SULPHANILAMIDE 659 Symptoms.—These may be classified as mild and severe. The mild symptoms consist of general malaise, headache, anorexia, vertigo, nausea, vomiting, visual disturbances, slight cyanosis and dyspnoea. The severe symptoms are abdominal pain, diarrhoea, numb- ness and tingling of the face, hands and feet, skin eruptions, fever, acidosis, cyanosis, met-hsemoglobinasmia or sulph-hEemoglobinaemia, crystalluria, oliguria, anuria, agranulo- cytosis, leucopoenia, delusions and delirium. Young ss reports a case where a man, aged 53, who was given daily 3 G. of Prontosil album for 18 days for an acute rheumatic infection, developed agranulocytosis and died! on the 23rd day. The post-mortem examination revealed complete myeloid aplasia. De and Konar^o report two fatal cases from Prontosil. In one case a male, aged 43 years, took one tablet containing 2.5 G. of Prontosil album thrice a day for five days from the 28th January 1939 to the 1st February 1939, and received intramuscular injections of 10 cc. of a 2.5 per cent solution of Prontosil rubrum for three consecutive days from the 30th January 1939 to the 1st February 1939. On the 3rd February 1939, he became cyanosed with a dry, coated and deeply cyanosed tongue and a temperature of 105°F. Later, he became comatose and died on the 5th February 1939. There was haemolysis of the red blood cells resulting in haemoglobinuria. In the other case a man, aged 22 years, took a tablet of Prontosil rubrum at 6 p.m. and another tablet at 10 p.m. on the 20th July 1939. Within eight hours the patient developed cyanosis with hsematuria and hsemoglobinuria, got a temperature varying from 103°F. to 105°F., became semi-conscious, at times delirious, and developed oedema of the lungs. He died on the 20th July 1939. The patient had great susceptibility to this drug. Treatment.—Sodium bicarbonate should be given to prevent acidosis. Ten to twenty millilitres of a 1 per cent solution of methylene blue should be given intravenously in cases of cyanosis. It also prevents the formation of met-hsemoglobincernia when adminis- tered with sulphanilamide. Large quantities of water should be administered to elimi- nate the drug. Pentnucleotide should be given intramuscularly for agranulocytosis. Blood transfusion is recommended when there is danger to life. Patients should be kept in bed during the course of sulphanilamide therapy and should be watched daily by their physician, who should do the white blood cell count at frequent intervals. It is suggested that magnesium or sodium sulphate should be avoided, as its administration concurrently with, or within "two or three days preceding the administration of sulphanilamide gives rise to sulph-hsemoglobinsemia,90 but, from investigations carried out on mice, Richardson Ol has come to the conclusion that magne- sium or sodium sulphate does not produce sulph-hgemoglobinsemia, while sulphides or compounds which are readily converted into sulphides, must be avoided, as they are most effective in the formation of sulph-haamoglobinsemia. Coal-tar derivatives should also be avoided during the treatment with this drug. Low residue diet should be pres- cribed and liquid paraffin should be administered daily to keep the bowels free. Post-mortem Appearances.—The stomach is congested. The spleen is congested and may be enlarged. The liver is congested and shows fatty degeneration. The kidneys are congested. The lungs are congested and cedematous. The brain and its membranes are congested. The bone marrow is aplastic in acute agranulocytosis. Chemical Analysis.—The sulphanilamide group of drugs may be extracted with acetone from neutral aqueous solutions in the Stas-Otto process. Several extractions should be made, filtered and evaporated to a syrupy consistence. The filtrates should be collected together, washed with acetone several times and evaporated to dryness. The residue should be dissolved in water, heated and filtered. The filtrate should be satu- rated with sodium chloride and treated with acetone, On evaporation to dryness, sulpha- nilamide with some sodium chloride is obtained as a residue and can be distinguished by the following tests : — 1. A few drops of p-dimethylamino-benzaldehyde solution (made by dissolving the substance in water acidified by strong sulphuric acid) added to a small fragment of the residue or a few drops of its solution produce immediately a yellow colour or orange precipitate. 2. A portion of the residue is dissolved in warm dilute hydrochloric acid, cooled in ice and mixed with 2 cc. of 1 per cent sodium nitrite solution. Two cubic centimetres of water and 1 cc. of 5 per cent B-naphthol solution are added to the whole mixture, when an orange-coloured solution or precipitate is found. 3. Heated in a dry test tube, sulphanilamide produces an intense violet colour, and emits the odours of ammonia and aniline on, further heating. 88. Brit. Med, Jour,, July 17, 1937, p. 105 ; vide Pearson, Brit. Wed, Jour., May 20, 1939, p. 1031, * 89. Ind. Med, Gaz,, July 1940, p. 385. 90. Paton and Eaton, Lancet, May 15, 1937, p. 1159. 91. Journal of Pharmacology and Experimental Therapeutics, Vol. 71 No. 3, March 1941, p. .203.