Drug-induced hepatotoxicity 2005

被引:122
作者
Maddrey, WC [1 ]
机构
[1] Univ Texas, SW Med Ctr, Dallas, TX 75390 USA
关键词
hepatotoxicity; liver injury; drugs; genetic polymorphism; acetaminophen;
D O I
10.1097/01.mcg.0000155548.91524.6e
中图分类号
R57 [消化系及腹部疾病];
学科分类号
摘要
The removal from the marketplace of several widely prescribed drugs due to hepatotoxicity has attracted considerable attention. Now under extensive review are means by which we can better identify hepatic risk prior to federal approval. Assessment of risk-to-benefit ratios regarding a novel agent with hepatotoxicity issues (especially one for a life-threatening condition) requires considerable judgment and education on the part of prescribers and patients. The spectrum of drug-induced liver injury is broad with simulation of almost all unknown liver disorders. Drug-induced liver injuries often have a somewhat characteristic signature, as regards type of injury (hepatocellular vs cholestatic) and time of onset. The diagnosis of drug-induced liver injury is often one of exclusion with initial suspicion based on circumstantial evidence. Factors affecting susceptibility to drug-induced injury include age, sex, concomitant use of other drugs, and genetic polymorphism in metabolic pathways involved in activation or disposition of therapeutic drugs. Drug-drug interactions present particular problems in patients, often elderly, who are receiving several drugs simultaneously. Mechanisms of drug-induced liver injury are many and varied. With many drugs, intermediary products produced during metabolism are highly reactive and toxic. In these situations, the balance between the rate of production of the metabolite and the effectiveness of the drug may determine whether or not hepatic injury occurs.
引用
收藏
页码:S83 / S89
页数:7
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