JAN. 20, 1912.1 ACETYL-SALICYLTC ACTD. [MzDICALJu3 12I After-History. mnouth it passes unchanged tlhrouglh the stomach, de- The boy was returned to bed with little hope; his colour was only-on reaching the alkaline intestinal ghastly, his breathing feeble and gasping; his pulse was 110, composing juices. very soft, but much improved by the saline infusion. I did not Cushny holds a similar view, for he states that the give him more saline, as I feared pulmonary oedema or systemic action of the drug is dependent upon its de- ,exudation. As a last resort I gave him strychnine nLiv, composition in the intestine into sedium salicylate. Accoid- ether ntv, hypodermically. He was devotedly nursed. Strych- ing to these authors, therefore, the actions of salicylic acid nine ntij, ether niiij, was given again in four hours, and half a and pint of saline was given per rectum later as oftein as he would acetyl-salicylic acid, administered by the mouth, are retain it. the same, except with regard to their local actions in the Next morning he was a little better, but extremely weak; stomaclh. This, I believe, is incorrect; and I shall report pulse 108. In view of the fact that I had not been able to observations in this paper which show that the pharnia- sponge out the blood, which must have been contaminated with cological action of the two drugys, after absorption, are not renal and hepatic exudation, I feared peritonitis, so gave him calomel gr. v, followed by mag. sulph. 5j hourly; an enema at the same, and that acetyl-salicylic acid is absorbed, at 4 p.m. was without result. He had further saline rectal injec- least in part, before decomposi-i n occurs. Solutions of tions, and in the night strychnine and ether were again given. the drug, which slhould be similar to those which occur Next morning the calomel and mag. sulph. were repeated with after the drug is administered by tlle mouth, were tested good result. for salicylic acid, making use of On August 29tll he seemed better; the bowels were opened a solution of fcrric again; the general condition of the abdomen was good. The chloride, whiclh gives a violet colotur witlh salicylic acid, exudation, which had been very copious, was less. but not. witlh acetyl-salicylic acid. This is the usual On August 30th he was better; the pulse varied from 86 to 92. qualitative test. for a salicylic acid, and it was uscd, in addition, to determine quantitatively, by a colorimetric Second Operation. method, the amount of salicylic acid or sodium C.E. was given by Dr. Crofton. I reopened the wound, salicylate sponged out sero-sanguineous fluid from the loin, then, with my formed from acetyl-salicylic acid. finger on the vessels, gently removed the clamp; no blee.ling occurred. I replugged the liver renit, put a cigarette drain down Suznnzary of Chemnical KrPerhimiets. to the reaioil, anid sutured the woun(d in layers with silk and, 1. A solution of the drug in cold water gives nlo violet colo-or for the skin, salmon gut. The peritoneum had retracted far, with ferric chloride. and was very difficult to bring togetlher. 2. A solution of the drug in boiling water gives a violet colour The general peritoneal cavity had not been shut off by with ferric chloride. adhesions; it was clean atnd dry; the extravasated blood and 3. If one dissolves the drug in cold water, and then boils, the flui(d had entirely disappeared; there was no peritonitis. intensity of the ferric chloride reactionl iniereases for several The patient stood the second operation most satisfactorily. minutes. The sinus healed in a few weeks, and the boy left the hospital 4. The drug, dissolved in water, at the temperature of the on October 25th. body, gradually decomposes, the amount decomposed varying I saw him oIn December 7th. He was strong and well; the witil the length of time for at least twelve hours. A colon-r scar was perfectly sound. metric method showed that the amount- of acetyl-salicvlic acid The following points seem to me very decomposed in twel-e hours wvas four times greater thain that in striking: three, and that verv little was decomposed ill lhalf an lhour. 