Aerospace Problems in Pharmacology and Toxicology

Back, Kenneth C.; Thomas, Anthony A.

doi:10.1146/annurev.pa.10.040170.002143

Cited by 46 publications

(9 citation statements)

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“…Mitchell et al in 1975 (5) postu-lated that the metabolites of INH are hepatotoxic based on their observations that rapid acetylators of INH were more prone to develop hepatotoxicity. The hydrazine moiety was specifically implicated as the injurious metabolite (6), and the view was further supported by the observations that the phenobarbitone pretreatment greatly potentiated the necrosis by acetylhydrazine and acetylisoniazid. Subsequent observation by Ellard in 1976 and1984 (7,8) contradicted the above-mentioned hypothesis.…”

mentioning

confidence: 88%

Study of oxidative stress in isoniazid-induced hepatic injury in young rats with and without protein-energy malnutrition

Sodhi

Rana

Vaiphei

et al. 1996

J. Biochem. Toxicol.

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confidence: 88%

Study of oxidative stress in isoniazid-induced hepatic injury in young rats with and without protein-energy malnutrition

Sodhi

Rana

Vaiphei

et al. 1996

J. Biochem. Toxicol.

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“…193 ical synthesis, and as therapeutic agents for the treatment of tuberculosis, depression, and cancer. Besides the liver necrosis found in therapy with isoniazid and iproniazid (4), hydrazines are known to produce many other toxic responses including methemoglobinemia, hemolysis, fatty liver, mutagenesis, and carcinogenesis (12). Although no evidence has yet been found that isoniazid is carcinogenic in man (13), the possible risk of neoplasia after long-term therapy with such drugs needs continual monitoring.…”

mentioning

confidence: 99%

Isoniazid and Iproniazid: Activation of Metabolites to Toxic Intermediates in Man and Rat

Nelson

Mitchell

Timbrell

et al. 1976

Science

217

126

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Acetylhydrazine, a metabolite of isoniazid, a widely used antituberculosis drug, and isopropylhydrazine, a metabolite of iproniazid, an antidepressant removed from clinical use because of high incidence of liver injury, were oxidized by cytochrome P-450 enzymes in human and rat liver microsomes to highly reactive acylating and alkylating agents. Covalent binding of these metabolites to liver macromolecules paralleled hepatic cellular necrosis. The metabolites formed from these and probably other monosubstituted hydrazines are reactive electrophiles.

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“…Since many hydrazines are known to be potent hepatotoxins, carcinogens and mutagens (BACK and THOMAS, 1970;DRUCKREY, 1973), the hepatotoxicity of various hydrazines was examined in animals. Since many hydrazines are known to be potent hepatotoxins, carcinogens and mutagens (BACK and THOMAS, 1970;DRUCKREY, 1973), the hepatotoxicity of various hydrazines was examined in animals.…”

Section: Isoniazid and Iproniazidmentioning

confidence: 99%

Concepts in Biochemical Pharmacology

Brodie¹,

Gillette²,

Ackerman³

1975

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This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned specifically those of translation, reprinting, re-use of illustrations, broadcasting, reproduction by photocopying machine or similar means, and storage in data banks. Under § 54 of the German Copyright Law where copies are made for other than private use, a fee is payable to the publlsher, the amount of the fee to be determined by agreement with the publisher. © by Springer-Verlag Berlin· Heidelberg 1975. Softcover reprint of the hardcover ist edition 1975 Library of Congress Cataloging in Publication Data (Revised) Main entry under title: Concepts in biochemical pharmacology. Handbuch der experlmentellen Pharmakologie. Handbook of experimental pharmacology. New series, v. XXVIII, 1, etc. Includes bibliographies. I. Drug metabolism-Collected works.!. Argy, W. P. II. Brodie, B. B., ed. III. Gillette, James R., 1928-ed. IV. Ackerman, Helen S., ed. V. Series: Handbuch der experimentellen Pharmakologle, v. XXVIII, 1 QP905.H3 Bd. 28, t. 1, etc. [RM301] 615'. 7 79-135957 ISBN 0-387-05134-1. The use of general descriptive names, trade names, trade marks, etc. in this pUblication, even if the former are not especially Identified, is not to be taken as a sign that such names, as understood by the Trade Marks and Merchandise Marks Act, may accordlngiy be used freely by anyone. PrefacePart 3 of the Handbook of Experimental Pharmacology (Concepts in Biochemical Pharmacology) applies the principles enunciated in Parts 1 and 2 to clinical pharmacology and toxicology. The major objective is to elucidate the many factors that determine the relationships between pharmacokinetic aspects of the disposition and metabolism of drugs and their therapeutic or toxic actions in man.Because of the more restricted information obtainable in human studies, this volume reflects the editors' bias that an understanding of pharmacokinetics is fundamental for assessing pharmacologic or toxicologic effects of drugs in humans. The first chapter is a unique primer on when to apply and how to use pharmacokinetic tools in human pharmacology. The second chapter explains the general assumptions underlying pharmacokinetic approaches both in simple terms for the novice and in mathematical form for the more sophisticated reader.Several chapters on determinants of drug concentration and activity discuss drug absorption, drug latentiation, drugs acting through metabolites, enterohepatic drug circulation, influence of route of drug administration on response, genetic variations in drug disposition and response, age differences in absorption, distribution and excretion of drugs, and pathologic and physiologic factors affecting absorption, distribution and excretion of drugs and drug response. The focus of these chapters is data obtained in human, rather than animal, studies. Most of the chapters contain new material never summarized previously.The section on drug interactions opens with a chapter in which all drug interactions are viewed as result...

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Aerospace Problems in Pharmacology and Toxicology

Cited by 46 publications

References 0 publications

Study of oxidative stress in isoniazid-induced hepatic injury in young rats with and without protein-energy malnutrition

Study of oxidative stress in isoniazid-induced hepatic injury in young rats with and without protein-energy malnutrition

Isoniazid and Iproniazid: Activation of Metabolites to Toxic Intermediates in Man and Rat

Concepts in Biochemical Pharmacology

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