^^ 1 rudex one, due to the irritation of the periphend ends* of the trigeinini. 

At« importance ia much increased by the consentaneous spjisni of the glottis, 

Oof iced by Kralschmer. It is possible that some of the aceidents happening 

^*''Jy in human anaesthesia are the result of such spasm. As stated by Dr. P. 

^^^il (Sifzunt^b. Wiener Ahul^ Oct- 187G), the alterations of respiraiiun are 

^JOietimes replaced by very irregular breathing. In either case, if the inhula- 

"^o of ether be persisted in, the respirations^ at first quickened, grow slower 

^^ slower, and less and less deep, until they are gradually extiugui."s!ied. 

*** Knoll experi men tally determined that these later respiratory changes are 

^^^ iijterfered with by previous section of the vagi ; that they follow the in- 

^'on of the narcotic into the blood ; that they are not due \(i di.'^turbnnces of 

"^^lation. or to a deprivation of the rei^piratory centres of their oxygen ; and 

B^^^o^lly concludes that they are produced by a direct action of the drug upon 

^ ^^utros, at first stimulant in its character, but subt^uently depressaoL 

, ^«20ordiDg to Prof Eulenburg, in the beginning of anieslhchia prudueed 

•^^f by ether or by chloroform, the patella ret! ex in man is iiiereasied ; but 

* ' **st this increase soou disappears wlieia cblorofbrm is employed, with ether 

^•^■'duree even into the narcosis {Hoffiuami nnd SchvaUj^., 1883, p. 117). 

^-T|>nn the lower animals ether acts mh u|>on ni.in, and it has been shown by 

^*^tle Bernard that the most primitive infusoria are susceptible to its influ- 

^ «=^i iU Propi^ Med., 187C, p. 77). 

-^ ^ the functions of the cerebrum arc affected before those of the othot 
'**t^lt>u« uf the nervous system, it is vei7 apparent that the brain is especially 

10 



It 




290 SYSTEMIC REMEDIES. 

sensitive to the narcotic. FloBrens {Cumpten-RmduB^ Yol. xxiv., 1847, pp. 
161, 242, 253, 340) found that, at a certain stage of etherization, pricking 
of the anterior or motor nerve-roots caused motor disturbance, although the 
posterior or sensory portions of the spinal centres ware completely insensible. 
After a more prolonged inhalation, the anterior or motor centres also failed 
to respond to mechanical irritation, although the functions of the medulla 
oblongata were regularly performed, and stimulation of its anterior centres 
gave rise to motor disturbanoo, and pricking of its sensory portions even 
caused manifestations of pain. When the inhalation of ether was maintained 
for a sufficient time, the sensory and finally the motor functions of the 
medulla oblongata were compromised, and death from paralysis of the respira- 
tory centres ensued. 

Longet (^Archives G^nSraleSy 4e s^r., tome xiii. p. 374) in part confirms 
and in part questions the results of Flourens. He states that he has found 
the sensory functions abolished very early, but has never failed in any stage 
of the narcosis to get a response from the anterior part of the cord. These 
apparently different results are simply due to the fact that, whilst Flourens 
used only mechanical stimuli, Longet employed powerfU galvanic currents. 

Flourens was substantially correct, and the order of the involvement of 
the nerve-centres in man and animals is — ^first the cerebrum, next the sensoiy 
centres of the cord, next the motor centres of the cord, next the sensory 
centres of the medulla oblongata, and finally the motor centres of the 
medulla oblongata. 

That ether is capable of impressing the nerves seems established by the 
experiments of Louget (loc cit.j p. 382) and of Series {Archives Ginindet^ 
4e s^r., tome xiii. p. 433). These observers found that the direct applica- 
tion of ether to a nerve produced a paralysis of the sensory fibres of that 
nerve ; so that pinching the nerve below the point of application caused no 
pain, although voluntary movement was preserved, and galvanization of the 
nerve-trunk above the point of application induced spasms in the tribataiy 
muscles : i.e., the power of conducting an impulse downwards was preserved, 
that of conducting it upwards was lost. By a longer application of tiie 
ansesthetic the function of the efferent as well as of the afferent fibres was 
abolished, temporarily at first, but, if the application were persisted in, per- 
manently. Practically, however, inhaled ether has no influence upon the 
nerve-trunks, because the nei-ve-centres are so much more sensitive to its 
influence that their functional power is abolished before the nerves are affected. 
Indeed, Conly {Soc, de Biof^^ie, February 13, 1876) found that in animals 
killed by ether, chloroform, or chloral the motor nerves and muscles preserve 
their function longer than in animals killed by sudden violence. 

Upon the motor system of organic life ether certainly acts, but much less 
energetically than upon the voluntary system. Thus, afler death from ether 
the vermicular movements of the intestine, although less active than nonnal, 
are very rarely, if ever, entirely absent. 



Ay^i:sTIIETJCS, 



291 



It has been shown by the KngUsh CUlor<>forTn Committee and oilier in* 
^cstijialors that ether increases very markedly the arterial pressure, iind that 
even in h prolonged ether narcosis there is usually no materisd diminution of 
llvia pressure antil manifest failure of respiration has taken place. The rise 
ef the pressure is probably due to an increiise of the power of the lieart 
tbd to a stiuaulation of the vaso-motor nerves.'^ Sunsoiu {^Chloroforin : ttn 
Acthn and Admumtration^ p. Oli, Pliila,^ 1S()(>) states that the vessels of 
ih« frog's web can be seen to contract durin*^ the inhalation of ether, and 
tliat this vaso' motor spasm is very permanent, and does not yield to pariil- 
}m and passive dilatation until the anaistliesia hud almost deepened into 
(ftiHih, Dr Bowditeh and Mr. Mioot also found {Boston Med, ds Sttrg, 
«^OMr«., May, 1874) that the vaso-motor eetitres are at first stimulated and 
tttterwurds depresaed. 

Injected even in considerable amount directly into the jugular vein of 
the mammal, or applied directly to the frojLr's heart, ether does not seriously 
repress the heart. When artificial respiration !» maintained animals bear 
■o enurmous amount of this drug without cardiac failure. When death is 
P''oduced by ether, the heart generally continues U) pulsate for a long time 
*««r the arrest of respiration. It is evident that ether is as little of & 
^^•iiac depressant as is alcohol. 

^t is frec[uently asserted that ether when added to blood coagulates it. 
^- Schmidt, howeveTi states that the coagulation is due to ozone which has 
ft generated by the ether and is contained in it, since freshly-distilled 
*>er does not coagulate albuminous substances. 
The researches of Wittich (Schmidt* s JahrUlcher^ Bd. cxlli. p, 212) and 
^' S^^hmidt ( TTrc/iow?'* ArchU\ vol xxix., 1864, p. 19) have shown that 
^*ieo ether is added to the blood of horses.f cats, or rat«, the red corpuscles 
**isappear in a very short time ; and, as their stroma cannot be demonstrated 
y tlie aid of reagents, this dii>appear!ince is due to its solution. The 
o^Mn^tin thus set free is disfiolved in the scrum, but the presence of the 
^«e»- soon causes it to crystrdlize. There is no proof that these changes 
^*^^*ttr to any extent when ether is inhtiled ; and the usual rapid recovery 
*^*^**tt \h» elfi^ts of the anicsthetic indicates that tliere is no profound altera* 
^•>»i fjf the blood, 

-iVti impi^rfect study by Tlarley of the effect of ether on the gases contained 
<imwn bl(md indii^tcs that ether does not exert much influence ufion their 
'orttanal amounts. It is, hnwevcr, quite possible that a more thorough 
v-«2^ti;rtition would give a dilierent result. 

TitKRAPKOTlcs. — As an anscsthetic, ether does not act with the rapidity 
i<^ I'luosantneas of chloroH>rnif but it ha^s the advantage of safety, So dan^ 






* Wieve there i« « pnpiT " On the Action of Elbi^r «fi ihn Circulntit>»i" in the DtHtn<sh«9 
^*^Hft fUr Uhirunjitt 1874, UJ- iv.; but t Imvo lint hti*) iujci?.?» tn tliit Vfjluiiic 
^^buti4i (iftc, ctY.y'p. 33) aiij^a ihut «omtitimci urj^tAtliKiittoa tuil» in the blood of Ibc 



292 SYSTEMIC REMEDIES. 

gcrous is chloroform, and so safe is ether, that there is no excuse for the use 
of the former agent under ordinary circumstances.* 

The reason of the safety of ether is that, unlike chloroform, it does not 
suddenly paralyze the normal heart.*}* It may kill by inducing asphyxia 
(cases, British Medical Journal^ vol. ii., 1873 ; Chicago Med, Journ., 1877, p. 
410 ; Le Progrhs Mid,, 1877, p. 677 ; New York Med, Joum., xxiii.,p. 179)4: 
but it does so slowly, and in the great majority of cases after warnings which 
can be overlooked only through the most reckless carele8sne8S.§ Many of 
the inconveniences which attend the use of ether can be obviated. Thus, in 
order to prevent the nausea which often follows the anaesthesia, the patient 
should avoid eating for at least six hours before the inhalation, and should 
take from one to two ounces of brandy just before commencing the latter 



Unlike that of chloroform, the vapor of ether should be administered in 
a concentrated form. When so inhaled, in most persons it will produce 
complete insensibility in from three to eight minutes, provided that no 
uncharged air be admitted during the time named.§ According to Br. 
Snow, air at 80° F. saturated with ether contains seventy-one per cent, 
of the vapor. This point is probably never reached in the practical use of 
ether, but the nearer it is approached the more rapid will be the induction 
of anaesthesia. 

The ordinary method of the administration of ether in Philadelphia is as 
follows : 

Out of stiff paper a cone is made of such size and shape that its base will 
fit closely over the nose and mouth of the patient. In this cone a napkin, 
a small towel, or a conical, hollowed-out sponge is to be placed. About an 
ounce and a half of ether having been poured on the napkin, the cone is to 
be closely applied to the face of the patient, and kept there. If anaesthesia 
be not complete in four or five minutes, a second dose of ether should be 
put on the napkin, care being taken that the removal of the appar&tus is 
only momentary. When patients are fastidious, and a few moments are of 

* Twenty-seven cases of sadden dcnth from ether are collected by Dr. TI. M. Lymao 
{Artificial Aueemhe»in, New York, 1881). In most cases the respiratory centres were 
already enfeebled. Bmin tumors, obstractions of the bowels, cancerous tumors, seem even 
more important cuntrnindications than cnrdinc disease. In disease of the heart ether is 
probably the safest of the anaesthetics ; but when there is great exhaustion of the nervous 
system its use requires great caution. Sudden pulmonic oedema, outpouring of bronchial 
mucu.o, and fatal cerebral hemorrhage have occurred during, or directly after, the antes- 
thesia. 

t For case in which a fatty heart apparently suffered sudden arrest, see Brit, Med, Joum., 
1887, ii., p. 602. 

X See also Gm. Hebdom., 1878, p. 583. 

§ Various inhalers have been invented for facilitating the use of ether, but they are very 
rarely used. For information on these points, see New York Medical Record, May 1, 1S06, 
and A'eio York Medical Journal, April, 1871. The inhaler of Dr. AUis is probably of real 
serrioe. See Philadelphia Medical Timet, vol. iv. 



ANM^TJ/KTICS. 



293 



ao inpcntuioe, the gradual commenoement of the inhalation is much more 
li lif i iUD t, as the Brat choking sensation is therehy to a great extent avoided. 

Id tisiiig ether at night, its inflanimablo nature must not he furj;uttcjj» I 
ItaTe mem fire flash from a candic through soiutj lour or five ft'et of diffui*ed 
Tapor to the 8|H>nge. The Hght should always be above the patient, as the 
high 5|)cciiic gravity of the vnpor of ether causes it to fall towards the floor. 

Adminij»tC'rod by the inoutli, ether has been used with adyantage in Tari* 
u>u& fornis of co/iV, but is generally inferior to chloroform. W^hen, however, as 
in Aomc cases of retrocedent or internal gout^ there is with the {uiinful gastric 
And iutetttitial spasm a condition bordering on collapse^ the stimulant pro|>er- 
tifs of ether make it very valuable. 

Ill sudden ginklng-E^pvlU^ either from poison or from natural causes, ether, 
mm « powerful and very quiokly-acting stimulant^ is oflen indicated. In some 
tmmm of this description it may even be adminiRterc^ by inhalation. Of 
OOVfse, under these circum»tarjcci$ its induenee should not be carried nearly 
Co die point of producing anaesthesia. 

Ail mi tmthelminhCy ether Itas been used by MM. B<^urdier and Lortet 
with Boeoeia against the tapc-worm. For tbis purpose, an ounce arjd a 
liolf may be administered at once, followed in two hours by a full dose of 
cttstor oil. 

Ill htjMtiTin, neuralgitty nenxms headetehe^ and Mpamnodtc neuroseMj such aa 
hicc*fU^h and atthmftj ether is occasionally employed with benefit. 

When ether is swallowed, it produces a sense of strangulation and choking, 
which seriously inteTferes with its use. For this reason, it is bc^t given in 
capi^ulcs, or in ice-wld water. Probahly large doses «re bciit administered by 
patting them, mlxud with an ecjual uuiuuut of bra tidy , un finely-cracked ice 
before drink iug. 

The dose is from one flui drachm to half a fluidouuce. 

OHLOROFORMTJM-OHLOROFOEM. 

MmiFNYL Chlouide — Tkrciilokii>e uf Foa.MYt. (C^nCl, — CnC\). 
- This itubbtance, which was discovered in 18HI by Mr. Samuel Guthrie, of 
8iickett*a Harbor, N. Y,, is produced by the action of chlurine upon alcohoL 
It is a colorless, limpid » and neutral fluid, wbieh is for practical purpt»6es uniu- 
fl.iiumj*ble» although it cun be made to burn witii a greenish flame {F(jwitr»§ 
Cft^rnixtr^, Am- ed., 18G9, p. 5Gt>). liA tante l^ hut and sweetish ; its odor 
ft^gjant and peculiar. It is soluble in alcohol and in ether, but when dropped 
into water it sinks, if pure, as transparent glubulea witiiout milkiness. The 
sWhoiic solution, when modorateiy diluted with water, forms an aromatic, 
ffWeecish liquid. It is antiaeptio, but docs not eoii^ulate albumen. 

In the U. S. PharmaeopcBia it is officinal to two forma. 



CMtXJROrOHMUM VeXALE— CoMM EBOIAL CHLOROFORM. U. S — The 

erude chloroform of commeree. Sulphuric acid, whcii »liaken with it, after 



294 SYSTEMIC REMEDIES, 

a time separates as a stratum of a dark-browDish color. This color is doe to 
a carbonization by the acid of the impurities in the chloroform. 

ClILOROFORMUM PURIPICATUM — PUBIPIED CHLOROFORM. U.S. The 

U. S. Pharmacopoeia directs that the commercial chloroform shall be purified 
by the action on it of sulphuric acid and bj subsequent neutralization with 
carbonate of sodium, and distillation in a retort containing quicklime. Piui- 
fied chloroform should respond to tlie following testa : Sulphuric acid shaken 
with it should not be colored ; it should not alter litmus blue, even after it 
has been exposed in a white glass bottle to direct sunlight for ten hours. 

Physiological Action. — Although somewhat of an ansdsthetic, chlo- 
roform applied locally is a powerful irritant. On the skin it produces redness 
and burning ; if the evaporation be restrained, vesication is induced by it. 
Taken into the mouth, it causes a burning sensation, and, when swallowed, a 
sense of warmth in the stomach. 

The vapor of chloroform, when inhaled, produces symptoms seemingly 
similar to those induced by ether, except that the choking sensations are 
absent, and that the stage of excitement is generally, but not always, shorter 
and less violent than that of etherization. 

Dr. Snow (On Anxsthetics^ London, 1858) divides the chloroform-narcosia 
into four degrees or stages, but the division adopted by Sabarth (Z)eM Cfdo- 
ro/omij Wiirzburg, 18G6) and most writers seems more useful. This dassifi- 
cation recognizes three stages. In the first of these, the symptoms are similar 
to those of alcoholic intoxication. This stage is generally very short, but in 
athletic persons, and especially in those who have been intempei-ate, it may 
be very long and very violent, and may persist after loss of consciousness. 
In drunkards, this excitement at times cannot be overcome without grave 
danger to life. During this first stage, although consciousness is not lost, 
the sensibility is generally blunted, but very rarely is it altogether annulled. 
Dr. Coleman (Sansom, Chlorofomi^ p. 55, Phikdelphia, 18G6) states, how- 
ever, that he has extracted his own teeth without pain ; and Dr. Snow relates 
the anecdote of a child who played with his toys during the operation of 
lithotomy. 

During the second stage, which is that of ansesthesia, the consciousness 
and sensibility are abolished, the muscles are relaxed, and the patient lies 
perfectly quiet This is the surgical stage, during which ordinary operations 
are performed. As already intimated, in some cases the first and second 
stages are united, so that violent excitement, muscular spasm, and rigidity 
may coexist with loss of consciousness and of sensibility. 

