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THE

PHYSIOLOGICAL AND THERAPEUTICAL

ACTION

OF THE

BROMIDE OF POTASSIUM

AND

BROMIDE OF AMMONIUM.

IN TWO PARTS.

EDWARD H. CLARKE, M.D.,

AND

ROBERT AMORY, M.D.

BOSTON:

JAMES CAMPBELL,

1872.

/^ HABVASO C01U6E IIBBARY

^cVe

C-

( /o. 2<;. /8SS\

Entered according to Act of Congress, in the year 1872, by

JAMBS CAMPBELL,

In the Office of the Librarian of Congress at Washington.

cambridgb;
prbss of john wilson and son.

MiCnORLMEO
KfHMNtSO

PREFACE.

When Dr. Amory, two or three years ago, com-
menced his study of the physiological action of the
Bromide of Potassium, I promised to supplement
his investigations by some account of its therapeu-
tical use and value. Circumstances prevented the
fulfilment of this promise at the time his paper
appeared in the Transactions of the Massachusetts
Medical Society. The call for a second edition of
his monograph has reminded me of my former
unavoidable neglect, and I have endeavored to re-
pair it by the preparation of the following paper.

The number of essays that have latterly appeared,
both in this country and Europe, from the pens of
physiologists and practitioners, on the Bromide of
Potassium and kindred salts, attests the . important
place which it holds in the present Materia Medica.
This importance is my apology for burdening the
medical public with an additional paper upon a

PREFACE,

drug about which some may think too much has
already been written. The honest observations of
the humblest observer are not altogether valueless ;
and I am glad to contribute my mite towards an
exact knowledge of the therapeutical applications
And just value of so important an article as the
Bromide of Potassium. The paper is not exhaust-
ive. It is only a contribution.

Boston, x8 Arlington Street,
March, 1872.

CONTENTS.

IPart S.

Therapeutical Action of Bromide of Potassium and Kindred

Salts.

PAGB

Bromide of Potassium 9

Absorption 10

Elimination ^14

Action while in the System 17

The Continued Dose 34

Action of the Toxic Dose . 57

Special Applications of the Continued Dose ... 64

Epilepsy ... 83

Hysteria 92

Antagonism of Bromide of Potassium and Strychnia 97

Bromide of Ammonium 102

Bromide of Lithium no

Bromide of Sodium 112

19 art I3F,
Physiological Action of Bromides of Potassium and Ammonium.

Absorption 115

Chemical Properties 123

Effects upon the Secretions 130

Elimination 134

Effect on the Blood-Vessels 143

Effect on the Nervous System 145

Conclusions 156

PART I.

THE

THERAPEUTICAL ACTION AND VALUE

OF THE

BROMIDE OF POTASSIUM,

AND SOME OF ITS

KINDRED SALTS.

By EDWARD H. CLARKE, M.D.,

PROFESSOR OF MATERIA MEUICA IN HARVARD UNIVERSITY ; FELLOW OK T)IH
AMERICAN ACADEMY OF ARTS AND SCIENCES ; FELLOW OF THU
MASSACHUSETTS MEDICAL SOCIETY, ETC, ETC.

*' EvBN at the present day, our Materia Medica is in a state of chaotic confusion ;
and its history is merely a summary of the fruitless efforts of thousands of gifted men,
searching as it were in the dark for the curative power of drugs." — James Rogbrs.
M.D., The Present State of Therapeutics^ p. 2.

*' Our knowledge [of remedies], though augmented of late years by the wonderful
advance of Organic Chemistry and Physiology, can scarcely yet be said to have passed
the threshold of inquiry. We must avow that this whole department of medical knowl-
edge, so important in all its bearings, is the one where most remains to be done to raise
it to the character of a science. . . . Despite these difficulties, the scope and prospect
of future attainment are ample and certain." — Sir Henry Holland, Medical Notes
mnd Reflections^ pp. 21, 22.

BROMIDE OF POTASSIUM.

INTRODUCTION.

T^HE therapeutical value of the bromide of po-
tassium rests solely upon clinical observation.
The only safe guide to its administration as a
therapeutic agent, however, is to be found in a cor-
rect knowledge of its physiological action. Hence
the importance of studying and comprehending the
latter, before endeavoring to ascertain the former.
It is moreover important to recollect that the state
or condition of the body in disease is not the same
as its state or condition in health. Pathological
state^ are different from physiological ones, and con-
sequently modify, in a degree proportionate to this
difference, the physiological action of all drugs.
This pathological modification of physiological ac-
tion is not so marked in the case of the bromide
of potassium, bromide of ammonium, bromide of
sodium, and bromide of lithium, as in that of many

lO BROMIDE OF POTASSIUM,

other articles, such as opiujm, alcohol, digitalis, and
the like ; yet it is sufficiently marked to deserve the
careful consideration of the practitioner.

Absorftion. — It appears from the researches of
Voisin, Laborde, Eulenberg, Damourette, and Pel-
vet, Saison, ZaepfFel, Bowditch, and others, as well
as from the experiments detailed in the second
part of this monograph, that the bromide of potas-
sium is easily and rapidly absorbed by any mucous
surface, and especially by that of the stomach.
When the stomach is healthy and empty, and when
the bromide of potassium is largely diluted with
water, the whole of a therapeutic dose passes into
the circulation in a short time, probably in less than
half an hour after it has been ingested.

If the above conditions do not exist or are modified,
there is a corresponding interference with absorption.
Thus if the mucous membrane of the stomach is
irritated as in some dyspepsias, or inflamed as in
gastritis, or degenerated as in organic disease, it
absorbs the bromide with a certain degree of difii-
culty, and indeed under these circumstances may
refuse to tolerate its presence at all, and so instead of
absorbing it throw it oflT by vomiting. Hence these
conditions generally contra-indicate the exhibition of
the bromides. Mere vomiting, however, is no contra-
indication. When vomiting is sympathetic, as in
some diseases of the brain, or during pregnancy, or

AND SOME OF ITS KINDRED SALTS, II

after the inhalation of ether, or during sea-sickness
and the like, the gastric mucous membrane appears
to absorb the bromide of potassium as readily as in
health.

When the stomach is empty and at rest, physi-
ologists tell us that it is neutral ; and, when it contains
food and is at work, that it is acid. Though the
bromide of potassium is a fixed salt, it is disturbed
by acids, and apt to be disturbed by the acids of the
stomach. If such a disturbance takes place, free
bromine is liberated, and gastric irritation and eruc-
tations are produced. In order to prevent this, in
case there should happen to be acid in the stomach
when the bromide is taken, some practitioners, imi-
tating in this respect the bromidal prescriptions of
the eminent Brown-S6quard, add an alkali, like car-
bonate of ammonia or carbonate of soda, to whatever
solution of the bromide they prescribe. Whether
this is done or not, it should not be forgotten that a
stomach crowded with food may not only delay
absorption, but decompose some of the bromide.

The bromide of potassium in powder, or in a
concentrated solution, is a slight irritant. The mu-
cous membrane does not like it in this shape ; and
when the bromide is presented to the stomach in
such a form, this organ is sometimes irritated by it,
aiM sometimes throws it up, and at any rate delays
the absorption of it for a time, in order to pour

12 BROMIDE OF POTASSIUM,

out water with which to dissolve it or to dilute its
solution.

These facts point out three obvious, practical,
and important rules which should guide the exhibi-
tion of the bromide of potassium, bromide of sodi-
um, bromide of ammonium, and the bromide of
lithium, so far as their absorption by the stomach
iS' concerned, i. They should be freely diluted with
water before they are swallowed. There should be
at least a drachm of water to each grain of the salt.
2. They should be taken when the stomach is empty
and practically free from acid. Their administra-
tion fifteen minutes before a meal, or three hours
after one, secures this condition, and is therefore the
best time for taking them. 3. They should be given
with caution to the stomach, when there is gastric
irritation or inflammation or degeneration.

Bromide of potassium is absorbed by the rectum
less readily than by the stomach. Still it can be
absorbed by the rectum ; and consequently, in case of
necessity, that organ may be used for the purpose
of passing it into the blood. The rectal mucous
membrane, unless inflamed or irritated, readily tol-
erates its presence, provided it is not injected in a
warm or a concentrated solution. In the proportion
of ten grains to an ounce of cool water, it is gener-
ally retained. A solution of greater strength than
this is apt to be rejected. It is always well to put

AND SOME OF ITS KINDRED SALTS. 1 3

the dose, which it is proposed to give per rectum,
into as much cool water, or better still into cool
water-gruel, as the rectum can comfortably hold.
Two advantages are gained by this : first, more
rapid absorption, because a dilute solution is more
rapidly absorbed than a concentrated one ; and,
secondly, less danger of its rejection. The rectum
does not fancy any more than the stomach an irri-
tating solution.

The skin is practically useless as a surface for
absorbing the bromide of potassium and similar
salts. Unless the solution has a temperature below
blood heat, — in fact, as appears from Dr. Amory's
experiments, considerably below blood heat, — it
refuses to absorb the salt from its solution at all. A
general bath, of such a temperature, is sometimes
employed as a therapeutic application, but could not
be safely used for the purpose of introducing two or
three times daily any drug into the blood.

The irritant qualities of a solution of the bromides
also forbid their hypodermic use. A therapeutic
dose of any of them, injected into the subcutaneous
cellular tissue, is almost sure to produce inflamma-
tion, and sometimes suppuration.

Hence it appears that the stomach and the rectum
are the only organs at the service of the physician
for the absorption of the above salts. Fortunately
these take them up, and pass them on so readily

14 BROMIDE OF POTASSIUM,

that it is unnecessary to use the skin or the subcu-
taneous tissues 'for this purpose. Of these organs,
the stomach is always to be preferred, when it is
available. When it is not, the rectum should be
resorted to.

Elimination. — The bromide of potassium and
kindred bromides are eliminated moderately by the
skin, chiefly by the kidneys, and scarcely at all by
other organs. This bare statement, however, is of
little value to the practitioner. Besides this, it is
important for him to know how much of any given
dose goes into the blood, how long it remains there,
and how much of it and how rapidly it passes out.
Without this knowledge, no correct notion can be
formed of how constantly or how completely the
blood and system of a patient can be kept charged
with the drug.

The first point, or how much goes into the blood,
depends, as we have already seen, only upon how
much is given. Provided the conditions of absorp-
tion are observed, an indefinite quantity, more than
should ever be given therapeutically, can be sent
rapidly into the blood. I have known a person to
drink a solution, containing several drachms of the
salt, which the stomach evidently disposed of in a
short time, without rejecting it.

Once in the blood, the bromide is of course car-
ried throughout the organization by that fluid. But

AND SOME OF ITS KINDRED SALTS. IS

it cannot get out as rapidly as it can enter. Elimi-
nation is not as rapid as absorption. Traces of it
appear in the urine within ten minutes after it is
swallowed ; * and, although it is not wholly elimi-
nated until several days after the last dose of it has
been taken, yet the major part of any given dose is
eliminated in less than twenty-four hours after its
ingestion. Indeed, elimination is so active for the
first eight or ten hours after ingestion, that the most
of any dose leaves the blood during that time.
Hence, any required amount may be kept in the
blood by giving it so often and in such quantities
as to make up for the loss occasioned by elimi-
nation.

This ratio of elimination to absorption should be
kept constantly in mind by the practitioner. If it
is desirable to keep the blood constantly charged
with it, a dose should be administered three times
during each twenty-four hours, and at nearly equi-
distant intervals. If the intervals are not equi-
distant, there is danger of having too small an
amount in the blood during a portion of the day.
This, in the treatment of certain diseases, — as
we shall see by-and-by, and especially in the
treatment of epilepsy, — deprives the patient of the
continued therapeutic action of the remedy. A fit

* M. Rabuteau, Soci^t^ de Biologic, July, 1868.

l6 BROMIDE OF POTASSIUM,

may occur just at the moment when a considerable
portion of one dose has been eliminated and before
another has been taken. Sometimes it is desirable
that the system should be nearly free from the bro-
mide during a portion of each day, and should be
well charged with it during another portion. For
this purpose, only one daily dose should be given.
Sometimes a cumulative action is indicated. This
is readily obtained by administering successive doses
at short intervals, — an hour or so apart. In this
way, it is made to enter more rapidly than it leaves
the blood. The inflow is greater than the outgo :
a constantly increasing charge is given.

AND SOME OF ITS KINDRED SALTS. 1 7

ACTION WHILE IN THE SYSTEM.

The therapeutic action of the bromide of potas-
sium varies so much with the dose, the manner
of giving it, and the pathological state of the sys-
tem, that it is well to consider each of these points
separately.

The dose of it may be single or continued ; and,
whether single or continued, it may be excessive,
and then its action ceases to be therapeutic and be-
comes toxic. Sometimes a dose, which in a physi-
ological condition of the system would be toxic,
becomes, in certain pathological states and owing
to these states or conditions, only therapeutic. The
reverse may occur. A dose that in the ordinary
or physiological condition would be harmless or
therapeutic becomes, in peculiar pathological con-
ditions, harmful or toxic.

By the single dose is meant the giving of it only
once in twenty-four hours, or two or three times in
twenty-four hours, with short intervals between the
doses. By the continued dose is meant the giving
of it twice or oftener in the twenty-four hours, at
equidistant intervals between the' doses, and for sev-
eral days, weeks, or months consecutively. The

l8 BROMIDE OF POTASSIUM^

excessive dose is either one that would be toxic in
any condition of the system, or one that is ordinarily
therapeutic, but in peculiar pathological conditions
is toxic. These variations refer to the action of the
bromide on adults. It is unnecessary to describe
the influence of age upon the therapeutic action of
the bromide of potassium, except to state in general
terms that children and infants tolerate greater, and
aged people less, proportionate doses than are usu-
ally given of most drugs.

Therapeutic Action of the Single {or Hypnotic)
Dose, — A single dose of the bromide — that is, one
given only once in the twenty-four hours — rarely
exerts upon the adult a therapeutic action of any
value, in a quantity less than twenty grains. Only
those who are very susceptible to its influence —
and there are some such persons — perceive any
effect from a single dose of ten, or even from one
of fifteen grains. The limits of the single ther-
apeutic dose are from twenty to sixty grains, the
average being thirty grains. Sometimes, though
rarely, on account of the state of the stomach, as in
the irritable stomach of pregnancy or of sea-sick-
ness, it is wise to administer this dose in divided
portions, giving a third or half of it, at intervals
of ten or fifteen minutes.

Twenty or thirty grains produce, soon after they
are ingested, a decided sedative action on the gen-

AND SOME OF ITS KINDRED SALTS, 1 9

eral nervous system. There are mental and physi-
cal lassitude, indisposition to effort, and indifference
to all slight causes of nervous irritation. The cry-
ing of children in the house, the rattling of car-
riages on the pavement, the irritation of worrying
or anxious thoughts, all are disregarded. The
sweet carelessness of doing nothing, the Neapoli-
tan's dolcefar niente^ is almost realized after such
a dose. This state is soon succeeded by drowsi-
ness, and drowsiness by sleep.

*'The hypnotic action," says Voisin,* referring to
his patients in the Bicetre, " was very remarkable
upon them, both by day and night. Some were
obliged to sleep for a few minutes at a time in the
midst of their work. None, in spite of whatever
efforts they made to the contrary, could resist sleep
directly after their evening meal. During the night
their sleep was calm, and in the morning it was dif-
ficult to arouse them."

In experimenting upon myself, I have found quite
a difference both in the quantity and quality of the
sleep following a single dose of the bromide of
potassium, which evidently depended fully as much
on the state of the system when the drug was taken
as upon the dose. I have several times taken forty
and fifty grains at night after a day of hard and

♦ Bulletin G^n^ral de Th^rapeutique, Tome 71, p. 102, 1866.

20 BROMIDE OF POTASSIUM,

exhausting work, and found that wakefulness, not
sleep, was the result. But if sleep did not follow
this dose, the general quietude and nervous seda-
tion just described did. At other times, when sim-
ply wakeful in consequence of mental labor during
the evening, but not exhausted, the same dose has
produced quiet and profound sleep. At other times,
when neither tired nor wakeful, a dose of thirty
grains has only produced more profound slumber
than usual. Whether the larger or the smaller
dose was taken, and whether wakefulness or pro-
found sleep followed, I could discern no disturbance
during the morning or day after taking it, beyond
a moderate increase of the urinary secretion.

The above results are the natural effect of the
action of the bromide upon different conditions of
the brain.

Dr. Hammond * has shown that " sleep is directly
caused by the circulation of a less quantity of blood
through the cerebral tissues than traverses them
while we are awake." It is also true that the quan-
tity of blood circulating through the brain may be
diminished so much as to prevent sleep. Too much
blood in the brain produces wakefulness ; a proper
diminution of that amount induces sleep. Too little

* Sleep and its Derangements, by William A. Hammond,
Af.D., p. 29.

AND SOME OF ITS KINDRED SALTS. 21

blood in the brain, as in some anaemic conditions of
that organ, or in excessive flowing, also produces
wakefulness; and an increase of the circulation
there is followed by sleep.

It appears, from the experiments of Brown-S6-
quard * upon the effects of the bromide of potassium
on the vasomotor nerves, that under its influence
^ the arterial vessels alike of the periphery and of
the nervous centres undergo a manifest contraction ;
from whence there results a topical oliga&mia of the
encephalon and of the spinal cord, and a conse-
quent diminution of the irritability of this organ.^
The experiments of Meuriot f upon the frog are to
the same effect, as are also those of Dr. Amory
described in another part of this monograph.

It is apparent, from these considerations, that the
bromide of potassium, by contracting the arterioles
of the brain and expelling temporarily a certain
amount of blood from them, may produce wakeful-
ness or sleep, according as the condition of the brain
is one of hyperaemia or oligaemia. In the first ex-
periment upon myself just detailed, the brain, like
the rest of the system, was exhausted after work-
It had become somewhat anaemic in consequence of
the expenditure of force, by which nerve-tissue and

♦ Nouveau Dictionnaire de M^decine et de Chirurgie Pra-
tique, art. Asthma, by G. S^e.

t L'Etude de la Belladonne, par le Dr. Meuriot, pp. 50, 51.

22 BROMIDE OF POTASSIUM^

blood had been correlated into labor during the
day. So much work had taken out of the organism
so much blood and so many nepve-cells. A further
oligaemia of the brain was produced by taking forty
or fifty grains of the bromide of potassium. The
cerebral circulation was reduced below the sleeping-
point, and sleep did not come till the effect of the
drug had passed off. As a matter of therapeutics
rather than of physiological experiment, a cup of
beef tea or a glass of wine, not fifty grains of the
bromide, was the proper agent to have put the
brain into the condition for sleep.

The second experiment on myself consisted in
taking bromide of potassium at night when I was
not physically exhausted, but only wakeful after
mental labor. In order to understand the value of
this experiment, it should be stated that two or three
hours of hard study or engrossing mental labor in
the evening will always, or nearly always, prevent
my sleeping at all for the first few hours after retir-
ing. This is so constantly the case that I am
obliged to avoid such sort of work at that time.
Forty grains of the bromide, taken on going to bed
after this sort of work, will send me into the land
of sleep directly. The fact is not difficult of ex-
planation. The cerebral circulation having been
increased by study, — /.^., by intellection or cere-
bration, to use recent terms, — just as the vascular-

AND SOME OF ITS KINDRED SALTS, 23

ity of the stomach is increased by digestion, the
brain becomes temporarily incapable of sleep. By
the physiological action of the bromide, the cere-
bral circulation is contracted and the brain made
capable of sleep, sooner than it would become so
without the aid of the drug. The third experi-
ment, that of taking thirty grains of the bromide at
night when neither the brain nor the system gen-
erally was unusually fatigued, simply shows (what
has been so often observed) that such a dose, taken
in the normal state of the system, does not interrupt
sleep, but renders it more profound.

These apparently unimportant experiments illus-
trate some valuable points in the clinical adminis-
tration of the bromide of potassium, especially when
given in the single dose which we are now consid-
ering. Thirty to sixty grains exert a decided hyp-
notic action upon an adult in a physiological or
normal condition, whether given by day or night,
— an action consequent upon the diminished cere-
bral circulation which the drug induces. If the
brain is already in an anaemic condition, it is not
wise to deprive it still further of blood, by the exhi-
bition of the bromide. If this is done, sleep may
sometimes follow ; but more commonly the result
will be the opposite. Hence anaemic conditions of
the brain contra-indicate, as a rule, the exhibition
of the hypnotic dose. Clinically, I have found

24 BROMIDE OF POTASSIUM,

this to be the case. The restless wakefulness which
is so apt to follow excessive flooding is relieved by
opium and alcohol, and aggravated by a full dose
of the bromide. A combination of the latter, how-
ever, with a stimulant, such as a glass of wine or
brandy, will sometimes in these cases produce a
most satisfactory result. In the convalescence from
typhoid fever, I have sometimes found the hypnotic
dose to be followed by sleep, and about as often by
the opposite. I suppose the difference may be ex-
plained by the varying vascularity of the brain in
different patients, or in the same patient at different
periods of convalescence.

The hypnotic action of the bromide of potassium,
which is most apparent if given when the brain is
not anaemic, — that is, when this organ is in a phys-
iological condition, or when it is in a state of con-
gestion or hyperaemia, — is of the highest value.

Dr. Hammond, in the work previously quoted,
speaking of the treatment of wakefulness, says : *
''Among the more purely medicinal agents, bro-
mide of potassium occupies the first place, and can
almost always be used with advantage to diminish
the amount of blood in the brain and to allay any
excitement of the nervous system that may be pres-
ent in the sthenic form of insomnia. That the first-

* Op. cit, p. 283.

AND SOME OF ITS KINDRED SALTS.

named of these effects follows its use, I have re-
cently ascertained by experiments upon living ani-
mals, the details of which will be given at another
time. ' Suffice it now to say, that I have adminis-
tered it to dogs whose brains had been exposed
to view by trephining the skull, and that I have
invariably found it to lessen the quantity of blood
circulating within the cranium, and to produce a
shrinking of the brain from this cause. Moreover,
we have only to observe its effects upon the human
subject to be convinced that this is one of the most
important results of its employment. The flushed
face, the throbbing of the carotids and temporals,
the suffusion of the eyes, the feeling of fulness in
the head, all disappear as if by magic under its
use."

Clinical observation confirms these teachings of
physiological experiment. The bromide has been
given as an hypnotic with excellent results in a
large variety of complaints; or rather, I should
say, in a large number of cases in which the con-
dition just described has existed. In order to
obtain satisfactory hypnotic results from the dose
we are considering, the routine practice of prescrib-
ing for the name of a disease must be abandoned,
and the condition of the brain, not the name of the
malady, be kept in mind. For example, during
the progress of an erysipelas, occurring in two indi-

26 BROMIDE OF POTASSIUM,

viduals, it will often happen that a nightly dose of
the bromide will be indicated in the case of one
patient and contra-indicated in the other. In like
manner it may be indicated or contra-indicated in
the same individual at different stages of an illness,
as in the instance of typhoid fever just referred to.

Insomnia, depending upon hyperaemia of the
brain, which is what Dr. Hammond calls the
sthenic form of insomnia, indicates the hypnotic
dose of the bromide of potassium at any age, in
either sex, and in any disease. It is perhaps need-
less to say that it will not always relieve the hyper-
aemic sleeplessness of every disease, in both sexes
and at any age. Such unvarying action is not to be
expected from this or any drug ; but it will relieve
this kind of insomnia so often and so satisfactorily,
that it forms one of the most precious resources
of the practitioner. When severe pain "murders
sleep," a dose of thirty or forty grains will not often
drive the assassin off, and procure the relief that
opium gives.

So far as my own clinical observation extends,
and I have used the bromide of potassium in quite
a large number of cases for the past few years, I
have found the cerebral — or, strictly speaking, the
encephalic — condition that indicated the single hyp-
notic dose we are now considering, to occur most
frequently as follows; viz., with the insomnia ac-

AND SOME OF ITS KINDRED SALTS, 27

companying mental anxiety, excessive intellectual
labor, hysteria, pregnancy, teething, the exanthe-
mata, simple and typhoid fevers, erysipelas, rheu-
matism, and a sort of hyperaestheria which I know
not how to describe by any other name than " gen-
eral nervous irritability." These are not the only,
or the most important affections in which the thera-
peutic action of the bromide of potassium and its
congeners may be invoked. They are only those
in which the single hypnotic dose has proved, in
my experience, to be most frequently indicated and
most efficacious. The frequent and the continued
dose, which will be considered presently, meet a
larger number of therapeutic indications than the
single one.

Examples are better than abstract statements,
and I will therefore venture to illustrate the above
remarks by a few cases.

