Disease, Metabolism and Reproduction in the Toxic Response by T. Godfraind (auth.), Philip L. Chambers, Paolo Preziosi,

By T. Godfraind (auth.), Philip L. Chambers, Paolo Preziosi, Claire M. Chambers (eds.)

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Additional resources for Disease, Metabolism and Reproduction in the Toxic Response to Drugs and Other Chemicals: Proceedings of the European Society of Toxicology Meeting Held in Rome, March 28 – 30, 1983

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Assuming the in vitro covalent binding of coumarin metabolites is associated with coumarin-induced hepatotoxicity in vivo, then these studies may suggest a possible mechanism of coumarin bioactivation. The lack of effect of sodium benzoate, superoxide dismutase, catalase and xanthine/xanthine oxidase would tend to discount the involvement of either hydroxyl radicals, superoxide anions or hydrogen peroxide in the formation of reactive [3- 14 C] coumarin metabolites. However, inhibition was observed with L-ascorbic acid which can reduce superoxide anions, semiquinones and quinones (Deamer et al.

In contrast, the free fraction of tolbutamide, an acidic drug which binds mainly to albumin, was significantly higher in cancer patients than in control plasma (Jackson et al. 1982). The therapeutic and toxicological significance of these observations is being investigated. 36 P. Turner Table 2. Some examples of enhanced drug toxicity associated with inherited diseases (after Rawlins and Thompson 1981) Inherited disease Drug Effect Hereditary methaemoglobinaemia Oxidising drugs Methaemoglobinaemia, cyanosis Porphyria Barbiturates, oestrogens, etc.

Thus, the situation may arise that a given dose of a drug which was appropriate for the patient a fortnight previously might no longer be appropriate. For instance, in hypothyroidism, cardiac output, liver blood flow, hepatic drug metabolism, glomerular filtration rate and renal plasma flow are decreased and return to normal as the patient becomes euthyroid with thyroxine treatment, thus necessitating dose adjustment in relation to changing organ function. While in animals numerous studies on the influence of abnormal levels of hormones on drug metabolism, drug response, and drug toxicity have 40 M.

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