The third stage is one of profound narcosis, with stertorous breathing, 
intense muscular relaxation, and abolition of ordinary reflex actions. This is 
always a condition of danger, and its induction, except under very peculiar 
circumstances, by chloroform, is absolutely unjustifiable. 

The pulse in the first stage of chloroform-narcosis may be quickened, even 



ANESTHETICS, 



295 



ftpptreotlj strengthened ; in the second stage it is gcnta^ly about normul ia 
fi^ecpiencw but is more or less weakened ; in the thtrd sLaf^o it may be rapid 
and weiik. Dr. Noel {Lotid, Med Record^ 1877, p. 457) calU attention to 
a eemc&t Tcnooa puUe, most marked in the e&ternd jugulars^ which ho 
■■irrtB ft«qacDtly occurs during the wakiQ<< up from chloroformisation. 
He beliefTes it to be a symptom of serious cardbc embarri^ment. E. Slmo- 
tiiii fouftd that the temperature usually ritjes during the fiist stage (.l^-.8^Ct), 
fiillB sliglitly during the second or remains abov^e normal, and fidls de<^idadly 
diLriDgtht! third stage {Ckntralh, Chirnrgxe, 1877, p. 234). 

In man the firit arrest of re'jpiratjori, so obvious in etheritationi rarely if 
©Ter ooeuni. This is probably in great measure owing to the chJorofurm 
Tapor, as employed, being much more dilute tEian the ether vapor. The 
«£Xpenmeots of Holmgren, KonLachmcr, and others have shown that upon 
tlie lower animals the respiratory actioc of eltloroform is similar to that of 
rUaer (see p. 281), exeepttiig in that it is much more intense. 

Dr, Baudin {Le Pro*jrh M*d>^ Sept. 1874) called attention to the pupil 
aa Q ^ide in chloroforoiization, stating that, akhougli at first it ia uniformly 
4tlated, afterwards it is uniformly immovably eontnieted, and thiit this is 
the period for operating, %Sehlilgcr is in accord with Dr. Baudin ; in one 
hundred and twenty out of one hundred and twenty-two cases ob^scrved the 
pupil was dilated during the stage of excitement^ during oompfete aniissthesia, 
narrowly contracted. He also states that if during anflesthesm the pupil re- 
turns to normal more chloroform is required, but if it suddenly dllatjcs danger 
is imminent. At present, however, the condition of the pupil ainuot be con- 
flderi?d a safe guide in ana^sthotization. Dogiel {Reickert*s Archio/Ur AuaL^ 
1866) affinus that in rabbiLi, during the st-agc of excitement^ the pupil is oon- 
Uscted ; during ans^thesia, dilated. Prof. 8chifF has strenuously uombuted 
the conclusions of Baudin; and in a very careful series of experiments on 
animals Dr. W, H. Winslow found that the state of the pupil varies very 
greatly in the same stage of anaesthesia. Thus, in complete anie.^thesia» 
aomctimes the pupil was widely dilated, sometimes contracted ; and death 
sometimes occurred with a dilated, sometimes with a contracted pupil ; in 
ibe former case probably being syncopal, in the latter asphyxial (^miad. 
Mfd, T*me$, vi.^ p. 275). 

The action of chloroform on the nervous system, like that of ether, ia 
ehioHy ufHin the brain and spinal centres. Carter ( British MedicaiJournal, 
Feb. I8G7) found that very decided unasmia of the brain can be seen in 
Buiiuals gubjecUid to its hifluenee after the cerebrum ha.s been laid bare ; and 
accident in man (Amcr, Jo urn, Med, <5c/., 1801*) has furnished the corrobo- 
rmtiou of hts experiments. Bernstein {SchnuWi JaJirbiicher^ Bd. cxlii. p. 
227) Im* demonstrated that its action on the jioriphend nerves is very 
alight. He found that there was no perceptible ditferonee in the condiitiing 
power of the two iichiatic uen'es of a frog, ehJoroformed ailer one of ita iliac 
arteries had been tied. It is doubtful how far the muscular excitement of 



296 SYSTEMIC REMEDIES. 

the second stage is due to real spinal exaltation and how far it arises from 
other causes. Bert asserts ( Omi/>^e«-/?cw{£w«, t. Ixiv., 1867) that it is purely 
psychical, and that there is during the production of anaesthesia a steady 
lowering of reflex activity. He rests this assertion upon the fact that, in 
animals chloroformed after section of the cord, there is no motor disturb- 
ance below the point of section, — ^a fact which certainly demonstrates at least 
that the muscular excitement and the convulsions are cerebral. 

In some animals the first efl'ect of the inhalation of chloroform upon the 
circulation is a decrease in the frequency of, the heart's action. Dogiel 
believes that this is due to a stimulation of the inhibitory centres, because he 
has found that it does not occur after section of the vagi. The afier-incrc&se 
in the rapidity of the pulse appears to be due, at least in part, to paralysis 
of the inhibitory centres, upon which chloroform seems to act as upon the 
oculo-motor centres, producing in them at first excessive functional activity, but 
afterwards functional paralysis. Both Kentschmer and Knoll (Joe. cit.^ p. II) 
have noticed in rabbits, when either ether or chloroform is inhaled through 
the nose, a moiuiiutary rise of arterial pressure corresponding to the arrest 
of respiration, and, like it, evidently produced by irritation of the peripheral 
trigeminal branches. 

The very careful experiments of the English Chloroform Committee ( J/«rf.- 
Chirurg, Trans., vol. xlviii. p. 326) proved that after the first half-minute of 
the inhalation of chloroform there is a progressive lowering of the arterial 
pressure. It would, a priori, appear probable that this is to some extent due 
to a vaso-motor paralysis ; but Sansom and Harley state that there is a spasm 
of the small vessels, which can be readily seen to occur in the web of the 
frog during chloroformization. Not until the third stage is reached, accord- 
ing to these authors, do the vessels relax into dilatation. K these observations 
are coiTect, chloroform first stimulates and afterwards depresses the vaso- 
motor centres. Elsewhere in the present work I have dwelt upon the fallacies 
of the observations of such as those just quoted, and the experiments upon 
arterial pressure of Prof. H. P. Bowditch and C. S. Minot {Boston Medi- 
cal and Surgical Journal, May, 1874) appear to prove that the fall of 
pressure is in part due to a paralysis of the vaso-motor centre. They found 
that after the exhibition of the drug in curarizcd animals galvanization of 
a sensitive nerve is followed by no rise of pressure, or a very slight one, 
and that compression of the carotids did not cause the customary vaso-motor 
spasm and rise of arterial pressure. 

On the heart itself chloroform undoubtedly exerts a steady, powerful 
depressing influence. Injected into the jugular vein, it instantly arrests the 
heart's action and destroys its muscular irritability.* Even the vapor of 
chloroform, when locally applied to the exposed heart, paralyzes it (^Edinh* 

• Qlovcr {Edinb. Med. Jonrn.y 1842), Qosselin {Arch. Gin., 1848), Anstie, H. C. Wood. 



ANJESTIIKTICS. 



297 



Jmim,^ IS42). WheD artificial respiration is maintained tlic effei!!; 
€>f clihiniroriu upon tlic heart is very apparent (Journ, Anat, and Phyiiol,^ 
xtii 220 j. It is» therefure, demonstrated that chbrofurm upplied in u suf- 
ficiently concentrated form desfroj/s (he confraci He power af t!w ht'(irt-mu9clt;. 

The respimtiona may at first be rendered slower by chlorofijrni, but nUer a 
time are generally quickened, and as the iiibidatinn w persist-od iu they lieeome 
more and more shallow, irre^lar, and distaut, and finally ceaae. 

In animals, without doubt, chloroform, when inhaled, usually producer 
death by abolishing the iuuetional puwer of the medulla oblongata and 
thereby arresting respiration. It haa been denied that oliloroform-vapor ever 
killa animala lu any other way.* This is, bnwever, a mistake.f If the 
ebJortiform vapor be administered in a very dilute foriir, the henrt generally 
cpntinues to heat for a long time ailer the oeesation of respiration. If the 
Tttpor littvc been Jess diluted, cardiiio and respiratory action inuy cease ahnost 
eimultaneonsly. If the vapor have been adiuuiistered in a concentrated form^ 
mrrtist of the heart*a beat may precede arrest oi' respiratioiLj 

When death is produced by chlorofonn in man, it U generally by cardiac 
arrest, stometiin^ by asphyxia. That syncope occurs proportionately more 
fr«M|uently in man than in animals, is Bimply because this farm of deaih is 
ftuddeu and unexpected. A»^ph}xia comes on gradually, ao that in man the 
tlifvmteniog xymptouis are perceived, and death i» averted by prompt meoa- 
Qftes, In animals, however, the object being to kill, nature is allowed to 
take its couri^e.^ 

Tlie evidence is not at present sufficient to enable a positive determination 
oa to wliether the action of the anaesthetic upon the heart, when a sudden 
futal syncope is produced, h a direct one, or whether it is a reflex one ( T. B. 
Lcnte, pH^choi, and Med, Lrqal Joitrnai^ Feb, 1875), due to an irritation 
of tlie peripheral filaments of the pulmonic nerves. Certainly those who 
believe it to be reflex have as yet brought forwarti no proof of their theory. 
As chloroform doe^ act directly upon the heart, it seems to me winer to bold 
to it9 direct action until it haij been demonstrated that it is impotf&ihle to 
prodooe syncope after division of the par vagum. The mere rapidity of the 
occurrence is of little importance, as pulmonic absorjition is practically 
instantaneims and the bliiod goes directly from the lungs to the heart. 
What is true of the theory of reflex syncope is also true of various other 
theories which have been brought forward to account for the chloroform 
deaths, I think they are unnccci>sary and unprovcn, although some are 



*S»c^ etpeoisllj, r«|)urt at tho French Cbtoroform CotDtnfiSion. Sftb*rth, /Mt Chhro- 
/nrm, p, 44. 

f OiQ»uU Snow, Oh AHKMthetitytf p. Ill; ADf>tio, Stimuitintit tMmi *V«r<?o|ic#; Hk:litirtI«VD, 
M^iimi T%m*9 mtd QazttU^ 1370: Chloroform Couamittec, Mrdiro-Chirwrtfifttt Ttnu^uc- 
rtoijt, ruL »!vti,; Vn1|»i(ili, L*^uu§ mr VAppareii VoMo-Moiturf rol. ii, p. t57» 

t Cotiip»r« Jottnt, AhhU and Phjfuint.^ xiii. 226. 

I Ft»r proof ibal o»rdiaa doalb doei oooar mmoag aaioaftlB, m« Jour. Anat, and Phynol*, 




298 SFSTEMia REMEDIES. ^^^M 

ingenious, and it is possible that death may take pfcwe at times in the r-^^,^ 
they suggest. Waiit of space preTeata my doing more than gidng 
ences to the most important papers^"^ 

According to Harlcy {Fhifsiological TrafinaciioM^ Londorj, 18t>5), 
tn m'hieh rh little as five per cent, of chloroform htia been added 
very liquid Lind of a bright arterial hue. After a time eiystftls form im 
Buett<.*lier ( VirchowU Arckivy vol xxxiL p. 12G) was> I believe, the fiwt to 
study these chaugea closely. The first alteration noticeable in the red hliKHi' 
diftks 18 a dirxiiuutiyu of their size, which A* Schmidt and F. Schweigvr- 
SeJdel (Btrichte J. ki/ni^. sac f us. GeittU*ch, iL Wiit&rniich,, tiMth-phi/s, A7., 
1807, p. 1 !;>(->) assert to be dae tt) coutraetion, becauae when blood ia treated 
with water until the red globules disappear^ and earbonio acid gas is panMid 
through the liquid until they reappear, on the addition of chloruforoi the 
flharply-eontoumd bodies will be seen to undergo marked contrueiioo. At 
was first ebown by Boettcher {he, cii,, p. 127) and oonfinaed by Schmidt 
and SL'liweiger-Seide), chloroform alone produces no other altemtiuu thaa 
contraction in the red blood^li^ks. If, however, air be admitted to blood 
containing chloroform, the corpu^*les rapidly disappear, dissolving in the 
flerum, out of wliieh, after a time, haematin crystallizes. Both of the aulhorJ- 
tiefl quoted believe that the latter ebanges are due to oxidation. 

Boettcher states {loc. ctt.^ p. 129) that chloru form- vapor mixed with air 
converts enough of the oxygen of the latter into ozone to react with iodinti 
Btarch paper ; and Schmidt and Schweigcr-Setdel have found that an ex( 
of carbonic acid in the blood interferes with the changes caused by 
form. Fnjm these factu it seems probable that their opinion as to the 
of the blood-changes ia correct. Harley {^loc. ciL) has studied the e^eot of 
chloroform on the absorption of gases in the blood. He states that when 
chloroibrm is added to fresh blood, and the mixture allowed to stand for 
twenty-four hours^ a marked increase takes place in the propi:>rtion of oxj 
and a lessening in that of carbonic acid. This is in accord with the th< 
just mentioned; for, atler the complete oxidation of the hmmato-glubulLu 
brought about by the chIori>form, further coisumpbion of oxygen could not 
occur, and, as it continued to be absorbed from ihe air, it would accumulate 
instead of being converted into c^arbonic acid. 

How far, during ordinary nareosLs, chloroform produces the changes just 
di^cribed in the blood, is somewhat unccrt^n ; but it would seem very im- 
probable that tliey occur to any great extent. A very sensitive test of th« 
destruction of the red disks in the body is found in the production of icteras; 
and icterus never follows anaesthesia. Ou the other hand, Huaeuumn 

• RiohArUson, Medicttt Timegnud Gnttitt, 1870. Ai)ifcw U. 8tiiith, iVrw York MmniitM 

Jonmaf^ ISTl;* p* 4ft. Conewlt also J. C. Reeve, Amerienn Joitrnal »/ the Medical Sci^nvm^ 

Oct. I8ft7,* Ht*nry M. GibboDs, Jr., f*iiv*Jic Mtdictti and Snryicnl JoHrmil, June, 1^A9; 

Snow, On Aimntheticti : SausfniJ, On Chiom/arm; Had 0. W. Copeland, Philudtlpkia 

^bdi^l Timett, p. 55D, 1874. 



ANMSTUETICS, 



299 



(^Sektmdi'tJahrbUehfT^ Bd, c!i, p. 84) intimates, on what authority I do not 
kjiow^ llmt tttler aMaesthc^iji bile-acids appear in tlie urine ; aud B<irt (Jonrtittl 
:^AMi%i4miif and Phtfsmhtytf^ ^I^y, 1870) has timnd that the oxygen of the 
Uood iiiidi*rgp€S during anic^thestH an iTscroasc, such m ILirley luis found to 
lui|ipcii when chloroform is added to 1>1(hmI oiiLside of the body* 

TheRxIPEUTICS, — As an ainEiitlxetic, chloroform possesses the advint ig«3 
of qtiickn^!i!« and pleasantness of operation, smalUieBS of dose, and cheapness. 
These advantaj^res are, however, so outbftliineed by the diingers which attend 
tta uac, that its employment under ordinary circumstances is unjustifiable. 
It kitb withuut wanting, so suddenly that no forethought or skill or care 
can guard against the fatal result. It kills alika the robust, the weak, the 
weU^ and the diseased ; even the previous safi' passage through one or more 
lahalatiuns is no guamntee against its lethal actiou. Statistics seem to indi- 
cate a tuortality of about one in three thousand inhalations f and hundreds 
nf mtierly nimeceasary deaths have been produced by the extraordinary per- 
ntenoe id its use by a i>ortiun of the profession. It ought never to be 
«Ba|i)oy«d except under especial cireuut^tances, as when a speedy action is 
denred in imftpcrul echtmpsia^ or when the bulkier anaesthetics cantiot be 
kraosportedf as in the field during war-time. 

In oUrtetric cases, chh)ryfona has been used even by those who give the 
prefbreooe to ether iu surgery. So far as I know, no death has as yet 
oecumHl from chloroform during pnriurifkm, although alarming effects hav» 
been induc<*d. The excitement of child-birth does seem to fortify the ^stom 
■gainst the deleterious iufiuenee of chloroform. But even in these cases I 
chink ether is just as useful as, and much safer than, its sbtcr'anassthetie. 

Various mechanical inventions have been made for the adnjiiiistration of 
chloroform ; but these inhalers do not appear to offer any advantages over 
the simple napkin, and, at least iu this country, are rarely, if ever, used.f 
A handkerchief or towel may be folded into a bird s- nest shape, and twenty 
or thirty drops of the anaesthetic be put upon this and then held close to the 
iDcmth. Br. Simpson advises that a towel be laid over the mouth and nose, 
ind the chloroform slowly dropped upon this until ansestliesia is induced. 
Whatever plan be employed, it is of vital moment that the vapor be well 
diluted : not more than three and one-half p'.-r cent, of it should be contained 
b the inspired air. 

