Drug-Induced Hepatotoxicity

doi:10.1059/0003-4819-104-6-826

Drug-Induced Hepatotoxicity

NEIL KAPLOWITZ, M.D.;
TAK YEE AW, Ph.D.;
FRANCIS R. SIMON, M.D.; and
ANDREW STOLZ, M.D.

Los Angeles, California

Abstract

Drug-induced injury to the liver can mimic any form of acute or chronic liver disease. Acute injury to the liver frequently is due to the action of cytochrome P450, which breaks down drugs into electrophiles or free radicals; these reactive metabolites can covalently bind to protein and unsaturated fatty acids or induce lipid peroxidation, respectively. These events may impair vital functions of the cell, such as maintenance of calcium homeostasis, leading to death; or hypothetically they may elicit a hypersensitivity reaction directed mainly at the liver. Glutathione and tocopherol play critical roles in cellular defense. Cholestatic disease caused by drugs results from a selective disturbance in bile secretion. Agents such as estrogens, chlorpromazine, and monohydroxy bile acids alter the chemical and physical properties of membranes, leading to impaired activity of carriers and pumps for bile acids and electrolytes. Certain drugs produce chronic liver disease that is pathologically identical to chronic active hepatitis, biliary cirrhosis, or alcoholic liver disease.

Article and Author Information

▸An edited summary of an Interdepartmental Conference arranged by the Department of Medicine of the UCLA School of Medicine, Los Angeles, California. William M. Pardridge, M.D., Professor of Medicine, is Director of Conferences.
▸Authors who wish to cite a section of the conference and specifically indicate its author can use this example for the form of reference:

AW TY. Hematoprotection by glutathione and acetaminophen toxicity, pp 830-1. In: KAPLOWITZ N, moderator. Drug-induced hepatotoxicity. Ann Intern Med. 1986;104:826-39.
Grant support: by Veterans Administration Research Funds (Drs. Kaplowitz, Simon, and Stolz); Smith Kline Beckman Postdoctoral Fellowship (Dr. Aw); American Liver Foundation (Dr. Stolz); and by grants AM 30312 (Dr. Kaplowitz) and AM 15851 (Dr. Simon) from the National Institutes of Health.
▸Requests for reprints should be addressed to Neil Kaplowitz, M.D.; Department of Medicine, Division of Gastroenterology, Section WIIIC, Wadsworth Veterans Administration Hospital; Los Angeles, CA 90073.