TY - JOUR T1 - CERTAIN ASPECTS OF THE PHARMACOLOGY OF THE SALICYLATES JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 353 LP - 382 VL - 97 IS - 4 AU - PAUL K SMITH Y1 - 1949/12/01 UR - http://jpet.aspetjournals.org/content/97/4/353.abstract N2 - The many intensive studies on the pharmacology of salicylates have revealed the principal features of their actions and physiological disposition. They are rapidly absorbed from all portions of the gastrointestinal tract, absorption being most rapid in the small intestine from slightly acid solutions. Distribution is throughout the body, appreciable amounts being within the cells. Degradation includes partial oxidation or conjugation with glycine or glycuronic acid. Excretion is moderately rapid, the free salicylate being excreted more rapidly when the urinary pH is high. The salicylates are among the least toxic of commonly used drugs; but rarely, even in moderate doses, they produce severe reactions, particularly in asthmatic patients. Large doses may produce a transient fall in plasma prothrombin, but there is seldom a hemorrhagic tendency. Nausea and vomiting are usually associated with high plasma levels and are primarily central in origin. Large doses of salicylates stimulate the respiration; this produces an alkalosis which may continue until a ketosis develops. Several decades of research on the salicylates have left many problems still unsolved. One of the most important is whether the salicylates act per se or through the degradation product, gentisic acid. In favor of the latter hypothesis is the beneficial action of gentisic acid in rheumatic fever (196). But there is some question whether the compound inhibits hyaluronidase (180, 197, 234), and the dose required in therapy is larger than would be expected on the basis of the fraction of salicylate known to be converted to gentisate (154); also the drug fails to prevent anaphylactic shock (166) whereas the salicylates are effective (50, 166). The metabolism of methyl salicylate has not been studied as intensively as that of salicylic acid and acetylsalicylic acid. It may be that it differs appreciably. The failure to demonstrate consistently an analgesic effect of salicylates may be due to inadequate methods of studying analgesia. The demonstration that salicylates prevent anaphylactic shock raises the question of the possible relation of this phenomenon to the mechanism of salicylate action in rheumatic fever. 1949 by The American Society for Pharmacology and Experimental Therapeutics ER -