When administered by the moutli in sufficient i^uantity, chloroform pro- 

• See Richttrd»uo. Mrdicnl Time* mtd (Jnztttft 1870 ; Jlftirjr M* ^iibbune, Jr., Pnvi/h Mni^ 
tf^iJ^^Hfitat, June, ISftQ; SquiUb, On Anifthetkm^ AW York Mrdifil Jotirtml^ April, 1871, 
l.jrtnvti bn* enllecieHl 3-12 fitt^e^ a( (Wcilli frfuiii ubbtroforin a^itiast 27 frotn ethor, und gived 
tb9 fftik» uf tlcAth iQ anoMtheflia, chlurofonn, 1 : 38ti0; olhor, 1 : ]A,542. Nilroui oxIJe 
■ |>pt a w bo b« tJie m(t»t of all the aowatbetlca, its ratio, ii«eofding to RotienBtein, being 

t For a itcieriptioa of inbalcrs, ■«« irorki of Siuiioai and Snow; aJao Alll«^ Phila, M^d. 



300 



SFSTEMJC nHMEDlEfi, 



duoee ajraptoniH similar to but much more permanent tban those wKteh P 
eauBee when irilnded. It fa, liowevcr, very rarely, if ever, need in this wtt^^ 
for its coiistitutionjil effect, but is sometimes of advftntnge in severe neitmlgitii^''^^ 
iVlieti quinia for any reason cannot be administered in an agne^ a euii- 
cient dose of cbloroforui (fSss to f3i) to produce a mild nareogis, given just 
before tlic expeetid time for the recurrence of tlio chilly will ujmally abort iu 

When cblorofonu b ttiken into the stomach, a eonsiderable portion of it 
is, without doubt, evaporated, m that the intestimd c^nal becomes filled with 
the vapor, Chlomforai, therefore, when so placed exerts both a local anodyne 
and a Btimulaut carminative action* For this rea^^on it la exti'etuely valuable 
10 all cases of rnlic^ and it will often even iiKsuage the pain of collcn piclOHum. 

Externally, as a rubefacient and anodyne, chloroform is very largely com- 
bined with other substances into liniments, which are especially useful in 
cases of chronic ni'tirafgic or rheumaftc paum. 

ToxicuLOOY.^Death may occur at any time during the inhalation of 
chloroforTn. In some cases it ha^i seemed to be instantaneous, but generally 
it is preceded by symptoms such as a change iu the expression of the face, 
which becomes very pale or livid, evident irregrularityof the respirution, and 
failure of the pulse : a shudder, or a violent convulsion, ur even a sudden 
access of maniacal excitement, has been noted in some case«. After death 
the heart is almost always found relaxed, distended, and its right side filled 
with bloiid. 

When death is threatened through asphyxia, the alternate dasibing of reiy 
cold and very hut wat.er upon the face and upper chest is often very effica- 
cious, Artitic'ial respiration should be commenced at ont^\ Famdiauion of 
the diaphragm, by pressing one pole firmly against the pit of the stomach 
and placing the other over the larynx and the root of the nock, has acted 
very favorably in s<jme cases* Dr, Richardson has shown (loc, ciL) that 
there is a danger of the excitability of the muscle being exhausted by a 
prolonged use of the g-alvanic Ktinmlus. The application should not, ther^ 
fore, be long continued, but should be alternated with artificial respiration. 
Whenever there is any failure of the heart's action, as is nriarly always the 
case, the body should be laid at an angle of 40°, with the head dowuwarda, 
BO as to favor the pa^ssage of arterialLzed blood to the brain (Dr. E, L. 
HohneK, Chicago MedicalJonrnnl^ Sept. 1868).* 

In artificial respiration, act with the patient, and not against htm. He 
will not cease to bre-athe at once, and wholly. Enjoin silence ; watch the 
first attempt at inspiration, and at the expiration compress the thorax, aiding 
its elastie reaciiuy, if libsolutely necessary, by Silvester's or some other quiet 
ntethud. See that the tougue is well forward. Dry external heat must be 

* T hixx^ nlluwcd \\i\i^ Hcntcnoc iu reimiiTi i\t it wa« in tbe liut edition* Since it was fini 
pobljahod, the uicthoJ haa bt^cn bruujjiit TorwartJ an new, tind «« baving originat4>d with 
N^Ulou {Pfiiinttrfphitt Mittivttt Tim^m^ K*\U, \y. and v.) The ftoPition of the patlebt ti of 
extreme impurta»o«. In auvero uatics tbe liuad should be pluoed vortieallj downw&rdi. ^h 



AN^ESTBETJCS. 



301 



▼igoroildj used, aotl the inspirL^d air should be At from 80^ to 85^ F., or 
evcD ltt^h<sr. Frictions and passive motion, to aid in the circulatioiij mast 
not ht foj^tten. Efforts at resuseitiition should be kept up for at least two 
hoam Nitrite of aniyl htis hiio.n used m a tiieuns of reeturln<jf th*i heart's 
AOtton^ but ite power must still be eonaidered entirely 9u6 judice (see N, K 
Jteii. Joum,, xxtv.^ p. 4G7)« 

Poisoning has beeo produced by the swallowing of chloroform. The 
sjniptotiis induced have been stupor, with contnicted, or, in later stages, 
ilikled, pupils^ and a stertorous respiration ^ which finally bceomes Tory 
irregular, shallow, and often disitant The amount necessary to destroy 
life probably varies greatly. Recovery has occurred afler the ingestion of 
iwo ounces (Stillc, Therapeutic^^ vol. it, p. 107), of one ounce {^Canatht 
Igcm^ei^ March, 1874), alt^n of three ounces without vomiilng {Bnt MttL 
JovfTu^ 1882, i. 776). Tlie treatment consists fu the use oi' the stomach^ 
pamp and of the various ordinary mcthod.H of arousing a narciitixcd patient, 
specially the Hlternate cold and httt douche, artificial respiration, and the 
very cautious use of diffu!>ible siiinuli if required. Death may occur during 
the oarcosis, or the patient may survive this and perish from io6aiumutiun 
of the trachea, oesophagus, and stomach, caused by the local action of the 
chluroforin. 

The recogtiitlou of chloroform as the probable cause of any given death 
cannot be based upon the f>ost-niorteTn appcaranccB. Indeed, the latter arc 
of no value in deciding such a tjuestion. The ansesthetic may, huwevcr, be 
noovered by distillation of the lungs and blood within a certain period 
of time after death. As to x}w. length of this time, so Air as I am awure, 
no investigations have bei n njadc. 

Experiments made at tlie Philadelphia Hospital and confirmed by Prof. 
JX4bcau {Aiimiks *V lli/gilue^ Jan, 1874) have proven that persons stmnd 
aalccp may be cblorofonncd without their being awakened. Anic?sth(\^ia 
cannot, however, be produced in any one partially awake, or even sleeping 
lightly, without his knowledge. 

Quite a number of professional men have been accused, and some con* 
victed on the charge, of cumuiitting rape on females in whom they were 
inducing anaesthesia. The women , no douhtj believed that tlicy had been 
violated ; but it is certain that in many of the cases, and probable that in all 
of them, they mbtook for the reid act the subjective erotic sensations induced 
Hy tlic chloroform or ether. The valuelassne^^ of the testimony of persiiins 
is to occurrences during the time of their intoxication with ansesihetica 
should be rexjogniied by law as a governing principle of evidence. 

AUMIMSTIIATION. — Internally, from fifteen drops to a fluidrachm of 
chloroform may be given in emulsion, or, as it has recently been stated, 
diasolvctl in glycerin (1 to 3). The deep injection of half a drachm of 
«hlori>f<inn has been r.^comraendcd very strenuously hy Prof. Bartholow in 
obstinate neuralgia ^ and has found some favor in France (^Buil. TlUrap^^ 



302 SYSTEMIC REMEDIES. 

xciii^ pp. 433, 471). In the odIj case iq which I have tried it, one ot tri- 
geminal nearalgia, the local symptoms oansed by it were so severe as to 
imperil the life of the patient The U. S. Pharmaoopcoia recognizes a tpirit 
(Spirittis Chloroformi — 1 to 10, U. S.), dose, one to two flnidrachms, and 
a mixture {MUtura Chloroformi, U. S.). From the commercial chlorofoim 
a liniment (^Linimentum Chloroformi, U. S.). 

Bichloride of Methylene was introduced to the notice of the profession 
by Dr. B. W. Richardson {Medical Timei and Gazette^ 1867, p. 478) as an 
ansesthetic similar to, but more pleasant and possibly safer than, chloroform, 
and has been pretty extensively used in London. It has never been largely 
employed in this country. There is no way of knowing how many timet it 
has been administered, but certainly lour deaths dependent upon or eoiaci- 
dent with its use have been reported (^Med, Timet and Oaz^y 1869, iL S24 ; 
Brit, Med, Jour,, Sept. 1871, and August, 1872, and London Lancet, 1877, 
iL 26). The recorded phenomena in some of these cases indicate that, like 
chloroform, the bichloride of methylene kills by paralyzing the heart. It 
is not probable that it will ever come into general use as an anaesthetic. 

The Bromide of Ethyl has been used as an anaesthetic, and at one time 
bid fair to become very popular. The occurrence of two deaths during its 
use, however, early arrested its successful career. It is a very prompt 
anaesthetic, in most cases acting even more quickly than does chloroform, 
but less agreeably to the patient. Recovery is very prompt. Its action upon 
the heart is the same as that of chloroform. Injected into the jugular vein, 
it arrests the heart, and one death produced by it was distinctly by syncope. 
In some cases it has seemed very irritant. It appears to be quite as 
dangerous as chloroform, and will probably never be used to any extent in 
practical medicine. 



CfLASS IX-EXCITO-MOTORS. 



XN thifl clnas are Included suvh drugs a^ Increase the reflex activity of 
die ipinal oentrea and thereby pve riae to disturbance of uiotiHty* The 
<mlj ropreacntatives of the cliu^ used by the practitioner of medicine are 
tliote drugs which oontaiii strychnia aa their acdre principle. 



HUX VOMICA-KUX VOMICA. U.S. 

The seeds of Strychnos nux vomicja, a middk-eized tree growing in the 
EmA Indies, whence the drag enters commerce. They are oircularj nearly 
flat disks, a little less than an inch in diiimcter, covCTcd with very short, satin- 
Hke, gmybb hairs ; intemally they are tou^h and horny, and are possessed 
of an intensely bitter taste. They contain two aJkaluids, — strychnia and 
bmcia,^ — existing in combination with an acid, the lyo^urfc of Pelletier and 
Oiventou, whioh^ according to FhLseuiann, is probably identical with malio 
udd. Brttcta^ which, unlike BtTychnia^ h wyt officinal, is readily reockgniied 
by the following test. When concentrated nitric acid is added to it, a beau- 
tiful scarlet or blood -red color k developed ^ which becomes yellowiish-rcdj and, 
by warming, yellow ; if to this yellow sointion, somewhat diluted, some chloride 
of tin or sulphuret of amuionium be added, it beconica a bcimtifnl reddish- 
riolet, I*hysi«»l*>giciiily and thcnipeuticaliy thw alkaloid \a similar to, but 
weaker than, strychnia. 

The diwe of the extract (Extrnctnm S^uci» Vonucmy U.S.) is from one- 
fourth to one-half of a grain, given in pili \ of the tincture { TinctuixJ iVi/cti 
Vomtcm — 1 to 5, U. S*)| tifteeo to twenty *five drops; of the nUtract (ji6- 
ttmctum Nnci9 Vomicm, U. S.), one to two grains; of the Jfuid extrad 
(^E/rac/nm Nuci$ Vomtcm Fluidum^ U* S ), two to three minims. 

STRYCHNIN A. U.S. 

As kept in the shops, strychnia ia a gray ish- white powder, but by sJow 
crystAllization from its alcoholic solution it may be obtained in octahedral or 
in quadrilateral prisms. It is soluble in about seven thousand parts of cold 
water ; in two thousand parts of boiling water ; very sparingly soluble in abso- 
lute alcohol, ether, and benzine ; freely soluble in boiling o£Bcinal dcohol, 
which deposits it on cooling. It is so bitter that it will impart a very intense 
Lute to twenty thousand times its weight of water. 

Strychnia yields a very pronounced violet color with many oxidizing re- 
^gants. The one most ordinarily employed is a mixture of concentmted sul* 



h'Sftt SrSTEMW REMEDIES. 

phuric acid and bicbromate of potassium ( Otir/s test). According to Dr. 6»^^ 
the tost m most deliciit^ if the alknloid be dissolved in a little eoneentral^>^^» 
milphurie acid on a plate, and the bichromate added to it, when a bluish an^^"^ 
then violet-purplish color is developed, passing finally into a dirty gi 
Davy% test consists In the substitution of a crystal of red prassiate of potM^ 
si am for tlie hjehromate, Marehand uses the peroxide of lead ; in this case 
the sulphtiric acid should contain one per cent, of nitric acid. Drs. Vrij and 
Van der Burg say that these tests are about equally sensitive, and are capable 
of revealing the one SLxty-thousandth of a grain of the alkaloid. Either the 
chlorate or the permanganate of potassium may be used instead of the bi- 
chromate ; indeed^ Dr. Guy claims that the permanganate is preferaVjIe to 
the latter. IP the strychnia be in quantity, it may be dissolved in very 
dUuta Bulphuric acid^ and solution of bichromate of potassium be added* 
when golden -red needle-like crystals of the chroma te of strychnia will sepa- 
rate. These dissolve, with the produQtion of a beautiful blue C5olor, in oon 
centmtcd sulphuric add. F. L, Souiicuschoin { ViertcJjahr€S$chriJ't filr Prakt. 
Phamiacie, 1871; says that if strychnia be dissolved in a strong solution of 
the sulpliate of aesquioxide of cerium a beautiftil eolor is induced, which 
generally passes into a cherry-red, and so persists for several days. 0r* 
FUchors test (Lancet y April, 1872) consists in the addition of solution of 
chloride of gold, and the testing of the precipitate by Otto's method. The 
physiological test for strjehnia is a very sensitive one. In it a fragment of 
the suspected extract, dbsolvod in a little acidulated water, is thrown into 
the cellular tissue of a small frog, which should afterwards be allowed to 
swim about freely, so that its unconstrained movements can be watched. 

Physiological Actios. — Strychnia acts in the same way upon almost 
all animals. According to Leube (ReicJiert^ g Arcfiiv filr Anatomi*^^ 1S67» 
p. G3(} ), however, it takes ten times as much to kill chickens as other birds, 
weight for weight; and amonn mammals the guinea-pig is very insensitive to 
it It has also recently been asserted that on some monkeys it bus very little 
influence {Boston Medical and Snrf^ical Jourmd^ 1872)* Its local action is 
that of a slight initant. 

When taken in quantities just sufBcient to produce sensible physiological 
effoots, strychnia in man inducc?s a feeling of restlessness, perhaps accompa- 
nied by tremblings in the Itmbs and some e^tiffness in the neck and jaws* 
When a somcw hat larger amount has been given, there may be general mu** 
cular twitchings and startings, with stiffness and stricture of the throat and 
chest ; formications or other abnormal sensations under the skin may nr may 
not be present. After poisonous doses the s^Tuptoms come on usually in from 
fifteen to twenty minutes, rarely after the hour, with great suddenness ; eome- 
times the ctmvulsions are preceded by partial epasms of the muscles of the 
extremities, but more often the patient is suddenly thrown down by a general 
tetanic spaam. In this the body is bent backwards and rests upon the heels 
and the heaih in a condition of prof nind opisthotonos ; the legs are rigidly 



EXCITO'MOTOnS. 



305 



I and the feet oTeried ; the arms bent and the hfunds olenulied ; the 

stttnng, wide open ; the oorners of the mouth oflen dmwn up so as to 

lee the rimg nardonictts. The seusea are ofkni sharpcfiad, but rini^inj; 

ia <:lit* ear^ and dimneaa of vision may be induced if the fits are sevi^rc. Tlie 

(iu?6 ia at first pule, but, if the fit ia ^ufBcteutly severe and be protnicted^ it 

beooflitiB livid from the interference with respiration. Consciousness iji not 

i^Mtedf ualea^ when u^phj^xiu becomes so pronounced t\& to threaten death ; 

m fi^ch QiUK'A M/nictinwM a period of insensibility precedes dissolution, but 

generally the intellect is clear to the moment of death* The muscles of the 

}9LW ire usually the last in the body to be afFected, but trismas fiuidly cornea 

Ott ia severe c/i»es. I have seen death occur in tliis first convulsion in ani- 

Ifnala; but Tardieu states that he kuows of no such instance in man (ciimpare 
oise of Dr, Demme, Sr^il Soc. Tear-Book, 1865-66, p. 441). After a time 
the paroxysm is at an end, the jaw drops, the muscles relax, and a perioil of 
^Im comeft on, to be suceeeded by a second convulsion like the first. Theso 
©onrulsioaa are excited by the slightest touch, by a draught or breath of air, 
•Teil by a loud sound ; but a firm grasp or hard rubbing of the muscles is 
woqueutly grateful* A slight rigidity b somotimos manifest between the 
ptrozjams, but no marked stiffness. The Bpasms are generally, but not 
■IwayB, very painful. There are often erections of the penis, and the imc^ 
*'*<1 urine may be passed iuvoluntarily. If the C4ise terminate favorably, 
^o c^jiivuLHions gradually lessen in intensity, and fade away, Imiving the 
paticQt exhausted, with a sore, tired feeling in the muscles. After death, 
tuortem rigidity is developed very quickly. Autopsies have revealed 
tluug but the asual congestive lesions of death from asphyxia, and, at times, 
dilutions of spinal hyperaemia. 