Case I. Insomnia following Mental Anxiety,
— A merchant, just passing sixty years of age,
was engaged, during the latter part of our late civil
war, in important mercantile transactions, which
placed and kept at risk'^large amounts of money.
He lost and gained a great deal. At times, a large
portion of his fortune was at risk. He naturally
became uneasy and anxious. He always worked
with friction. His temperament was nervous. He

28 BROMIDE OF POTASSIUM,

could not leave his business at his counting-room,
but carried it home with him. It followed him
through the evening and into his bed-room, and little
by little drove away his sleep. At first, he only lost
an hour or so of his usual sleep ; ,but gradually he
slept less and less. He could not drive off at night
the anxious speculations of the day. In* other re-
spects he was well. His color, flesh, appetite,
strength, and general condition were excellent.
After about three months of this sort of imperfect
or half sleep, he asked my advice. It was useless
to advise him not to be anxious : he knew and ac-
knowledged the importance of this, and had tried
to make his will keep his brain still at night, but ,
unsuccessfully. He took thirty grains of the bro-
mide of potassium on going to bed, with great but
not complete relief at first. After a few nights,
however, his sleep became natural. For a period
of three or four months, he took either thirty or
forty grains, nearly every night, on retiring. When
he omitted it, he slept less well. At the end of this
time, the causes of his anxiety ceased to operate,
and he slept sufficiently without the drug. He ex-
perienced no disturbance from taking it; neither
acne nor any apparent bromism. It is possible
that, in this case, the bromide prevented serious
trouble. There had been insanity in the patienfs
family, and the danger of the development of in-

AND SOME OF ITS KINDRED SALTS, 29

sanity by prolonged sleeplessness is not a small
one.

Case II . Insomnia following Mental Anxiety.
— A lady, past middle life, worn by nursing her
husband, who was slowly wasting away with cir-
rhosis of the liver, and anxious with the knowledge
of his inevitable fate, began first to sleep lightly,
and then scarcely to sleep at all. Her appearance,
while making my usual visits to her husband, at
length attracted my notice. I found on inquiry,
that, though well provided with hired nurses and
night-watchers, she not only frequently left her bed
at night, but slept very little while upon it at any
time. In other respects, excepting an organic affec-
tion of the heart, of long standing, she was well.
She took of the bromide of potassium a nightly
dose varying from fifteen to thirty grains, according
to circumstances which she soon learned to recog-
nize, with the most satisfactory result. After taking
it every night .for two or three weeks, she re-
acquired the habit of sleep, and then only took
her hypnotic occasionally.

Case III. Insomnia accompanying Teething. —
A male child, of an irritable and nervous constitu-
tion, — which he came honestly by, for both his
father and mother were of the neuralgic and fidg-
ety sort, — was troubled through his whole first

30 BROMIDE OF POTASSIUM,

dentition, from the cutting of the first incisor to that
of the last molar tooth, by wakefulness to an extra-
ordinary degree. He slept little himself, and per-
mitted those who took charge of him to sleep less.
Lancing his gums at appropriate times gave some
relief, but not much. Various hypnotics — not
including opium, however — were tried, none of
which were of any service except the bromide
of potassium and the hydrate of chloral. These
were given alternately — that is, one of them for
a week or two and then the other for a week or two
— during the major part of his dentition, and with
the desired result. It was found by experience that
he required not less than ten, and generally as
much as fifteen and sometimes twenty grains of the
bromide to put him to sleep. His general health
did not suffer from the treatment. On the contrary,
when the anodynes were not given — and they were
occasionally omitted — he not only did not sleep,
but his general condition was unsatisfactory during
the following day. At the close of dentition, he
slept without artificial assistance.

When sleep is prevented by acute pain, the bro-
mide of potassium is rarely of service as an hyp-
notic. It is not an anaesthetic, like opium. But
when there has been acute pain, which has passed
away and left the system racked, restless, and un-

AND SOME OF ITS KINDRED SALTS. 3 1

able to sleep, the bromide is often an excellent
sleep-compeller. In rheumatism, when the acute
stage has passed and the muscles and joints are
weary, partly from the disease and partly from
protracted confinement in bed, the bromide is a
better hypnotic than opium or narceine or hydrate
of chloral. In the early stages of typhoid fever
and erysipelas, I have frequently found the single
hypnotic dose to be of great service.

As a preparation for the exhibition of opium, the
bromide of potassium is sometimes of value. I have
noticed that thirty grains of it, given an hour or
two before the administration of a dose of opium,
will enhance the anodyne influence of the latter.
Individuals who do not tolerate opium well, who
are excited and not soothed by legitimate doses of
it, whose skins are made to itch or whose nervous
systems are badly affected by it, can often be
made not only to tolerate it, but to derive great
benefit from it, provided the bromide of potassium
is administered to them before they take the opiate.
For this purpose, the dose should not be less than
thirty grains ; and sometimes forty or fifty grains
are requisite. Dr. J. M. Da Costa, of Philadel-
phia, has noticed this corrective influence of the
bromide of jf)otassium over opium, and lately pub-
lished several cases in illustration of it.* In order

* American Journal of the Medical Sciences, April, 1871,
PP- 359^3-

32 BROMIDE OF POTASSIUM,

to increase the hypnotic action of opium, the bro-
mide should be given about an hour before opium
is taken. In order to correct the unpleasant action
of opium, it is better to follow Dr. Da Costa's
method, and give the bromide some hours — three
or four — before giving opium. The nausea, which
so often annoys a patient perhaps for hours after
the soporific effects of opium have passed oflT, may
be relieved, or at least mitigated, by a dose of the
bromide, taken as soon as nausea appears.

But it should be stated that bromide of potassium
will not invariably prevent or correct the unpleasant
action of opium. It is easy to conceive of condi-
tions of the system in which the former, instead of
correcting, would aggravate the disturbing action
of the latter. In cerebral anaemia, for example, or
after excessive loss of blood, it would be rational to
expect that the soporific, though not the anaesthetic,
action of opium would be lessened by the conjoint
administration of bromide of potassium. Opium,
in therapeutic doses and for a certain period after it
is taken, produces hyperaemia of the brain, which
gradually passes away into oligaemia, and sleep
follows. Dr. Hammond * has demonstrated this by
several ingenious experiments. The bromide, as
we bave previously seen, produces more or less
cerebral oligaemia. If opium and the bromide of

♦ Op. cit., p. 25 et seq.

AND SOME OF ITS KINDRED SALTS. 33

potassium are simultaneously administered to a
patient with an anaemic brain, it would naturally
follow, after the primary stimulant action of opium
has passed away, that the sedative action of the
bromide would reinforce the secondary sedative ac-
tion of the opium, and possibly lead to disagreeable
results. At any rate, whatever may be the correct
physiological explanation of the matter, we know
from clinical observation that, while the bromide of
potassium will often correct the unpleasant results
of a dose of opium, it sometimes fails to do so ; and
sometimes, though rarely, leads to greater second-
ary depression after opium than if it had not been
taken.

It appears from these observations that the sin-
gle or hypnotic. dose of the bromide of potassium,
by which is meant one of not less than fifteen grains
and not usually above fortj'-, is indicated in any
disease, when appropriate conditions of the nervous
centres exist, to control insomnia, restlessness at
night, general nervous irritability, or abnormal
reflex excitability. The same dose is contra-indi-
cated, whatever may be the disease, even when the
same symptoms of insomnia, irritability, or hyper-
aestheria exist, provided the appropriate conditions
of the nervous centres that have been referred to-
are not present. This is only another way of say-
ing that, in prescribing the bromide of potassium, as

34 BROMIDE OF POTASSIUM,

<
in the exhibition of all drugs, the condition of the

patient, and not the name of a disease, must be pre-
scribed for.

Depression, exhaustion, weakness, irritability,
and the like, connected with or dependent upon
oligaemia of the nervous centres, contra-indicate
the single hypnotic dose. Increased depression and
greater restlessness, instead of sleep and quiet, are
apt to follow its administration when thus given.

THE CONTINUED DOSE.

Physiological Action. — It has already been stated
that tJy the continued dose is meant the exhibition
of the bromide of potassium two or more times in
the twenty-four hours, with equidistant intervals be-
tween the doses. By this method of administration
the blood is kept constantly charged with the drug.
When only a single dose is given, or two or three
doses are given so near together as to form substan-
tially one dose, the major part of the salt is elimi-
nated in the course of a few hours, and consequently
the blood is practically free from it more than half
the time. The difference between the single and the
continued dose is the difference between keeping
the blood constantly charged with bromide of potas-
sium, and allowing the blood not only to free itself
from one dose, before a second one is administered,

AND SOME OF ITS KINDRED SALTS. 35

but making the interval between the doses so long,
that the blood shall be practically a longer period
uncharged than charged with the salt.

The observance of this difference is important
physiologically and therapeutically. The neglect
of it explains much of the confusion and discrepancy
that may be found in the statements of different
observers. Many of the phenomena, both physio-
logical and toxicological, that follow the exhibition
of the continued, do not follow that of the single dose.
And, what is in fact a corollary from this, many
therapeutical results may be obtained by the con-
tinued that cannot be got from the single dose. It
is also to be remarked that, although few or no prac-
titioners write as if they were aware of the important
difference here referred to, yet the largest number
of their observations evidently are founded on the
action of the continued dose. Physiologists, on the
contrary, seem to have experimented oftenest with
the single dose. Their experiments with regard to
the physiological action of the bromide upon the
vasomotor nerves, the nerve centres, and the circu-
lation, have been mostly made on animals to whom
they have given a single dose, or at most two or
three doses near together.

The daily amount of the continued dose varies
from thirt}'" to one hundred and twenty grains ; and
it should be given in divided portions, at equidistant

36 BROMIDE OF POTASSIUM,

intervals during each twenty-four hours, and on an
empty stomach. Ther/e is not any marked thera-
peutic action on the adult in a quantity less than
ten grains three times a day, and it is rarely neces-
sary to exceed three times that amount. There
are cases in which forty grains three times a day,
or twenty grains six times a day, are indicated.
Sometimes it is wise to divide the doses unequally,
and give, for example, ten grains in the morning and
ten at noon, and thirty or forty grains at night
When more than one hundred grains are given con-
tinuously for any length of time, some of the toxic
phenomena of the bromide are pretty sure to appear.
I have repeatedly given thirty grains every four
hours daily for several days consecutively, making
one hundred and eighty grains in the course of each
twenty-four hours, not only without harm, but with
evident advantage to the patient. In a few instances
I have exceeded this quantity. It is hardly neces-
sary to say that in these cases there were abnormal
conditions of the system, which antagonized the
physiological action of the bromide, and rendered a
toxic dose therapeutic.

The principal phenomena following the continued
dose are : acne ; salivation and salt taste in the
mouth ; irritation of the fauces generally, with
oedema and redness,* and sometimes with pale-

* Voisin, Bulletin G^n^ral de Th^rapeutique, ut supra.

AND SOME OF ITS ^KINDRED SALTS. 37

ness * of those parts ; moderate anaesthesia of the
pharynx; laryngo-bronchial weakness, sometimes
with cough and sometimes with a changed or whis-
pering voice, rarely with aphonia; a fetid or
bromized breath ; occasional stammering ; increase
of renal secretion ; diminution of mucous secretion
generally; slight constipation, and in a few rare
instances diarrhoea ; sense of mental and physical
languor or weakness ; sometimes temporary im-
pairment of the memory ; general aspect of hebe-
tude and indifference ; more or less somnolence ;
repression and occasionally temporary abolition of
sexual desire and .power; impaired locomotion,
which, when the dose is excessive, resembles the gait
of locomotive ataxia ; diminished nervous sensibil-
ity in general, and especially diminution of reflex
senjsibility ; and, finally, an increase of destructive,
without a corresponding increase of constructive
metamorphosis, and consequent emaciation.

Hearing and vision are unaflfected. The con-
junctivae, like the fauces, are often congested ; but
we have the authority of Laborde f for the statement
that the optic nerve of a bromized person exhibits
no alteration, discoverable by the opthalmoscope.
The pulse and heart are unaffected, except in doses
so large or long continued as to be toxic : the same

♦ Gubler, Bulletin G^n^ral de Th^rapeutique» 1864.
t J. V. Laborde, Archives de Physiologic, May^ 1868.

38 BROMIDE OF POTASSIUM,

is true of the temperature. When the dose is ex-
cessive, the heart acts slower and feebler, and the
temperature is lower than normal. The capillary
circulation is materially affected, not only of the
nervous centres, as has been previously pointed out,
but of the whole system. This, however, is inde-
pendent of the heart and large arteries. There is
sometimes slight nausea directly after a dose is
swallowed, which soon disappears ; but as a rule,
and with very few exceptions, the appetite and
digestion are unimpaired : the former is often in-
creased. Tactile sensibility, the sense of temper-
ature and of tickling, appear to be imperfecdy
conducted, but really are unimpaired. Intellection
and emotion may seem to be sluggish, but when
roused they act normally. A consciousness that the
currents or sources of psychical force are hampered
sometimes makes an intellectual patient, who is
moderately bromized, reason himself into depression ;
but spontaneous depression is rare. When the
bromide acts favorably, a sense of buoyancy, com-
fort, and relief rather than of depression accompanies
its exhibition. It exerts no direct action on the
globules of the blood, nor does it alter the. chemical
constitution of the secretions, however much it may
check or increase them.

The importance of some of these phenomena
demand a more detailed account of them.

AND SOME OF ITS KINDRED SALTS. 39

Acne do not always appear after taking the
bromide of potassium. I am aware of no data by
which to determine the proportion of those who do
to those who do not exhibit these phenomena. As
a guess, founded only on my own observation, I
should say that two-thirds of the persons to whom
I have given bromides continuously suffered from
acne. I do not recollect ever to have seen it follow
the single dose previously described. The number
and continuance of the eruption are variable. In
some individuals it is sparse, and each pustule is
small ; in ^others it is abundant, and many of the
pustules are large. It affects the face, scalp, and
back rather than other parts of the cutaneous sur-
face. The pustules appear in successive, but irregu-
lar crops. They vary in size from a millet-seed
to a large pea. Generally they disappear without
suppuration, each individual pustule lasting only a
few days. In some cases, suppuration occurs : when
this takes place, each pustule lives longer than it
otherwise would ; and as new pustules are constant-
ly cropping out, the eruption may become unpleas-
antly copious. A moderate degree of heat with
some itching usually attends the eruption, but this
is not invariable. No permanent scar or mark
remains after the disappearance of the pustules,
though a red spot points out where they have been
for some time after their departure. I recollect the

40 BROMIDE OF POTASSIUM,

case of a young lady, twenty five or six years of
age, whom I subjected to the continued influence
of bromide of potassium for more than a year, and
in whom the eruption was so copious and the pust-
ules so large as to remind one of variola. Many of
them suppurated, and smooth red spots remained
to mark their existence for several months after she
had ceased to take the drug. In her case, the acne
were more troublesome than I have ever observed
in others. The cause of the eruption has not been
fully ascertained. Some attribute it to the local
irritation attending its elimination by the skin. So
little passes out from the system by this avenue,
that this explanation cannot be considered satis-
factory, until the truth of it has been demonstrated.
I should think it more probable that deranged nu-
trition of the skin,'' resulting from the action of the
bromide upon the peripheral nerves, might induce
the eruption; that it might be a neurosis, like
herpes. Beyond its disagreeableness, it is not
important. It temporarily disturbs the vanity, and
sometimes the physical comfort of many who take
bromide of potassium, but does no other harm. Its
appearance, therefore, should not lead to a discon-
tinuance of bromidal medication, when this is con-
tinuously indicated. In former times, and not veiy
long ago, such an eruption would have been re-
garded as evidence that the drug was driving pec-

AND SOME OF ITS KINDRED SALTS. 4 1

cant humors from the body. I have met with
persons who, entertaining some such notion, fe-
licitated themselves upon the pushing out and con-
tinuance of the eruption, which they regarded as a
blood-purifying process.

Few, who take the continued dose of bromide of
potassium, escape the infliction of a disagreeable
salt taste. The salivation, which frequently but not
invariably attends this, is not copious, but merely
disagreeable. Both result from the elimination of
the salt by the faucial mucous membrane and sali-
vary glands. They are commonly accompanied
with a fetid or bromized breath. All of these phe-
nomena — the taste, salivation, and bromized breath
— are not disagreeably apparent, till after the
bromide has been taken for a considerable period.

A good deal has been said about the anaesthesia
of the pharynx, that may be produced by the bromide
of potassium, and attempts have been made to utilize
it for • surgical manipulations or operations in the
pharyngeal region. No great success, however, has
attended such efforts. According to Voisin, this
local anaesthesia does not appear after a less dose
than thirty grains. It is not always produced by
this dose ; but, if two or three such doses are given
several hours apart, there will be impaired sensi-
bility of the pharynx for several hours after the
administration of the last dose. Consequently, a con-

42 BROMIDE OF POTASSIUM,

tinued daily dose of above half a drachm generally
affects the sensibility of the pharynx, in proportion
to the amount taken above that quantity. But only
one part or kind of the sensibility of the pharyn-
geal mucous membrane is impaired or abolished.
"We should distinguish," says a late writer, * "two
kinds of sensibility in the region of the vail of the
palate, — a functional sensibility and an ordinary
sensibility. The ordinary sensibility varies with
different individuals ; but it is not the measure of the
functional sensibility. The latter varies little. This
functional sensibility is the same as the sensibility of
the intestine ; and like the latter, it depends, accord-
ing to M. Claude Bernard, upon a ganglion, the
spheno-palatine. It has its special mode of irrita-
tion, which is neither pricking nor burning, but the
lightest contact. If the touching even \chatouille'
men^"] exceeds the physiological limit, vomiting is
produced. Bromide causes this to disappear at
once. Movements of deglutition remain intact in
bromized individuals, and are not performed with
less energy than previous to the treatment. When,
by titillation of the uvula, no eflbrt of deglutition or
of vomiting is induced, it is apparent either that the
pharynx and palate no longer conduct the tactile
impression, or that this impression is not reflected.

♦ Emile ZaepfFel, Thfese pour le Doctorat, &c. Paris, 1869.

AND SOME OF ITS KINDRED SALTS. 43

As the reflex power of the cord has lost none of its
energy, and there is no want of precision of move-
ment, we must admit that the periphery alone is
affected."

It is not so clear, as this writer would have us
believe, that the reflex power of the cord is un-
affected in bromized individuals ; but the distinction
which he draws tj^tween the ordinary and the spe-
cific — or, as he calls it, the functional — sensibility of
the pharynx is a true and important one. The latter
is the only one, which is impaired or abolished by
bromide of potassium. Hence, in bromidal anaes-
thesia of the fauces, cutting, pricking, or any sur-
gical operation near them, like excision of the uvula
or tonsils, is felt as much as ever ; but the contact
of a finger, or an instrument like a laryngoscopic
mirror or a sponge, is readily tolerated. The prac-
tical advantages resulting from a knowledge of this
fact, in examinations of the throat and larynx, are
obvious.

A changed or whispering voice, aphonia, slowing
of the respiration, diminution of the force and fre-
quency of the heart's action, and diminished animal
temperature appear only when the bromism is so
complete, as to exceed the limits of therapeutic action
and become toxic. They are evidences of too long-
continued or of excessive doses, and should warn the
practitioner that he is on the limits of danger. In

44 BROMIDE OF POTASSIUM,

I
some persons the elimination of the salt is so rapid

that it is very difficult to excite any of these phe-
nomena. I have one patient, who has repeatedly
taken more than thr^e drachms daily, for several
days consecutively, without one of these symptoms
of excessive bromism. Others exhibit some of
them after comparatively small doses. Different
rates of elimination in different individuals are
probably sufficient to explain these differences of
action.

The hypnotic action of the bromide of potassium
has already been described when speaking of the
single dose. It remains to be remarked upon this
point, that the continued dose keeps up a sort of
semi-somnolent state, whereby the system is predis-
posed to sleep, and slumber at night rendered more
profound. When only the hypnotic action of the
bromide at night is indicated, and it is found that
an average or a tolerably large single dose, given
at bed-time, is insufficient to produce sleep, a better
result will be obtained, and less of the drug given,
by administering two moderate doses through the
day, and a somewhat larger one on retiring, than
by crowding large doses near together at night.
Thus I have often seen better and more sleep
follow ten grains given in the morning, and ten at
noon, and twenty at bed-time, than sixty grains
would produce in the same individual, given in one

AND SOME OF ITS KINDRED SALTS, 45

or two doses near together in the evening. The
hypnotic action of hydrate of chloral, hyoscyamus,
cannabis Indica, lactucarium, ether, chloroform, and
sometimes of opium, at night, is reinforced and other-
wise favorably modified by the continued dose of
the bromide of potassium. The following case is an
illustration of the above statement : —

Case IV. — A gentleman, sixty-five or sixty-six
years of age, who had suflfered, while in London
some years previously, from an acute and danger-
ous cerebral attack, and recovered from it there,
was alarmed by sleeplessness and some other symp-
toms, reminding him of his illness in London, while
at his country residence in the summer and autumn
of 1870. By the advice of a neighboring physician,
he took bromide of potassium, hydrate of chloral,
and other anodynes, at night, unsuccessfully. When
he returned to his city home, he came under my
care. I proposed the same remedies. He objected
to them on the ground that he had already tried
them suflSciently, and without eflfect so far as sleep
was concerned. It appeared on inquiry that he had
repeatedly tried, on some nights, thirty and forty
grains of the bromide, and on other nights as much
of chloral hydrate. He was directed to take a com-
bination of the bromide of potassium and bromide of
ammonium, ten grains of the former and three of

46 BROMIDE OF POTASSIUM,

the latter, before breakfast and before dinner, and
double the amount at night. The experiment was
successful. He slept well. After continuing this a
few days, twenty grains of hydrate of chloral were
substituted for the nightly dose of the bromides,
and on the whole with a more satisfactory result.

It is needless to recite similar cases. They would
add to the bulk, not to the value of this paper. I
have so often observed the hypnotic effect at night
of the continued daily dose, that I am sometimes at
a loss which to select, in the treatment of insomnia,
the single hypnotic dose at night, or the continued
daily dose. When the former will produce the
effect, it is preferable, because the organization is
not subjected so continuously by it to the influence
of the remedy, as by the continued dose. The
former is discharged from the system during a part
of each twenty-four hours, while the latter is not.
One other practical point deserves to be stated in
this connection; viz., when the continued daily
dose is exhibited, there is not apt to be any notice-
able somnolence by day, or profounder sleep at
night for the first two or three days. This comes
on later, as soon as the system has become impreg-
nated with the drug, or is what might be called
therapeutically bromized. Hence, if a hypnotic
action is indicated at night, and the continued

AND SOME OF ITS KINDRED SALTS. 47

dose IS selected, the physician should not be dis-
couraged, if the desired result is not immediately
obtained.

The somnolence during the day of the continued
dose is little more than a sense of quiet and comfort.
It sends a person to sleep easily if there is nothing
to prevent sleep, but does not interfere in the slight-
est degree with reading, writing, or the ordinary
avocations of daily life.

The increase of the renal secretion, which accom-
panies the elimination of the bromides, is not so in-
variable nor so large as to render them serviceable
as diuretics. In like manner, their influence over
the peristaltic movements of the bowels, and upon
the secretions of mucous membranes is not sufficient
to make them of value in the treatment of ordinary
diarrhoea, or for the purpose of checking the secre-
tions from mucous surfaces generally.

Repression of sexual desire and power, like anaes-
thesia of the fauces, is not produced by a single dose
of the bromide. This phenomenon does not usually
occur^ till the salt has been taken for several days
continuously. The extent of it is exceedingly
variable. In some individuals it merely amounts
to a moderate diminution of desire : in others there
is a temporary impairment of power. In all cases
there is return of the ordinary genital condition, as
soon as the drug is eliminated. Referring to this

48 BROMIDE OF POTASSIUM,

point, ZaepfFel* remarks, that ''the bromide of
potassium seems to affect particularly the phenom-
ena of reflex sensibility, whose seat, according to
some authors, is in the orifice of the ejaculatory
capals. The passage of the bromized urine over
this orifice produces a local anaesthesia there, and
so takes away the point of departure of the reflex
action (the excitp-motory point) of an erection."
Advantage may be taken of this physiological
action of the bromide in the treatment of certain
emissions, and of some forms of genito-urinary irri-
tation. The genital erethism, sometimes occurring
in young girls at the commencement or establish-
ment of menstruation, and which sometimes induces
epileptiform attacks, is particularly amenable to
bromidal medication. Certain irritable conditions
of the bladder are likewise favorably modified by it.
These matters, however, will be referred to more in
detail, presently, when the application of bromide
to the treatment of special diseases is considered.
The point here emphasized is, that bromide of po-
tassium produces local anaesthesia of the orifices of
the ejaculatory canals, only when large and con-
tinued doses are given.

The most curious, interesting, and important phe-
nomena of the continued dose are the sense of im-

♦ Op. cit., p. 30.

