Advances in Pharmacology by Silvio Garattini and Parkhurst A. Shore (Eds.)

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By Silvio Garattini and Parkhurst A. Shore (Eds.)

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Potentiation of the ethionine liver damage by chlorpromazine has been described by Popper et al. (1957). Using the same technique, we found that chlorprothixene did, and the chemically related amitriptyline did not potentiate ethionine liver damage. Neither drug has been associated with jaundice in man. Iproniazid, which by itself did not cause necrosis of the rat liver, significantly potentiated carbon tetrachloride toxicity, but had no effect on liver damage induced by ethionine, phenylhydrazine, and ally1 alcohol (Zbinden and Studer, 1959).

I t is n witk open field for the clinical pharmacologist to study drug effects in patients 44 GERHARD ZBINDEN with many different endocrine imbalances, and these data must be incorporated in the over-all evaluation of a drug. V. Drug-Related Factors Affecting the Outcome of Animal Toxicity Experiments A. SPECIFICITY OF DRUG-INDUCED TOXICMANIFEST~ATIONS Tissue and organ changes observed in toxicity experiments niay be due to specific actions of the drugs. Sometimes however, they are only indirectly relatcd to the major pharmacological effect, or occur as a completely nonspecific conscquence of the experimental procedure.

Abstinence syndrome. If chronically administered drugs are suddenly withdrawn, abstinence syndromes may occur indicating a certain physical dependence. The dog is particularly sensitive and may, as experiments with barbiturates (Fraser and Isbell, 1954) and meprobamate (Essig, 1958) indicate, show symptoms similar to those observed in humans. During the chronic toxicity study it is useful, therefore, to discontinue drug administration, a t least in some dogs, for 1 or 2 weeks and to look for withdrawal symptoms such as tremor, ataxia, salivation, convulsion, and loss of weight.

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