In regard to the method in which strychnia produces the above symptoms, 
obvious tluit the alkaloid is primarily absorbed ; and experimental proof 
8o superfluous that I will only mention the fact that Masing \\i\& found 
^ etrydinia in the blood. 
It 'm very plain that convulsions can be produced by a drug in only five 
I ^ys ; first., they may be epile]>tiform, — i.^., cerebral ; second, they may con- 
^■»**ivnbly be due to a stimulation of the peripheral ends of the motor nerves ; 
^■•o^ixi, they may conceivably be caused by irritation of the peripheral ends 
^f^ **'^^ sensory nerves \ fourth, they may be muscular, — i.^., due to a direct 
^^■ctiQu Qjj ii^jj muscles j fifth, they may be spinal. 

^ "at the v'ouvulsions of strychnia-poisoning are not cerebral, is proven by 

"^ faet which has been frequently noted, and which I have confirmed, that 

^^^J are not aflfected by Bection of the cord, or, at least, are only so far affected 

HP ^ l>e more severe in those portiuna of the body removed from the cerebral 

^^'*<stice. Tliat they are not due to irritation of the peripheral mot^r nerves 



and 



^'^ not muscular is proven by the exporiniejit of Valentin (Pnthftbtgle 



«r A'i^rivrt, p. 327, Lei|;»ic, 18tit), who found that the injection of a sulu- 
^^ of etryt'hnia through the blood-vessels of the amputated leg of a fVog 

20 




30G 



SyS7EMlC REMEDIES, 



bdd no ijiilueiic^r upon the muscles. A very beuutlful experiment of Bror"^^ 
S^uanl ( Cftmptc&'Rtmhts^ 1849) oonfimis this, autl also dcuionstratra th^^, 
the convukiojiti Jo not arise Irom hypcr-excituhility of the peripheral uffewi^ 
nerves. The ul^servcr last mentioned found ttiat when the spinal cordwi 
cut just below the. origin of the nerves supplying the fore tegs of a frog, 
all the blood-vessels going to the lower section of the cord wer« also sevi 
BO aa to isolate the latter, on the exhibition of stryehniii convulsions occurrtMi 
in the anterior part of the body, whilst in the posterior Bcgment quiet ttud a 
normal reflex activity were maintained, although the blood was carrying tho 
poison to every part of it except the spinal oord. The philosophy of this is 
evident. The anterior section of the cord, receinng the poison^ pive rise to 
convulsions j the posterior section, receiving no poison, maintained its usual 
status. 

Tills experiment of Brown-Sequard has been refK?ated a great number of 
times by M^I. Miirtin-Magroji and Buisson (Jmirimlde la Phyn'oloqle, 186t\ 
t iii, p. 130) with similar results, excepting that in some very rare instanoet 
slight convulsions were induced in the posterior portion of the body. These 
exceptional phenomena appe^ir to have been due simply to a niiuute portion 
of the poison reaching the spine by inhibition, since, when by an operative 
procedure not necessary here to detdl (ioc. ci^,p. 131) tlie posterior section 
of the cord was completely isolated and access of the poison by diffusion 
rendered impossible, spasms never cMicurred in the posterior partof tlie body. 

Strychnic convulsions must be spinal, because they do not arise in any 
of the other possible methods. This conclusion is abundantly confirmed by 
direct experiment. Thus, Van Decn {Ph^/siologie de Ui MoeUe ipinihrt) 
and Valentin {Ioc. cit,^ p. 320) have shown that when the alkaloid is 
placed upon the spinal cord, and allowed slowly to diffuse itself, the usual 
convulsions occur, but are at first confined to those muscles whose nerves 
have their origin near the p<^*int of appllc4ition, and afterwards spread from 
muscle to niuwele as the poison creeps through the cord. Dr. A, J. Spenoe 
{Ediuhurtjh Midkal Joitrnal^ »Tuly, 186C) has performed similar experi* 
ments, with similar results. He first bisected the apex of a frog's heart so 
as to allow all the blood to dmin from the body, and then, cutting through 
the cranium, laid a httle piece of nux vomica within it upon the bnun so 
that the poison would diffuse down through the spinal cord. The result 
was that first the muscles of the throat, then those of the fore legs, aud sa 
on iu regular order, were affected.* 



• Some of tlio phettomfsna stAtcxl by Dr. Sponee to fa&re debarred arc At pr««etit t-erj 
difReuU to explaiD. Thus, ho noted Ihftl ft« the poipon tmreled down the cord ibero 
wat A time when irrilntioD of iho foro feet cauted only Fpa^in io th<»tii *, lafer in ibe 
ftxperimout, irritftiicm af the front feci e&ust^d spikSiii of buth the froDt and hind fret, 
■kUhough tm'tation of the Latter did not produce other than norniAl reflex tnovementi; 
later »ti\] ill the poisoning came n stage when irritatioD of the frnnt Icg^s wiui powerIe«t 
to caa^e fipasm m the hind legs, although irritation of the latter would duw oaaf« tpwn 
ts the foriziiT. 



EXCITO-MOTORS. 307 

JSpiiud Cord.^-Qhndu Bernard (Le^owmir U'H Snbsfances tcxiqut*, Paris; 
denied that strychnia produces excitation of the spinal motor centres, hc- 
cMiisewhco all the posterior nerve-roots are cut, no con vulaionij occur, whcrc-ns 
if a single afferent root b© allowed to remajti^ irritation of it^j peripheral 
ibrillas cauaca freneral tetanic spasms. Allowing the truth of his experiment^ 
fHet ., liL* (Itfduotiou certainly is not warrantiihle.* The non -oa'urri'nee of eon- 
"nalsiun,? may depend upon the fact that the reflex mutur jL^nni^lioinc cell«? are 
incapable of originatiDg an impulse, and id strychnia^poi^niDg are simply la 
•ttch a condition of over-excitability as renders them exceedingly sensitive to 
filig^lit irritations and ciiuses them to respond most energetically to peripheral 
ittipuLsttS so feeble as not to he felt in health* That the motor centres are acted 
"ipoii by strychnia m proven not only by the experiment^i that have beeu 
*U"ead5 detailed, but by the following ingenious one of Van Been {Physi- 
®^*<yiV <le la Moelk ipinibre). That investigator removed the viscera, vessels, 
®**5.^ from a frog, so as to leave nothing below the second cervical vertebra 
•'Ut tlie bones, nerves, and muscles ; then, opening the spinal cord in the 
'^^S'^o of the third vertebra, he cut entirely through the anterior columna 
^^^^ ^e cord, and finidly divided all the tissues, so that the anterior portion 
^^P* the frog was connected with the posterior solely by the posterior columns 
^^^ the oord* When one or two drops of a solution of strychnia were placed 
"^ the mouth of the prepared batrachian, tetanus, confined to the anterior 
^^giuent of the body, was developed j and it was also found that whilst 
'^«~itation of the posterior feet caused in them only ordinary reflex move- 
***^iita, in the front legs tetanic spasms were simultaneously induced. It 
*Pl>eara to me proven by the evidence adduced in this and the preceding 
p8***agraphs that strychnia is a powerful stimulant to the motor cells of the 
fsptixcU cord; including in this term the whole spinal tract up to the pons 
^iH^olii, As shown by Spttzka, and confirmed in my htbtjmtory^ enorriiuus 
Qos^^ of Btrychnia injected inL<3 a vein kill sdraoHt instantiiTieously without 
th^ production of a spasm. Such doses probably kill the nerve-centres just 
*^ l^J'i^t doses of a cardiac stimulant overwhelm and paralyze the viseus, 

J^utor Nervei. — The action of strychnia upon the motor nerves has been 
^ ^^txbject of conaidenihle controversy. That the convulsions occur inde- 
pentiently of any such influence, if it exists has been already shown. After 
deA.t1i from strychnia, the fuuclions of the motor nerves are always found to 
l)e more or leas impaired, so chat gulvanization of the norvo-trunk either 
prcxluoes only very feeble eontructions in the tributary muscles, or else none 
iH.* Of this fact there would seem to be no doubt; it has been 

^•'. 8[»lUk^ [Chica^fo /'#ttm. Ment\ and ^Verr. £>*«.» ri. 216) iiffirms timt A frog witli nil 

- ii»>rj Dfirvo-rtKiU nod the nerves of speolitl nvnBe divided etill dertilopa letsnas wUon 

^*^'>Ot& ii odmititHtered. It wmild be jilningo if tm noted j& pbjBiolo^sL a« Claad« 

"ti ihuuM iu»k« to groM An error in experinientiition. 

*«"- \Y. 11, KU[jp nl^inai tliftt be h-ts fautid iu tbirtjr-aeven expfirltfienta the motor 

*jniiii|iftired in tbe frog a Tier doAlb from atrjobaia {Journ. Meni. and iVerc« i^^'-* 




308 



SrSTEMIC REMEDIES, 



attested on the evidence of personal experiment by many observers, amo^^^ 
whom are Matteucci (Tivt'ti iki Pheitom. eiectio-ph^moL, Paris, ISU^^' 
Moreau (Comptes-Rendtu Soc. Ue BioL, 1855), M. Aiubrusali {Guz. MiC* 
1857, p. 525), Wiuicb {Bertc/U Forlschritie AmU., 1857, p, 434), KiiUik^ 
(^lli'cfiows Atchhy Bd. x. p. 2li9, 185 (i), and Vulpiaii {Atch, de Ph^MiU.^ 
Nov. 1870, p. 125), Now, it is evident that tbia absence of response may be 
due to losH of foiictiotml j:Ktwer in either muscle or nerve, Somctimea the 
mustle miiy be at lUuk; but, ws Matteuct'l (ioc. ciL) liimU% aud as bas beea 
noted by many observers, not rarely — lodeedj most generally — in the frpg 
galvanization of the nerve failfi to elicit response, although the muscle pre- 
serves ita irniability. M, Ch. Kiuhet (Compt. Rend., xci. p. 131) detcT- 
inincd ex perimeu tally that if active artitieiul respirutiun be maiutuiued, 
enormout} dosea of strychnine injected into the vein of a uaawmal puntlyic 
iho motor nerves. M. Vulpiau (Ibid,^ xciv. 55G) has coufirmed these 
resultis : m that it may be considered proved that in the warm- us well aa in 
the t'o!d4>hH>ded animal htryehuine depresses directly the motor nerves. 

It having been proven that the functional power of the motor nerves is 
destroyed in strychnia-poison in ji:, the question arises, la this destruction a 
direct action of the poison ^ or Is it simply the exhtiustion of over-use, due to 
the intense activity of the nerve during the stage of spasm ? 

It cannot be gainsaid that tbe power of tbe nerve ia lesfijened by the strain 
upon it during the convulsions; and Kbiliker concludes ( Virchow^s Archtv^ 
Bd. X., 1850) that thia is tbe sole cause of the uerve-pamlysia, because 
when he cut tbe sciatic nerve of a frog and exhibited atrychnia the divided 
nerve would respond to galvanic stimuli after all functional power had been 
lost in the nerve whose connection with the centres was intact^ Granting 
the experimental fact, it would only prove that contact of tbe pobcin was 
not the sole cau.se of the motor-nerve pandysls, as it is plain although both 
nerves suftiTod this contact, yet the uninjured suffered it plu3 exhaustion 
from excessive use. The conclusion Ls^ moreover, opposed by the fact attested 
by Vulpian {Archiites de Pk^Mulugle^ 1870, L iii. p. 120) and other observers, 
that an enormous dose of strychnia kills llie frog without the induction of 

Oct* 187S), It Ib inoontioiv&ble that ail prevluux obterv^ri should bo miaiakeo in their 
obferviaiona. It has betjii fiugijysied liint tbe cfiect^ ufioti iho mpLor nervo* unuAlty attfib- 
uttnl l«» stryebniur have been due to bruetii tiouhnmiruiliiiif it ; 4*nil Pr. K«bert P. K<*bto« 
if*hU<t. MetL fiwtfi, ix. 228} baa found nervcB iiJUiniHtive in iinicDnlt kilbU willi brucw; 
» re*aU in accord with Ibe esiierlujoifit^ mude upmn Run* u^euleuU by Prof* JMounier, of 
tlenflvju Dr, Liiutonbjwsb hvus shown^ bow«vor* that cbemioally iiure Rtryobniii hn pairs tbe 
rnueliun of tbe motor Dervoi. an^J tbiil in *omo frug?*, or nntU^r Botue life eonJition*, bmcin 
btif nn efl'uut u(>an the uorvot. It wr^ld seem tbiU both of tbe»e alkaloids iui|»a)r tbe 
tiinotiDii* of the laolor nervoa, but that under certain oaudilionB tbe norvc* hare Kfe^ter 
re«i»«ting powers tban uj-uab It i* [jr«i>bubiy different ttatea of hualth rathtT ibfto different 
e|tecif!« of I'rogn, n^ bolieviMi by Liiuteabjiub, that cause tbe tiiverRity of reealt** Tha ym- 
iibililj of & btray galvnuic current b«ing directly transmitted by it nerve txi » tuiuoU 
uiust al»</ nut bv forgotten. 



KXCiTO^MOTORfi, 



30d 



bj generml fmralysis, with total loss of power in the nerve-trunks. 
Evidently in such case the action of the poison on the nerves niust be <ltfect 
MM. Martin-Mttgron and Btiisson have investigated {Joumfitde h Phf* 
fMt^'t^ I860, t ill. p. 342 ) very eljiboratcly this action of strychniA upon 
tht nerres, und the ourrectncss of tlii'ir e^fieriments and results seems to 
mm acftrcely quostionable. They Jcmnd (foe, c//., p. 347) that if the Rciutie 
IMrre of a frog were cut and a sufficiently large dose of the etrychnia admin- 
mered, the divided sciatic lost it.s irritability, although, unle^ the dose was 
W€fy lftrgt% not so soon as did its fellow. Vulpian (Joe. ciV., p. 12G) has con- 
Snoed ihia; and the opposite result of Kolliker no doubt depended upon his 
not naiiig sufficiently lun^ dosoi* of the alkaloid or upon hi» testing the nerve 
Uw early. Martin-Ma^on and Buisson also tied all the tissues of a fix^g's 
leg exct?pt the nerve, and then, on exhibiting strychnia, found that convul* 
aions oeoaed in the poisoned much sooner than in the non-poisoned leg^ and 
thai at a certain time irrttations of the poisoned foot would induce tetanic 
ipttSDis onfy in the nnn-poimfted jnemher^ — prmif that the afferent nerve-tibrea 
of the poisoned leg were not affected, and that the motor nen*cs were juini- 
lyied wherever the poison had access to them ; and that to this, not to spinal 
exhaustion, was due the genend paralyms. 

M, Vulpian {if*c, f*>„ p. I'il) affirms that he has repeated thb experiment 
many tiuiea, and always obtained the same result as Marttti-^Ugrou and 
Btiiflaon. It would i^mm to prove that etrycbnia in very large do^cs para- 
lyx«9S *he efft^rent, but not the afTerent nerves; and that the oollapiie of 
ftrychnia-poiauning in the frog is largely due to the affection of the motor 
trunks^ and not to exhiiastion of the spinal cord. Again Vulpian {he. c*/., 
p. 122) found that the nerve protected by tying iti* vessels preserved its 
irritability alW the non-prot4*cted nerve li»d b'^t Its functioiiid fw^wcr The 
evidence ap|>ear» to be as complete as it can, and to show that in strychnia- 
poisoning, at least in the frog, the motor nerves lose their furjctional power 
partly through cxhaoj^titm and partly thrnngh a direct action of the poison 
upon them. As Fraser has di.icuvercd for atropia, Vulpian (locctt,, p. 128) 
has found for strychnia: namely, that after a tinie, — say from some hours to 
two days, — if the dose has been of the right sin^, the strychnio paralysis 
paaMis offj the motc»r nerved are found to have regnined their power, and the 
coDVutsions reappear, and continue hours or days. 