AND SOME OF ITS KINDRED SALTS. 49

•

paired mental force, loss of memory, depression,
and diminution of general and of reflex sensibility,
as well as the sense of physical weakness that is
sooner or later complained of. Accompanying
these, the face wears an expression of hebetude,
the limbs move sluggishly, and the whole body
becomes somewhat indiflferent to subjective and
objective impressions. When the quantity or contin-
uance of the dose is so excessive as to become toxic,
these symptoms are exaggerated into complete hebe-
tude or idiocy, hallucinations and paralysis.

It is to be observed, however, that when the con-
tinued dose is restrained within therapeutic limits, —
and it is of this we are now speaking, — the impair-
ment of mental and physical force is more seeming
than real. Of this I have been repeatedly assured by
patients. A well-known clergyman and author, to
whom I was obliged to give the continued dose,
often spoke to me of this state of mimotic mental
and physical weakness, which attracted his atten-
tion in his own case, and upon which he curiously
speculated. He said that he was disinclined to talk,
read or study, to walk or work ; that he was quite
indifferent to many objective annoyances that com-
monly irritated him ; that in fact he was superla-
tively lazy, indifferent and sleepy. And yet, by a
slight effort of the will, he found that he could con-
verse, study, compose, walk, work, and fret as well
« 4

50 BROMIDE OF POTASSIUM,

as ever. He entered his pulpit on Sunday with an
indifferent step, and commenced his sacred exercises
there without his usual buoyancy. But the neces-
sity and excitement of the hour and place dispelled
all this. He conducted the services as well as ever.
One Sabbath he thought himself unusually de-
pressed and weak, and, in spite of my previous
assurances to the contrary, almost believed his
mental force was dwindling. After the service, he
asked a confidential parishioner about the matter
that troubled him. The reply was reassuring:

" Dr. , you never preached with greater anima-

tion or better than to-day." In this case, as in all
others that I have ever seen, the discontinuance of
the treatment was directly followed by relief from the
troublesome sense of weakness and depression. In
some individuals, the memory is oddly affected.
Single words are forgotten ; or one syllable is con-
stantly dropped out of a word, whenever that word
is spoken by the patient ; or two words are invaria-
bly interchanged. Thus a lady, twenty-eight or
thirty years of age, suffering from chronic ovarian
disease, to whom I gave about twelve grains three
times a day, making a continued daily dose of nearly
forty grains of the bromide of potassium, began,
after she had taken it two or three weeks, to ex-
change two words for each other. She called a
buckwheat cake, a comb ; and a comb, a buckwheat

AND SOME OF ITS KINDRED SALTS. SI

cake. At the hour of her morning toilet she would
direct her maid to bring her a buckwheat cake, and
arrange her hair. At breakfast, if there were
buckwheat cakes on the table, she asked for a comb
to eat. At first this was thought to be delirium, and
naturally alarmed myself as well as the family.
But, as it never went beyond this, our alarm on this
'point soon subsided. Moreover, as the mutual
exchange of these two words was invariable, her
family and attendants became accustomed to her
acquired idiosyncrasy, and adapted themselves to
her new nomenclature. Once, during the existence
of this peculiarity, I undertook to convince her that
she had transposed these words, and that a comb
was the spoken sign of a comb and not of a cake.
The effort was unsuccessful. She never transposed
or confused the ideas of cake and comb, only the
words or signs. Shortly after she discontinued the
use of bromide of potassium, this peculiarity dis-
appeared. She adopted the ordinary signification
of buckwheat cake and comb with no consciousness
of change in her language. This occurred five or
six years ago. My patient is now well, and has
never exhibited any other symptom of cerebral
disturbance. I have talked with her since about
this odd mental phenomenon, but she would never
acknowledge any recollection of it. Voisin * men-

♦ Bulletin Gfenferal de Th^rapeutique, 1866, vol. 71, p. 108.

52 BROMIDE OF POTASSIUM,

tions a similar instance. It was that of a hospital
patient, who, while subjected to the continued influ-
ence of bromide of potassium, forgot certain sylla-
bles or parts of certain words, and when writing or
speaking did not write or utter these. Thus he
called " quelques q — ques," and sometimes he du-
plicated one or two syllables of a word. Such
instances are curious, and perhaps will some time^
be found instructive illustrations of aphasia. They
are hints of a distinct organ of language. They
suggest the notion that, inasmuch as the drug we
are considering paralyzes reflex before it does ordi-
nary sensibility, language may be the expression
or correlation of a peculiar reflex power.

Intimately associated with the sense of impaired
mental 'force and loss of memory is the diminu-
tion of excito-motory or reflex sensibility. This
is produced by a smaller continued dose than that,
which is followed by an interference with ordinary
sensation. Anaesthesia is a toxic, not a therapeutic
result of the administration of the bromides. Di-
minished reflex sensibility, however differently phys-
iologists may explain the fact, is one of the most
frequent phenomena of bromidal medication that
has been clinically observed, and is therapeutically
one of the most important. M. Gubler * has seen
such medication " diminish the excito-motory action

♦ Bulletin G6n6ral de Th^rapeutique, 1864.

AND SOME OF ITS KINDRED SALTS. 53

of the spinal cord, and thereby resolve tetanic con-
tractions and restrain reflex movements." A. Voisin *
not only testifies himself to its action in diminishing
reflex power, but quotes M. Claude Bernard to the
same effect. Laborde,t relying upon experiments
on animals, regards its primary action as one tfiat
impairs the control of the spinal cord over reflex
phenomena, at the same time pointing out its great
influence over the general nervous system, affecting
both the central and peripheral nerve extremities.
The clinical observations and physiological experi-
ments of Brown-S^quard largely illustrate the same
fact. Eulenberg and Guttman % satisfied them-
selves of the paralyzing influence of it over the
nervous system, including both reflex and gen-
eral sensibility. The experiments, detailed in the
second part of this Memoir, illustrate the manner in
which it modifies reflex action by " producing oli-
gaemia of the tissues and nerve substance." Martin
Damourette § has corroborated the experiments and
conclusions of Voisin as to its control over excito-
motor action. Puche, || whose investigations upon
its physiological action on man, nearly thirty years

• * Bulletin G6n6ral de Th^rapeutique, May, 1871 ; Ibid. 1866.
t Archives de Physiologic, May, 1868.
% Gazette des H6pitaux, No. 77, 1867.
§ Gazette des H6pitaux, F^v. 1868.

II Still^, Materia Medica and Therapeutics, article Bromide of
Potassium.

54 BROMIDE OF POTASSIUM,

ago, were strangely ignored by his contempora-
ries, pointed out the disturbed locomotion, muscular
weakness, and an,aesthesia, which physiologists refer
to or connect with reflex power. Echeverria * found
anaesthesia of the skin and mucous membranes, a
tottering gait, inability for any sort of effort, and
other indications of subdued reflex power, conspic-
uous among his epileptic patients. My own clin-
ical observations are to the same effect. Inertia
of look and movement, diminished susceptibility to
physical and psychical irritants, disregard or forget-
fulness of customary disturbants, and a general
blunting rather than abolition of sensation, some-
times local in the fauces, sometimes in the genital
apparatus, or upon the skin, and sometimes general
throughout the whole organization, so that I could
not ascertain that one part was more affected than
another, have been among the most constant phe-
nomena of the continued dose that I have witnessed.
These occur, in varying degrees of course, but so
corstantly, that I have come to regard them as the
in variable results of such medication.

Clinical observation has confirmed the teachings
of physiological experiment. Different observers
have given different explanations of the fact, but all
agree as to the fact itself; viz., that, by means of

♦ M. Gonzalez Echeverria, M.D., on Epilepsy, p. 317.

AND SOME OF ITS KINDRED SALTS. 55

the bromide of potassium, the practitioner can at
will, and almost to any extent and for any length
of time, diminish -or blunt, not only the normal
reflex sensibility, but also the frequent abnormal
reflex hyperaesthesia of his patients. The advan-
tage which an intelligent physician can derive from
such agent, in ameliorating suffering, cannot be
over-estimated. There is scarcely any disease in
which the indication to diminish reflex sensibility
may not sometimes exist. The particular diseases
in which this indication is most likely to occur will
be referred to farther on.

The disturbing influence of the continued dose
over metamorphosis of tissue, which has hitherto
only been referred to, deserves the careful attention
of the practitioner. Dr. Roberts Bartholow * has
been led, by his interesting experimental investiga-
tions upon the physiological action of the prolonged
administration of the bromide of potassium, — the
continued dose of this paper, — to regard its inter-
ference with secondary assimilation, and the conse-
quent lessening of the retrograde assimilation of
tissue, as one of its four predominating actions.
The other three, which I have already sufficiently
described, he considers to be diminution and ulti-
mate neutralization of the sexual appetite, weakness

♦ Cincinnati Lancet and Observer, 1865.

S6 BROMIDE OF POTASSIUM,

of the muscular system, and irritation of the stom-
ach when considerable doses are given. Dr. Z.
C. McElroy,* of Zanesville, Ohio, in a recent ingen-
ious essay, — which, however, is founded less on
clinical observation and experimental investigation
than on a priori reasoning, — arrives at the conclu-
sion, " That, from the inherent relations of bromine
and the bromides to the organic tissues and struct-
ures of the human body, their physiological and
therapeutical effects must always be those of promot-
ing destructive metamorphosis, or waste : first, of
all matter b^low the normal dynamic condition;
second, of tissue or structure of type or form for-
eign to the human body; and, lastly, of the normal
tissues themselves." Dr. Amory's experiments f
have led him to a similar result. Relying on
clinical observation, not on precise experimentation,
I am satisfied that the continued dose increases
destructive without correspondingly increasing con-
structive metamorphosis; and that, consequently,
it may gradually produce emaciation and pallor.
Fortunately, however, if it does not increase, it does
not check constructive metamorphosis. It does not
prevent the normal repair of the body, even if it
hastens the waste. Moreover, by a generous diet
and other appropriate concomitaijts, constructive

* New York Medical Journal, July, 1870.
t Vide Second Part.

AND SOME OF ITS KINDRED SALTS. 57

metamorphosis may be aided so as to neutralize the
wasting action of the continued dose. In this way,
the bromide may be given for years without pro-
ducing emaciation or loss of color, or real dimi-
nution of strength. I have administered it to a
considerable number of persons, of both sexes, —
certainly not less than twenty, — for two and three
years continuously. Combined with an appropriate
regimen, — which included iron, wine, quinia, &c.,
— this was done not only without injury, but with
manifest advantage. Their color, weight, and
strength were as good at the close of the treatment
as it was in the beginning, and with some of them
better.

Action of the Toxic Dose. — It has already been
stated that the quantity of a toxic dose of the
bromide of potassium cannot be fixed' precisely.
What would be toxic in a physiological condition
may and often will be only therapeutic in a patho-
logical one. Moreover, individual idiosyncrasies
largely modify the dose. Some persons tolerate
easily an amount, that would produce decided bro-
midal intoxication in others. Echeverria * has sel-
dom " seen forty grains repeated thrice daily for five
or six days without determining bromism." My

* Op. cit., p. 315.

S8 BROMIDE OF POTASSIUM,

experience confirms this statement. In fact, I have
generally noticed some of the symptoms of bro-
mism, other than acne, after thirty grains have been
taken thrice daily for a week or two. One hundred
grains a day, given in divided doses at equidistant
intervals, and continued for several days, may be
regarded as the maximum therapeutic dose. More
than that quantity is generally toxic. It is not to be
forgotten in this connection, what has previously been
insisted upon, that a given quantity — say one hun-
dred grains — is less likely to prove toxic if given in
one dose, or two doses near together, than if given in
divided and equal doses, and at equidistant intervals
throughout the twenty-four hours. By the latter
mode of administration, the blood retains more of
the salt, and for a longer time than by the former.

The symptoms of a toxic dose are only an in-
crease, or an exaggeration of those of a therapeutic
one. The fetid breath becomes nauseous ; oedema
supervenes on congestion of the uvula and fauces ;
the whispering voice sinks into aphonia; sexual
weakness degenerates into impotence ; muscular
weakness becomes complete paralysis ; reflex, gen-
eral, and special sensations disappear ; the ears do
not hear, nor the eyes see, or the tongue taste ; the
expression of hebetude becomes first that of imbe-
cility, and then that of idiocy; hallucinations of
sight and sound, with or without mania, precede

AND SOME OF ITS KINDRED SALTS. 59

general cerebral indifference, apathy, and paralysis ;
the respiration, without the stertor of opium or
alcohol, is easy but slow; the temperature of the
body is lowered; as the bromism becomes more
profound, the patient lies quietly on his bed, unable
to move or feel, or swallow or speak, with dilated
and uncontractile pupils, and scarcely any change
of the color of his skin or face; the extremities
grow gradually colder and colder; the action of
the heart becomes feebler and slower, tiU it ceases
altogether.

This picture, drawn from a case that will be
narrated presently, is admirably supplemented by
Echeverria's description of bromism, as it was ex-
hibited by his epileptic patients. He says : * "In
those relieved by full doses of bromide of potas-
sium, forty, fifty, sixty, or seventy-five grains have
been administered every third or fourth hour, occa-
sionally, until producing bromism. The .symptoms
then exhibited have been, — congestion with, swell-
ing of the fauces and of the tongue ; redness of the
conjunctivae and cheeks ; dilation of the pupils, dim-
ness of sight, thickness of speech; slowness of
pulse and respiration; increased secretion of the
salivary glands and kidneys ; in some instances
hallucinations of sight and hearing, and mania, —

* Op. cit., p. 317.

6o BROMIDE OF POTASSIUM,

on three occasions of a suicidal nature. The swell-
ing of the fauces, extending to the Eustachian tube,
has determined deafness in some cases, but readily
disappearing on discontinuance of the bromide.
The anaesthesia of the skin and mucous membranes
has been very conspicuous at this stage of intoxica-
tion, as also a tottering gait, with inability to steady
exertion of any kind (writing, buttoning up the
clothes, &c.), and an overwhelming drowsiness.
In no case has the appetite to eat or to smoke been
completely lost. I have long ago noticed that fe-
tidity of the breath, usually an accompaniment of
the exhibition of the bromide of potassium, occurs
earlier and more remarkably in those who do not
attend to regular cleanliness of the teeth.'*

When bromism occurs, even if it is excessive,
the discontinuance of the drug is sufficient to relieve
the patient. As soon as the salt is eliminated, the
functions resume their ordinary action, and health
returns. Death from the bromide of potassium is
rare. The following cases, therefore, — one of
excessive bromism and the other of probable death,
— are interesting illustrations of the toxic dose.

Case V. Efilefsy — Bromism — Recovery. —
A lawyer, from a neighboring city, actively en-
gaged in professional work, who added the excite-
ments of politics and the pleasures of authorship to

AND SOME OF ITS KINDRED SALTS. 6l

the labor of th6 law, had an epileptic attack, di-
rectly after making a long and exhausting argu-
ment in court.' In the course of the next few
years, he had several other attacks.^ He con-
sulted Professor Brown-S6quard, who prescribed
a mixture, of which the principal ingredient was
bromide of potassium. Not long after the treat-
ment was instituted, that distinguished physiolo-
gist and physician left America for Europe, and
the patient continued the treatment without any
medical supervision. He took the drug four times
daily, taking treble the amount at night that he
took at anyone of the other three doses. It was
taken at nearly equidistant intervals through the
day, and his total daily amount averaged about
eighty grains. He took this quantity daily and
uninterruptedly for nearly four years ; and then,
finding himself troubled with a group of uncomfort-
able symptoms, he put himself under my care. He
was thoroughly bromized. He had the vacant ex-
pression, tottering gait, oedema and anaesthesia of
the fauces, somnolent condition, whispering voice,
slow and feeble pulse, and mental and physical
weakness that have already been described. His
hand trembled so much that his attempts at writing
were illegible. His friends thought he was " break-
ing up," and his wife anxiously asked me if his
brain was not softening, and he was not becoming

62 BROMIDE OF POTASSIUM,

imbecile. His appetite and digestion were unaf-
fected. He was pale and had moderately emaci-
ated. Fortunately, he never had hallucinations or
mania, or defective vision. The sequel of the case
can be briefly told. A discontinuance of the bro-
midal medication and a tour in Europe dispelled all
of these uncomfortable symptoms. As "soon as the
bromism disappeared, his health returned. This
was several years ago. It should be added, for the
credit of the treatment that Dr. Brown-^S^quard
instituted, that the epilepsy has not reappeared. So
many years have now elapsed since a fit occurred,
that the patient may be regarded as well ; a most
fortunate escape from a dire calamity.

Case VI. Cerebral Disease — Bromism —
Death. — A general officer in the regular army
of the United States, about fifty years of age, was
in active service through our whole late civil war.
His duties were arduous and his labors incessant.
He participated in the labors, dangers, and expos-
ures of the last, long siege of Richmond, and also
in the excitements and triumphs of the short and
decisive campaign, that terminated at Appottamox
Court House. Soon after the war was over, he
showed symptoms of mental aberration. He was
treated at Washington for a short time, and then
sent to Boston. Before leaving Washington, his

AND SOME OF ITS KINDRED SALTS. 63

physician prescribed bromide of potassium, and di-
rected his attendant to give it to him freely enough
and often enough to keep him quiet. He travelled
slowly from Washington to Boston, stopping a few
days at intervening places. His attendant, putting
a literal interpretation on the physician's directions,
gradually and steadily increased the dose. I saw
him on the day of his arrival in Boston. He took
in divided doses, during that day, at least four
hundred and eighty grains. This dosQ. was re-
peated the next day ; for it was not till then, that
I ascertained what and how much he was taking.
As soon as this was known, the bromide was dis-
continued. The sort of mania he was in disap-
peared shortly after the discontinuance oi the medi-
cine; but a heavy, stupid, and paralyzed state
remained. He died in about a week, without
emerging from this condition. Unfortunately no
autopsy was possible; and whether he died from
cerebral disease, or from bromism, or from bro-
mism superadded to cerebral disease, I could not
determine. Probably, from the history of the case,
he had fatal cerebral disease, upon which bro-
mism was superinduced : at any rate, he was thor-
oughly bromized.

BROMIDE OF POTASSIUM,

SPECIAL APPLICATIONS OF THE CON-
TINUED DOSE.

The preceding analysis of the action on man of
the single, continued, and toxic dose of . bromide
of potassium exhibits two distinct groups of phenom-
ena, — one therapeutic and the other disagreeable
and toxic.

They may be arranged as follows : —

THERAPEUTIC GROUP.

Sleep.

Anaesthesia of reflex power of

fauces.
Reflex anaesthesia of genito-uri-

nary organs.
Diminished reflex sensibility of

system generally.
Contraction of cerebro- spinal

arterioles.
Repression of general nervous

irritability.
Control of reflex convulsion.

DISAGREEABLE AND TOXIC
GROUP.

Acne.

Salivation.

Aphonia.

Slow respiration.

Slow and feeble pulse.

Increase of destructive meta-

morphosis.
Tottering gait.
Cerebro-spinal anaemia.
General paralysis.
Hallucinations.
Mania.

Diminished temperature.
Cessation of heart's action.
Death.

It is the duty of the practitioner, whenever he
employs bromidal medication at all, to secure such
of the phenomena of the first group as may be
indicated, and to avoid as far as possible all of
the second group. This may be accomplished by

AND SOME OF ITS KINDRED SALTS, 65

careful attention to the physiological action of
the bromide, which has already been pointed out ;
and especially by keeping in mind the ratio of
elimination to absorption.

The special therapeutic applications, of which
the continued dose of the bromide of potassium is
capable, have been rendered obvious by the pre-
ceding investigation of its physiological action. It
will not be inappropriate however, and it may be
useful, to supplement this account by a brief state-
mient of some of the special diseases or pathological
conditions in which it has been found by experience
to be serviceable.

As a preface to this, it is well to bear in mind
two important observations of Echeverria, taken
from the work previously referred to : one is, that
strong coffee may be advantageously given with
meals, or through the day, when large doses of the
bromide are continuously administered. He says :
'* The operation of the remedy seems aided by this
practice, and the supervention of bromism very
materially delayed. "* His other observation is, that
the association of the bromide of potassium with the
arseniate of potash avoids the disagreeable eruption
that has been previously described. "From five to
eight minims of Fowler's solution, added to each

*Op. cit., p. 318.
5

66 BROMIDE OF POTASSIUM,

dose of the mixture of the bromide, will prevent the
cutaneous eruption. . . . We, however, fall short of
this result if alkaline baths are not employed in con-
junction, or if the eruption be not previously arrested
on discontinuance of the bromide." I have only
recently met with these observations, and have not
yet had any opportunity of verifying them, but
shall improve the first occasion of doing so. The
authority of Echeverria, however, renders them
deserving of careful attention.

The continued dose of the bromide of potassium
may be advantageously used in a large variety of
pathological conditions, the most of which are em-
braced in the following classes. It may be used : —

1st, As a palliative or comforter of nervous symp-
toms in many diseases of dissimilar character; as
pneumonia, bronchitis, rheumatism, gout, simple
and continued fevers, conjunctivitis, ovarian disease,
and the like.

2d, As a moderator of reflex action in certain
local maladies : as irritation or inflammation of the
fauces, bladdet", and vagina ; emissions ; reflex
nausea and vomiting ; and nymphomania.

3d, As an anodyne or anaesthetic in various
neuroses : as in some kinds of headache and neu- .
ralgia ; angina pectoris, pertussis, asthma, and dur-
ing the menopause.

4th, As a moderator or sedative of general reflex

AND SOME OF ITS KINDRED SALTS. 67

power in spasmodic and convulsive diseases ; as
epilepsy, hysteria, and chorea.

5th, As a vascular sedative in hyperaemia of the
brain and spinal cord.

This last indication underlies all the others ; for
the preceding analysis of the physiological action
of the bromide of potassium has shown that to it
all the other indications must be referred. There
is, however, an obvious practical advantage in
dividing them into separate groups. Let us look
at each of the above groups of indications more
carefully.

1st, A Sedative in Dissimilar Diseases. — The^
judicious employment of the continued dose, as a
palliative or comforter of nervous symptoms in the
management of disease, will depend largely on the
intelligence, good sense, and ingenuity of the prac-
titioner. Disagreeable or uncomfortable symptoms
of a nervous character, — known by the vague terms
of nervous irritability, nervous hypersesthesia, ner-
vous derangement, restlessness, flying pains, and the
like, — without being pathognomonic of any disease,
are very apt to accompany all sorts of maladies, and
especially affections of the nervous system. Every
physician recognizes them clinically, and has to com-
bat or control them. Various means, not exclusively
drugs, adapted to the idiosyncrasies of patients, and
the varying conditions of disease, are employed in

68 BROMIDE OF POTASSIUM,

the treiatment of them. Of the drugs employed for
this purpose, the bromide of potassium is perhaps
the best. It may be given in any disease, where
the above vagu^ sort of symptoms exists, in whatever
dose it is necessary to employ for the control of the
nervous disturbance or hyperaesthesia, and for any
length of time short of producing bromism. I have
used it very largely for many years past, in this
sort of way, and with most satisfactory results. It
may be combined with other drugs, with which it
is not chemically incompatible, or made an adju-
vant to almost any treatment. It often renders a
patient insensible to the discomforts of his position ;
and this is no small matter. I recollect a gentle-
man, who was convalescent from acute rheumatism,
who took it for a while, and after a few days dis-
continued it. "Why did you leave that medicine
off?" said his wife to me the day after its discon-
tinuance : " my husband was so good-natured while
he took it." If good-naturedness during sickness
can be purchased by bromide, it is well to make the
bargain.

When bronchitis assumes a spasmodic form, and
the cough is out of proportion to the physical signs,
bromide of potassium affords more relief than opium.

It palliates the pain ef conjunctivitis only when
it is given in doses large enough to subject the
whole system to its influence.

AND SOME OF ITS KINDRED SALTS, 6g

It possesses no curative action over simple, con-
tinued, typhoid, or other fevers, but as a moderator
of reflex excitability affords the comfort just spoken
of; and by diminishing the congestion of the brain,
that so often accompanies some forms of fever, may
aid materially the resolution of the disease. If the
brain, during any period of fever, by reason of im-
paired nutrition or other cause, becomes anaemic
instead of congested, and is consequently irritable,
the bromide is more likely to do harm than good.
Ten grains, three times a day, is generally enough
to afford sufficient palliation of these discomforts of
fever or of convalescence. Double this amount may
be given if necessary. Sometimes a single hyp-
notic dose at night is better than the continued dose.
Generally, however, the latter is preferable.

2d, An AfKEsthetic in certain Local Maladies, —
As a moderator of local reflex action, in the treat-
ment of local maladies, the continued dose of the
bromide of potassium is often of service.