1. The severitv of tihe injury: (a) The kidney was 5. The drrug dissolvres in a solution of blaking socla or in a ruptured completely away froim its pelvis and vessels and 1 per cent. sdlution of sodium carbonate witliout decomposinga partially split; (b) the liver was extensively torn, and a into a salicylate. If eitlher of these solutioins is kept at tlhe portion completely detached. temperature of the body decomposition gradually occurs, but 2. The fact that very little 13 decomposed at the end of hslf an houir. the renal vessels were only bleeding 6. The drug dissolves in a 0.2 per cent. solution of hbyro- comparatively slowly, suggesting wonderfully efficient chloric acid without decomposition. If the solution is kept at re. raction. the temperature of the body decomposition gitadually talkes 3. The slowness of the pulse at the time of admission place. and the slowness of its rise. I think that this may be These experiments indicated that the decomposition of accounted for by rupture of the suprarenal with absorption acetyl-salicylic acid in a medium such as the gastric or of its secretion. intestinal juice is a gradual process, and tllat thirty-to 4. The capability and activity of the peritoneum in forty minutes after the drug is exhibited, at which ti'me dealing with a conisiderable quantity of blood and exuda- its pharmacological action is frequently evident, very little tion so completely in four days. of the drug is decomposed. I believe that this is true, because I can show that the analgesic and antipyretic actions of acetyl-salicylic acid are more potent than those ON of salicylic acid, which could not be the case if acetyl- ACETYL-SALICYLIC ACID, WITH SPECIAL salicylic acid were decomposed by tlie intestinal juice, as REFERENCE TO ITS VALUE IN Martindale and Westcott, Cushny, and others state. I should judge, therefore, that as a rule the greater part TYPHOID FEVER. of acetyl-salicylic acid is absorbed undecomposed. BY GRAHAM CHAMBERS, B.A., M.B., ASSOCIATE PROFESSOR OF CLINICAL MEDICINE, UNIVERSITY OF Pharmacology. TORONTO; PHYSICIAN, TORONTO GENERAL HOSPITAL. The principal difference in the pharmacological action of the two drugs-salicylic acid and acetyl-silicylic acid- ACETYL-SALICYLIC acid is formed from salieylic acid, is due probably to the presence in the latter of tlle OH radicle acety], because the introduction of this group into C6H4COOH, a compound as a rule augments both the analgesic and by replacing the hydrogen atom of the hydroxyl group antipyretic actions. For instance, acetanilide, which is by the radicle acetyl, CH3CO. The chemical formula of the acetyl derivative of aniline, and acet-phenetidine acetyl-salicylic acid is therefore (phenacetine), which is the acetyl derivative of phenelidine, are more analgesic and antipyretic in character than C aniline and phenetidine respectively. C6H4 \COOH. The aspirin is protected. The Analgesic Action. Many of the physical and chemical properties of acetyl- Nowadays the analgesic property of acetyl-salicylic acid salicylic acid are very similar to those of salicylic acid. is fully recognized, and it is extensively used in the relief Like the latter, it is a solid, crystalline, very slightly of pain. lu has the advantage over acetanilide, anti- soluble in water, and freely soluble in ether and alcolhol. pyrin, and phenacetine of being less injurious to the blood It also resembles salicylic acid in being a monobasic acid, and other tissues of the body. but differs from the latter in being less stable. For in- The principal indications for the exhibition of acetyl- stance, it is decomposed by boiling with an alkali or a salicylic acid as an analgesic are the relief of the milder mineral acid into a salicylate or salicylic acid. Martin- forms of pain, sucll as that of sore throat, tonsillitis, dale and Westcott state that heating the drug in presence myalgia, pleurisy, etc. My surgical colleagues tell me that of moisture decomposes it into salicylic acid, and that the it is very valuable in the relief of pain of diseases of solution in water effected by means of sodium bicarbonate bone and joints, and I have found it, in doses of 5 grains contains sodium salicylate and sodium acetate. They every three hours, of considerable value in the relief of also state that when the drug- is administered by the pain of malignant disease. I 22 Tc BRITJOR A PASSAGE OF CAST OF BLADDER. '[JAN. 20, 1912. The Antipyretic Action. a moderate degree of perspiration, and to me they seemed Salicylic acid may be said to act as an antipyretic in clearer mentally and more- willing to carry out other parts two ways, namely, by its action as an internal antiseptic, of the treatment, such as the drinking of water, etc. and by its action on the heat centres, sweat apparatus and I have been especially impressed with the marked other parts which enter into the regulation of the tempera- diaphoretic and antipyretic actions of the drug. Three ture of the body. In acute rheumatism the lowering of grains every four hours had frequently considerable effect, the temperature after the exhibition of large doses of and in most cases 5 grains at the same periods produced salicylic- acid is probably partly due to its antiseptic action, profuse diaphoresis. In only one case were we compelled because in many cases there is an abrupt fall of tem- to increase the dose above 5 grainf.