Circufnti'on. — Strychnia has a very deL^ded influence upon the eirculutmn. 
Drs. liichter {Zeitmhri/t J) ratmn. AM,, ISttJ, xviii;), :\Iayer {MrtLJnhfb, 
(L k. k, Ot9ell/teha/t dfr Aerzfe zu M'lVn, 18T2, p. 112), Schlesinger i lf*tti^ 
1874)» and Klapp {Jonmal of Mi^ntiU Dmmea, OcL 187B) have all found 
that a decided rise of arterial pressure oi>mos on before or about the titue of 
the firht convuUion. The rise is not due to the convulsion or to the inter- 
ruption of the circulation, as it occurs in curarized animals in which artiliciiil 
roipiration is maintained. Both Eichter and Mayer aflirm that the small 
irt«rie« can be seen to contract under the influence of the strychnia, and 



310 



SYSTEMIC REMEDIES, 



lectio^ 

I 



conclude that the riae of the pressure id due to Taso-motor spasi 
ako touod that lifter paralysis of the domiiiant vaschmotor ceutres bj aectioi^ 
of the cord J strychoiik produ<ied no rise of the arterial pressure, or if \ 
iriB caused, it waa very slight. A different experimental result has^ 1 
ever, beeo reached by Schlesinger (Joe, cit,). Th\n iovestigator found i 
the rise after ihe division of the cord both absolutely and relatively eio 
that produced in the normal animal. It is worthy of note that in three of "i 
the fifty experiments made by Schlesinjrer upon rabbits, the strychnia failed 
to elevate the pressure after section upon the cord. Schlesinger explains 
the apparently opposite results reached by himself and by Mayer by ihe 
fact that the latter investiar>itor employed rabbits, and further states that in 
six experiments made by himself on dogs, he four times obtained rasutts 
simitar to those of Mayer. Klapp experimented upon the cat, dividing not 
only the spinal cord, but also all the cfirdiac nerves of the neck. Under 
these circumstances no rise of pressure followed the injection of the strychnia^ 
A very plau?ible explanation of the peculiar results obtained by Schlesinger; 
is that given by Klapp : namely, that he failed to make a perfect aectioD of 
the oord, Klapp having found that a few fibres are sufficient to can^ up 
the impulse. Further experimentation upon rabbits is necessary before any 
final judifiuent can be passed upon the work of Schlesinger, but the drift 
of the whole evidence is to show that much of the rise of the arterial 
pressure produced by strychnia upon the normal animal is due to vasO'iDotor 
spasm. It is well known that afler divi^iion of the cord stimulatioD of a 
sensitive nerve fails to e-ause vaso-motor spasm and rise of arterial pressure. 
Schlesiuger found that in the strycbnised animal the contrary to this is 
true. This curious asserted fact receives some support from the experiments 
of Kin pp. In the majority of instances he failed to get a decided rist, but 
in a few cases he did. The expknation of Schlesinger is that in the normnl 
animal the peripheral impulse can only reach the vaso-motor nerves by first* 
going to the dominant centre, but that strychnia so alters the functional 
couditions of the spinal cord as to allow the peripheral impulse to phty all. 
through the local ^-aso-motor centres, which undoubtedly are in the eordj 
and to cause a general vaso-motor spasm by producing innumerable local; 
apasms. This theory may be true, but must yet be considered as stthjitjice. 

It has been shown by the experiments of Klupp that the primary sttum- 
lation of the vaso-motor centres by strychnia is folJowcd by fall of arterial. 
preesure and vaso-motor palsy ; abo that very large doses produce an imme-^ 
diate depression of the vaso-motor centres and fall of the arterial presauns* 

There is some apparent conflict of testimony in regard to the influence of 
strychnia upon the inhibitory cardiac nervous system. Dr. Carl HcineniannJ 
who has investigated at some length ( VirchMv*s At^ckiv, Bd. xxxiii« p. 3SI4| 
the influence of the drug upon the heart of the IVog, finds that large doseai 
cause diminished frec|uency of the cardinc movements, with diai^tolic pausesJ 
According to liia cxiRTimcnls, these j>hcnomena are not due to slimuli 




EKCJTO-MO TORS. 



311 



of the intiHiitory oenres, since tliey occur after aection of the vsigi (p, 403), 
©or are the peripheral vagi paralyzed » since galvanization of one of these 
tiery«0 causes immediate diastolic cardiac arrest (p. 4()6)» Mayer {he, cii,) 
ham also found that the peripheral vagus ia not paralysed, since he could 
sospend the action of the heart in the poisoned animal by galvanization of 
iJie par vaguoi. Klapp Yu^b also reached rei«iilts confirniatijry of tho«e of 
Hctnemanti. On the other hand, Martin- Maf^on and Buisson affirm (/oc. 
ct/., p, 352) that in all of very many ejt peri toe nts, ailer a ^eater or leas 
leag^th of time, the pncutnogastrics lost thi*ir power of transniittint;^ an 
i«pulsc?. The reconciliation of these results is very diffii-ult- posiiibly 
Murtin-Magron and Buisson employed a strychnia containing very largely 
of bmcia; possibly enormous doses of strychnia do affect the peripheral 
tngi, but not until very late in the poisonings although when small dos»es are 
eniploycdf even death may oceur without very decided paralysis of these 
Dervea. That the different results are not due to the use of different 
auimals ia evident, since, although Mayer used hounds, both Heinemann 
and Klapp employed the same aniuinls as did Martin-Magron and Buis.<^on, 
fix., frogs. Dr. L Steiner has found the action of strychnia much more 
aaarked when it is placed upon the posterior than on the anterior face 
of the frogs heart, ako that the strychnia acted much more promptly 
and severely upfui the separated sinus venosus than upon the ventricles or 
attriclos, and hence concludes that the strychnia acts especially upon the 
^uigltaof the sinus* His experiments and conclusions have been confirmed 
by Kiiipps and are probably correct. 

Upon the Uor)d strychnia lui^ probably some action. llaHey found that 
blood shaken tor twenty-four hours with air contained 11.33 parts of oxygen 
and 5.^6 parte of carbonic acid; whilst blood treated in a precisely similar 
mannt^r^ except in the addition of stryelmia, yielded 17-80 parts of oxygen 
and 2.73 parts of carbonic acid. He concludes from this that strychnia arrests 
oxidation in the body ; but the dtxluction seems to me out of all proportion 
to the fact. 

K^€. — ^The effect of strychnia upon the normal eye has Ijeen recently 
studied by V. Hip|»el ( Wirkung de^ Str^thnins auf die nonnalt itnd krunkc 
Ati^n^ Borlini 1873) and Cohn ( Wiener Medtz, Wochemcltnjt, Nos. 4^, 47, 
1873), with rather different resdtB. They both, however, found the sharp- 
Heft of vision increased.* 

Ti! KaAPKCfTlcs, — As a vegetable bitter, strychnia is, of course, a tonic, 
stimuluting to a greater or leas degree the digOi^tion, be^nides acting more 
universally on nerve-power. But it is more than a mere sloniachie : clinical 
experience has shown that it is a most useful tonic when there is general 
rekxation and loss of nerve-power. A portion of Ita value arises, it may be, 



• Ff>r th« (]<!tiin» of their itudteff the r<MMlcr \» rer«rred to the -triginal papcr» or to tk# 



mm 



812 SYSTEMIC REMEDIES. 

IVom ite aotion opon the spinal motor ncrro-oentree ; but in all probability H 
influences other portions of the cord, affecting the vaso-motor centres, and 
most probably also the trophic centres, if they exist Be these things as 
they may, clinical experience has abundantly demonstrated the value of the 
drug as a tonic in general functional atatiy and relaxaiiim. 

The great influence of strychnia upon the function of voluntary motion 
early led to its use in cases of paralygis^ oflen with the result of doing harm 
rather than good. Its peculiar physiological action being known, it becomes 
very evident that it can be useful only when the paralysis is dependent upon, 
or at least accompanied by, a depressed state of the spinal or other motor 
centres. Whenever there is inflammation or irritation of these latter^ strych- 
nia may do great injury by increasing such irritation, and must never be 
employed. Like galvanism, in hemiplegia it can do only a very limited 
amount of good, and should not be exhibited until irritation from the dot 
has ceased. Andral and others commend it especially in lead-jmra lysis. 

Since attention was so signally called to the value of strychnia in amau- 
rotic affections by Nagel, of Tubingen, in 1871, numerous observers have 
published extended series of cases in which it has been used with strangely- 
varying results. They have for the most part, however, served to verify the 
favonible results obtained by Nagel (Die Behandlnng der Amaurosen und 
Amblifopeen mit iStrycknin^ Tubingen, 1871). His sanguine exptictationa 
regarding its use in nerve-atrophy have met with disappointment in the 
hands of other observers. It is now conceded that in atrophy of the essen- 
tial nerve-structure little is to be expected from strychnia or any other 
means. It is most useful in cases which have not yet reached the stage of 
atrophy, but present slight if any ophthalmoscopic changes. The chalky or 
gr<^nish-white and cupped nerve-entrance is not always, however, sufficient 
cause for pronouncing the case hopeless, for these appearances are nut always 
safe indications of the amount of injury done to the axis-cylinders. Its value 
in amaurosis from abuse of alcohol and tobacco is undisputed. Also in 
amblyopia from disuse, — e.y., in strabismus and paresis, — afier the parallelism 
of the visual axes has been restored, under its use normal sharpness of vision 
is much more rapidly attained. In cases where the ophthalmoscope reveals 
but slight change in the retina and nerve, — e.g.^ slight striation of retina 
around the disk, the margin of which is somewhat obscured, or in those 
disturbances of the anastomotic circulation at the nerve-entrance, witJi or 
without diminished sharpness of central vision and oontraction of the field, 
— strychnia is of marked benefit. The distressing headache and giddiness 
associated with these nerve-troubles which thus manifest themselves in the 
eye are frequently relieved by the use of strychnia, even though the nerve is 
quite atrophied and the eye blind. There is much difference of opinion as 
to the method of its administration, but better results in the hands of most 
observers follow its hypodermic use. The temple would seem to be a better 
locality than the arm, as improvement in the corresponding eye has been fre- 



EXCITO^ MOTORS, 313 

qtientlj dbnrved, while \t& fellow remained m befbre. It should be ^ven iti 
^nutuAllj-iDcreasing doses, l>cing ^t>veriied by the trilerance of tlie action oi 
the drug. Cotumcncing with one-thirtieth of a grain, it can, usually, in a few 
w«eks be carried up to one>tenth or oven one-fiflh of a grain onoe or twice 
daily, those doses causing only a twitching in the calves of the legs, or a 
ali|;ht aenae of oonatriction atwut the throat, 0>ming on in from ten to fiflecn 
itiinut««i after their administration, and J^ubsiding in the course of an hour or 
twcK It ia necessary to maintain the physiologicaJ impression of the drug to 
insure the be»t resulta,* 

Dr. J. Milner Fothergill has recently drawn attention to the value of strychnia 
m» a naspiratory stimtilant in d^Rpnaa dependent upon puliuonie affections, such 
»« chrunic hronchifUy cmpht/arma^ and phthUu, In long-t^turulbig Lrouchitti^ 
iir "• wtn/er-cnitf/h^^' with a diliit'?d rij;ht h<»art, the conibinalion of ^Irychnia and 
digitalis in his hands him acted exceedingly well. In other ca-ies ho is aocua- 
toxi]«d to add the strychnia to ot^linary stimulant coui!;h mixtures. 

In fi^^pepsttt or count tpnf ton or duirrhiEa^ connected with nr<Miy of the 
visceral luusodar ooat, strychnia is a very valnable remedy. In vjirious local 
piaral^'SGS, such us prolnptte of the rectum^ atonic ret eat km uf %mnt^ aionk 
ineonHnrncr^ and ions of voluntary motion in cert^iin groups of mnsclea IVott 
testipurary injury to the supplying nerve or even from so di^ep-seatod a disease 
as infa utile pa rait/ fie, it is uat'ful. There is reason to believe that it sometimes 
duci^ good in these caaes by influencing the nutrition of the affected muscle 
or the peripheral nerves; and it should be injected into ihv affected part 

Toxicology, — ^Sufficient has alrcutiy been said in regard to the general 
sytnptomsof strychnia-puisitniiig. It only retnaius to discui** the diagnoais^f 
Tills is especially imptirtant^ because strj'chnia is frequently used criuiinally, 
mud because not rarely it is impossible for the chemist to detect it atler death. 
The only disease with which poistniing by it may be readily confounded is 
letantia, in its various fhrms of idiupathic, rheumatic, Irauiuatic, infantile, 
aod hysterical. It has been nssertcd that in fatal eases the duration of the 
attack will always distinguish between uatund tetanus and that prodnced by 
|K)ison. Dr. Louis Starr^ however (Philadelphia Mcdicnl Timr$, vol iii. p. 
31 n, reports a case of traumatic tetanuB fatal in less thou twelve hours after 
Uie first appearance of muscular twitchings^ and within one hour and a half 
after the first convulsion j and according to Jaccond dcitth has occurred 
fifteen minutes after the reception of the injury {^Pathohgie Interne^ i. 441). 

Tlie following table shows^ I think, in as clear and brief a manner as 
|<iif«»ible the differences J between traumatic or idiopathic tetanus (No. 1), 

• Th»» paragmph wm written hj Dr. S. D. Rii»»^y, and is «^j»ri?*iive uf the retnlta «t lh« 
l'niv«r«ity llosjiittt), whcrci he it rhifif a.fiiflnt»nl of the Q|4rtb»liiio]ogieaI Cliniiu 

t A Imii^n fouQcl in uoo oue by MurU Roaeiithiil mnj poistbl; bo obnrHctcristio. It i« 
nitntertmf nnnU croff-rvnti in thu hvnrt-uiusale, aaoompaniod by iiniiU extr»ri»8*tioa# 
^ Sttr't^itf^md'htitrnn^ 1^70, p. ',VA\\. 

X Columa Ko. 2 U from kq ttotonl oii«. Bet Trial of Mrs. Wharton, New Yitrk Mtdieal 



314 



SYSTEMIC REMEDIES. 



hysterical tetanus (No. 2), and strjchnic poisoning (No. 3). The references 
in column No. 3 are to authorities who affirm that the symptoms there given 
are peculiar to poisoning. 



Hn L 



No. 2. 
Oommenced with blindnetsand 
weaknen. 



Matcnlar Bymptomi nraally 
eoinmenca with pain and ntiff- 
neM of the baclc of the neck, 
lometiraee with flight mascular 
twitchings; come on gradually. 

Jaw one of the earl t est parts 
affncted; rigidly and perBlstently 
aet. 



FeniSstent muscular rigidity, 
▼ery generally with a greater or 
less degree of permanent opis- 



thotonos, omproethotunoe, pleur- ilons had ceased the opisthotonos 
osthotoDos, or orthotonos. and InteDM rigidi^ lasted for 

hours. 



Consciuusnen presonred until 
near doath, as In strychnic poi- 
Boning. 



No. 3. 

Begins with exhilaration mod 
restlessnem, the special senses 
being nsnally ranch sharpeiii'd.* 
Dimness of rision may in soms 
cases be manifested later, after 
the derelopment of other nymp- 
toms ; but even then it is rare. 

Mnacalar symptoms deTelop 
very rapidly, commencing in the 
extremities, or the cunvnlsian, 
when the dose is Urge, seizes the 
whole body »iniultaiieoiMly.t 

Jaw the last part of the body 
to be affected : its muscles relax 
first, and, even when during a 
seTereoonTvlHiun itisset,itdmi« 
as soon as the latter ceases^ 

HuiiCQlar relaxation (rarely 
a slight rigidity) between the 
conrnlsions, the patient being 
exhausted and sweating. If re- 
covery occur, the eonvnlsions 
gradually cease, leartng merely 
muscular soreness, and some- 
times stiflhesB like that felt after 
Tiolent exercise { 

Oonsciousness lostas theseoond Oonsdousnes^ial wnys preserred 
conrulsion came on, and lost with during con rulsiuns, except when 
every other convnlsiou, the dis> the latter become so intense that 
turbance of oouficiousness and death la imminent from suffoca- 
motilitr being simultaneous. tion. In which case tometiwifa the 

patient becomes Insensible from 
asphyxia; | which dimes on dur* 
Ing the latter part of a convnl- 
siou, and is almost a certain pre 
cursor of death. 



Muscular symptoms com- 
menced with rigidity of the 
neck, which gmdually ** crept 
over the body,** affecting the 
extremities lant. 

Jaw rigidly set before a convul- 
sion, and remained so between 
the paroxysms. 



Persistent opisthotonos, and In- 
tense riisidity between the con- 
vulsions; and after the convul- 



Drangbts, loud noises, etc., pro- 
duce convulsions, as In strychnic 
poisoning. 

Hay compUin bitterly of pain. 



Kyes open, rigidly fixed, dnring 
the convulsion. 



The slightest ** breath of air^ 
produces a oonvnlslon.f 



Desired to be (knned. 



Crying- spells, in which he Patient may scream with i«ln, 

"sobbed violently,** and "cried ir may express great apprehen- 

like a child,'* alternated with the dons, but " crylng^epells** would 

convulsions. appear to be impossitde. 

Eyes closed. Eyes stretched wide open.*^ 



* Taylor, On Poitomif p. 683, Wormlcy, Mvro-Cheminiry of Poitoiit, p. 536. 

t Wormle.v, p. 5:56. Still6, Therapeutic*, vol. ii. p. 148. 

X Taylor, On PniMotm, pp. 134, 682. Wormlcy,— pp. 536, 540, 541. Tardieu, Snr VEm- 
po{*onnemeHt, p. 924. 