Ordinary sore throat is not benefited by it. But
when there is frequent or constant irritation of the
fauces, provoking useless and disagreeable efforts
of hawking and spitting, which is unattended with
redness or swelling, relief may generally be ob-
tained from the continued dose of the bromide. It
is of little use in these cases, unless it is exhibited
in quantities large enough to destroy, or at least

70 BROMIDE OF POTASSIUM,

diminish, the reflex sensibility of the parts. Twelve
or fifteen grains, given three times a day, are com-
monly sufficient for this purpose.

Difficult deglutition of a spasmodic character,
whether hysterical or otherwise, is sometimes com-
pletely relieved by the continued dose. The fol-
lowing case illustrates its fortunate action in this
respect : — f

Case VII. Difficult Deglutition — ^ Cough -< —
Recovery. — A lady, sixty two or three years of
age (residing in the country at some distance from
Boston), took care of her grandchildren, through
a scarlet fever, in January, 1870. During their
sickness she had more or less sore throat, without
being seriously ill. After their recovery, she be-
came hoarse, and subject to violent paroxysms of
coughing. In a few weeks she began to experience
difficulty in swallowing, especially in the swallow-
ing of liquids. A variety of measures were tried,
by her attending physician, for her relief; but they
were not successful. As one of her sisters had died
of malignant disease of the throat, both her physi-
cian and herself were naturally apprehensive of a
similar difl[iculty in her own case. I saw her in
consultation three months or thereabouts after the
commencement of the difficulty.

She was pale, emaciated, but able to sit up and

AND SOME OF ITS KINDRED SALTS, 7 1

walk about. By a strong effort, and with evident
physical difficulty, I saw her swallow a mouthful
of solid food. Liquids were apparently swallowed
with still greater difficulty. At any rate, she com-
plained more of the swallowing of these ; and when
she made the effort, some of the liquid, whether it
was water, milk, tea, or broth, regurgitated out of
her nose. The cough occurred only in paroxysms,
which were violent, and sometimes suddenly aroused
her from sleep. Her appetite was good, but she
could not get down as much food as she craved.
There were no signs of disease of the lungs. The
upper part of the fauces was pale, rather than red-
Lower down, the mucous membrane appeared, in
the laryngoscopic mirror, congested. No tumor or
growth was discovered.

The continued dose of the bromide of potassium,
in combination with the iodide of potassium, was
advised. She took ten grains of the former and
two of the latter three times a day for several weeks.
There was a manifest improvement of her condi-
tion in about a week after the treatment was com-
menced, and in three months she was able to swal-
low with comparative ease. I saw her a year later,
and the improvement continued. She then called
herself well.

The anaphrodisiac and sedative action, upon the
geni to-urinary apparatus, of the continued dose of

72 BROMIDE OF POTASSIUM,

the bromide of potassium may sometimes be ration-
ally invoked in the treatment of seminal emissions
and nymphomania. When the former are kept up
or excited by local irritation or erethism, they may
be controlled to a greater or less degree by giving
enough of the bromide to diminish, or remove any
excessive local excitability. If they have what may
be called a central origin, and are the consequence,
not the cause of sensual and erotic feelings, the
continued dose of the bromide will materially aid
the patient in his efforts to repress the desire that
annoys him. In order to accomplish this object, at
least twenty grains should be given during the day ;
and twenty or thirty more in a single dose on
retiring.

It is important, however, to remember in this
connection, that the most effectual treatment of these
emissions is a moral one. The advertisements of
charlatans, and the books of pseudo-physiological
writers, who, under the guise of instructing the
young, seek only to fleece them, have frightened a
great many persons into the belief that emissions,
which are often only natural and physiological dis-
charges, always and necessarily lead to death, or
to what is worse than death. In Niemeyer's Prac-
tice * a case is referred to, where a man had an

♦ German edition, vol. ii. p. 103.

AND SOME OF ITS KINDRED SALTS, 73

abundant loss of semen with each dejection for at
least ten years, without any injurious influence upon
his health. A little physiological information upon
this matter, judiciously imparted by the physician,
will often do more good than the bromide of potas-
sium or any other treatment.

The continued dose controls sexual excitement in
the female as well as in the male. Stills testifies*
to its efl[icacy, in what he calls '* those sad instances
of hysteroidal excitement which verge on nympho-
mania;" and truly adds, "In all these aflfections,
small doses of the medicine are unavailing. Not
less than twenty grains, three times a day, will exert
a decisive control over excessive sexual propensities,
even in adolescents ; nor can its effects be expected
to be permanent, unless advantage is taken of the
improvement it occasions to invigorate the system
by the combined resources of food, exercise, and
habits of living."

Reflex nausea and vomiting are sometimes, not
always, admirably controlled by the continued dose.
When the stomach will not retain the medicine
long enough for it to be absorbed, it may be admin-
istered by the rectum, till the nervous centres are
quieted by it, and then the stomach will generally
retain it. In order to obtain the greatest benefit

* Therapeutics and Materia Medica, vol. ii. p. 800.

74 BROMIDE OF POTASSIUM,

from it, in these cases, it should be exhibited in
doses large enough, and near enough together, to
bring the nervous system decidedly under its seda-
tive influence. When this result is attained, the
sedative action should be kept up continuously for
several days or weeks, long enough, at least, for
the irritation or congestion of the nervous centres
to pass away, if this is possible.

Neither inflammation of the bladder, nor of the
mucous membrane of the vagina,' yields to the con-
tinued dose of the bromide of potassium ; yet there
is occasionally a sort of irritability, or hyperaesthesia
of these parts, that is happily modified by it. Fre-
quent micturition and incontinence of urine, con-
nected with nervous disturbance, of a local or
general character, are ameliorated and sometimes
permanently relieved by it. In like manner, vagi-
nismus occasionally yields to the sedative influence
of the bromide of potassium. In the treatment of
the latter malady, local injections of a solution of the
salt, held in the vagina for ten minutes at a time,
twice a day, may be advantageously employed in
connection with the internal administration of the
medicine. Small doses are of little value in these
cases. Enough must be given to take away the
reflex excitability of the palate, as in the treatment
of epilepsy, before the difficulty is relieved.

3d, An Anodyne or Ancesthettc in Various Neu--

AND SOME OF ITS KINDRED SALTS, 75

roses. — The bromide of potassium, either in the
single or continued dose, possesses very little direct
anaesthetic power. It will rarely stop pain directly ;
but indirectly, by removing some of the causes of
pain or diminishing reflex or general sensibility, it
sometimes renders an important service in a variety
of painful and distressing maladies.

The functional derangements of the brain and
nervous system, which so frequently accompany
the menopause, have been more fortunately con-
trolled, in my experience, by the continued dose of
the bromide of potassium than by any other drug.
The common symptoms at that period, of timidity,
irritability of temper, inquietude, broken sleep, ap-
prehension of serious evil, flushing of the face and
head, numbness, deranged sensation, and the like,
are commonly ameliorated and sometimes com-
pletely controlled by it. This is particularly true
of the flushing of the face, — that wave of heat and
redness, which many describe as rolling up to and
through the brain, and which they dread as the
precursor of paralysis. It is scarcely necessary to
say, that it would not be judicious to administer
the bromide, through the whole period, often three
or four years, during which the constitutional
change in the female system that attends the meno-
pause is going on. It should be given only when
the symptoms of nervous disturbance are excessive.

76 BROMIDE OF POTASSIUM,

When it is exhibited, the largest relief will be ob-
tained by giving it continuously, and in doses suffi-
cient to bring the system fully under its influence^
Its sedative action should be kept up for two or
three weeks, and then the treatment should be dis-
continued. The same course may be resumed,
whenever the condition of the patient warrants it.
The importance of appropriate hygienic, moral,
and tonic treatment, as supplementary to .the use
of the bromide of potassium, in these cases, need
not be insisted on.

Among the numerous remedies that have been in-
voked for the relief of angina pectoris, the bromide
of potassium should not be forgotten. Not much
can be expected from it, in this intractable malady ;
yet the little it can do is sometimes of great value.
At the time of this present writing, I have under
my observation a great sufferer from this complaint,
who has obtained more relief, after taking" the bro-
mide, than after taking any other drug that I have
given him. Here, as in many other diseases that
have been mentioned, small doses do very little good.
Ten or twelve grains should be given three times a
day, for a considerable period ; and when a par-
oxysm occurs, thirty grains additional should be
administered at once, and this dose repeated in half
an hour, or an hour, if necessary.

Whooping cough and asthma, like angina pec-

AND SOME OF ITS KINDRED SALTS. 77

toris, are only occasionally benefited by the con-
tinued dose of bromide of potassium. But it is this
'Occasional benefit which it is well for the practi-
tioner to bear in mind. I know of no methods or
symptoms by which to discriminate a case of asthma
or whooping cough, that can be favorably influ-
enced by the bromide, from cases of these diseases
ttat are utterly rebellious to it. My use qf it, there-
fore, in these maladies is wholly empirical. But a
good result is obtained often enough to induce me,
^Q many severe cases of pertussis, to try the effect of
putting the patient well under the sedative action
of the bromide, and keeping him under it for a week
or two at least. Trousseau * quotes with approba-
^on, in his "Clinical Lectures," the following
recipe for the treatment of asthma, which he says
"C derived from an American source : —

B Potassii lodidi 32

Decoct. Polygalae 53

Tinct. Lobelise 36

Tinct. Opii Camphor 36

^f tliis mixture, the taste of which must be experi-
enc^d to be appreciated, he advises a tablespoonful
to o^ given two or three times a day. The addition
^^ "t^n grains of the bromide of potassium, to each
Qoa^ of the above mixture, will materially enhance

• Clinique M6dicale, torn. ii. p. 409. French ed.

78 BROMIDE OF POTASSIUM,

its control of asthma, without adding much to the
disagreeableness of its taste.

Little can be expected, either from the single or
continued dose of bromide of potassium, in the treat-
ment of ordinary neuralgia or ordinary headache.
But there are classes of both of these affections that
are especially amenable to it.

Dr. Anstie has clearly pointed out the kind of
neuralgia which is relieved by the bromide, and I am
glad to reinforce my own observations by his state-
ments. He says : * " Four very different types, at
least, of narcotic-stimulant drugs, are useful in neu-
ralgia." These he calls the opium t}''pe, the bella-
donna type, the chloral type, and the bromide of
potassium type. Of the last, he has given the fol-
lowing admirable description : f " The use of bromide
of potassium in neuralgia is a subject of great im-
portance, and which requires much attention and'
discrimination. In common with, I dare say, many
others, I made extensive trial of this agent when it
first began to be much talked of; but was so much
disappointed with its effects in neuralgias, that at one
time I quite discarded it in the treatment of those
affections. Renewed experience has taught me,
however, that though its use is restricted, it is ex-

* Neuralgia and the Diseases that resemble it. By Francis
£. Anstie, M.D. p. 185. English ed.
t Op. cit, p. 191.

AND SOME OF ITS KINDRED SALTS, 79

tremely effective, if given in appropriate cases and in
the right manner. For the great majority of neural-
gias it is quite useless, and, what is more, proves often
so depressing as indirectly to aggravate the suscepti-
bility of the nervous system to pain. The condi-
tions, sine quzs non^ of its effective employment seem
to be the following : The general nervous power,
as shown by activity of intelligence, and capacity
of muscular exertion, and the effective performance
of co-ordinated movements, must be fairly good, and
xthe circulation must be of at least average vigor ;
the patient must not have entered on the period
of tissue degeneration. Among neuralgics who
answer to this description, those who will benefit by
the bromide are chiefly subjects — especially women
— in whom a certain restless hyperactivity of mind,
and perhaps of body also, seems to be the expres-
sion of nature's unconscious resentment of the neglect
of sexual functions. That unhappy class, the young
men and young women of high principle and high
mental culture to whom marriage is denied by fate
till long after the natural period for it, are especial
sufferers in this way ; and for them the bromide ap-
pears to me a remedy of almost unique power. But
I wish it to be clearly understood that it is not to the
sufferers from the effects of masturbation that I think
the remedy specially applicable : on the contrary,
it is rather to those who have kept themselves free

8o BROMIDE OF POTASSIUM,

from this vice, at the expense of a perpetual and
almost fierce activity of mind and muscle. The
eflfects of solitary vice are a trite and vulgar story i
there is something far more difficult to understand,
and at the same time far more worth understanding,
in the unconscious struggles of the organism of a
pure-minded person with the tyranny of a power-
ful and unsatisfied sexual system. It is in such
cases, which it needs all the physician's tact to ap-
preciate, that it is sometimes possible to do striking
service with bromide of potassium ; but it will be
necessary to accompany the treatment with strict
orders as to generous diet, and very likely with
the administration of cod-liver oil."

" Having decided that bromide of potassium is
the proper remedy, we must use it in suiEcient
doses. Not even epilepsy itself requires more de-
cidedly that bromide, to be useful, shall be given
in large doses. It is right to commence with mod-
erate ones (ten to fifteen grains), because we can
never tell beforehand that our patient is not one of
those peculiar subjects in whom that very disagree-
able phenomena — bromic acne — will follow the
use of large doses. But we must not expect good
results till we reach something like ninety grains
daily. Let me add that it is not, so far as I know,
by reducing any * hyperaesthesia ' of the external
genitals, of which the patient is aware, that the

AND SOME OF ITS KINDRED SALTS. 8l

remedy acts- I have not seen such a nexus of
disease and remedy in these cases."

It should be added to the above that the daily
dose, whatever that may be, that is sufficient to
control the neuralgic condition, should be continued
for several weeks after the pain is subdued, or no
permanent relief will be secured.

Headache, that accompanies grief, anxiety, be-
reavement, or any sort of mental worry, yields
readily to the bromide of potassium. But pain in
the head, that ushers in an attack of fever, or ac-
companies any acute inflammation, as pneumonia or
pleurisy; or that arises from constipation, or de-
ranged digestion, or cold, and the like, — is rarely
even palliated by the bromide. Whenever head-
ache arises from anaemia of the brain, it is more
likely to be aggravated than relieved by bromidal
medication.

Persons, especially females of a nervous or hys-
terical diathesis, who are subject to that form of
sick headache in which the cerebral symptoms not
only precede, but predominate over the gastric
ones, often derive considerable benefit from the
bromide of potassium. It should be administered
as soon as there is the slightest warning of a com-
ing attack, and in a dose of not less than twenty
grains. This should be repeated every hour till

the nervous system is brought thoroughly under

82 BROMIDE OF POTASSIUM,

its influence. At the same time, the patient should
remain quietly on a bed or sofa, with the dress
loosened so as to allow of an unimpeded circula-
tion, and the extremities kept warm, till the usual
period for a threatened attack has passed by.

In some cases, a better way than this is to give
the continued dose daily for several months, during
the intervals between each attack. By such a pro-
cedure, the intervals are prolonged, the severity
of the headaches diminished, and occasionally the
attacks arrested. The experienced practitioner
need not be reminded that this course alone, how-
ever much it may palliate, rarely, if ever, eradicates
sick headaches. They are too deeply grained into
the constitution, by long-continued errors of diet or
regimen, or by unhealthy modes of life, or unhealthy
surroundings, to be rooted out by an agent that
simply diminishes cerebro-spinal hyperaemia and
reflex sensibility. In the administration of the
large dose, at short intervals, first mentioned, a
combination of carbonate of ammonia, or of the aro-
matic spirits of ammonia, with bromide of potassium,
gives speedier relief than the latter alone.

4th, A Controller of Reflex Power in Convul"

sive Diseases, — The most important sphere for the
employment of the continued dose of bromide of
potassium is to be found in the application of its
physiological action to the pathological conditions

AND SOME OF ITS KINDRED SALTS. 83

of convulsive diseases, especially of epilepsy and
epileptiform maladies. Its use in this way is of
recent origin. For our present knowledge of its
control over many forms of convulsion and spasm,
we are indebted to some of the ablest living observ-
ers; especially to Sir Charles Locock, Drs. Rad-
cliffe, Reynolds, Mac Donnell, Duckworth Williams,
Echeverria, A. Voisin, Bazin, Hardy, and most of
all to the distinguished Brown-S^quard, whose per-
sonal labors two continents have reaped the advan-
tage of, and whose researches are valued wherever
medicine is recognized as a science.

It would require a treatise on epilepsy, as well as
one on the bromide of potassium, to point out pre-
cisely how the physiological action of the latter can
be advantageously adapted to the different forms
and phases of the former. The limits of this paper
do not admit even of a sketch of epilepsy ; and I
must content myself, therefore, with a statement of
the obvious fact, that the more accurate a phy-
sician's knowledge of the disease in question is, the
better and more satisfactorily will he be able to
employ bromidal and other medication in the treat-
ment of it. The extent of our present knowledge
•

of it can be ascertained by an examination of the
researches of Brown-S^quard, Dr. RadclifFe, and
Dr. Reynolds, and especially of the recent admi-
rable work on epilepsy by G. Echeverria, of New

84 BROMIDE OF POTASSIUM,

York. The knowledge obtained from these or
from kindred treatises, supplemented by his own
clinical experience, must teach the practitioner how
to use the bromide of potassium in the treatment of
this terrible disease.

The following directions for its use, from the pen
of one, not less familiar with the physiological action
of the bromide than with the natural history and
pathology of epilepsy, possess the greatest practical
value, and deserve the physician's careful attention.

A. Voisin says : * "It is only within the last twenty
years that the therapeutics of epilepsy have acquired
any fixed principles. Herpin of Geneva first, dur-
ing this period, affirmed the curability of epilepsy,
which to-day has become assured.

" The largest degree of success at present is due
to the bromide of potassium. First employed in
England, in 1853, by Locock, it was first used in
France by Bazin and Hardy ; and in the hands of a
large number of physicians has yielded excellent
results.

"The bromide of potassium should be pure, free
from iodine and chlorine. It should be given a few
minutes before meals, in doses very gradually in-
creased, and varying from two to twelve grammes
(30 to 180 grains), or more, daily. But as the

* Bulletin G6n6ral de Th^rapeutique, May, 1871.

AND SOME OF ITS KINDRED SALTS. 8$

doses employed must vary largely with individuals,
according to their age, constitution, and force, I
have employed for many years a method which
has given me the best results, and which consists in
determining the condition of reflex nausea, by intro-
ducing a spoon as far as the epiglottis. I have
remarked that a therapeutic dose of the bromide of
potassium is not attained till reflex nausea is sup-
pressed : it is not till then that the bulb is certainly
acted on, and its excito-motory force diminished.
I have been fortunate enough to have this criterion
of the therapeutic action of the bromide of potassium
approved by M. CI. Bernard, in his lectures at the
College of France.

^ The study of other reflex phenomena, such as
lachrymation, cough, and sneezing, enables us to
follow the action of the medicament upon the bulb
and the spinal cord.

^ The dose of the drug should not be increased
beyond the suppression of reflex nausea; but it
should be given continuously, and with perseverance,
for years together, if the malady is ameliorated, or
in process of cure. At the end of two years of
amelioration or of cure, the remedy, instead of being
administered every day, may be given every second,
third, or fourth day, provided reflex nausea is always
and certainly absent. It is only after several years
have passed, without epileptic phenomena, that treat-

86 BROMIDE OF POTASSIUM,

ment should be discontinued. Earlier than this,
the administration of the remedy should always be
continuous. Intermission is a great mistake. A
chronic malady demands chronic medication. The
bromide of potassium should almost be made the
aliment of an epileptic, till he is cured.

"Certain therapeutic indications, peculiar to the
bromide of potassium, always make me augur
favorably of its action in epilepsy. Thus, hypnotic
manifestations, general lassitude, an easy and rapid
disappearance of reflex nausea, and an anaphro-
disiac action, are favorable auguries in the treatment
of an epileptic by the bromide of potassium. When,
on the contrary, the anaphrodisiac, hypnotic, and
sedative action is negative, and when the reflex
nausea is slow to disappear, there is reason to
believe that the bromide will produce no eflfect,
and that it will be necessary to resort to other medi-
cation.

'* The bromide of potassium can be advantageously
employed in all forms of epilepsy, idiopathic and
symptomatic, as well as in cases of epileptiform
phenomena, even when they are allied to idiocy
and cretinism. Not that it can cure them all, but
it can mend them all ; and the explanation thereof
is perfectly physiological. Because all convulsive-
phenomena of an epileptic character are the products
of an exaltation of the excito-motory force, of the bulb.

AND SOME OF ITS KINDRED SALTS. 87

^^ bromide of potassium can always moderate and
^^^iti, if it cannot suspend them. But while recom-
^^^nding the employment of the bromide of potas-
^^Xim, in preference to other medicaments, for all
^^nvulsive affections of an epileptic character, I
^cnsider that its utility is the greatest in cases
"^here epilepsy is idiopathic; or where it is the
Result of great impressionability, or exaltation of
Sensibility ; in those where it has been produced by
intense emotion, painful impressions, fear, onanism,
snd venereal excess ; in those, finally, where it is
the hereditary consequence of neuroses, like hys-
teria, chorea, and even of epilepsy itself. More-
over, if the bromide of potassium does not always
cure, it nearly always moderates the malady ; and
diminishes, or almost suppresses, the nervous ere-
thism, shocks, and twitchings of the epileptic.

**The bromide of potassium can suppress the
aura, even when unable to dispel completely the
attacks. It has less influence over absent-minded-
ness [les absences] and vertigo than over the
attacks.

''The proportion of those with whom I have
been able to suspend the epileptic phenomena has
gradually become larger and larger, since I dis-
covered the criterion of reflex nausea. In reality,
whilst I was able to report, in 1866, a suspension of
the malady in one-fourth of the cases, I can now

88 BROMIDE OF POTASSIUM,

obtain the same result in one-half of the adults
treated. With children, on the contrary, the pro-
portion of success is scarcely one-fourth.

"Pidoux and G. S^e think that the bromide of
potassium does not cure epilepsy ; and that, if it sus-
pends or retards the attacks, it does so by replacing
them with preludes and incomplete attacks. In the
first place, this opinion is not tenable in face of
the observations, already numerous, that establish a
cure, without a trace of the evil left; and then it is
to be remembered, that the principal indication of
the cure of epilepsy is to be found in this, that the
attacks begin to be replaced by preludes and in-
complete attacks, just as confirmed epilepsy is
always preceded for a certain period by preludes
and incomplete attacks. So that when, under the
influence of any medication, an epileptic has only
incomplete attacks and preludes, he should be con-
sidered on the way to a complete cure.

^ The administration of the bromide of potassium
demands, when it is to be long continued, certain
precautions, without which there is danger of being
obliged to suspend its employment. Thus diuretics
should be regularly given, in order to increase the
urinary secretion, and the elimination by the kid-
neys of the bromide of potassium, and to prevent
certain cutaneous eruptions, that patients find very
disagreeable. Iron should be frequently associated

AND SOME OF ITS KINDRED SALTS. 89

with the bromide of potassium, so as to prevent the
ansemia and cachexia that its long-continued use is
apt to induce, and to prevent certain affections of
an evil character, that may occur with those who
take large doses of it for many years.

**! have noticed that the bromide of potassium
generally succeeds less well with children than
with adults ; perhaps, because the epilepsy of child-
hood is more frequently allied, than the epilepsy
of adult age, to congenital states of the nerve
centres; or to cerebral lesions of a scrofulous or
tuberculous nature; or, more likely still, as the
drug is very rapidly eliminated in childhood, only
a slight impression is made on the spinal cord, and
the reflex actions, of which I have spoken, are with
difficulty suppressed. From eight to twenty-two
grains may be given to children, two or three years
old ; from thirty to seventy-five grains, to those be-
tween five and ten years of age : and from thirty-five
to one hundred and eighty grains, to those between
ten and fifteen years old.* The bromism, which
I have often observed in children, and which is
characterized by depression, loss of appetite, great
prostration of strength, and pulmonary catarrh, is
never grave, if the drug is immediately suspended.

• These quantities refer to the amount taken through the
whole of each day, not to each individual' dose. — Tr.

90 BROMIDE OF POTASSIUM,

In adults, on the contrary, bromism is manifested
by the gravest phenomena of pulmonary catarrh
and adynamia, or rather of the most intense ataxia.
The action of the bromide of sodium is the same as
that of the bromide of potassium. The doses of it
are not quite so large."

The testimony of Dr. West, the eminent London
professor and sagacious physician, to the efficacy
of the bromide of potassium, in the treatment of the
epilepsy of children, is a valuable confirmation of
what has been previously stated with regard to
the bromidal medication of epileptics. He says : *
''I may be expected to say something as to my
experience of specifics for epilepsy. I have tried
all, or almost all, in favor of which any reasonable
evidence could be adduced, and all have failed.
The only one which has appeared to me to exert
any specific power over epilepsy is the bromide of
potass ; and in a few instances its results have been
most remarkable. It hardly ever fails to arrest the
frequency of attacks ; now and then it has seemed
entirely to prevent them ; and the crucial test of
arresting fits by bromide of potass — of suspending
the remedy and seeing the fits return, and of once
more putting a stop to them by the resumption of

♦ Lumleian Lectures, on some disorders of the nervous system
in childhood, by Charles West, M.D., pp. 45, 46. Am. ed. iS/i.

