Drug-induced hepatotoxicity.
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.
D000082:Acetaminophen / Q000378:metabolism / Q000633:toxicity; D001646:Bile / Q000378:metabolism; D001647:Bile Acids and Salts / Q000009:adverse effects; D001711:Biotransformation; D002470:Cell Survival / Q000187:drug effects; D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology; D056487:Chemical and Drug Induced Liver Injury, Chronic; D002746:Chlorpromazine / Q000009:adverse effects; D002779:Cholestasis / Q000139:chemically induced / Q000628:therapy; D002908:Chronic Disease; D003278:Contraceptives, Oral, Hormonal / Q000009:adverse effects; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D004734:Energy Metabolism / Q000187:drug effects; D005609:Free Radicals; D005978:Glutathione / Q000378:metabolism / Q000502:physiology; D006801:Humans; D008658:Inactivation, Metabolic; D008054:Lipid Peroxides / Q000096:biosynthesis; D008099:Liver / Q000378:metabolism; D008103:Liver Cirrhosis / Q000139:chemically induced; D008105:Liver Cirrhosis, Biliary / Q000139:chemically induced; D008107:Liver Diseases / Q000175:diagnosis / Q000378:metabolism / Q000473:pathology; D009336:Necrosis / Q000139:chemically induced; D010084:Oxidation-Reduction; D010100:Oxygen / Q000378:metabolism
D001647:Bile Acids and Salts; D003278:Contraceptives, Oral, Hormonal; D005609:Free Radicals; D008054:Lipid Peroxides; D000082:Acetaminophen; D003577:Cytochrome P-450 Enzyme System; D005978:Glutathione; D010100:Oxygen; D002746:Chlorpromazine