§ Taylor, Oh /'omoiis, pp. 134, 136, 682. Wormley, pp. 636, 640, 541. Tardieu, pp. 
924, 938, 939. Ilusomann, Hundbuck der Tnxicologie, p. 168. 

fl Wormley, p. 536. Taylor, Medical Jurxepmdencef pp. 331, 332. Wharton and Stills, 
MedicalJurittprndenct, paragraph 757. Tardieu, p. 923. StiII£, ThempeHlicn^ p. 148. 

f StilI6, Therapeutic*, p. 148. 
*^Still€, Therapeutic; p. 148. Wormley, p. 536. Tardieu, p. 924. 



EXCITO-MOTORS, 



315 



Sfa.1 No. 2. No.*, 

The 0p»fma In l^f must bans Lrgf •tJfl1]r<^teii^M,w1i)i foci 
bMQ iMitSal, M th« fiHtt wore eYort«tt,* u tlie ipMjmu mffr«t *ll 
cnwed unU toM liivrrttitl, which the miiactM of tlie )«(. 
could tiut hik|ii>«n if mt\ lUe riiUk 
clofl wcPH lnirult«<l, l>i»aiu*o tU* 
raii«c]«« of eTPwii^n, Iwiiig terj 
tnacb Ui« *tn.iinn'r, won 3(1 of ob^ 
ceMltjr uvertom« tlieftntngunlfUc 
miuclM, uid the f4H>t tM9 everted* 

Deftth from strychDui in man and other mammals mostly occurs in a oon- 
Tuloon, and under these circumstances is tind*iubt«dly due to aa|>ljyxiii, caused 
bj the unyielding spasm odicaHy-contracted muscles. In frogs, death must 
occnr from other causes, since a fro^^]^, as shown by Claude Bernard, will live 
for days after removal of it« lun*;s, probably by breathing throuj^h it* skin. 
The causes of death in the frog are not hard to find when the pliyfiiologieal 
action of ihc dmg is known. The lymph and true hearts (Kolliker, Irtc. 
cit, ; HarJcy, Lancet^ July, 1 !^5G) are very much affecte<l, but the chief 
factor is no doubt paralysis of the motor nerves. In man, death Bometimefl 
occurs not in n paroxysm, but during relaxation, and probably then is tlic re* 
suit not only of the exhaustion fullowing effort, but al^o of the direct action 
of the poison on tlie nerx'e^. 

The minimum fatal dose of Btrychniii is probably something under half a 
grmin ; the latter quantity has several times produced death, once in a man 
in twenty minutes (Gu^'s Hostp. Rep,^ 18*35, vol. xi. p. 20B) ; one-third of 
a gruin given at intervals in fractional doses has produced such alarming 
ayioptoms as to indicate that in a single dose it might readily destroy life ; 
the y)^ gmiti is said to Itave killed a child three and a half months utd 
(Phttrffi. Jffurn. aiui Tran$,, viii. 101 U ) ; but ten grains (Tschepke, Deunchet 
KHmk^ 1861), twenty ^ins (A. E. Connor, Ohh Med, Recorder^ 1879, 12), 
also twenty two grain!* (Dr Qw. (jray, Bnf, Med,^ 1880^ i. 477) t^iken on a 
fiill stomach and ret^iined two hours, have failed to cause death, in each case 
probably on account of slow absorption. 

In treating poisoning by strychnia, a chemical antidote should be at once 
admintstercd, such as tannic acid, or iodine, or one of its soluble salts. As, 
however, the eompouTids formed in the stomach by these substances are not 
permanent, a quick emetic must follow their administration. For the treat- 
ment of the symptoms, various substances have been recommended, Aeo* 
nite, Calabar bean, t tobaceo, or their alkaloids, would appear to be indieated 
a^ physiologically antidotal The evidence brought forward by Dr llau^hton 
and others is not sufficient to establish clearly the especial value of tobacco, 
and in the experiments of M. Amagat iJourn. de Th^nip.^ 1875) nieotia 
M»eiDed to have no power in prevent iog the death of rabbits which had 



♦ Tarflieti, |». 924; al- t^, which I buve n«gl«ol<rd to oore, «nd at prwcnt 

wriiitig have out nt hin^ 

^ T«« oiMM» of r«eoy«if/ verj dt^ubifolly ttttnbuUibl« to Calabar (xMint Ohio Mtd* lit* 
<t9rd9r9 iv^. 164. 



316 SYSTEMIC REMEDIES, 

received a fatal dose of strychnia. Further, it is obvious that the use of 
aconite, or of tobacco, in large doses, is accompanied with grave danger, on 
account of their influence upon the heart, and we have in bromide of potas- 
sium a substance devoid of any such objection, and apparently as complete 
a physiological antidote to strychnia as are any of the substances above 
named. The chief question is as to whether the bromide has sufficient 
power and swiftness of action. In Dr. C. L. Bard*s case* {PhiUi, Med. 
TimeSf i.), recovery after the ingestion of three grains of the alkaloid, with- 
out vomiting, occurred, under the exhibition of a half-ounce dose of the 
potassium salt and " its continued use in smaller doses for an hour or so.'' 
The symptoms were as intense as was consistent with life, but general relaxa- 
tion was produced in thirty minutes after the ingestion of the counter-poiaoD. 
Chloral was stated by Liebreich, its therapeutic discoverer, to be antagonis- 
tic to strychnia, and it undoubtedly is so in a measure ; but M. Orr (^Gazette 
Midicah^ July 6, 1872) stated to the French Academy that he had ex- 
perimentally proven that the dose of chloral which Liebreich had relied on 
as being mortal to rabbits was very often not so, that the same was true of 
strychnia, and that consequently the investigation of Leibreich was not to be 
relied on as proving the respective antidotal powers of the drugs ; and, ftir- 
ther, that experiments had shown him that if a certainly-fatal dose of chloral 
were given to a rabbit, the hypodermic injection of strychnia did not affect 
the result, but that his own researches had not gone far enough to establish 
the exact relations of the drugs. Prof. Bennett {British Med. Jovr., vol. ii., 
1874) has made an elaborate study, which agrees with the experiments of Orr 
in showing the non-efficiency of strychnia in chloral-poisoning, but also proves 
that chloral is of great value in poisoning by the alkaloid. Out of twenty- 
one rabbits which had received much more than the minimum fatal dose of 
strychnia (gr. ^^-^ to the pound) fifteen were saved by the use of chlora1| 
and a few days later were killed in from ten to twenty minutes by a repetition 
of the original doses of strychnia. Dr. Bennett found that the chloral admin- 
istered after the supervention of convulsions had less effect in saving life in 
direct proportion to the length of time between its administration and that 
of the poison. Prof. Uusemann (^Arch. Exper, Path, uml Therap.^ x.) 
found it possible to prevent death by chloral in rabbits which had received 
five or even six times the minimum fatal do8e of the alkaloid. In two cases 
(^Edin. Med. Jonrn.^ April, and Lancet^ April 10, 1875), in each of which 
about four grains of strychnia had been taken, the good effect« of the chloral 
were very marked. Alcohol has been strongly recommended by some au- 
thorities (Amugat, Sta echini) as antidotal ; and when the great muscular 
relaxation of drunkenne^js is remembered, it seems very probable that the 
commendation has some basis. Prof. Husemann (loc. cit.) has, however, 

* Fur other Buccc.xsfnl qimq;?, sec New Remedie^f vol. li. p. 255; also, Chicago lliwl. Mm 
ammer, xxxix., 1879, 280. 



EXCITO-MOTOnS. 



81T 







ihown that alcohol can scareelj be looked \i{^on oa a real anUgoniBt t4> the 
ilkaloid. 

The bfst ireatnjcnt of ptrycbniapoLsoniiiL^ is appurently to be found in 
e conjoint UMt! of cblural an J ibe bromide of potajte^ium, with, when con- 
Mom are very threatening, inbalationa of nitrite of aniyl, eiheri or even 
loroforni. Half an ounce of ihe bromide with half a drachm to a'draebui 
f chloral may be given at once in a severe case ; and every twenty minutes 
tirurard^f if necessary, two drachms of the first and fifteen ^ains of the 
l-emody, 

ca^es, artificial respiration U]i*;ht poe^ibly be of service. It is 
^Bfident that the oonvubud muscles will often resist such efforts as are usually 
BMde to furcti air into the lungs of man as successfully as they do the uu- 
aausted •tnigglea of nature ; and Karley states that he has found artificial 
HspimtioQ of no use whatever in animals. On the other hand, Leube 
{Archives Anai, ti Physiol,^ 1SG7), in an apparently very careful series of 
tl|)griments, found that artififial respiration has great iBfluenee in saving or 
prolonging life, according to the amount of the poison iuirested. In bis ex^ 
peri meats, the dose which ordinarily produced coovulsioris did not do this so 
long aa artificial respiration waa kept up ; and the *' lethal dose" did not kill 
if artificial respiration was maintained for four houra, although opistfiotonos 
waa induced in some cases. Jochelsohn only sueceedetl in prolonging life 
(RoMbtich'i Untermchmigtn^ i., 92), but Rosenthtil, according to Huse- 
^^mann^ obtained similar results to Leube, and >r Schiff {Schmidt' t Jar- 
^BftifeA^r, Ed, oxii. p. 43) has, in a aeries of experiments, corroborated in the 
^Vlpaln facts the results of the German investigators, although disagreeing 
^■vith them in minor particulars. He found that animals in which /orcii^^tf 
I irtificiaj respiration was maintained survived doses much larger than those 
I ordinarily fatal The artiBcial respiration was pcrfljrmcd by inserting a 
canula into the trachea, and filling the lungs by force. Klapp also found 
artificial respiration of service. None of the ordinary methods of artificial 
^^iteapiration in man are, however, sufficiently powerful to be of any value. 

^H Administration. — As a tonic, strychnia may be given in pill ; but when 
^Hgt is desired to push it until its phybiologicjil effects arc manifested, as in 
^Kiome cases of paraJy^i\ it should be always administered as the sulphate in 
^^ solution, because death has occurred from an irregularity in the solution of 
j the pills in the alimentary canal and tho consequent simukiuieous letting 
loose of a lai^e amount of the alkaloid. There is no proof of a cumulative 
ction of this alkaloid when given as above directed. Dose, one-twentieth 
grain, gradually increased jpro rr nata* 

Stbycijnin.e Sulphas. \],S.— Sulphate ofStn/chnhw occurs in minute, 
ismatic crystals. It is soluble in water, and therefore preferable to the 
Ikaloid for hypodermic use. Dose, onc-twentielh of a grain. 




318 SYSTEMIC REhfEDIES. 

BauciNE. — L. WintzeDreid (^Dissert. laaug,^ GkDOva, 1882), in an elab- 
orate investigatioD, finds that brucine acta as a stimulant to the spinal oord 
and a paralyzant to the motor nerves, but does not influence the cerebrum 
or the sensory nerves : in the higher animals, at first it increases the arterial 
pressure, and afterwards lessens it ; paralyzes in large doses the vagi ; causes 
death by asphyxia, and in other ways acts like strychnine. 

Iqnatia. U. S. — The seeds of Strychnoe Ignatia, a tree growing in the 
Philippine Islands. The St, Ignatim Beans are pale brown, about an inch 
in length, less in breadth, often angular, with three or four faces, covered 
with a very fine, scarcely visible down. They have been compared by some 
to an olive in size and appearance. They contain largely of the igasurates 
of strychnine and of brucine, and are identical in their therapeutic value with 
nux vomica. The only officinal preparations are the abstract (^Abstractwn 
Ignaiist^ U. S.), dose, one grain, and the tvicture (^Tinctura Ignatlae, — 1 to 
10, U. S.), dose, twenty minims ; the dose of the extract {^Fxtractum Igna- 
tisty U. S. 1870) is one-fourth to one-half a grain. 



GLASS X.-DEPRESSO-MOTOHS. 



TJiTDEft this heading are considered certain drugs which are used for the 
parpoee of lessening the activity of the spinal cord. Thoy have^ except in 
^i^ partleulai, but Little in common in their action, and miust be studied 
iodividuallj. 

FHYSOSTiaMA-OALABAR BEAN. U.S. 

A.n irregular, kidncy-shaped beanj about an iiitjh in length and three- 

mrtHa of an inch wide ; the product tif the Physostigma venLniosuiUj a per- 

ooni^ woody creeper of Calabar, Africa, where the bean has been uaed by 

w>e natives am aa ordeal test for criminals, witches, etc., since time immemo- 

^^- It cmntains an alkaloid known as phj/sostitjfmia^ or escn'na. The most 

reliable testa for the alkaloid ore as follows. A watery solution of it or of its 

■Wts containing potassa, soda, or lime, on exposure to the air, becomes red, 

***d finally yellow, green, or blue: this is said to occur when only one one- 

*^tiucirL'<j-thoujJ5andth part of the alkaloid is in the solution. Chloride of gold 

^oro^ji duwn from the solotiou a blue precipitate, out of which tbe gold is 

®^*<^ii reduced. According to Dr J. B. Edwards (Mtdical Ti men and Gazette^ 

1 06*4)^ ^th strong sulphuric acid and bichromate of potassium physostigmia 

,yields II violet color, passing into red. This point needs investigating, in 

'^mtion to the well-known strychnia test. The pbyaiok^gical lest consists in 

^-ne placing of a drop of the suspected solution in the eye of a rabbit, wheOj 

~^ ptij^ostigmia be present, contraction of the pupil will be produced in from 

«t to twenty minutes. A second alkaloid, cakibartna^ ha^ been found 

^y -K. Harnack and L> Witkowski {Arch. Experim, Pnth, and Fkarm,^ 

^Oi iw cspecijl abundance in conimcrcial extracta. As Prof IJarnack 

*«» succeeded in producing it from physostigmia {Ibid.^ Bd. xii.), it is a 

'*^*<iral suspicion that it ij* formed by deeompoyition of the pbysostigmia 

Uriug the preparation of the extract. It ia much leas soluble in ether 

^^Inhariuat n<:curdltig to Ma dboovererg. Is Ji letaDiEiog^ oigfiiit fc*!^uuib1iri«f NtrycWtiia in 

.. "^tiiju ujHin fruj^s anil other of tbe lower hjxiiikiU. Pruf> Jlufietiiiiiiiti IVmiid„ howevisr, 

, ^^ erukV "Cttlttbarinum puruin" iictu in nn entirely ulii'gimilar miirnier, hitt llorEifUsk; 

m^ **lKoini LhaL thb cominuroial arllde onntains littk or no calnbirinn iinc An:h, Ej-pvr^ 

^* muA Theriip,, Bd. viii. 125j ijc. 434; x. vtOl), It is p*ia-*ibtu tliml |iliv.^o^Ugmijfc ba« a 

^ £^ tf iiclencjr lu undurgo varmus documpojditions, ntid to jtroUuce uuilur diiToretit cir43iita<- 

m divenfl derivAtire nlkaJoids. 

319 



■AM 



320 SYSTEMIC RRMEDIES. 

than is physostigmia, from which it may be separated by means of that 
menstruum. 

Physiological Action. — When an animal receives a small fatal dose 
of Calabar bean, after a time muscular tremors appear, and almost imme- 
diately the animal falls to the ground, or lies down, in a state of perfect 
muscular flaccidity. The pupils generally contract, and the respirations 
become slow, irregular, and oflen stertorous. All reflex actions are almost 
at once diminished, and this diminution grows greater and greater, antil it 
ends in their complete abolition. So long as the condition of the motor 
system allows of it, evidences of sensibility are manifested whenever the 
animal is in any way injured. According to Clementi Papi {SchmxdCt 
JdhrhUcher^ Bd. cxlii. p. 287), the voice is completely lost. The muscular 
tremors persist during the whole period of paralysis, and, indeed, even after 
cessation of the respiration. They vary greatly in intensity, and in some 
cases are so severe (Eraser) as to simulate general convulsions. As tha 
minutes go by, the rhythm of the respirations becomes more and more 
affected, and at last death takes place quietly, consciousness being preserved 
until the last few gasping respirations close the -scene. The pupils some- 
times, but not always, dilate immediately after death. According to the 
experiments of Dr. Fraser, the bodily temperature is alightly elevated. 

Ailer a small lethal dose of the poison, the fatal result is always duo to 
failure of the respiration, and if the body be at once opened the heart is 
found still beating ; indeed, it has been seen to continue to do so for one and 
a half hours after death (Fraser). If a very large amount of the drug be 
given, the animal falls almost at once, paralyzed, with only a few muscular 
twitchings. The pupils contract, and in a very short time the gasping 
respiration ceases. The heart is now found distended and passive, but often 
will contract under the stimulation of a galvanic current 

The symptoms induced by the drug in man are completely parallel with 
those that occur in the lower animals. They are giddiness, lessened heart- 
action, great muscular weakness, with, in most cases, contraction of the pupil, 
and sometimes with vomiting, and still more commonly with purging, which 
may be very free. A pupil of Gubler took 0.15 grain of the sulphate of 
eserina, and suffered, after a time, nausea, giddiness, and intense muscular 
weakness, so that he could not st^ind ; three-quarters of an hour afterwards 
he vomited some of the solution mixed with bile, but his strength did not 
bepjin to return for two and a half hours. 