AND SOME OF ITS KINDRED SALTS. pi

the medicine — has, on some occasions, established
its value beyond question. In the great majority
of cases, however, the amendment has not entirely
maintained itself: the system has, after a time, be-
come habituated to the remedy ; and after several
augmentations of the dose, each of which has
seemed to renew the old influence, I have been
compelled to discontinue it, in consequence of the
depression of the pulse, the general loss of power,
and the appearance of the peculiar pustular erup-
tion, which occasionally follows its long-continued
use. In other cases, too, the agent which at first
worked wonders ceased to have any influence.
The constitution tolerated the increased dose, but so
did the disease : the patient continued to take the
medicine, but the fits, though once controlled, re-
turned after a time just as before.

" Still, with all these drawbacks, the bromide
remains the only agent which, in my hands, has
made the least approach to the character of a
specific. I always employ it, when I can find no
distinct indication to guide me. I confess that I
use it empirically ; for I have found no means by
which to distinguish beforehand the cases where
the bromide will do permanent good, from the
other, apparently similar, but much more common
instances, in which its influence is merely tem-
porary."

92 BROMIDE OF POTASSIUM,

My personal experience of the bromide of potas-
sium, in the treatment of epilepsy, is so small that
it scarcely deserves mentioning, after what has been
previously quoted from Voisin, West, and Eche-
verria. I should not allude to it, were it not that
out of the twelve cases, -five males and seven females
(two being under eight years of age, and ten adults) ,
that my note-books have a record of, three seem to
have radically recovered. Neither of these three
has had a fit for many years ; and every case of
recovery from this sad disease deserves to be pub-
lished, for the encouragement of physicians and
patients alike. Six of the remaining nine are
under treatment at the present time ; and three of
these have not had an attack for a year. Of the
other three, one has died, and two have not been
benefited by treatment. The whole twelve were
treated by the large and continued dose that has
been described. Perhaps it should be mentioned
that this small group of cases occurred in private
practice.

Hysteria, — The paroxysms of ordinary hysteria
are more advantageously treated by such remedies
as cold aflfusion, inhalation of ether, and what are
called antispasmodics, than by the bromide of potas-
sium. But if the paroxysms are epileptiform, their
treatment by this remedy is nearly always successful.

AND SOME OF ITS KINDRED SALTS, 93

The course pursued should be the same as in the
treatment of epilepsies, except that it need not be
continued so long. A course of from six to twelve
months 9 depending on the severity of the case and
its duration previous to the commencement of treat-
ment, is commonly sufficient.

As a prophylactic in hysteria, uncomplicated with
epileptiform convulsions, bromidal medication often
yields a precious service. The continued dose quiets
the hysteric or hyperaesthetic temperament, and
bridles it, so that the necessary crosses of daily life —
the irritations of existence — are less likely to excite
an explosion. Many cases might be given in illus-
tration of this remark, but to do so would only add
to the bulk of this paper, which has already largely
exceeded the limits originally intended for it.

While administering the continued dose in cases
of hysteria, the practitioner should remember that it
is not curative : it simply holds the nervous system
quiet, controls an abnormal excitability for the time
being. Other remedies, often moral, sometimes di-
etetic or hygienic, sometimes tonic, and sometimes
purely local, must be used in conjunction with the
bromide, so as to remove the cause of the malady.

This last remark leads to another, in reference to
the opinion quoted from M. Voisin in a preceding
paragraph, viz., that the bromide of potassium cures
epilepsy. In the first place, the word cure^ as indi-

94 BROMIDE OF POTASSIUM,

eating the action of drugs, is inappropriate ; secondly,
I conceive that the bromide acts in epilepsy as in hys-
teria, simply by keeping off the attacks long enough
for the organization, by constructive metamorphosis,
to rebuild nerve tissue, so that the latter becomes
incapable of epilepsy. When a surgeon applies a
splint to a broken bone, the splint holds the bone
still, so that osseous reconstruction is possible.
What a splint is to a fractured bone, bromide of
potassium is to an epileptic medulla, or to hysteric
nerve centres. The medulla is kept quiet long
enough for it to grow into health, if it is capabl
of doing so. Neither the splint nor the bromid.
can be properly called curative, though they
be indirectly so. The practical advantage of
ing at the action of the drug in this way is,
while the physician keeps his patient's nervo"*-
system under the control of the continued dose, ^
will, with this notion in his mind, be likely to
carefully after the equally important matter of
constructive metamorphosis.

Bromide of potassium is not often used in
treatment of chorea, but it occasionally does
cellent service in that complaint, especially wt>-
associated with Fowler's solution of arsenic.

5th, A Vascular Sedative in HypercBmia of
Nerve Centres. — Brown-S(5quard, Laborde, Vois^ ^
and others, have demonstrated, what has aire 3 ^J

AND SOME OF ITS KINDRED SALTS. 9$

been largely insisted on, that the arterioles of the
cerebro-spinal axis are constricted by the action of
the bromide of potassium, so that the nerve centres
are made by it to carry less blood than they other-
wise would. Whether this is accomplished by the
direct action of the salt on the central or peripheral
extremities of the nerves, or on the capillary blood-
vessels themselves, is matter of greater interest to
the physiologist than to the therapeutist. The lat-
ter is concerned chiefly with the important fact,
that the bromide of potassium furnishes him with
the means of diminishing to a limited extent, and at
will, the amount of blood circulating through the
brain and cord. This action underlies and explains
the physiological phenomena, and consequent thera-
peutic indications, that have hitherto been pointed
out. Little remains to be said, then, under this
head, except to refer to the fact, that in cases of
spinal irritation and spinal pain, and neuralgia any-
where, dependent on spinal congestion, the obvious
indication is to employ the continued dose long
enough to re-establish permanently a normal circu-
lation in the nerve centres. I have often used it in
this way, and with the happiest results.

When speaking of the value of the continued
dose in dissimilar diseases, no allusion was maae
to its employment in ovarian and uterine difficul-
ties, because there was a practical advantage in

BROMIDE OF POTASSIUM,

reserving that to the present time. Every physician
is familiar with the neuralgia, reflex excitability,
and hypersesthesia that is so apt to accompany
these complaints. Apart from whatever loc^l treat-
ment may be necessary, there is probably no drug
which affords greater relief than the bromide of
potassium to these distressing symptoms. But it is
to be remembered — and this is a sufficient reason
for introducing the subject in this connection — that
neuralgia, reflex excitability, and hyperaesthesia
arising from spinal congestion and spinal irritation,
may exist in the uterine region, without a trace of
uterine disease. These symptoms do not necessarily
imply disorder of the sexual organs of the female,
and do not always demand a local examination.
When they are dependent upon spinal hyperaemia,
a larger and more permanent relief may be ration-
ally expected from continued bromidal medication
than when local uterine and ovarian disease causes
or complicates them. When they are dependent
on spinal derangement, local uterine treatment is
more apt to aggravate than relieve them. There
are many cases, especially among the unmarried,
with whom it is desirable to try the continued dose
of the bromide of potassium before resorting to a
local examination.

AND SOME OF ITS KINDRED SALTS, 97

ANTAGONISM OF BROMIDE OF POTASSIUM

AND STRYCHNIA.

M. Saison* has called attention to the physio-
logical antagonism of bromide of potassium and
strychnia. This antagonism is most marked in
the action of the two agents upon the medulla ob-
longata and the cord, and least marked on the
brain. The bromide produces capillary constriction
and oligaemia of the bulb and cord ; strychnia pro-
duces capillary dilatation and hyperaemia of the
same parts. The bromide relaxes, and strychnia
causes convulsions. The bromide produces relax-
ation and deficient reflex excitability; strychnia
causes contraction and increased reflex excitability.

M. Saison says : '' I have made numerous com-
parative experiments of these two antagonizing
agents, — injecting strychnia into one limb and
bromide into the other. There were convulsions
and tetanic stiffening, with lengthening of the
strychnized foot: no convulsions and relaxation
of the other. Next I injected a mixture of the
solutions of strychnia and bromide. The convul-
sions Were very feeble, their total duration abridged,

♦ Thfeee. Paris, July, 1868.
7

98 BROMIDE OF POTASSIUM^

and the animals lived longer than after an equ
dose of either agent singly. I have even been at
to keep alive a strychnized frog more than an hoi:
by injecting bromide from time to time."

Here, as elsewhere, clinical observation su
plements and confirms physiological experimei
When these two agents are administered simull
neously to man, a larger dose of both of them
required in order to bring about their specific acti<
than when they are given separately. My atte
tion was first called to this antagonism by Profess
Brown-S^quard, in a consultation with him. I ha
since noticed it in several cases. Ordinarily, br
mide of potassium and strychnia should not
administered together ; yet it would be rational
give them simultaneously, provided it was desiral
to obtain the maximum action of the bromide
the brain and bulb, and its minimum action on I
cord. By their conjoint exhibition the influence
the bromide of potassium upon the circulation
the cord is antagonized, but not that upon the bra
Strychnia exerts its minimum action upon the bra
and its maximum action upon the cord. Th
are congestions of the brain, especially of its gi
matter, which it is desirable to diminish; whiN
is equally desirable, at the same time, to Keep
the nutrition, so as to prevent oligasmia of the co
When bromide of potassium is used in such ca^

AND SOME OF ITS KINDRED SALTS. 99

the addition of strychnia antagonizes the action of
the former on the cord, without materially inter-
fering with its influence over the encephalic cir-
culation. At any rate, this is the best explanation
I can give of the happy conjoint action in certain
cases of these two drugs, whose physiological action
OJ^ the cord is so opposite.

The following case,* reported by Dr. Charles B.
®illespie, of Freeport, Penn., is a clinical illustra-
tion of the physiological antagonism of these two
Agents, and of the control of the toxic action of
®^ry chnia by bromide of potassium.

lSE VIII. — "I was called, December 17, to
an, some miles in the country, who, the mes-
er reported, had fallen down in a fit, and had
^^l^nt cramps. I found the patient lying on his
^^^3 on a small trundle-bed, with his hands tightly
^"^^t: cubing the bed-frame, and, at every movement of
^-^ attendants, thrown into the most violent clonic
ims. On lifting his head, I recognized the pa-
as one who had, that same morning, purchased
my clerk three grains of strychnia, for the al-
purpose of killing rats. It was evident that he
taken the poison himself; and the wretched
confessed that he had taken nearly all the

American Journal of Medical Science, Oct. 1870. p. 420.

lOO BROMIDE OF POTASSIUM,

strychnia some two hours before, for which he was
now heartily sorry, and begged me to save him,
solemnly promising that, if his life were only spared
this time, he would never attempt the like again.

"This short explanation was interrupted half
a dozen times by the most terrible spasms. His
pulse was 70, hard and contracted; respiration
good. The whole surface of the body was quite
cold ; great anxiety in the expression of the face ;
sight and hearing perfectly normal. On giving
him drink, the great difficulty was in getting the
cup to his mouth, without throwing him into con-
vulsions ; but when once there, he would gulp the
contents down spasmodically in great mouthfuls.
He had but little control over his arms : as soon as
he let go his grasp on the bedstead, they would
jerk violently, and continue thus until he laid
hold of something solid and immovable.

" The spasms were evidently becoming more vio-
lent and frequent, and beginning to implicate the
muscles of respiration. Not having the remedy I
desired with me, I gave him a teaspoonful of the
fluid extract of hyoscyamus; and then hurrying
home, weighed out one ounce cf bromide of potas-
sium, which I dissolved in three ounces of water. Of
this solution I ordered one half-ounce every thirty
minutes ; and I felt so confident of its efficacy in
this case, that I intrusted the administration of the

AND SOME OF ITS KINDRED SALTS. lOI

remedy to a carefully instructed attendant, and did
not revisit the patient till next morning, when I
found him out of danger. The paroxysms had
gradually become less violent and frequent; and
by the time the last dose of bromide was taken, at
midnight, he was able to get up without assistance,
and walk to his own room. The only bad effects
remaining were excessive muscular and nervous
prostration, with an occasional slight convulsive
shudder, which, however, entirely passed off through
the day ; and in thirty-six hours' time he was up, and
at his usual business.''

It is to be regretted that the above report does
not give the total quantity of bromide of potassium
•which the patient took. Each half-ounce of the
solution contained eighty grains, and he was or-
dered to take this every half-hour. How many
times he took it does not appear. It is fair to infer,
however, that he took more than half an ounce in
the course of two or three hours, and possibly the
"whole ounce.

102 BROMIDE OF POTASSIUM,

BROMIDE OF AMMONIUM.

Physiological Action. — The behavior of the bro-
mide of ammonium in the human body, so far as its
absorption and elimination are concerned, has been
found to be the same as that of the bromide of po-
tassium. What has been said of the latter in this
respect, therefore, may be applied to the former.
There is the same facility of absorption and of
elimination, and the same variations of them with
varying conditions of the stomach and its contents.
The taste of the bromide of ammonium is rather
more strongly saline and disagreeable than that of
the bromide of potassium, and is therefore less
readily taken. When swallowed, the stomach toler-
ates one as well as the other ; at least this is true of
moderate doses. In large quantities, the ammonium
salt is more irritating to the mucous membrane than
the potassium salt. The two may be united in the
same prescription, if there is any reason for doing
so ; and they will pass into and out the body as
readily as if they were not travelling in company.

It appears, moreover, from the researches of physi
ologists,* that the bromide of ammonium, while i

* Vide Experiments with the Bromide of Ammonium, Part 2.

AND SOME OF ITS KINDRED SALTS. 103

the system, exerts upon it an action similar to
that of the bromide of potassium. It may be given
so as to deaden 'the reflex sensibility of the fauces
and palate, to diminish the cerebro-spinal circula-
tion, and to lessen general reflex sensibility. It is
also apt to produce acne on the cutaneous surface, of
the same character as that which so often accom-
panies the exhibition of the other bromide'. Mental
activity is repressed by it ; and large and continued
doses will induce a sort of hebetude and intellectual
dulness. Dr. Brown-S^quard is of opinion that
the bromide of ammonium exerts a special influ-
ence over the medulla oblongata and upper parts
of the spinal cord,* and deduces some important
therapeutic indications therefrom.

But, notwithstanding the similarity of the physio-
logical action of these two salts, the more unpleas-
ant taste and greater irritating qualities of the
bromide of ammonium render it less agreeable to
patients, and less convenient of administration than
the bromide of potassium.

Therapeutic Action. — The bromide of ammonium
is not largely used alone. It has been recommended
by a few practitioners in pertussis, and is undoubt-
edly capable of rendering some service in that com-

♦ Lectures on the Diagnosis and Treatment of Functional
Nervous Affections, p. 82.

I04 BROMIDE OF POTASSIUM,

plaint, in the way of diminishing spasmodic action,
and especially of allaying hyperaesthesia of the
pharynx and larynx. It has also been recom-
mended in nervous affections, particularly those of
the ganglionic system, and in glandular enlarge-
ments. From my own observation of its action in
these affections, I am not inclined to regard it as
equal in therapeutic value to the bromide of potas-
sium.

Its principal therapeutic value is to be found in its
association with, and not in its substitution for, the
potassium salt. I have not observed that the hyp-
notic action of the single dose of the latter agent is
increased by associating bromide of ammonium
with it ; but the sedative influence which the con-
tinued dose of the bromide of potassium exerts
over the reflex power of the nervous system seems
to be increased by such an addition. Ten grains
of the bromide of potassium, with three or five
grains of the bromide of ammonium, given together,
three times a day, produce a greater sedative influ-
ence than twelve or fifteen grains of either of them
administered three times a day separately. Pro-
fessor Brown-S^quard first called attention to the
increased sedative power obtained by the association
of these remedies. Speaking of their united action,
he says : * " I have observed a very curious fact in

* Lectures, ut supra, pp. 86-7.

^ND SOME OF ITS KINDRED SALTS. 105

CDying together the bromide of potassium and

l^romide of ammonium. I have ascertained

without producing the phenomena which con-

s what has been called bromism (anaesthesia

e throat, nostrils, &c., weakness, especially

'tl^.e neck and spine, lack of will, sleepiness,

I^^^lity, &c.), I could give in a day sixty grains

^tve bromide of potassium and thirty grains of

^ "bromide of ammonium, while, if I replaced

^ "^Mrty grains of this last salt by only twenty

__ of the other salt, so as to give eighty

^^i^e bromide of potassium alone, bromism was

. ^^^^lly produced. And also, if, in place of the

, ^^ grains of bromide of potassium, I added to

thirty grains of bromide of ammonium from

^^ ^^^ty to twenty-five grains of this last salt, bro-

yf^ ^^ M^

'^sn was again produced. So that ninety grains,
a larger dose of the two remedies taken to-

^ -ier, did not produce bromism; while a smaller

^^ of either employed alone did produce it. If
^^ call bromism a bad eflfect, and if we call a good

^ct the favorable influence of these remedies in
^t^ilepsy and other neuroses, it can be said that their
^^sociation in certain doses diminishes their bad
effect, while it increases their good eflfect.''

Fcheverria * states, on the contrary, that he has

♦ On Epilepsy, p. 316.

Io6 BROMIDE OF POTASSIUM,

not " recognized any marked adjuvant effect *' from
the addition of the bromide of ammonium to the bro-
mide of potassium, — a mixture " which renders more
unpalatable to the patient the already disagreeable
taste of the solution of bromide of potassium.^ My
personal experience, based not so much on the
treatment of epileptics as on that of neuroses in
general, leads me to coincide with the opinion of
Professor Brown-S^quard. The combination of the
two salts exerts a happier sedative influence than
either of them separately.

It is interesting and instructive, in this connec-
tion, to compare the rules laid down by Voisin, for
the exhibition of the bromide of potassium in epi-
lepsy, which have been previously quoted, with
those laid down by Brown-S^quard for the exhibi-
tion of the mixture just described in the treatment
of the same disease. The similarity of the two
statements enhances the value of each. Brown-
S^quard says : * " There are rules relative to the
treatment of epilepsy by the bromides of potassium
and ammonium, employed together or separately,
which are of so great importance that I will take
this opportunity to mention them briefly, postponing
the details till I treat especially of epilepsy. These
rules are : —

Op. cit, p. 83.

AND SOME OF ITS KINDRED SALTS, 107

** I. That the occurrence during the day of the
sleepiness caused by those remedies can be avoided
"by giving relatively small doses in the daytime, and
a much larger dose late in the evening.

**2. That the quantity of these medicines to be
taken each day must be large enough to produce an
evident, though not complete anaesthesia of the fauces
and upper parts of the pharynx and larynx : that
daily quantity being (according to the idiosyncrasy
of the patient) from forty-five to eighty grains of
the bromide of potassium, and from twenty-eight
to forty-five grains of the bromide of ammonium,
when only one of these salts is employed, and a
smaller quantity of each, but especially of the sec-
ond, when they are given together.

^ ^. That, considering that the bromide of potas-
sium (and, in a small degree, also the bromide of
ammonium) very rarely produces any good eflfect
against epilepsy, without producing also an acne-
like eruption on the face, neck, shoulders, &c., and
^hat there seems even to be a positive relation be-
tween the intensity of the eruption and the efficacy
^f the remedy against epilepsy, it is most impor-
tant to increase the dose when there is no eruption,
and also when the eruption is disappearing, unless
the dose given in the twenty -four hours is already so
large that any increase of it produces great sleepi-
ness in the daytime, a decided lack of will and

Io8 BROMIDE OF POTASSIUM^

of mental activity, dulness of the senses, droopi
of the head, considerable weakness of body, and
somewhat tottering gait.

"4. That it is never safe for a patient ta
either of the bromides, or both, and receiving ben^^iCt
therefrom, to be even only one day without his me
cine, so long as he has not been at least fifteen
sixteen months quite free from attacks. Indeed 9 it
is very frequent that patients neglecting this r^jJe
are seized again with fits, after an immunity ^>f
several or of many months, one, two, or only a fS^'w
more days after the interruption of the treatm^:»3.t.
In several cases, even after an apparent cure
ten, eleven, or twelve months, and, in one instan.
of thirteen months and a few days, there has b
a reappearance of the disease, after the treatm.^^^^
had been abandoned for only a few days, or a we

" 5 . That the debilitating eflTect of the bromi
in patients already weak — as in most epileptics
ought to be prevented or lessened by the use
strychnine, arsenic, the oxide of silver, ammor^
or cod-liver, cold douches or shower baths, a:^^*- *
of course, wine, and a most nourishing diet.*

* In making use of strychnine or arsenic, it must be kept
mind that not only the bad influence of the bromides, but ^^
their favorable influence against epilepsy, can be diminisb^^
by these powerful agents (especially strychnine), and that it ^ "^
therefore, necessary, when these agents are used, to increase **'^*

Jc.
es

AND SOME OF ITS KINDRED SALTS. IO9

"6. That iron and quinine — which are gen-
erally injurious to epileptics, except in cases in
^hich their nervous affection is caused, or at least
iggravated by chlorosis, anaemia, or malarial ca-
chexia — are more particularly injurious in cases
n which. the bromides are taken.

" 7. That a gentle purge every five or six weeks
jsually gives a new impulse to the usefulness of
the bromides against epilepsy."

Dose, — ^The bromide of ammonium may be given
in the dose of thirty grains or less : more than that
amount given at once is apt to irritate the stomach.
It may be administered in water or syrup, or with
a bitter infusion or tincture. If there are indica-
tions for doing so, it may be united in a prescription
with bromide of potassium, iodide of potassium,
iodide of ammonium, iodide of sodium, bromide of
lithium, carbonate of ammonia, valerianate of am-
monia, carbonate of soda, chloric ether, and the like.

dose of the bromides. The antagonism between strychnine, j

which acts in increasing the reflex faculty of the nervous cen- \

ires, and the bromides, which diminish this faculty, may be so |

great as to produce almost a complete annihilation of the in- 1

fluence of the bromides and partly that of strychnine. In one »

case 132 grains a day of the bromides were taken without the !

least appearance of bromism, and without any controlling effect j

over epilepsy, when the patient was taking about one-third of a :

grain of strychnine a day; while he was strongly bromized j

under the influence of 80 grains a day of the bromides, when j
he was not taking strychnine."

no BROMIDE OF POTASSIUM,

BROMIDE OF LITHIUM.

The bromide of lithium is a white, deliquescent
salt, having a saline and somewhat bitter taste. On
account of its deliquescence, it should be exhibited
in solution and not in powder. It contains about 92
per cent of bromine; and in this respect differs
from the bromide of sodium, which contains 78 per
cent of bromine, and from the bromide of potas-
sium, which contains 66 per cent.

The physiological action of the bromide of
lithium is very similar to that of the bromide of
potassium and bromide of ammonium. It pro-
duces sleep, diminishes reflex sensibility and
muscular power. According to Weir Mitchell,* it
causes more rapid and intense sleep than the bro-
mide of potassium. I am not aware of any experi-
ments that have been made with it for the purpose
of determining its rate and time of absorption and
elimination. It is probable that in these respects it
resembles the bromide of potassium, as it does in
its therapeutic action. My clinical experience with
it, which is not large, confirms the statements of
Professor Mitchell in the article just referred to;

♦ American Journal of Medical Science, Oct. 1870, p. 443.

AND SOME OF ITS KINDRED SALTS, III

viz., that it "acts efficiently in some cases of epi-
lepsy where bromide of potassium has failed ; that
it, is thus efficient in lesser doses than the salt just
named ; and that, as an hypnotic, it is superior to
the potassium salt and the other bromides." The
only objection that I know of to its use is its cost,
which, at present, is so great as to prevent its general
employment. When the bromide of potassium fails
to exert its ordinary physiological action, — a failure
which sometimes, though rarely, occurs, — or when
the stomach becomes disgusted with it, or the sys-
tem unpleasantly affected by it, the bromide of
lithium may be advantageously substituted for it. I
liave met with cases in which the bromide of potas-
sium produced quiet and pleasant sleep for a time,
sind then failed to do so, and in which the lithium
^alt at once acted as the potassium salt did at first.

• It may be given in the dose of from ten to twenty

grains or more, three times a day. It is not often

tihat it will be requisite to give sixty grains a day.

Xiike the bromide of potassium, it may be exhibited

in the form of a single comparatively large hyp-

xiotic dose at night, or in the form of the continued

<lose, repeated several times a day and for weeks

together. The continued use of it will produce

acne as rapidly and as decidedly as the bromide of

potassium. '

112 BROMIDE OF POTASSIUM.

BROMIDE OF SODIUM.

