TY - JOUR T1 - ON THE TOXICITY OF DRUGS AFTER HEMORRHAGE JF - Journal of Pharmacology and Experimental Therapeutics JO - J Pharmacol Exp Ther SP - 291 LP - 303 VL - 31 IS - 4 AU - HARRY GOLD Y1 - 1927/08/01 UR - http://jpet.aspetjournals.org/content/31/4/291.abstract N2 - 1. The results of the present series of experiments show that after severe hemorrhage (15 to 25 cc. per kilogram) there is a marked increase in the susceptibility of the cat to strychnin, physostigmin, chloral hydrate and ouabain. 2. Certain possible factors concerned with the increased susceptibility were studied in greater detail with strychnin which, in one instance, was fatal in a dose equal to about one-fourth of the average for normal animals. 3. The increased susceptibility is of short duration and the tolerance of the animal may return spontaneously, partly in forty-five minutes, and completely in two hours in some cases, before the blood pressure is restored to normal and simultaneously with partial restoration of the blood volume. 4. A marked reduction in the alkali reserve of blood has no effect upon the tolerance to strychnin. 5. Retaining a normal blood pressure by vasoconstriction after severe hemorrhage does not secure normal tolerance to strychnin. 6. Normal tolerance is restored temporarily by the injection of Locke's solution equal in quantity to the blood removed. 7. The increased susceptibility after hemorrhage in the cat does not depend upon the loss of blood colloids. 8. Evidence is adduced which suggests that the diminished volume of circulating fluid is an important factor in the causation of increased susceptibility, not by reason of the greater concentration of the drug in the blood stream, but because the volume of blood controls another factor, namely, distribution of blood to various organs of the body. The increased toxicity of drugs after hemorrhage may be due, in part at least, to a redistribution of the blood resulting in its carrying a relatively larger percentage of the drug to the vital structures, than occurs in the normal animal. ER -