These tremors have been seen after so-called pure physostigmia by Ross- 
bach and Frohlich. Kohler, llossbach, and others have even affirmed that 
Calabar bean produces a tetanic intoxication. A plausible explanation of 
these singular observations, and of many of the discrepancies of authorities, 
is to be found in the discovery of calabarina. Its discoverers state that it 
produces first a violent tetanus, and afterwards paralysis. It is plain how 
its presence in varying amounts in Calabar bean preparations would modify 



DEPRESSO-MO TORS. 



321 



their i«!tioii. The researches of Kohler^ of Vintscli^u, and of Rossbach and 
Frohlieh, are especially open to doubt, on account of their statements that 
CiiJabar beaQ tetanizes. It ia very probable the extracts used by them con- 
tained Urg<3ly of cakbarina. 

The qucfitioti here natundly ariaes^ To what is the paralysis so proroinetii 
in poisoDiQg by Calabar beau due ? It is endent that the suspension of 
reflex action can have only tliree sources : paralysis of the spinal cord, of the 
ncrrc^trunks, or of the muscles. I shall examine the action of the drug 
np€m these organs in inverse order, 

Mu»des. — The niuM'ular twitchings which have already been spoken of 
Have been mistaken for convulsions by M. Vintschgau {SUzung$herichte der 
J/ci/A,-JVyi/. Chsae d. k. Akad. d. Wksenscha/lm , Wien^ 18(j7, Bd. Iv., 
Abih, ii., p, 49), who, indet'd, concluded thiit Calabar bean acU like strych- 
^i^ because violent convukive tremors uecurrod, after injection of a dose of 
'^oe poison under the skin, in all parts of a frog whose tliacs he had tied* 
Evidence to be brought forward hereafter^ however, shows conclusively that. 
^ere was M)me fallacy in this esperiment. The fact that the must^ular 
"ttovemeuts continue after dexith indicates that they are due to a direct action 
^f the drug upon the muiw^Ics theiuselves. This conclusion is thoroughly 
^5*^blished by the experiments oF lAn.schkewich (Virchojcs Archw^ 18C6, 
*W- XXXV. p. 294), of Fraser (loc, at,), and of Leven and Laborde (Schimdt^g 
^fthrhucher^ Bd. cxivi. p. 136). All of these investigatdrs have noted thafc 
af^r death these contractions arc increased by exposure to the air and by 
*jireet stimulation of tiie muscles ; and Fraser has found that they occur in 
tile frog during life after section of the fiujiplying nciTC^ and also iit a muscJe 
Actually cut out of the body* Lasehkewich hiw confirmed the latter fact in 
^•^e case of warm-blooded animals, and Lcvt^n and Laborde have proven that 
J»»*evious destruction of the lower eitd of the spinal cord tii a *^iihi(.':ipig does 
**^t prevent the development of the muscular twitchin^s in the bind legs. 
Alt>n^ugh Calabar bean does, therefore^ have some direct influence upon the 
^>iU8cles^yot the paralysis produced by it h m no sense the result of this 
inftueace, which appears^ indeed, to be of an exciting rather than of a pura- 
^yxtng character, since at the time of death the contractility of the muscle 
^a m no wl^ diminished: on the contrary^ Fra^ser has noted that in poison- 
^•ig bj Caittbar bean the supervention of rijj;or mortis and of loss of funo* 
BpAOQal power in the muscle is very greatly delayed. 

■ -ATfnirt, — The paralysis caused by the pby^^sti^jjma la not due to an action 
^^ tile ucrve-truuks, since Dv. Liiacbkewit:b, Dr. Vintscbgau (7oc. ciV., p. 161)^ 
B *^^ Jilw Dr. Fraficr, have found that when the galvanic current is apj>liod to 
^^« crura! nerve of either cold- or warm-blooded animals rapidly killed with 
^PPpiAhtr bean, contructions are freely induced in the tributary nmscles. 

Wecil, tlie Scotch investigator, cjirrying his experiuieut^ still further, and 

^^n); lioliwite instruments which it is not necessary here to describe, discov- 

I ^^^ that when the artery going to a hind leg was tied in a frog before the 

31 



322 SYSTEMIC REMEDIES. 

administration of the poison, after a quick death the rate of conduction of 
impulse was as rapid in the nerve to which the poison had had free access, as 
in its protected fellow. Notwithstanding these facts, the drug is not entirely 
without influence upon the nerves, since Dr. Fraser has found that when the 
blood-vessels of a frog's leg are tied, and the animal slowly poisoned by a 
small dose of the extract, whilst even many minutes after cessation of respi- 
ration both nerves seem equally intact, yet finally a time comes when the 
nerve of the poisoned leg refuses to react to the galvanic stimulus, although 
the functional power of the protected nerve, as well as of the muscles, is still 
perfect. This loss of functional power is probably rather in the termination 
of the nerve than in the trunk, for Dr. Fraser found that when all the blood- 
vessels supplying the gastrocnemius muscle were cut in a frog and the animal 
poisoned, at a certain time irritation of the craral nerve produced spasms 
of the gastrocnemius alone. It is to be noted that this perturbation of the 
peripheral nerves has only been seen in the frog when slowly poisoned, in 
which case the heart continues to beat long afler the cessation of respiration, 
so that the nerves are, as it were, macerated in a solution of the poison. 
Its existence, even in this feeble degree, is denied by Hamack and Wit- 
kowski. In frogs, and still more in warm-blooded animals, nerve-paralysis, 
if it exist at all, is of such slight intensity as to be of no practical im- 
portance. 

The afferent nerve-fibres probably preserve their function afler the motor 
fibres have been affected, as was seemingly proven in Dr. Fraser*s experi- 
ments {loc, cit, p. 19) by tying the vessels in the left leg of a frog which 
was afterwards poisoned with strychnia, when it was found that reflex move- 
ments were excited in the lefl leg by irritation of the right foot long after 
irritation of the left foot had ceased to cause movements in the right leg. 

Dr. Fraser studied to some extent the effect of a strong solution of the 
poison when applied locally to a nerve, and found that the efferent fibres were 
affected before the afferent, and that finally the function of both of them was 
abolished. 

Sptnal Cord, — Since the abolition of reflex activity has its origin neither 
in the muscular system nor in the nerve-trunks, it must be spinal. The truth 
of this conclusion, arrived at by exclusion, has been abundantly demonstrated 
by direct experiment. Thus, Fraser, Harnack, Witkowski, and others have 
found that if in the frog a peripheral nerve be protected by tying its artery 
and the batrachian be poisoned with Calabar bean, the paralysis in the 
protected limb occurs pari passu with that in the remainder of the body. 
Again, Fraser divided the spinal cord of a frog, and then cut or tied all the 
blood-vessels going to the posterior section of it. After thb, the animal 
was poisoned with physostigma, and, whilst the usual symptoms developed 
themselves in the anterior portion of the body, reflex actions were unaffected 
in the posterior part. Further, Dr. Fraser has found that when the poison 
is applied directly to the cord, fibrillary contractions, due probably to a local 



DKPRESSO-MO 1 OES. 



323 



imtaut tnflaenee, lire induecd in the muscles supplied from below the point 

uf uppliciitioii; but in a little while nil raovemenLs o^asc, and even galvautza- 

tiou of the cord is itself unable to elicit response. It seems eoiupletely 

oitjiblisUed by the evidence which bus been brouij;ht forward that the most 

fmititincnt effect of Caliibar bean i& a (Ifpremant action upon the sjimal 

Kecentlj, however, it has been osaerted by Pupi (Schmidt*s JahrhUcher^ 
f Bd. cxlil p. 287) ihut there is in frogs, preceding the stage of depression, 
of exaUariun of rv^flex action ; and also, on the strenjrth of some experi- 
[letita upon ttoituats with one-sided section of the optic thalamns, that the 
ji(ii>t6itof voluntary movetnent itj Cahibiir bean poisoning la paralysis 
the conducting fibres pos^inj^ from the upper brain to the spinal centres, 
r h^ve not been able to protiure the ori^^inid paper of Dr, Papi {Gazz. 
J^rti^,^ 18G8), but his conchLsions seem to me highly iraprobable. The 
(>rininry stage of reflex activity probably was produced by caiubarina preseafc 
m the extract used by him. 

Gircnlation. — Harley [loc, cit.^ p, 151) and Papi {loc. cit,^ p. 287) assert 
Wtoif. Culabar bean hiis little or no influence upon the heart; but they are 
tiodonbu^dly in error. According to Harnack and Witkowski, in the frog 
Under the influence of the poison the heart's contractions become slower 
•^»<1 »tronger» When a mammal is poisoned with small doses, the cardiac 
a^otioii of the drug is subordinate to that upon the nerve-centres; but, aa 
li^a |>ecn shown by Dr. Frsiser, when very large doses of the poihon are 
•^^^uinistered, especially if they be injected into the jugtiliir vein, death 
'^*^-*»'»lis from ayncope or from consentAneous failure of the cardiac and the 
*'"'^*i>initory function, and the heart is found arrested in diastole, flaccid, but, 
*^^*2ording to Dr Fraser and to Drs. C, Arnstein and P. Sustschinsky {Vn- 
*^'"«»<c/i. Ph/aiohfjf. Lnhor. WUrzhnig^ zwoit<jr Theil, p. %^)^ responding, 
"^-Houjrli feebly and uncertalidy, to direct stimulation. In the frog, I^sabach 
•^n^X Frbhlich {FhannnL UntersttcL i., p. 5t>) have found that the arrested 
^^^J't is inseni<ible to stimuli* 

"VVhen smaller dose^ of the poison are exhibited, there is sJowing of the 
*^e5«^^*a action, a^ has been notod by Laschkewich (foe, cU.j p. 298), by Eraser 
cr.ciV., p. 48), by Dr. J. Tachau (Archwihr Heilknmle^ 1865, p. 70)^ aid 
other observers. Although, according to the experiments of Fraser, there 
«^l first a slight fall of the blood-pressure, probably due, as he believes, to 
^^aitii^hcd pulse-frcf[uency, yet, in spite of the latter, the arterial tennion 
^^Ti recovers itself, and remains for a long time much above the normal point, 
^ •^ ilf at the ?^mc time t!ie individual cardiac beata are greatly increased in 
J*^*"^JiigLh (Fraser, Bczold and O.itz*). Finally, the arterial pressure falls tar 
'^^ow normal, and the power of the heart is gradually extinguished. 



(/<* 



' 1 huro not !»ef;n the ariginnl paper of theio nuthontics In the Oenirnlhlntt fUr Med, 
*^l«mtntikft/t^ lSOi« but f|U4>te ihvw Trutn the prtpur of At-QiituiD and Sustscbinskj. 



324 SYSTEMIC REMEDIES. 

The question as to the exact method in which these changes are wronght 
IS of very difficult answer. The long diastolic pauses and the slow strong 
beat of the heart suggest at once that a chief action of the drag is upon the 
inhibitory cardiac nervous system. Tachau, however (foe. d^., p. 172), found 
that after section of the vagi the poison produces these phenomena in an even 
more intense degree than in the normal heart. As this has been confirmed 
by Laschkewich (foe. cit,)^ by Fraser (foe. eilf., p. 49), and by Harnack and 
Witkowski (foe. et/., p. 419), it must be accepted as a proven fact, especially 
since Vintschgau has found (foe. eiV., p. 71) that if in the frog the brain and 
the medulla be destroyed, physostigmia still acts in its usual way on the 
heart.'*' Tachau considers that this demonstrates that the cardiac phenom- 
ena of Calabar bean poisoning are not due to an action of the drug upon 
the inhibitory nerves. Arnstein and Sustschinsky, however, admitting the 
fact, deny that it warrants the conclusion. Their idea appears to be that it 
is conceivable that a substance should so act upon the peripheral inhibitory 
nerve-endings as to cause them to influence the action of the heart without 
any external impulse, and consequently when separated from the nerve- 
centres. With our present knowledge, the possibility of this seems some- 
what doubtful. Moreover, Koliler, Harnack, and Witkowski have all found 
that in the frog Calabar bean still lessens the pulse-rate af\er complete paralysis 
of the peripheral vagi by atropiaf {Archiv /, JExper. Path, und Pkarm.^ 
Bd. i. p. 280). Kohler believes that his experiments prove that the Cala- 
bar bean paralyzes the cardiac accelerator nerves. It will be remembered, 
however, that Vintschgau found that Calabar bean exerts its normal influ- 
ence upon the heart after destruction of the accelerator centres. Whatever 
may be the action of small doses of physostigmia upon the vagi and accel- 
erators, it seems to me that it must be considered established that the general 
cardiac symptoms are due to a direct action upon the heart-muscle or its 
contained ganglia, and that any increase of the inhibitory activity must be 
of such slight amount as to be of no importance. 

In regard to the action of the drug upon the peripheral vagi, the follow- 
ing risumi of the evidence is of interest. Arnstein and Sustschinsky found 
that the excitability of the peripheral cardiac vagi is increased by Calabar 
bean. They first tested the effect of graduated galvanic currents applied to 
the divided vagi in the animal to be experimented with, until the exact 
strength of the weakest current capable of causing diastolic arrest was de- 

* The fact that Calabar bean acts in ita usual manoer after section of the par vaj^am 
indicates that it has no influence upon the inhibitory centres, — a conclusion confirmed by 
Arnstein and Sustschinsky {lor, cit., p. 102), who found that an injection of the drug 
into a carotid — i.e., into the inhibitory centre— did not cause any marked immediate 
diminution in the number of the cardiac pul.«ations. 

-j- Kossbach and Frohlioh (Inc. eit., p. 50) assert that in fro^, although the vagi are not 
more excitable before than after the poisoning, stimulation of the venous sinuses and of 
the auricles has much more than the normal influence, which is very extraordinary if 
true. 



DEPRESSO-MO TORS. 



325 






^^>ei 



flooilltted, and then exhibited the drug nod tested the nerves afterwards. 

They used in these experiments both rabbits and painea-pifrs, and found 

that, without a single exception, current much weaker than those which 

previously were barely eflFtictive would, after the poisoninj^, atop the heart ; 

abo^ the super-excitability of the peripheral inhibitory nerves was shown by 

the fact that under the influence of the drug the diastolic arreat continued 

much lorj^^er than normal after the withdrawal of the stiniulu.H from t!ie 

vajri. Hhei^e experiments have been directly corrohonited by liovs^sbach and 

Frohlich upon the mbbit (loc. eit., p. 57). Dr. Fraser's expcrimtnts upon 

-he local cardiac application of the drug are also sceminjrly confirmative of 

ose of Arnstein and Suntisehiusky, for he found that when the poison waa 

ut directly on the hearty or into one of its chambers, it caused a prolonged 

diastolic pause, foilowed by contractions, interrupted by pauses, and finally 

■^esutuption of regular eontraotiona, or else by diastolic arrest, the heart still 

retaining its power of responding, in an embarrassed manner, to stimuli. 

These experiments certainly seem to prove that Calabar bean does cause 

exeiiaiion of the peripheral cardiac apparatus. Arnstein and Suetscbinsky 

rurtW confirm them by other experiments of exoceding interest They 

ijeetd into rabbits such amounts of atropia as completely to paralyze the 

riphcral cardiac vagi, so that the strongest currents when applied to the 

nerves failed to influence the heart's action, and then restored finictional 

pGton to the pneumogas tries by injections of Calabar bean^ so that cur- 

TQDts of moderate intensity caused diastolic arrest. These experiments, if 

■ccurate, prove that physostigma is a powerful excitant of the peripheral 

▼ag\, Kohicr (toe. ctV,), using the frog, imd Rossbach and Friihlieh, using 

the mbbit, failed to resuscitate the atropinized vagi by means of Calabar 

bean, bat it is evident that a negative result in such a case might be due 

U> an improper proportion in the doses of the counter-poison, or in the 

tttropia being employed in overwhelming amount. In warm-blooded aui- 

umiIs, at legist, the vagi are not paralyzed during life by pljysostigmia, as 

i» evinced by the experiments of Arnstein and Sustschinsky (/(><?. cit.y p. 

101), ooufirmed by Harnack and Witkowski (loc. cf/., p. 433). Some of 

the results obtained by Fraser (he. cit,^ p, 36), confirmed by Rossbach 

«acl Fralich, apparently contradict, but in reality accord with them. In the 

>Tog Uiere was, indeed, at last a loss of functional power in the vagi, but not 

mit very long after the cessation of respiration, after all the nerves of 

^mntnty motion had lost their functional power, — t.f., after death would 

^■^® Occurred in a mammal Harnack and Witkowski affirm that the 

*in i]Gv«5r lose their power in the frog to lessen the rate of the heart-beat, 

«thou^fi unable to cause diastolic arrest. 