The bromide of sodium closely resembles in its
appearance, taste, solubility, and physiological
action, the bromide of potassium, bromide of
ammonium, and bromide of lithium. Its taste is,
perhaps, rather less unpleasant than the others.
M. Voisin regards its physiological action and
therapeutical value as equivalent, or nearly so, to
the bromide of potassium. Dr. Amory has been
led by his experiments to regard it as a less valu-
able therapeutic agent than the potassium salt. It
possesses no decided advantages over the other
bromides just named, and therefore it is not desir-
able to substitute it for them in the treatment of
disease.

•'

PART II.

EXPERIMENTS

ILLUSTRATING THE PHYSIOLOGICAL ACTION

THE BROMIDE OF POTASSIUM AND
BROMIDE OF AMMONIUM

ON MAN AND ANIMALS.

By ROBERT AMORY, M.D.,

amnual lscturbr for xsjo-jz on the physiological action of drugs on

man and animals, in the medical department op harvard

university; fellow of American academy of arts

AND sciences; fellow of the MASSACHUSETTS
medical SOCIETY, ETC

PROPOSITIONS.

A. — Bromide of Potassium is absorbed readil/ by anj por-
tion of the healthy mucous membrane with which it is placed
in contact.

B. — This drug is largely and mainly eliminated with the
urine ; during the first day the largest portion passes out of the
system, less during the second day, and so on until there is none
left in the system.

C. — The skin assists in the elimination of this drug from
the system on the second as well as the first day.

D. — The loss of reflex action is due to the diminution of
blood in the periphery of the nerves, and also of the central
nervous system ; this last occurring after the first.

E. — The action of Bromide of Potassium on the nervous <
system may be explained by its action on the capillary, arterial, .
or central circulation.

PHYSIOLOGICAL ACTION

THE BROMIDE OF POTASSIUM
AND AMMONIUM.

CHAPTER I.

ABSORPTION.

DROMIDE of Potassium is absorbed readily by
the mucous membrane of the mouth. This
proposition is illustrated by the following experi-
ments : —

Exp. I. — Under the effects of ether, a dog was

operated upon for ligature of the oesophagus.

^'^'Tien this had been accomplished, a solution con-

*^niiig i6o grains of this salt was placed in the

^outh of the animal. In ten minutes after the con-

toct of the drug with the buccal mucous membrane,

^tne blood (3j.) was drawn from the carotid artery,

^^d, examined by means of chlorinated water and

bisulphide of carbon, gave the peculiar reaction of

the liberation of bromine; viz., a reddish-yellow

color.

The bromide must have been absorbed by the
iDUCOus membrane of the mouth and pharynx, for

Il6 PHYSIOLOGICAL ACTION OF THE

great care was taken to prevent the contact of the
solution with any other tissue.

Exp. II. — A strong solution of this same salt
was retained in the mouth for five minutes, and then
thoroughly ejected ; the mouth was carefully rinsed
out with fresh water and wiped dry, and again
rinsed. The solution was kept in the anterior por-
tion of the mouth, and by the tongue prevented
from touching the pharynx.

The examination of 25 cubic centimetres of urine,
passed two hours and a half afterwards, indicated
the presence of a large amount of the bromide.

In these and other experiments not here related
the bromide was present in the blood of dogs and in
the urine of man, to whom the drug had been admin-
istered by means of the mucous membrane of the
mouth only; and it is thus proved that bromide

of potassium can readily be absorbed by this por -3--

tion of the mucous membrane. There is no doubts ^=Dt
that the absorption is rapidly accomplished. Thia^ f s
is shown in these two experiments and by the fol — -Tl-?
lowing : —

Exp. III. — Ten grains in an aqueous solutions ^n
were introduced by an cesophagean tube into th^^^e
stomach of a rabbit. Six minutes after, 3 iss. ofer-^f
blood taken from the carotid artery were careful l^^ -Y

BROMIDE OF POTASSIUM 6^ AMMONIUM, 1 1?

analyzed * and found to contain (by calculation from
the amount of bromine obtained) three and three-
fifths milligrammes (or y^^ of a grain) of bromide
of potassium. We supposed the weight of the rab-
bit to be 6 lbs. or 5,250 grains ; by calculution, the
inference seems reasonable that, if there was as
much of this salt in the rest of the blood as in this
specimen, we had recovered about one-third of the
"vrhole quantity given. Considering that in an analy-
sis of thirty-five centigrammes of bromide of potas-
sium, which had been previously dissolved in an
ounce of urine, one-tenth part was not recovered in
the process, it is fair to suppose that more of the salt
might have been recovered in the above-named
experiment than we actually obtained. In six min-
utes, therefore, a large portion of the drug was
absorbed. Compare this with an experiment made
upon man: —

Exp. rV. — Eight grains of the salt were swal-
lowed, and the mouth carefully rinsed out with
water and wiped several times. Five minutes after,
3 ij. of saliva were collected, which, analyzed
qualitatively, was found to contain a large amount
of a bromide; an intense brownish-yellow tinge

* The details of this analysis will be reserved for another
portion of this paper.

Il8 PHYSIOLOGICAL ACTION OF THE

was given to bisulphide of carbon by the addition
of two or three drops of strong chlorine water. In
another experiment, a slight indication of the p:
ence of a bromide occurred in urine collected tweni
minutes after the ingestion of twenty grains.

Exp. V. — Some blood, drawn from the carotic^^d
artery of a rabbit ten minutes after the exhibitioc^K-^n
of lo grains by the stomach-tube, failed to show thi
presence of any free bromine. By adding,
ever, the chlorine water, a bromide was decbi
posed, liberating the bromine.

Exp. VI. — The body of the experimenter w^ --^as
immersed for fifteen minutes in a warm bath (9^- j6^

F.), containing an ounce and a quarter of bi 0-

mide of potassium to 20 gallons of water. T^^fte

urine passed during the night and following moi n-

ing was retained, and then a portion carefully test«^«sd
for a bromide. No indication of its presence
discovered. In this case no eruption of the
occurred, showing that prolonged contact of f
drug does not irritate the skin.

Exp. VII. — At another time about 3 ij. of ttn^^*
salt were dissolved in a foot-tub containing five g^^-
Ions of water. The feet and ankles were th ^^ ^
immersed for 18 minutes, the temperature of ^ ^ ^^
water being kept at about 72^ F.

BROMIDE OF POTASSIUM ^ AMMONIUM, 1 19

The urine passed three hours after showed, by
flie usual test, that a salt of bromine was present in
it. It is important to state that no bromide had been
taken for four weeks previous to this experiment.

Supplementary Exp. {a). — Thinking that the
results of these two experiments might be doubted,
they both were repeated under somewhat different
conditions. I asked my friend Dr. to dis-
solve S X. of br. of pot. in xx. galls, of water at a
temperature above 98^ F. He informed me that
there was not quite enough water to cover his whole
body, which was kept immersed for 12 minutes, the
temperature of the solution varying from 108® to
Xo2^ F. ; he afterwards washed the body with fresh
"Vvater, and then wiped it dry. He reported that he
ielt more languid than usual after a hot bath (the
temperature of the water was very high) , and im-
agined that he experienced a saline taste half an
l>our after the bath. I carefully analyzed his urine
C5 "^O Passed during 12 hours after the bath, but
c^ould not find the least trace of a bromide.

(3) At night I soaked my feet for ten minutes in
^ solution * of this drug, and the next morning took
^ cold sponge bath containing 5 ij. of the bromide
t:o a pail of water. 5 iv. of urine passed during
^tiiat day gave a very decided reaction of a salt of
"bromine. Thus by a warm bath no bromide had

♦ Temperature of 70® F.

I20 PHYSIOLOGICAL ACTION OF THE

been eliminated nor absorbed; while after a cold
bath its presence in the urine proved its absorption
by the skin. This agrees fully with the statement
quoted by Dr. Stills, * that in a warm bath at 96^ F.
the body exhales, and at a temperature below 80**
the body imbibes moisture.

This drug can be absorbed also by the rectum ;
because, in the following experiment, —

Exp. VIII. — A rectal injection of beef tea, con-
taining an ordinary dose of bromide of potassium,
was given to a patient, and the urine passed during
the next 18 hours collected. 5 ij- of this gave a
decided reaction of a salt of bromine. This and
other experiments since undertaken prove that the
rectum will absorb this drug, when dissolved in a
vehicle which will prevent the local irritation of the
mucous surface. When given in a small amount of "
warm water by the rectum, irritation may be induced,
with a tendency to diarrhoea and tenesmus.

Prop. A. — These and other experiments not-z:
here related prove that bromide of potassium is^
absorbed readily and rapidly by the mucous mem —
brane, generally^ and that it is not readily absorbec^-
by the skin except at a temperature below that of^
blood heat.

* Materia Medica and Therapeutics, vol. i. p. 53.

BROMIDE OF POTASSIUM ^ AMMONIUM, 1 2 1

Is bromide of potassium decomposed in the sys-
tem, and may a chemical transformation explain its
method of action?

Dr. Bill, in a number* of the American Journal
of Medical Sciences, states that there may be a
chemical interchange in the blood between chloride
of sodium and bromide of potassium, and says that
when bromide of potassium meets chloride of sodi-
um, chloride of potassium and bromide of sodium
result; that is, outside of the body. He also
states that, as there is an excess of chlorides elimi-
nated after the use of this drug, perhaps its action
may be explained by there being a diminution of
the chlorides in the blood. I have taken consider-
able trouble to determine the correctness of this
theory, and can find no other authority for this
chemical reaction, and cannot see how such a the-
ory can be proved by the known methods of chem-
istry.

His argument is based upon the fact that there is
an increase in the amount of chlorides eliminated
ty the urine after the ingestion of the bromide in
closes less than what may endanger life. He tabu-
lates a report of the quantity of chloride of silver
obtained from the urine of a person taking daily
doses of the bromide ; and, also, finds an increase

♦ July, 1868.

122 PHYSIOLOGICAL ACTION OF THE

in the amount of potassium eliminated by the kid-
neys. He does not, according to this table, sepa-
rate the bromide of silver from the chloride of silver.

Consequently an increased amount of the mixed
bromide and chloride of silver (which are thrown
down together by nitrate of silver), found in the
urine after the use of this drug, proves no more
than that the bromides and chlorides are eliminated
together in the urine. In some analyses which were
conducted under my supervision by Dr. Wood,* it
was found that this increase in amount of the nitrate
of silver precipitate was due to the union of bro-
mine and chlorine with the silver, and the br6mine
was then separated, leaving, I should judge, only
the normal amount of chlorine behind.

In our experiments the proportion of bromine to
chlorine eliminated was as 2 : i.

Another refutation of this theory might be ad-
duced from the fact that bromide of sodium rarely,
if ever, produces a physiological action which is
similar to that produced by the bromide of potas-
sium, f

* Instructor in Chemistry Med. Dept. Harvard University.

t Though it is stated by Voisin that the action of bromide of
potassium and of bromide of sodium is the same, this is not con-
firmed by my experiments with the latter. Bromide of lithium^
on the contrary, does produce an action similar to that of bro-
mide of potassium, and is used by Dr. S. Weir Mitchell in
practice on account of its more intense action. If a solution

BROMIDE OF POTASSIUM ^ AMMONIUM, 123

CHAPTER II.

CHEMICAL. PROPERTIES OF BROMIDE OF POTASSIUM.

It would be in place here to mention some of the
chemical properties of bromide of potassium, and
especially to give in detail the process by which our
investigations were conducted.

This is a very fixed salt, losing no weight by
fusion at a red heat. The stronger acids with
difficulty liberate the bromine at an ordinary tem-
perature. Potassium has a stronger affinity for
chlorine than for bromine, and a stronger affinity for
bromine than for iodine. If to a solution of bro-
mide of potassium a drop or two of strong chlorine
vrater be added, the bromine is set free in the liquid ;
and ether, chloroform, or bisulphide of carbon will
absorb the gas, producing a strong brownish-red
tinge to either. The bisulphide of carbon we found
the most serviceable in this process.

This is a very delicate test, M. Rabuteau* having

of the bromide of lithium is poured into the ear (previously
reddened by stimulation) of a rabbit, it causes a sudden pallor
of the ear, which lasts for several hours after, the temperature
also being noticeably lower.

* Gazette Hebdomadaire, April 24, 1868.

124 PHYSIOLOGICAL ACTION OF THE

discovered an exceedingly small quantity ; the only
objections to this method being that the organic
matters in the urine interfere with its reaction, and
that an alkaline fluid may also prevent the decom-
position. To overcome these difficulties, we evapo-
rated the urine to dryness, and then ignited the
residue, keeping it at a red heat for about half an
hour. Then to the solution a drop or two of nitric
acid was added, until blue litmus paper was changed
to red. Next the chlorine water was added, drop
by drop, until the peculiar reddish color was visible.
This color was concentrated by the addition of two
or three drops of the bisulphide of carbon, which,
on agitation, absorbed all the bromine and settled
at the bottom of the test-tube. Too much chlorine
forms a white precipitate, chloride of bromine*
therefore caution is required in adding the chlori«:r\^
water. Sometimes in the decomposition of t^Mci^
organic matters the bromine escapes, so that t - -^^
addition of a small fragment of pure soda or
may be placed in the urine to take up the bromini
M. Rabuteau prefers the soda to potassa, becai
the former is more easily decomposed by nitric a«
and chlorine. This was our test for the presei
of a bromide.

The process for calculating the amount of a bm^ro-

* Op. cit.

BROMIDE OF POTASSIUM ^ AMMONIUM. 1 25

mide present may be best described by giving a
detailed account of one experiment : —

Exp. IX. — Thirty-five centigrammes of bromide
of potassium were dissolved in an ounce (31
grammes) of urine. The urine was evaporated
to dryness, charred and ignited. The residue was
then treated with boiling water and filtered from the
carbon. But little of the coloring matter of the urine
was present in the filtrate. Nitrate of silver was
then added in excess, and the mixture allowed
to stand twenty-four hours. The precipitate was
washed thoroughly with boiling water, acidulated
with a few drops of nitric acid. This precipitate
consisted of a mixture of the bromide and chloride
of dilver, with some of the coloring matters of the
urine. To free the latter, an excess of ammonia
Vras added to dissolve the mixed bromide and chlo-
ride, leaving the coloring matters behind. The
residue was washed with water. The filtrate was
acidulated with nitric acid, and bromide and chlo-
ride of silver again precipitated. This precipitate
>vas then washed with acidulated water as before.
The filter paper had previously been dried and
>?veight ascertained. This, after being dried, was
now weighed with its precipitate and found to have
increased to the amount of 6.075 grammes. Of
this a portion was placed in a crucible, the weight
of which had been previously ascertained.

126 PHYSIOLOGICAL ACTION OF THE

The weight of crucible without contents was 6.705 grms.
The weight of crucible with contents was 7*025 gpms.

Thus the bromide and chloride of silver

weighed 320 grms.

This portion was then fused in the crucible, and
chlorine gas, washed in sulphuric acid, was passed
over by means of a porcelain tube fitting into the
platinum cover of the crucible. The chlorine dis-
places the bromine which is set free. (This process
must be continued till the crucible ceases to lose
weight.) From the loss in weight the amount
of bromine may be calculated from the following
proportion : * —

1. ««The difference between the equivalents of
chlorine and bromine : the equivalent of bromine =
the loss of weight : x." Thus 44.54 : 80 = loss of
weight : X

From the amount of bromine originally in the
crucible may be calculated the amount of bromine
in the whole precipitate as follows : —

2. Weight of the whole mixed precipitate :
weight of that in the crucible = x (bromine in the
whole) : bromine in the crucible.

From the amount of bromine in the whole mixed
precipitate, the amount of bromide of potassium
recovered may be determined thus : —

* Quantitative Chem. Anal. Fresenius, by Bullock & Vacher,
p. 446, 1865, ChurchiU, London.

BROMIDE OF POTASSIUM 6^ AMMONIUM. 1 27

3. Equivalent of bromine : equivalent of bromide
of potassium = weight of bromine found in the mixed
precipitate : x (or bromide of potass.).

From these three problems the result of the pre-
ceding experiment was obtained. It was supposed
that the bromine discovered in this process was
united with potassium which was found in the urine.
The method of obtaining the amount of this is so
difficult and protracted that we are contented with
Dr. Bill's * statement, that in his experiments the
potash was increased '' fourfold " in the urine when
bromide of potassium was taken.

The result obtained was as follows : —

Weight of whole mixed precipitate . . = 0.607 g^ms.
„ „ crucible with contents . . = 7.025
„ „ „ without „ . . . = 6.705

„ „ bromide and chloride of silver = 0.320
First weighing after passing over the

chlorine := 7.020

,, loss of weight = 0.005

Second weighing afler continuation of same

process = 7.012

„ loss of weight = .013

Third weighing = 6.991

„ loss • . . . = .034

* American Journal of Medical Sciences, July, 1868.

128 PHYSIOLOGICAL ACTION OF THE

Fourth weighing := 6.965 g^ms.

„ loss = .060 „

Fifth weighing = 7.025 „

„ loss := .060 „

Sixth weight the same. Then using the rules of pro-
portion above stated, —
44.54 : 80 = .060 : X =^iii grm. or bromine in cru-
cible.
320 : 607 = .III : X = .211 grm. or bromine in the

whole amount of precipitate.
80 : 119.11 = .211 : X = •314 grui. bromide of po-
tassium.
Thus of .350 of a gramme dissolved in urine
•314 »> ?? was recovered.

.036 lost by impure chemicals and an insufficient
laboratory.

This was the result of our first quantitative anal-
ysis for bromide of potassium, and the process is
given in detail to show that all ordinary caution was
exercised that could occur to our minds.*

The details of the analyses to be hereafter men-
tioned will not be transcribed.

M. Rabuteau mentions in a recent publication,!

♦ In these analyses the ordinary commercial nitrate of silver
(lunar caustic) was used, which may be the cause of our not
obtaining more accurate results. This would not, however, in-
terfere with the relative results, which are the main points to be
considered.

\ Gazette Hebdomadaire, 1868.

BROMIDE OF POTASSIUM b* AMMONIUM. 1 29

that having tested the urine for ^ two months, and
having found a salt of bromine each time, and this
when only one gramme had been given, he was so
much surprised that he obtained some urine from a
person who had not been taking a salt of bromine,
and still found a trace of bromine present by the
qualitative test before mentioned. In seeking for
an explanation of this phenomenon, he ascertained
if a quantity of urine exceeding one hundred and
fifty grammes (5 vj.+)* was employed he almost
invariably detected some bromine. In any less
quantity no bromine was perceptible in ordinary
urine. Therefore he is disposed to add this m'etal-
loid to Bernard's list f of fourteen simple bodies
found in man and the higher order of animals.

♦ We never employed in our analyses more than one hun-
dred grammes at any one time.

t See CI. Bernard, Sur les Substances Toxiques et M^dicamen-
teuses, Paris, 1867, p. 40.

130 PHYSIOLOGICAL ACTION OF THE

CHAPTER III.

EFFECTS UPON THE SECRETIONS.

We will now consider the effects of bromide of"
potassium upon the secretions. The quantity of the
saliva does not appear to be modified in any degree.
This drug appears to a very great extent in thi&
secretion, and can be detected for twenty days * after"
one gramme has been taken. Several times I hav^
detected its presence in the saliva within a very few
minutes after its administration, and have provedl
its presence for a long time afterwards, almost as
long as it is present in the urine. Voisin states that
this drug appears very early in the saliva, and
remains there as long as it can be detected in the
urine. His statements are confirmed by some ex-
periments of Rabuteau, before alluded to; and, as
I have not found any cause to doubt these observers,
the details of my experiments have not been given.
There seems to be no chemical decomposition with
the gastric juice.

When pure, it at first may stimulate the mucous
membrane to throw out its mucus ; but, after one or

* Gazette Hebdomadaire, 1868, p. 582.

BROMIDE OF POTASSIUM b* AMMONIUM. 131

- - — ■_ . - ■ _

two days' use, its tendency is to dry up this secre-
tion in the mouth and fauces, and especially in the
excreta of the intestinal canal, which, with a few
exceptions, are dry, hard, and infrequent.

Excretions. — With regard to its effect upon the
kidneys there is much debate. Does it or does it
not produce diuresis ? It is difficult to judge of this
from various reasons. The quantity of urine passed
in twenty-four hours varies in different persons, and
in the same person at different times. The state of
the weather, of the skin, of the general health,
diarrhoea, constipation, quantity and fluidity of
blood, all show their effect upon the urinary secre-
tion. Therefore, it is almost impossible to place an
individual constantly in the same relations. This
may explain some of the inconsistent results of
various experimenters.* If bromide of potassium
does augment this excretion, it is probably due
to the change of blood tension in the kidneys, on
which Bernard has found that the activity of kidney
secretion in part depends. f Dryness of the mouth,
fauces, and of the excreta of the intestinal canal fol-
lows its continued use, and the stools become dry,
hard, and infrequent. The constipating effect upon

♦ Gazette Hebdomadaire, 1868, p. 582. Damourette and Pel-
vet, Bulletin G^n^ral de Th^rapeutique, vol. Ixiii. p. 296.
t Liquides de TOrganisme, Bailli^re et file, t. 2, p. 155.

132 PHYSIOLOGICAL ACTION OF THE

the intestine, shown by these effects, is probab
caused by a diminished secretion from the mucoi
surface, by a diminution of the reflex sensibility ai
of the muscular contractility. This may be seen I
its action on the pharynx and all the external portioi
of the mucous membrane. That this effect is n
caused by the immediate contact of the drug may 1
known from the fact, that the injection of a weak
a strong solution of this salt into the rectum w
create an irritation of the bowel, causing the evacu
tion of any faeces contained therein.

I have heard of two cases of chronic constipatic
relieved by a dose of the bromide, and where ha^
been taken large doses of the ordinary catharti
without producing an intestinal discharge ; in ott
instances one or two doses * of the bromide h?
caused an evacuation of the bowels. These faer
carefully and repeatedly analyzed, give no ind
tion of the presence of a bromide.

In such cases the primary effect of the
seems to be exerted upon the muscular f
inducing their contraction and thus causin
excessive peristalsis, from which there results,
times, a violent expulsion of the faeces.
however, the use of the drug is prolonge

* In these cases, if the use of the bromide was conti
longer time, the faeces gradually became more solid in
and finally the bowels became constipated.

BROMIDE OF POTASSIUM b* AMMONIUM. 133

sensitiveness is less marked ; and the reflex action
becomes diminished.

Other cases have been recorded where this hyper-
catharsis was so marked that the drug was discon-
tinued.

Out of thirty-seven cases treated for epilepsy by
this drug,* two patients had to discontinue its use,
because catharsis was produced. These cases are,
however, very rare ; and we are disposed to place
them all under the same conditions.

The excretion, from the pulmonary mucous mem-
brane, after the continued use of this drug (that is,
when the systein is under its influence), is dimin-
ished ; and, if the influence is maintained, a dry and
annoying cough may be induced, f Hoarseness,
aphonia, dry cough, laryngeal pain, sub-crepitant
rMes,t ^U demonstrate this dryness of the mucous
surface. If, however, the drug is impure, it hav-
ing been sometimes combined with the iodate of
potassium, opposite results may take place ; that is,
a catarrhal affection of the mucous surfaces. The
difficulty of expiration, § oppression, &c., tend to
show a loss of muscular contractility in the pul-
monary tissue.

* Williams, abstract in Boston Medical and Surgical Journal,
Ixxi. p. 422.

t Hameau, Gazette Hebdomadaire, x868.

X Voisin, Bulletin G^n^ral de Th^rapeutique, Ixxi. p. loi.

§ Ibid., p. 102.

134 PHYSIOLOGICAL ACTION OF THE

Milk drawn from the breasts of a lady who had
been regularly taking bromide of potassium was
analyzed for the bromide, and no trace of the salt
could be detected.*

CHAPTER IV.

ELIMINATION.

Let us next pass to the elimination of this drug
from the system, its ways and conditions, before
examining its action upon the economy. Voisinf
has stated that, as the breath smells strongly of
bromine after the continued use of bromide of
potassium, it may be partially eliminated in this
way. If this is a fact, then this salt must be
decomposed, and the bromine, being volatile, may
escape. We find a bromide ia the saliva, urine,
and sweat, and in each of these a large amount of
potash.

Exp. X. — We find that three different persons
exhaling for fifteen minutes, after the continued use
of bromide of potassium, through glass into a test-
tube filled with water and bisulphide of carbon, do

♦ Medical Times and Gazette. f Op. cit.

BROMIDE OF POTASSIUM b* AMMONIUM. 13S

not produce the yellow color of bromine. On
adding a few drops of strong chlorine water, the
bisulphide does not change its color. Therefore
we conclude that bromide of potassium is neither
decomposed nor eliminated by the breath. The
peculiar smell this eminent experimenter distin-
guished is probably no other than that produced
by other salts of potassium, such as the chlorate of
potassa and the iodide of potassium.* As this
drug, passing through the mouth, mingles with the
saliva and the mucus from the mouth, pharynx,
and nose, there could not be any use in analyzing
the excretions from the mucous surface of the lungs.