^U Hinting up the evidence in regard to action of the drug upon the 
'*• ifi plain that no positive conclusion can be reached, although it seems 
k^i.**- ^ that the drug first increases and then lessens the power of the 
^*toi^ nerves over the heart 



326 SYSTEMIC REMEDIES. 

As already stated, a very promineDt phenomeDOD in Calabar bean poiaon- 
ing is rise of the arterial pressure. This, of coarse, may be of cardiao 
origin, or it may be due simply to a contractioD of the arterioles ; or it may 
arise from a combiDatioa of these causea Bezold and Ootx (quoted by 
Arnstein and Sustschinsky, p. 87) found that the arterial pressure still rose 
under the influence of the drug after section of the spinal cord high up, — 
t.e., afler general vaso-motor paralysis. Harnack and Witkowski also found 
that when the vaso-motor centres were paralyzed with chloral, physostigmia 
causes very decided increase of the arterial pressure. It is evident the 
increased force of the circulation produced by physostigmia must, at least in 
part, be due to a direct action of the drug on the heart. 

The fact that the rise of arterial pressure produced by Calabar bean is not 
so great in animals whose cords have been divided as in those uninjured cer- 
tainly indicates, though it does not prove, that the increased arterial tension 
of physostigmia-poisoning is in part due to vaso-motar npasm. Dr. Eraser 
believes that Calabar bean does produce this spasm; but his evidence is 
insufficient to establish his conclusion. It consists simply of some experi- 
ments upon frogs in which the spinal cord was divided, and, the animal being 
put on a '' frog-plate," the arteries of the web were watched whilst Calabar 
bean was exhibited. Dr. Fraser believed that under these circumstances 
the arteries contracted considerably at first, and afterwards dilated. Dr. 
Harley (PrcuUitioner, 1869, vol. iii. p. 163) states as the result of his studies 
that Calabar bean can be seen, when applied locally, to cause conduction of 
the veins, the arteries remaining unaffected ; whilst Fraser, in contradiction 
to this, believes that he has demonstrated that the local application of phy- 
sostigma produces dilatation of the arteries. It is not necessary here to re- 
iterate my objections to such evidence as this. If, under the circumstances 
of the first-mentioned experiments of Dr. Fraser, Calabar bean contracts 
the small vessels, it must be by a peripheric, not centric, action, since the 
vessels were separated by the division of the cord from the vaso-motor 
centres. It is plain that this is in direct contradiction to Dr. Eraser's ex- 
periments on the local application of the drug. Again, it is contradictoiy, 
rather than confirmatory, of that furnished by the study of the blood-pressure. 
The only logical conclusion seems to me to be that at present we have not 
proof that Calabar bean acts upon the vaso-motor nervous system. As the 
increase of the arterial pressure is in great part, if not altogether, due to 
the increased energy put forth by the heart under the influence of physo- 
stigmia, and as that influence is exerted directly upon the heart-muscle or its 
ganglia, it is evident that physostigmia directly causes the heart to put forth 
more effort, or, in other words, stimulates it. The final diastolic arrest (the 
loss of the power of responding to stimuli) shows, however, that at last the 
poison paralyzes the heart. In considering the general physiological action 
of the drug, it must not be forgotten that its influence upon the heart is 



DEPRESSO-MO TORS. 



327 



^Qtiretj subservient to its tnfiuence on the nervous systetDT^ and that death 
^Hl the EDammal occurs before the stage ofcardtac palsy i» rutieheiJ, unless tho 
^Brig be injected directly into the heart in orerwhelmlng doee, 
^H I do not believe that phy»oi*tigma has much action upon the hlomi, Cer- 
^■ilnly itA influence upon the nervous system is a direct one, since Lewisson 
^^itcwhert* 9 Avchw^ 1870) has found that it acts upou the *'8ult fmj;" a« npon 
^Hhe oormtl animal, Fmser^ however, etat&s that ufler death from this poiiwm 
the blood ooiigulates slowly and loosely, and the red disks in duixs and in 
^^nibbita present varioaa irregukrities of outline, ainong which may be noted a 
^hrell-tnarkcd stellar crcnation, but that the respiratoiy function of the blood 
b not interfered with. 

InteMtmeM. — Intestinal pcristdsis is very much increased by the action of 
CBlftbar bean (Westennann, Schmidts JiiJirbiicher, Bd, cxxxviii, p, 21*0; 
Papt, liiiL^ Bd. cxlii. p, 2S7 ; Fraser, loc, cit., p, 57), After poisonous 
doees there is at first a stage of exceedingly active movements in the bnwcl«; 
then spafimodic tetanic contraction of the intestines occurs, so tliat their cali- 
bre 18 very much diminished ; and finally relaxation and diltitatiun take 
place. Aller death the vermicular movements are found verj" much lessened 
^■LFmser), or altogether ahoU.shed (Taehau^ he, cit.^ p, 73). 
^H Tlje action of Calabar bean upon the intestines appears to he peripheral, 
^■ae to contact of tho poison in the blood with the muscular fibres or the 
^Hinglionic nerve-cells in the waits of the bowels. For Westermann (loc. ciV., 
^^ 291) found that extirpation of the cardiac ganglion had no eifect up(in the 
action of the drug, but thai lying of the mesenteric and of tho ecBliao arte- 
lies^ b<*fore poisoning, prevented any increase in the peristalsis. Calabar 
bean probably influences intestinal secretion. Its action upon the salivary 
glands ifl of^en decided, and according to Heidenhain is not prevented bj 
_Wopia. 

^B Eye, — Calabar bean, as is wcU known, strongly contracts the pupil, both 
^nrhcn applied to the eye and when exhibited internally. Evidently, as in 
^Bhe case of atropia, the pupillary action of Calabar bean should be t^tudiod 
^^piB two points of view, the local and the constitutional. 

The closeness of the analogy between the pupillary action of atropia and 

that of Calabar bean b seen in the fact that, like the former, the latter, as 

shown by the experimenta of V^ and Leven on chickens ( 0^nptf$-Rcndu$ 

^B^ la SoctiU de Biohgte^ 1SG5, p. 161), does not affect the irides of birds. 

|9bu9^ analogy would seem to prove that the influence of Calabar bean is 

directly upon the peripheral nerves of the iris, 
^m Although, then, I am not able to cite any direct experimcfital proof, yet 
^Kl fieems to me scarcely doubtful that the contraction of the pupil produced 

• For • ditaussJon of the pcouliar cftrdiao rGlations of phj9ott}|^ctti« And tinj«<^nrtD, teo 
tb« pftfter by llamank ond Witkuwski. Th"»o authors believe Ihiit CnlttHur beiiL leU 
\ oatiaa rbe hi«iirt arrefied in di&ptcite, not hf paruljxing the carili&Q iubibUory ifc|}p*- 
VtM| but by iiitoulftllns the (mnliao miuole. 




328 SYSTEMIC REMEDIES. 

by Calabar bean is always a local, peripheral inflaeDce, whether the dmg 
be placed in the eye from the outside or be carried to the general circula- 
tion. It is evident that the myosis may be caused in one of three methods : 
by paralysis of the 83rmpathetic fibres, by stimulation of the oculo-motor 
fibres, or by a conjoint action upon both sets of nerve-endings. In which 
of these ways the drug acts, we are not yet able to decide. 

It has been held by various authorities that if galvanization of the sympa- 
thetic fibres in the neck fail to expand a contracted pupil, the myosis must be 
due to paralysis of the sympathetic. Evidently, however, this is claiming 
too much, for, as pointed out by Griinhagen ( VircAow'* Archiv^ Bd. xxx. p. 
521), it is conceivable that an oculo-motor spasm can exist of such intensity 
that the antagonistic nerve is unable to dilate the pupil. The question arises 
very pertinently at this point. What is the fact in regard to Calabar-myosis? 
Does or does not galvanic stimulation of the cervical sympathetic dilate the 
pupil ? The testimony is somewhat conflicting. Dr. Griinhagen (Joe, cit,^ 
p. 521) says that dilatation always occurs, although to a slight extent («pi 
heschriinkteii Masse) ; whilst, on the other hand, Dr. Gustav Engelhardt 
(^Untersuchuugen aus dem Physiologischen Lahoratorium iih WUrzburg, 
zweitcr Theil, p. 526) has found that galvanization of the cervical sympathetic 
has no effect upon the contracted pupil. The experiments of Fraser (Joe. «*/., 
p. 60), of Bernstein and Dogiel, and of Rosenthal (^Reicfiert's Archiv^ 1863), 
would seem to reconcile these differences, and by their accord, to prove that 
under the maximum influence of Calabar bean the sympathetic is powerless, 
whilst when the contraction is the result of a milder influence of the drug, 
stimulation of the cervical nerve will cause a certain amount of dilatation.* 
Fraser, and also Engelhardt, have found that if the poles of a battery be 
applied directly to an iris even most profoundly contracted by physostigma, 
immediate dilatation occurs. These facts, for reasons stated above, do not 
absolutely prove, but they certainly render it highly probable, that Calabar 
bean paralyzes tJie periplieral sympathetic nerve-fibres in the iris. It is, 
however, almost equally probable that there is a consentaneous stimulation 
of the uculo-nwtor terminations ; for the myosis caused, like the mydriasis 
produced by atropia, is an active, not a passive, condition, and is not only 
much more forcible, but is also much more complete, than that which follows 
section of the cervical sympathetics. If the observation of Ilossbach and 
Frohlich be correct, that overwhelming doses of the physostigmia finally 
dilate the pupil, it is evident that the oculo-motor stimulation is replaced 
after such doses by oculo-motor palsy. 

Urine and Elimination. — No study, that I am aware of, has been made 

* Recently Rosshach and Frohlich affirmed that galvanisation of the sympathetic still 
causes dilatation, even when the action of the physostigmia is most rigorous. As it is 
scarcely conceivable that the various other investigators should have been so much in 
error, it is probable that Rossbaoh And Frdhlioh used such strong currents that they were 
directly transmitted to the iris. 



DEPRESSO-MOTORS. 



329 



^^Meras to the elitnination of Calabar bean or its action on the urinary 

secretiou in heulth. Dr, Mcrson (Jonnutl of Mental ScL, Jnn, 1875) has 

fuund that iti general parulyiiis under its influence urea mid the other solids 

of the urine ore decidiMily diiuiuished. The physostigma probablj eacaipeb 

■pith the nsnal secretion, and ia a ca.'WJ of poisoning its presence eould prob- 

^hbly be detected by dropping some of the fluid in the eye of tui animal, 

^B THXaAPStXTICS. — The physiological action of Calabur bean has su^^csted 

^Bl0 use in tipasmodic aflectionH, in atony of the muscular coats of the boifel, 

^viod in variouti dit^ises of the eye. 

The action of Calabar bean upon the ^inal cord YQry early led to its use 
in 0pii«m(Klio afiectioos, and especially in teianux, in which diseueo it has been 

I nore fredj etnployed during the lajjt ft-w yearH than any otlier remedy except 

^HQHttlo. In the paper of Dr. B. Il4:)emyr (#SV. LoaU Medical and Suiyt'cal 

^Kloifnta/^ 1873, p. 3G7) are collected forty-seven cases, of which twenty 

Hfroved fatal. To these I am able to udd the tliirteen whose references are 

giren below,* making in all sixty ciises, with thirty-three recoveries and 

lircnty- seven deaths, — ^not a very flattennj; record. 

It is, however, proper to state, as affeeting the value of these statistics 
tliAl much of the Calabar bean extnict which has been ofl^ered in the market 
la practically inert, and in all fjrobability in some of these easea the drug did 
laot have a fair trial \ and that when especial care was taken by certain 
CfebHcrvers better results were achieved, although on bo small a scale as to 
B^ftve the issue in much doubt. f 

In trmnu$ neoncUorum^ Calabar bean has been employed with re-sults cer- 

^Ainlj no more encouraging than those obtained in tetanus. In chorea it 

\3»B also been used by some practitioners with asserted advantage, but further 

experience hardly justifies its administration (see Bull, Gin, Thirap,^ 

Imxix., 85, 541), 

The physiological action of physostigoia upon the nnstriped intestinal 
:Biiiacle>fibres hi\s led to ita employment in atont^ of the muscular coat of the 
lH}web and other similar organs. Dr. V. Subbotin {ArcJiiv/, Kltn, Med., 
Bd. y. p. 28 5 1 1869) has used the extract with the happiest results in a 
ease of cJironic bronchial catarrh with intense d^qmarn^ believed to be due 
10 weakness of the bronchial muscular fibres ; and aW in one of apparently 
^phtntum ttimor^** with c/ironic vUe9iuud dtfttpepiia and catarrh. In con- 
tttpaiion dependent upon relaxation, it is also said to be useful. 

• Fat A I* Cariw. — Fcnwiok, 1 ((?^i*sf"i* ,Vcr/»V*W /o«r»a/, 1869, p. 300); Frniiioltii, I 

IThe Burttfr, Ovi. I, U7\)i Lttbortlti, 1 {HrtlUh Medical Jourtutl, Juao, !S72) ; Valdi- 

tkwo, 1 {Pkitftfielphin MmUcal Timev, rot. i. p. 455); Tysoo, 1 {Ibid^t p. 41S); Johnson, 

I {Ihid,^ p. S73) ; I iLimdutt lancet^ 1874). KKcov'Eitieii,'— FoQwiokf 1 {Qltitijtm MrUital 

\mmat, 1M(SU» p. 300); Newnuui, I {Meditnt Ejramintf^ July* 186fi); W. W. K««n, 1 

^kilndtffthm Mfdif^fti Time*, vol. 1. p. 193); J. II. Piuakarrl, 1 {ftud,, p. 138); Oaiming- 

l ( Britfh Mtdicn / Jv N r Htt/, i ., 1 8 7 4 ) ; I ( Cinemna ft Laneet, Sept, 1 878 ), All IhoiQ oaao» 

lot ih« traumatic form of the di«oa»e. 

' t For « fArorabtc rooor'J, ece Wivtaun, Otttagmo Mtdicai Jvitmalf K. S*, 1809^ TOL 1. p. 

i I eonAalt liJto London Practitioner, 8«pt. 18(19. 



330 SYSTEMIC REMEDIES. 

Calabar bean has also oeen employed in stryehntorpoiiontn^^ and a reooveiy 
obtained af^er the ingestion of three grains of the latter alkaloid is reported 
by Dr. J. W. Key worth {Glasgow Medical Journal, N. S., 1869, i. 54).» 

In epilepsy, some trials have been made of the drug, but its value is very 
doubtful. Drs. Harnack and Witkowski have found that in epileptic guinea- 
pigs physostigmia causes a succession of fits lasting for hours and days. They 
have further noted a similar influence upon man. Recently attention has 
been called to the employment of Calabar bean as 2l galactogogue, the extract 
being applied to the breast itself {Brit, Mtd, «/oiim., ii., 1876, p. 554). 

Administration. — Calabar bean is usually administered as an extrad 
{Extractum Physostigmatis, U. S.), the commencing dose of which is one- 
tenth to one-fiflh of a grain. The dose of the tinctvre ( Tinctura Phgso- 
stigmatiSf U. S.) is twenty to forty minims. The alkaloid is preferable on 
account of its certainty, but care is requisite not to use it too freely. 
Bouchut has found that in children one-twentieth of a grain, given hypo- 
dermically, will produce very decided symptoms, which entirely pass oflT in 
about three hours. It is probable that one-fifleenth of a grain, repeated 
every three hours, will be found to be a moderate dose for the adult. It 
should always be borne in mind that, in tetanus and other severe diseases, 
it is necessary to augment the dose until an effect is produced. Harnack 
gives the minimum fatal dose of cserina as for dogs four to five, rabbits three, 
cats two to three milligrammes. The frog resbts these doses successfully. 

Toxicology. — So far as I know, Calabar bean has not been used, either 
in Europe or in this country, with criminal intent. In Liverpool seventy 
children were accidentally poisoned at one time {Medictil Tim^s and Gazette^ 
Oct. 1864, p. 406). Many of the victims vomited spontaneously, and thus 
relieved themselves. Those brought to the hospital were in a state of ex- 
treme prostration and muscular relaxation. They appeared to suffer almost 
no pain, only some of them saying they had a little ** belly-ache." Among 
some thirteen examined, only one had the pupils contracted. The only child 
who did not recover was excessively weak, and, crying out suddenly, was 
dead of sudden syncope. The heart was found relaxed and flabby, both 
sides equally full of blood. In the ca.se of a strong man, who had eaten 
half a bean {St. BartlioL Hasp, Rep., 1879, xv.), the symptoms were great 
muscular weakness, tightness across the chest, temperature of 96.6° F., very 
ilow, intermittent, irregular pulse, collapse, without vomiting, purging, con- 
traction of the pupils, or abdominal pain. 

In 1864 Dr. Kleinw'achter treated a case of poisoning by an unknown 
quantity of atropia with Calabar bean, apparently with great benefit. Dr. 
Boumeville detailed in 1867 some experiments which seemed to show that 
there is a real antagonism between Calabar bean and the mydriatic, and in 

• Tbe subject of the aecerted antagonism between chloral and Calabar bean will b« 
gladied In the article on chloraL 



I 

I 



DEPRESSO^MO TORS, _ 

1870 {IlrvHt Photop-aphiqiu: des HopiUmx) p