I do not consider that the saliva assists in the
elimination of any drug, because, unless accidentally
expelled, it passes into the stomach and is again
absorbed into the economy. The ease and rapidity
of the absorption of this drug by this secretion have
already been mentioned.

That bromide of potassium is expelled with the
urine has been noticed by Voisin, Damourette and
Pelvet, in the ^^ Bulletin Gdndralde Thdrafeutique^^
and by many other observers. My experiments

♦ It may perhaps be noticed that after the use of certain
alkalies a fetid smell is given off by the mouth, and a disagree-
able taste experienced by the patient ; so also is the same effect
noticed in certain persons who have a habit of biting and chew-
ing up portions of the lining membrane of the inside of the
mouth and lips.

136 PHYSIOLOGICAL ACTION OF THE

and observations have been made with the particu-
lar view of determining under what conditions this
occurs; and if certain conclusions here mentioned
are not altogether new, the recital of them may be
pardoned, inasmuch as the results arrived at are
independent of others, and because the same chemi-
cal process * has not been carried out by any of the
above writers. Great care and much time have been
devoted to this subject ; and the results, it is hoped,
may be of practical value.

It has been already stated that M. Rabuteau has
found bromine in normal urine. This, however,
could be found only in a quantity much exceeding
one hundred and fifty grammes. It. would be
proper to state that at no time did we use so large
a quantity as this in our analysis. This observer
states that he has found for twenty days traces of
a bromide in the urine of a person who had taken
only one gramme (grs. xv.) of this salt, and that
traces could also be found in the saliva of the same
person during the same period.

In our experiments we could find traces only at

the end of forty-eight to fifty-two hours after a

single dose. If, however, the dose was continued

for a few days, the presence of a bromide was

. apparent for a much longer time, varying with the

♦ Vide p. 127 et seq.

BROMIDE OF POTASSIUM &* AMMONIUM, 137

amount taken and the time the exhibition of the drug
was continued. The results of the experiments
of M. Voisin * must be doubted, if M. Rabuteaufis
correct; the idea of the former being that there
is a small quantity of bromine present in normal
urine ; for in their chemical analysis, 325, 400, and
1 ,000 grammes of urine were used ; and the quantity
of pure bromide of potassium crystals varied con-
siderably in each analysis. From the 400 grammes,
.40 were obtained; from 1,000 grammes, .095 ; and
from 850 grammes, 3.75 grammes. Their method
of analysis is not related.

Always, during the first forty hours after an
ordinary dose, I found distinct signs of the presence
of a bromide. The experiments were repeated
very often, and the same result was obtained.

Exp. XI. — During twenty hours, fifty grains of
bromide of potassium were taken in five different
doses. The urine passed during the first twenty-
four hours was preserved, and amounted to fifty-one
ounces. Of this about two ounces were analyzed
for the quantity of bromide eliminated by the kid-
neys ; from this amount a little more than one grain,
and, by calculation, from the whole fifty-one ounces
28^"^^ grains were recovered. Thus more than one

♦ Op. cit. t Vide p. 131.

138 PHYSIOLOGICAL ACTION OF THE

half the amount of bromide of potassium was elimi-
nated during twenty-four hours after the first dose
was taken.

Another experiment was undertaken for the pur-
pose of finding how much of the drug was elimi-
nated during the second twenty-four hours after
a dose of the drug whose action we are consid-
ering.

Exp. XII. — Ten grains were taken, and, of the
thirty ounces of urine passed during the second
twenty-foul: hours, two ounces were carefully ana-
lyzed ; and, by our process and calculations before
mentioned, there were recovered about three and
three-quarters grains. Thus a third of this salt is
eliminated during the second twenty-four hours.

These, combined with other experiments for quali-
tative analyses for a bromide, show that —

Prop. B. — Bromide of potassium is largely and
mainly eliminated with the urine, and during the
first day the largest quantity passes out of the sys-
tem, and less during the second day, and so on till
there is none left in the system.

Several times were the faeces analyzed and tested
for the presence of a bromide, but always with a
negative result. A large amount of caustic soda
was added before each analysis to allow any free

BROMIDE OF POTASSIUM ^ AMMONIUM, 139

bromine, which might have been volatilized during
the ignition of organic matters, to combine in the
formation of bromide of sodium. We are forced
to conclude either that our chemical process in itself
was deficient, or that bromide of potassium is not
eliminated with the faeces. In some subsequent
investigations for the action of bromide of ammo-
nium, the faeces were carefully collected and ana-
lyzed by two members of my class, and no trace
of a bromide could be detected. Considering that
so large an amount of the salt is eliminated by other
organs and the easy absorption by the mucous mem-
brane, it is fair to suppose that, ordinarily, the
bromide of potassium, when given in small doses,
does not pass through the intestinal canal, but is
absorbed before it can mingle with the effete con-
tents of the bowels.

M. Voisin stated that, because an eruption of the
ekin occurred after the continued use of this drug,
this organ assisted in its elimination. Acne may
"be produced from the action of this drug ; but why
may it not be caused by the altered condition of
the capillary circulation, and thus induce those
inflammatory conditions of the skin due to an
obstruction of the circulation? Indeed M. Hardy
in his lectures {Sur les Maladies Cutandes Acctden^
telles) considers modification of the circulation an
important and often neglected cause of acne. As

140 PHYSIOLOGICAL ACTION OF THE

we shall endeavor to show hereafter, bromide of
potassium does produce a certain effect upon the
capillary circulation. To show that this salt is
eliminated by the skin, the following experiment
was tried, and repeated twice with a similar
result.

Exp. XIII. — In the first experiment, forty grains
of the drug were taken in two doses three hours
apart. Immediately after the second dose I entered
a hot-air (commonly called a Turkish) bath, and
remained in it one hour, and during that time col-
lected four ounces and a half of perspiration. By
a careful analysis, there was found little more
than one-third of a grain of bromide of potassium
in this amount of sweat. It may be remarked that
this amount of excretion from the skin was abnor-
mal ; but, by the researches of Valentin,* the daily
amount of sweat is about 2f pounds, or S xxxii.
According to approximate calculation, about two
grains might have been eliminated in twenty-four
hours through the skin.

This, confirmed by repetition at other times,
proves that the skin assists in the elimination of
this drug ; and moreover we are able by —

♦ Text Book of Physiology, Valentin, translated by Brintoi
London, 1853, P* 258. '

BROMIDE OF POTASSIUM ^ AMMONIUM. 141

Exp. XIV. — To determine whether during the
second day the elimination by the skin continues.
Five ounces of sweat were collected in a hot-air
bath, entered thirty hours after a dose of eighteen
grains of bromide of potassium. This sweat, treated
in the usual manner, showed the presence of a
large amount of a bromide.

We may then conclude that —

Prop. C. — The skin assists in the elimination
of this drug from the system during the second day
as well as the first.

Summary of the Means of Elimination.

Of the various organs which carry off the effete
matters of the human economy, two only eliminate
this drug; viz., the skin and urine. In the exhala-
tions from the lungs and the contents of the rectum,
we cannot find any evidence of the presence of
this drug.

142 PHYSIOLOGICAL ACTION 'OF THE

CHAPTER V.

EFFECT ON THE BI^OOD-VESSELS.

When bromide of potassium is applied in an aque-
ous solution to the interdigital membrane of one
posterior extremity of a frog, the web of whose
other foot is observed through a microscope, the
circulation in the arterioles is seen to be hurried,
and, the venules become filled with blood of a
lighter shade than is generally observed. Soon
the circulation grows slower in the arterioles and
the calibre of these vessels diminishes, and the
supply of blood in the capillary system is scanty,
whilst there is less than before in the venules and
arterioles.

Half an hour or more after this, when the animal
has become calm, the blood returns to the capil-
lary system in rather larger amount than before;
and in a little while the constriction or tetanus of
the arterioles is noticed, which continues some time.-
The blood in the venules diminishes and approache
more to the color of that in the arterioles.* If th

* While making these investigations, I attempteti some obse
vations on the circulation in the crania of a frog. During
manipulation some blood-vessels were severed, and the field
vision became afloat with blood corpuscles. The addition

BROMIDE OF POTASSIUM &» AMMONIUM. I43

muscular tissue be now observed without the aid of
a lens, it will be found to be pale and exsanguine,
which is due to this modification in the supply of
blood to the capillary system. This same pallor
of skin has been noticed by Voisin in his patients
who have been for some time under the influence
of bromide of potassium.

Meuriot explains the action of this drug upon the
circulation, as compared with atropine, in the follow-
ing words : " It is seen that bromide of potassium
acts much more energetically upon the contractility
of the vessels than atropine. . . . The bromide of
potassium exaggerates the arterial tonicity, teta-
nizes the arterioles, slackens or arrests the circula-
tion, and produces an oligaemia of the tissues." *

Some experiments have been undertaken in Ber-
lin, by which it has been proved in a satisfactory
manner that upon frogs the sedative action of this
drug is upon the vasomotory nervous system. The
translation of one of these is here given : —

Two frogs were selected, as nearly as possible

the solution of bromide of potassium changed their color to a
peculiar rose-red. This occasioned some surprise, but was sup-
posed as something, perhaps,* accidental, though unaccountable.
However, on reading a memoir by M. Meuriot, I find this same
observation with regard to the color produced by the bromide
of potassium. This bright red color is probably due to an
excess of arterial over venous blood in the capillary system ;
and, as the tissue around is pale, this color is remarkable.
♦ L* 6tude de la Belladonne, Paris, 1868, p. 50.

J44

PHYSIOLOGICAL ACTION OF THE

of the same size : one was used to correct the experi-
ment ; the other was poisoned with potass, bromid.

FROG NOT POISONED.

The metronome was regulated
to lOO vibrations per minute.
The legs of the animal were
loosely bound together in the
middle with soft woollen cords,
which would not compress the
limbs. A vessel of a given size,
and with an estimated quantity
of distilled water, was placed
under the feet; then quickly,
and at once, all six toes of both
feet were cut off at the same
height. The time, during which
the observation was carried on,
was two minutes, or 200 vibra-
tions of the metronome.

The blood, flowing by drops,
from each foot was counted, and
received into the vessel. (The
binding together of the legs
being easy had no influence on
the value of the experiment.^

Number of drops falling into
the vessel : —

Right leg. Left leg.

I ^

in two minutes. <

FROG POISONED.

(This frog before poisoning
drew his foot out of the sulphu-
ric acid mixture, after nine beats
of the metronome.)

Waiting till the reflex power
in the left leg had sunk to thirty,
and in the right to forty-five
beats ; then all six toes of both
feet were cut oflf at the same
level.

In two minutes only two
drops exuded from the right
leg.

The left plexus ischiadicus
was then divided.

In two minutes ten drops of
blood flowed from the left leg.

This is a very valuable experiment, the results
of which were confirmed by repetition ; and shows
conclusive!}'', in another way, that the action of this
drug is through the vasomotor nerves upon the
blood-vessels.

BROMIDE OF POTASSIUM &- AMMONIUM. I4S

CHAPTER VI.

EFFECTS ON THE NERVOUS SYSTEM.

It might be supposed, from what has been said,
that the nerve-cells are impaired by the action of
this drug, and that the conductibility of nervous
impressions is interfered with. Nerves from ani-
mals poisoned by this drug will convey an electrical
current, and electricity will pass through a strong
solution, or even through the solid salts of bromide
of potassium, isolated in a glass tube, without any
diminution of the electric current. The retardation
of the circulation must have some dependence upon
the vascular nervous system.

M. Laborde * made some experiments to deter-
mine the condition of reflex action, which ate well
worthy of examination.

He, at first, caused a frog to absorb by the
interdigital membrane three centigrammes of this
drug. The animal immediately moved spontane-
ously after the poison was absorbed. Then he re-
mained quiet, but withdrew the extremity if irritated
by pinching, pricking, or galvanism. This re-

♦ Archives de Physiologic, 1868, p. 422.

146 PHYSIOLOGICAL ACTION OF THE

sponse ceased in twenty minutes, in the posterior
extremities first, and then in the anterior. In another
experiment with the same dose the heart pulsated
for two hours after cessation of responsive action.
In several of these experiments with this same dose,
he reports that a state of tetanism, lasting two
minutes, occurred in eight to ten minutes after the
absorption of the poison, which was then succeeded
by a collapse. Also at first the muscular fibres
contracted, afterwards became relaxed, and would
not contract when stimulated.

Now these phenomena all point to the same effect
as that noticed in the circulation : over-stimulation
of the power of contractility, soon followed by a
state of relaxation or collapse.

To what may this be due? To the direct con-
tact of the salt with the tissue? We have seen
that almost immediately a large portion of this
drug is absorbed and carried by the blood through
the various organs and tissues. We have seen no
cause to suppose the decomposition of this salt, but
that it is bromide of potassium in the blood, in the
urine and the sweat.

An experiment was suggested to me by this
thought.

Exp. XV. — Both of the sciatic nerves of a frog
were exposed and were isolated by glass rods.

BROMIDE OF POTASSIUM 6- AMMONIUM. H7

Galvanism caused an equal amount of contraction
in both limbs. A sponge was then saturated with
distilled water and placed on the right sciatic nerve,
and another sponge was; saturated with a solution of
bromide of potassium (3 j. == grs. xiij.) and placed
on the left nerve. The galvanic current was then
applied to each in turn. The right foot responded
to the stimulation. The left foot did not respond
to the stimulation. The left was then thoroughly-
washed with distilled water from a wash-bottle, and
then the galvanism applied. The left foot now
responded ; the bromide sponge was again applied,
and the response ceased. The nerve and tissues
were again washed, and the bromide sponge was
applied to the right nerve, the water sponge to the
left. The left foot contracted by the stimulation.
The right foot did not contract by the stimulation.

This experiment was repeated several times
with a similar result, the bromide sponge always
preventing transmissibility of the shock through
the nerve, while the other, water sponge, did not.
These sponges were then applied to the brachial
plexus of each side, the nerves being isolated on
glass rods. The poles of the battery were applied
one on the nerve, the other on the extremitv. The
same result followed the application.

This experiment did not hold good with other
animals, such as dogs and rabbits, in all of which the

148 PHYSIOLOGICAL ACTION OF THE

transmission of electric current was not prevented
by the saturated solution of the drug. It is probable
that the local irritation of the drug may in some
way have caused a partial anaesthesia of the nerve
operated upon.

M. Pelvet,* in speaking of this drug, says that
it successively attacks the properties of the sensitive
and motor nerves, the brain, cord, medulla, and
the muscles. The contractility of the heart out-
lives every other organ. Respiration is indirectly
affected.

Eulenberg and Guttmanf say that two to four
grammes (3 ss. — 3 j.) injected f hypodermically
into rabbits kill them in ten minutes, with signs of
paralysis of the heart. Internal administration had
the same effect. Sensibility and the power of vol-
untary movement were diminished. They observed
always a corrosion of the mucous membrane of the
stomach and infiltration of blood. In smaller doses
they noticed quiverings in the muscles. They con-
sidered that this acted like other salts of potassium,
and presented nothing characteristic of bromine.
Pure bromine injected in much larger quantities had
no such effects, and did not cause death.

On the contrary, M. Laborde considers that bro-

- - ^

♦ Gazette Hebdomadaire, Dec. 6, 1867.

t Idem, July 5, 1867.

X Near the vicinity of the heart.

BROMIDE OF POTASSIUM &» AMMONIUM. 149.

mide of potassium is the only drug that produces this
peculiar action. Bromide of sodium and potassium
had an entirely different effect, even when the latter
caused death.

With this last observer I am more* disposed to
coincide, for his experiments were made with much
care and ingenuity, and more clearly demonstrate
his views. He states that potassium exalts the
power of motility. He endeavors to show, by a
very interesting experiment, that bromide of po-
tassium does not destroy the volition, but affects the
spinal cord and reflex system only.

One frog is decapitated and laid on the table ; in
another he causes the absorption of twenty-five cen-
tigrammes (four grammes or less) . The first loses
tlie sense of reflex response to stimulation, and after-
wards exhibits the usual symptoms of tetanus, &c.
The decapitated frog shows no loss of reflex action,
but is now caused to absorb the same dose of this
drug. The absorption occupies a longer time ; but
when it is accomplished this animal also loses reflex
response to irritation, and is soon in the same condi-
tion as the first frog. From this M. Laborde con-
cludes that bromide of potassium produces paralysis
of reflex action, and has nothing whatever dependent
upon the volition of the animal experimented upon.
In Eulenberg and Guttman's experiments, it may be
noticed that they supposed paralysis of voluntary

ISO PHYSIOLOGICAL ACTION OF THE

movement in warm-blooded animals. This, how-
ever, would be difficult to determine from paralysis
of the sensitive nerves ; and, as M. Laborde * by
his experiments on frogs would show, that not only
is there voluntary movement in one or two of these
experiments, but that, in the two decapitated frogs
(in which volition was put in abeyance) , the power
of reflex action is not lost until after the probable
absorption of the drug ; and, as we know that this
reflex action is very persistent and of long continu-
ance in beheaded frogs, is it not possible that MM.
Eulenberg and Guttman confounded the absence of
volition with the loss of reflex action ?

Prop. D. — The loss of reflex action is due to the
diminution of blood in the periphery of the nerve,
and also in the central nervous system, this last oc-
curring after the first. Thus we may get loss of
sensation first, and then paralysis of reflex action.
This is not strange if we compare the syncope
produced by excessive haemorrhage, in which there
is anaesthesia and loss of reflex action. Primarily,
increased rapidity of the heart's action is caused
by the obstruction to the circulation in the smaller
arteries and capillaries, from reduction of their
calibre. This is a physiological law laid down by
Marey.f But, probably, the same influence which

* Op. cit., p. 423. t De la Circulation du Sang, Paris, p. 307.

BROMIDE OF POTASSIUM &* AMMONIUM. 151

the drug exerts upon the muscular contractility of
the arteries would eventually enervate the cardiac
pulsations.

The first effect produced by a moderate dose is
acceleration of the pulse, which in an hour is suc-
ceeded by a retardation and diminished impulse.
Thus, this drug has been recommended in nervous
irritability of the heart where there is hypertrophied
muscular tissue from disease of the mitral valve.
Eulenberg and Guttman showed its local action
upon the heart, and they thoughrt that the drug
caused paralysis of that organ.* In a large dose
applied locally, this would very naturally happen ;
but when applied to an extremity, slowly received
into the circulation, a less amount would produce the
physiological action peculiar to the drug, without
producing paralysis of the heart. In large, or very
poisonous doses, Laborde noticed that frogs died
very rapidly in a state of muscular relaxation. In
moderate doses producing the poisonous action more
slowly, the period of tetanism of the muscles occurred
first, and subsequently relaxation and death, in which
state the muscles remained relaxed for some time.f

♦ Still^, Materia Medica and Therapeutics.

t This apparent difference may be understood, if we consider
that an over-dose would not allow the blood-vessels to contract
and to pass through the succeeding steps that we have endeav-
ored to point out in the observations on the capillary circulation.

152 PHYSIOLOGICAL ACTION OF THE

We have seen by direct experiment that when
bromide of potassium in solution, or in a solid form,
is placed upon the muscular substance, and elec-
tricity is applied, the muscular fibres contract both
in frogs and warm-blooded animals. Therefore
this drug does not destroy muscular contractility.
M. Laborde,* however, observes that the peripheral
extremities of a nerve in a frog under the action of
this drug, separated from its central portion by a
ligature, conduct electricity and produce contrac-
tions in the limb ; but the central portion (above the
ligature), stimulated by electricity, does not pro-
duce contractions in this limb. From this he infers
that the action of this drug is upon the spinal cord,
and not upon the extremities of the nerves ; in other
words, he infers that in frogs, in other animals and
even in man, bromide of potassium arrests the reflex
functions of the spinal axis, and that afterwards the
extremities of the nerves lose their vitality, and
lastly the muscular fibres their power of contractility.
Now following out this theory with regard to the

In this case, the vessels are paralyzed and the blood becomes
stagnant, thus producing congestion where a therapeutical dose
produces oligcemia. Congestion in the brain would cause,the
stupidity and torpor which occurs. There is the same harmony
of action upon the blood-vessels and the rhuscular fibre : where
we have tetanus of the former we have tetanus of the latter;
relaxation of the former, relaxation of the latter.
* Op. cit., p. 439 — Exp. VII.

BROMIDE OF POTASSIUM 6- AMMONIUM. 153

heart, we should have the same phenomenon ; viz.,
the nerve (par vagum perhaps) is paralyzed by the
drug in the ordinary sequence, — that is, after
the nervous centre has lost its vitality, — but that the
muscular contractility is preserved, keeping up the
cardiac pulsations for a longer or shorter time after-
wards. This would seem a very plausible explana-
tion ; but then we must not lose sight of the fact that
Eulenberg and Guttman, in large doses injected near
the region of the heart, produced paralysis of this
orgd^. Was this caused by enervation of the nerve,
commencing at its central portion, or by destruction
of the muscular contractility? If both of the pneu-
mogastric nerves are severed, the animal may live
several hours with great impediment of circulation
and respiration, and finally die in a state of exhaus-
tion. Taking into consideration this fact, and that
muscular contractility persists after death, we should
infer that the drug causes paralysis of the nerves
which regulate the heart's action. Now in frogs
the power of muscular contractility is very active
and persistent, much more so than in any warm-
blooded animals.* Laborde's observations were

♦ We know that cardiac nerve-ganglia maintain their vitality
and the cardiac pulsations continue even after the heart is sepa-
rated from the body; and the ventricle will beat even when
separated from the auricle in frogs. Likewise respiration in
frogs is maintained by the skin, as has been before mentioned.

154 PHYSIOLOGICAL ACTION OF THE

founded on experiments performed on this animal
only, and therefore must be accepted with due
caution in regard to the action of this drug on the
warm-blooded animals, and especially on man, in
whom the nervous sj'^stem is arranged with so much
more perfection, and so much more widely distrib-
uted, and the functions more subdivided. In all the
experiments which I have qj^served on warm-blooded
animals, the cardiac pulsations ceased within a few
minutes after the signs of respiration. Electrical
stimulation produced muscular contractions, whether
applied to voluntary or involuntary muscles, to
nerves either peripheral or central.

Prop. E. — The action of bromide of potassiuro
on the nervous system may be explained by its action
on the capillary, arterial, or central circulation; it
modifies reflex action, by over-stimulation and sub-
sequent paralysis of the vasomotor system, thus
producing oligaemia of the tissues and nerve sub-
stances, depriving the latter of the vitalizing
properties of the blood. There is ^probably no
alteration of the nerve substance or cells.

In what other way can be the explanation of the
eSicacy of this drug in certain forms of epilepsy,
accompanied by a capillary injection of brain or
spinal axis, or in hysterical epilepsy caused by
exaggerated reflex sensibility? Bromide of potas-

BROMIDE OF POTASSIUM &- AMMONIUM. 15S

sium, though the most certain of all remedies to
reduce the number of epileptiform convulsions in
certain cases, rarely produces a permanent relief
after the omission of the drug.

The efficacy of belladonna may be explained in
the same manner, though the action of this drug *
on the capillary circulation is perfectly distinct from
that of bromide of potassium.

We repeat, then, that the action of this drug is
perfectly explicable, by its action upon the circula-
tion, and that the modifications of reflex sensibility
may be due to the same cause. If the circulation
in a. limb is temporarily or permanently arrested by
disease or ligature, that limb loses reflex action,
and likewise sensibility. Is it necessary to lay the
blame upon the spinal axis? But it may be said
that this method of reasoning does not explain the
primary excitement caused by this drug. It most
certainly does ; for we have always an excitement
of the circulation, both capillary and central, when
this drug is first received into the economy, and
then a subsequent sedation of the circulation.

* Vide Boston Medical and Surgical Journal, March 11,
1869.

15^ PHYSIOLOGICAL ACTION OF THE

CHAPTER VIL

CONCLUSIONS.

I. — Bromide of potassium is easily absorbed by
the mucous membrane wherever they are placed in
contact.

II. — This drug is easily absorbed by the skin,
provided • the water in which it is dissolved is below
the temperature of 75^ F. If the temperature is
above 96° F. it is not absorbed.

III. — The elimination is conducted by the skin
and kidneys ; as the saliva is a secretion, its pres-
ence in this fluid is not a proof of its elimination.

IV. — In therapeutical doses, bromide of potas-
sium is not eliminated by the intestines or lungs.

V. — Bromide of potassium passes out of the
system without decomposition. As most of the
chemical transformation of drugs takes place, ac-
cording to Bernard, in the laboratory of the kidneys.
Dr. Bill's theory in regard to the interchange be-
tween chlorine and bromine in the blood, probably,

BROMIDE OF POTASSIUM &- AMMONIUM. 157

is erroneous. If there is an interchange, it is in the
kidneys, or outside of the body (in other words)
that the transformation must occur.

VI. — The effects of the drug are produced by its
direct action upon the blood-vessels or the vaso-
motor system which control the contraction of these
vessels, which explanation may account for all the
physiological or therapeutical conditions brought
about by the exhibition of this drug.

VII. — There is probably no different or oppos-
ing action in proportion to the dose administered.
The larger* the dose, the more intense and the
longer the action upon the vasomotor system.

VIII. — Its action upon the general nervous sys-
tem is secondary, and dependent upon that of the
vasomotor nerves. That it affects certain parts
where there may be a determination of blood is not
contrary to the known laws of physiology. Lack
of healthy resistance to disturbing influences allows
the blood-vessels to be dilated, and, consequently,
surcharged ; the presence of this drug stirs up the
opposing influence which contracts these vessels.
This influence would be exerted upon the diseased
portion of the system more powerfully than upon
the healthy portion.

* Not exceeding forty grains

IS8 PHYSIOLOGICAL ACTION OF THE

IX. — Bromide of ammonium, in almost every
respect, has the same action as bromide of potas-
sium. This, I infer, from the results of more than
twenty experiments (some of which are herewith
appended).

Exp. XVI. — A guinea pig.

At o o' o''. — 4.30 grammes (sixty-one grains
about) of bromide of potassium in solution, dis-
solved in 3 vj. of water, was injected by means of
an cesophagean tube into the stomach.

o 5' o". — Respiration 108 and regular, though
inclined to be spasmodic ; circulation very rapid.

o 15' o". — Temperature (rectal) 34.8' (C.);*
the animal is sluggish, though sensibility is still
preserved.

o 20' o". — Pulse about 60, and from this time
increased in rapidity though it decreased in force.

o 25' o". — Death, preceded for a few minutes
by gasping and spasmodic respiration. Heart
ceased beating within a very short time of the
cessation of respiration.

Autopsy — immediately after death. — Trachea
and oesophagus uninjured. The heart contracts by
stimulation. The stomach was finely injected on
the external surface, though pale on the internal

* Normal rectal temperature in this animal is 38° C.

BROMIDE OF POTASSIUM &^ AMMONIUM. 159

surface, with here and there a few dark-colored
(haemorrhagic) spots, at which the mucus is easily
separated from the submucous cellular tissue. The
brain substance and spinal cord were pale. The
membranes at base of the brain and around the
spinal cord were injected with venous blood.

Exp. XVII. — Forty-five grains of bromide of
ammonium in half an ounce of water were injected,
in the same manner as above, into the stomach of a
guinea pig.

3'. — The rectal temperature is 38^ C.

5'. — The respiration becomes jerky, — 125 to the
minute.

10'. — Cardiac pulsations 108. The animal
seems stupid, but sensibility to irritation preserved ;
unable to walk ; lays on its belly, with the legs
extended helplessly behind it.

13'. — Gasps for breath; rectal temp. 36.5° C.
On pinching in the vicinity of the brachial plexus,
or the crural, clonic convulsions are produced,
speedily becoming tonic, with marked opisthotonos,
and in this state the animal —

28'. — Dies, and the muscular spasms are re-
laxed. At the moment of death the faeces and semi-
nal fluid or mucus (a gelatinous cylindrical mass)
were ejected.

Autopsy — fifteen minutes after. — Heart and mus-

l6o PHYSIOLOGICAL ACTION OF THE

cles contracted to electric stimulation. Stomach
had the same vascular injection as in Exp. XVI. on
its external surface. The contents were squeezed
out, and the cavity, blown up with air, was dried
and varnished. The veins of the cerebral mem-
brane were injected, as well as the venous sinuses
at the base. Lungs normal, float on water. Heart
normal.

Exp. XVIII. — 3 ij. of bromide of ammonium
in 3 iij. of water were placed in the stomach of a
large-sized healthy rabbit.

3'. — Begins to show signs of drowsiness, stopping
in his jumps and letting his head fall over to one
side ; sensibility unaffected. Expels some faeces.

7'. — Pulse 400.

9'. — Falls on to his belly, all extremities extend-
ed ; sensibility heightened, starts at a sudden sound
or touch ; head turned to one side.

14'. — Is taken up by the ears, and then is
seized with clonic convulsions, accompanied with
cries ; pupil is dilated ; lays quiet upon the floor.
Cardiac pulsation 80, irregular ; spasmodic muscu-
lar contractions of face and forelegs.

23'. — Another » cry, followed by convulsions.
Sensibility to touch subsided.

28'. — Another slight convulsion, followed by
muscular relaxation and death.

BROMIDE OF POTASSIUM ^ AMMONIUM, l6l

■ ■ ■ — ■ — "

Autopsy, — On opening the skull, a gush of dark,
venous blood came out ; capillaries not injected, audi
consequently could not be distinguished ; braiarsubr-
stance pale, cerebellum as well as the heniispheres4;i
veins at the base of the skull injected ; a clpt in pia
mater of middle lobe of hemispheres; oni either side
of the choroid plexus were clots^ the plexus itself
being distended ; a clot in left lateral Ventricle al-
most filling it ; lungs floated on water ; little urine
in bladder, — none had been injected from com-
mencement of the administration of the drug. Grs.
vi.-^ff of bromide of ammonium were collected from
the contents of the stomach.

Exp. XIX. — A piece of the skull of a rabbit
{\ of an inch x J an inch) was carefully removed,
exposing parts of both hemispheres. Ten minutes
after the operation, grs. x. of the same sialt, dis-
solved in water, was ~ placed into the stomach
through an oesophagean tube. The blood-vessels
of the membrane covering the exposed surface of
the brain were plainly visible to the naked eye or
through a lens, and were filled with dark blood.

Seven minutes after, a contraction of the vessels
and a shrinking of the brain-substance were plainly
apparent. Ten minutes after, the color of the blood
gradually changed to a peculiar light-red (rose-
red).

l62 PHYSIOLOGICAL ACTION OF THE

45 min. Capillary injection and expansion of the
brain-substance ; animal is quiet, and the capillary
injection is less marked. Slight muscular spasms
along the muscles of the back. The brain resumes
its natural prominence, then becomes slightly
shrunk ; and the capillary injection entirely disap-
pears, leaving the brain pale. Two drops of a
strong solution of the same salt are applied to the
brain; a few minutes after, the capillary injection,
caused by the application, is succeeded by anasmia,
in which the veins are injected, the capillaries
empty, and the brain-substance expanded. This
is soon succeeded by the same effects as noted
above, and the brain remains pale and shrunken,
in a state of oliga*mia, in which the veins as well
as the other vessels are diminished in calibre and
'devoid of blood. The animal was then killed, as
there was no time for further observation. The
urine showed the presence of a bromide.

Exp. XX. — The nerves of a frog's leg were dis-
sected out as high up as the lumbar vertebrae, and
soaked in a strong solution of bromide of ammo-
nium ; electricity, applied above and below, caused
muscular contractions in the limb. The central
end of the nerve was cut off at the spinal cord.
The nerve of the other leg, treated in the same
manner, caused the same result.

, BROMIDE OF POTASSIUM ^ AMMONIUM. 163

Exp. XXL — The soft parts and bone of a frog's
thighs were cut off, leaving the sciatic nerves un-
touched. The nerves were immersed in a bath of
a saturated solution of bromide of ammonium, the
extremities emerging upon one side of the bath and
the trunk upon the opposite side. The poles of the
electric battery were applied to different parts of
the trunk and to the extremities. The current was
transmitted in every case, producing muscular con-
tractions in the trunk and limbs. One nerve was
then divided, and the poles were applied upon the
trunk and upon the cut nerve in such a way that
the fluid conducted, though feebly, the electric
current.

Exp. XXII. — Perspiration collected during a
Turkish bath, without any of the drug being taken^
gave no sign of a bromide on analysis.

Exp. XXIII. — 5 iij. of urine collected during
twelve hours after a rectal injection of bromide of
ammonium, grs. xx. in beef tea, showed the pres-
ence of a bromide.

Exp. XXIV. — 3 j. of gastric-juice containing
bromide of ammonium, grs. x., treated with caustic
soda and then tested, indicated the presence of a
bromide.

164 PHYSIOLOGICAL ACTION OF THE

Exp. XXV. — Grs. x. of bromide of ammonium
were given in a piece of meat to a dog with gastric
fistula. Seven minutes after, 3 j. + of the contents
of the stomach were drawn off, which, twice care-
fully analyzed, indicated no trace of bromine.

Exp. XXVI. — Less than a grain of the bromide
of ammonium, placed upon the web of a frog's foot,
caused, in the other foot, observed under the micro-
scope : 1st, a contraction of the arterioles and ven-
ules ; 2d, dilation of the artery only ; contraction
of the venules persists.

Ten minutes after the application —

3d, the arterial pulsations remain about the same
in force and frequency : the arteriole is contract-
ed to half its first capacity ; current moves more
slowly.

Exp. XXVII. — Grs. ij. of bromide of ammo-
nium were placed upon the web of a frog's foot, and
the other foot placed under the microscope.

In twenty minutes the arteriole became contract-
ed as above. The pulsations in the arterioles grad-
ually decrease, and the blood from the venules is
received into the larger veins, which, after a while,
in turn become emptied, thus producing what is
called oligasmia, or exsanguineous tissue. In all
these cases observed, when there was struggling.

BROMIDE OF POTASSIUM ^ AMMONIUM, 165

the circulation moved more rapidly, and the blood-
vessels were filled with more blood.

Exp. XXVIII. — One of the students in my class
took at 7, P.M., grs. xl. of bromide of ammonium in
S j. of water. Went to bed at 10.30, having noticed
only a slight excitement of the circulation, flushing
of the face, prickling sensation in the skin, and
tightness at the temples.

At 2.45, P.M., on the next day, took a rectal in-
jection of grs. xl. in some mucilage of starch. .

In 45 minutes experienced the same excitement
of the circulation as noticed above, besides feeling
a slight nervous excitement, such as he has after
taking wine.

I GO'. — Pulse 81.

I 10'. — Pulse 80.

I 15'. — Pulse 81.

1 30'. — The nervous and vascular excitement
subsided.

2 00'. — Felt as usual ; spent the evening in jovi-
ality and felt no sleepiness. At night, pulse 75,
slept well, and had a good appetite for breakfast;
dejection normal, but less in quantity. Urine,
passed twenty-three hours after the last dose, gave
distinct indications of the presence of bromine.

Exp. XXIX. — Another of the students tooled at

l66 PHYSIOLOGICAL ACTION OF THE

lo, P.M., grs. xl. of bromide of ammonium in a
claret-glass of water, on an empty stomach. Pulse,
before taking the dose, 80.

15'. — Pulse 88.

30'. — Pulse 80.

40'. — Vascular excitement, and Exhilaration as
after taking morphine. This gradually decreased,
and was lost in a lit of drowsiness.

I 15'. — Found himself nodding, and then re-
tired; respiration was normal; skin cool and
moist.

Arose the next morning at half-past six, feeling
as well ^nd bright as usual. Had a dejection
during the day. Towards evening he noticed un-
easiness in the bowels, and the next day decided
diarrhoea set in, and lasted for twelve hours. No
griping or distress was induced, except that the
abdomen felt as if distended with flatus. He never
had diarrhoea, and could see no cause for this
attack ex^cept from the drug.

Exp. XXX. — At 12 o'clock, before retiring to
bed, the same experimenter took ammonii bromid!,
grs. XX., on a full stomach. Within half an hour,
felt as though he had taken a dose of opium, though
less excited. Thinks that he fell asleep without
the aid of the drug ; dreamed of trying to pass
urine into a bottle, but could not do so on ac-

BROMIDE OF POTASSIUM ^ AMMONIUM, 167

count of being constantly in a crowd of men and
women.

Took the same quantity at 5.30, a.m., on an
empty stomach. Collected the urine before taking
the second dose, which on analysis showed the
presence of a bromide.

/ CHAPTER VIII.

EXPLANATION OF THE ACTION OF THE DRUG.

When the drug has been received into the circu-
lation, its action is exerted upon that branch of the
vasomotor system, which causes the contraction of
the arterial vessels, thus reducing the supply of
blood to all tissues, but acting more especially upon
those which are superabundandy supplied. At
first, for a short time, there may be some vascular
excitement; within an hour, and especially after
the continued use of the drug, the arterial sedation
is accomplished, and may last for several hours.
The central organ is also quieted, and thus we
obtain a diminution of blood in the nervous centres,
as well as elsewhere, modifying the activity of their
functions.

Professor Brown-S6quard has reported some
experiments in the first volume of his yournal de

l68 PHYSIOLOGICAL ACTION OF THE

Physiologies which illustrate many of the symptoms
peculiar to large (but not poisonous) doses of bro-
mide of potassium. In these experiments it is well
shown that muscular irritability could be excited
by the injection of red blood, even after cadaveric
rigidity had ceased, and that ligature of the aorta
could prevent this muscular irritability in one hour
and thirty-six mirutes from thre time of occlusion of
the artery.

I know of no authentic case of poisoning in man
from bromide of potassium. I have no doubt that
death could be induced, but the size of the dose
must be very considerable. That much harm may
be done by too indiscriminate a use there can also
be no doubt, as probably a continued use of the
drug will interfere with the process of assimilation.
I consider its continued and prolonged use contra-
indicated in anaemia or chlorosis. That it is a spe-
cific against epilepsy is erroneous. Such cases as
proceed from anaemia of the cord or any part of the
brain will not be ameliorated by its use. When
there is congestion, there will be benefit. Again, if
the dose could be administered only when an attack
is anticipated, it would be following out the indica-
tions of its physiological action ; and in some cases
this idea could be prosecuted.

1 cannot conclude this paper without publicly ex-
pressing my sincere thanks to those gentlemen of

BROMIDE OF POTASSIUM b* AMMONIUM. 169

the Medical Classes of 1868-69 who gave me
their thoughtful and attentive assistance, and of
acknowledging that many of the results derived
from the foregoing experiments would not have
been attained had I not received such skilful and
careful aid.

INDEX.

PAGB

A.b8orption, by the stomach, aided by combination with an

alkali lo

Absorption by the mouth 1 16

by the skin 12, 118

by the rectum 13, 120

rapidity of 116

Acne sometimes follows continued dose 39

description of, and cause 39, 139

Ammonium, bromide of 102, 158

elimination of . ' 163

therapeutic action of 103

therapeutic dose of 109

physiological action of 161

in combination with bromide of potassium . 104

Anaemia and chlorosis, use of bromides in 168

Anaphrodisiac action 71

Anaemia of the brain 23

Anaesthesia of the pharynx 41

of ejaculatory ducts 48

Anaesthetic, bromide of potassium not always an ... . 29

Angina pectoris 76

Anodyne in various neuroses 75

Aphasia, caused by continued dose 50

Aphonia, an evidence of excessive dose 43

Assimilation, secondary, modified by continued dose • • « 55

A^sthma, and Trousseau's prescription for 77

Aura, in epilepsy 87

172 INDEX,

FAGS

Bladder, inflammation of, not improved by bromide ... 74

Blood, circulation of, how influenced by bromide .... 142

globules not altered by bromide 38

Brain, experiments illustrating action on 161

Bromide of potassium, decomposition in the system and

theory of Dr. Bill 121

Bromide, changes color of blood to roise-red 142

in normal urine 128

does not appear in secretion from mammae . . . 134

Bromism, cases illustrative of 60-63

a possible death from 63

. c.

Capillary circulation, effects of bromide on 143

Chemical analysis of bromide, qualitative 124

quantitative 125

Circulation, affected by continued dose 34

^ • single dose 21

Coffee, used in conjunction with bromide of potassium . . 65

Conclusions from physiological action 156

Constipation produced by bromide of potassium .... 131

Convulsive disease, the controller of reflex power in . . . 82

Cure, meaning of this word 93

Death, rarely caused by a large dose 60

Decomposition of bromide of potassium . 121

Degli.tltion, difficult, a case of with use of bromide ... 70

Diarrhoea, occasional production of by use of this drug . 132

Doses, single 17

therapeutic action of 18

continued, physiological action of 34

difference between single and continued 35

toxic 36

INDEX. 173

PACK

Elimination, ratio of, to absorption 14, 134

^ exhalations of lungs 134

by faeces 139

by saliva 135

by the skin 140

summary of methods of 141

ways of 134

Epilepsy Sa

action of bromide explained in 154

signs of favorable effect upon S6

idiopathic 87

of children 90

rules for treatment of 107

Erethism 72

Erysipelas, use of bromide in 31

" Excretions, on the urinary 131

Exhibition of bromide of potassium, rules to guide in . . 12
Explanation of the relief of insomnia by bromide of potas-
sium 23

Explanation of physiological action of drug 167

Experiments of Laborde to show maintenance of volition

and diminution of reflex action 149

Fetid breath, following continued use 41

occurs in those who neglect to cleanse their

teeth 60

attributed to its effect upon mucous membrane

(note) 135

Progs, physiological action of bromide on 150

its local contact with nerves of 146

Globules of blood not altered b^ bromides 38

174 INDEX.

^- FAG.

Headache 8i

Hearing and vision not affected by bromide . 37

Hyperaemia of nerve centres .... 94

HyperjEsthesia modified by the use of bromide 55

Hypnotic action dependent on condition of brain .... 21

Hypnotic dose I9» 44

Incontinence of urine 74

Indications and contra-indications 26

Insomnia, cases of, accompanying teething 29

following mental anxiety, &c.} cases of . . . 27, 29

physiological causes of 20

Iron, to be used with bromides 88

Length of time of presence of bromide found in urine . . 136

Lithium, bromide of no

its use when bromide of potassium fails .... ni

experiment illustrating local action of .... 122

Masturbation 79

Memory and impaired mental activity- a result of the con-
tinued dose 49

Menopause, functional derangements in, how controlled . 75

Metamorphosis of tissue, increase of destructive .... 56

Nausea and vomiting, reflex 73

Nervous irritability relieved by bromide of potassium . . 27

Nervous conductibility, modifications of 146

Nervous system, effects on 145, 162

Neuralgia 78

Nymphomania 73

INDEX. 17s

FAGB

CEdema of uvula, a sign of bromal intoxication .... 58

Oligsemia, caused by bromide of potassium 21, 142

Opium, bromide of potassium in connection with .... 31

explanation of their combined action 3^

Ovarian diseases, disturbances in 95

Paralysis of heart caused by concentrated local action of

bromide 151

Pathological conditions in which the bromide of potassium

can be used 66

Powdered bromide irritates mucous membrane 11

Prophylaxis in hysteria .* 93

Puche, investigations of, on bromide of potassium thirty

years ago .' 53

Propositions, A 120

B. 138

C 141

D 150

E. 154

Pulmonary mucous membrane, excretion of 133

Reflex sensibility diminished by contyiued dose . . % . 5a

Reflex response, Laborde's researches on 149

Secretions, effects on 130

Sedation, of heart 151

Seminal emissions *li

Sensations blunted by the continued dose 54

Sensibility, dulness of, induced by continued dose .... 38

Sexual desire sometimes repressed by continued dose . . 47

Single dose 17

176 INDEX.

FAGS

Sodium, bromide of zia

Strychnia, antagonism to bromide of potassium .... 97

case illustrative of 99

foot-note on 109

Summary of therapeutic and toxic phenomena as effects

of bromide 64

Summary of physiological action of bromides 156

•

Temperature, lowered, a sign of brdmal intoxication ... 59

Tetanism of muscles and vessels due to contact of drug . . 146

Therapeutic applications of bromide of potassium ... 65
Therapeutic and toxic group of phenomena following use

of bromide ' . . . . 64

Toxic dose of bromide 36

its action 57

symptoms of 58

Typhoid fever, use of bromide in 31

Uterine diseases, disturbances in 95

Vascular sedative, experiment to illustrate 144

Vision and hearing unaffected by bromide 37

Vomiting, use of bromide generally contra-indicated . . 11

Wakefulness, from exhaustion, not relieved by bromide . . 20

experiments to show action of bromide upon 19, 2a

Whooping-cough 76

LIST OF AUTHORS REFERRED TO IN

THIS MEMOIR.

y. V. Laborde. Archives de Physiologic, Tome I., Part V., 1868.

Eulenberg and Guttman. Gazette Hebdomadaire, 1867, p. 426.

Damourette and Pelvet. Bulletin G6n6ral de Th6rapeutique, Tome LXXIII., p. 293^

Bowditcht H. P. Graduation Thesis^ Boston Medical and Suxgical Journal, 1868.

Rabuieau. Gazette Hebdomadaire, April 24, 1868.

y. N. Bill. American Journal of the Medical Sciences, July, 1868.

Williams. Medical Times and Gazette. (Abstract from, in the Boston Medical and

Surreal Journal, Vol. LXXL, p. 422.)
Voisin. Bulletin G6n6ral de Th6rai)eutique, Tome LXXL, pp. 102, 106, and 153 et

sequitur. Ibid., May, 1871.
Packard. American Journal of the Medical Sciences, July, 1868.
Hodgkins. Medical Times and Gazette, Aug. i, 1868.
E. Ireland. Medical Times and Gazette, Aug. 29, 1868.

yoknsony W. O, Boston Medical and Surgical Journal, Vol. LXXVIL, p. 497.
Stone, A. y. „ „ „ „ N. S., Vol. L, p. s^..

HaUy y. S. „ „ „ „ „ II p. 78.

BraTnan^ C. B, ,, „ ,* ,, „ „ p. 282.

Burr, D. S. „ „ „ i, %% i, p. 383-

Monroe t W. F. New- York Medical Journal, Vol. VI L, p. 327.
Cersoy. American Journal of the Medical Sciences, 1868, p. 543.
Presenilis. Quantitative Chem. Anal. (Bullock and Vacher), p. 446.
Bucquoy. Bulletin G6n6ral de Th6rapeutique, Tome LXX-, p. 371.
Mesnet. L'Union M^dicale, by Boston Medical and Surgical Journal, New Seriei».

Vol. I., p. 144.
Hubbell. Boston Medical and Surgical Journal, Vol. LXXVL, p. 426
Begbie. Braithwaite's Retrospect, Part LV., p. 267.
Hanteau. Gaz. Heb., April 24, 1868.
Garrod. Medical Times and Gazette.
Meuriot. L'Etude de la Belladonne, Paris, pp. 50, 51.
Marey. De la Circulation du Sang.
Stilli. Materia Medica and Therapeutics.
Bernard. Liquides de I'Oi^ganisme, Tome IL, p. 155.

Bernard. Sur les Substances Toxiques et M6dicamenteuses, Paris, 1857, p. 40.
Adrian. R^cherches sur 1e Bromure de Potassium, Bulletin G^^ral de Thtok*

peutique, Tome LXXVIL, p. 15.
Rahuteau. Cutaneous Absorption of Bromides, &c., Gaz. Heb., 1869, p. 546.
Nunnely. Practitioner, London, Dec. 1869, p. 350.

178 LIST OF AUTHORS REFERRED TO,

Puche. In Still6's Materia Medica and Therapeutics, article Bromide of- Potassium.

Rahuteau* Soci6t6 de Biologie, July, 1868.

William A . Hammond. Sleep and its Derangements, 1869, pp. 29 and 283.

G. S€€. Nouveau Diet, de M6decine et de Chirurgie Pratique, article Asthma.

y, M. Da Costa, American Journal of the Medical Sciences, April, 1871, pp. 359-63.

Gubler. Bulletin G6n6ral de Th^rapeutique, 1864.

Etnile Zaepfel. Th^se pour le Doctorat, &c. Paris, 1869.

Erdenberg and Guttman. Gazette des Hdpitaux, No. 77, 1867.

Martin Damourette. Gazette des Hdpitaux, F6v. 1868.

Stille. Materia Medica and Therapeutics, article Bromide of Potassium.

•Gonzalez Eckeverria. On Epilepsy, p. 317.

Roberts Bartholow. Cincinnati Lancet and Observer, 1865. •

Z. C. McElroy. New York Medical Journal, July, 1870.

Felix von Niemeyer. Text-book on Practical Medicine, German ed., Vol. II,, p. 103.

Trousseau. Clinique M6dicale, Tome II., p. 409.

Francis E. A nstie. Neuralgia and the Diseases that resemble it, English ed.. p. 185.

Charles IVest. Lumleian Lectures, on some Disorders of the Nervous System in

Childhood, American edition, 1871, pp. 45, 46.
Saison, Th6se, &c., Paris, July, 1868.

Charles B. Gillespie. American Journal of the Medical Sciences, Oct. 1870, p. 420.
£rown-Siquard. Lectures on the Diagnosis and Treatment of Functional Nervous

Affections, pp. 82, 86, 87.
■S". Weir Mitchell, American Journal of the Medical Sciences, Oct. 1870, p. 443.

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