Fraser A G
Department of Medicine, University of Auckland, New Zealand.
Clin Pharmacokinet. 1997 Aug;33(2):79-90. doi: 10.2165/00003088-199733020-00001.
The frequent use of alcohol (ethanol) together with prescription drugs gives any described pharmacokinetic interaction significant clinical implications. The issue is both the effect of alcohol on the pharmacokinetics of various drugs and also the effect of those drugs on the pharmacokinetics of alcohol. This review discusses these pharmacokinetic interactions but also briefly describes some other effects of alcohol that are clinically relevant to drug prescribing. The use of several different study designs may be required before we can confidently state the presence or absence of any alcohol-drug interaction. Short term administration of alcohol in volunteers is the most common study design but studies of social drinking and prolonged moderate alcohol intake can be important in some situations. Community-based studies may illustrate the clinical relevance of any interaction. Alcohol can affect the pharmacokinetics of drugs by altering gastric emptying or liver metabolism (by inducing cytochrome P450 2E1). Drugs may affect the pharmacokinetics of alcohol by altering gastric emptying and inhibiting gastric alcohol dehydrogenase. The role of gastric alcohol dehydrogenase in the first-pass metabolism of alcohol is reviewed in this article and the arguments for and against any potential interaction between alcohol and H2 receptor antagonists are also discussed. The inhibition of the metabolism of acetaldehyde may cause disulfiram-like reactions. Pharmacodynamic interactions between alcohol and prescription drugs are common, particularly the additive sedative effects with benzodiazepines and also with some of the antihistamine drugs; other interactions may occur with tricyclic antidepressants. Alcohol intake may be a contributing factor to the disease state which is being treated and may complicate treatment because of various pathophysiological effects (e.g. impairment of gluconeogenesis and the risk of hypoglycaemia with oral hypoglycaemic agents). The combination of nonsteroidal anti-inflammatory drugs and alcohol intake increases the risk of gastrointestinal haemorrhage.
酒精(乙醇)与处方药的频繁联用会使任何已描述的药代动力学相互作用具有重大临床意义。问题既在于酒精对各种药物药代动力学的影响,也在于这些药物对酒精药代动力学的影响。本综述讨论了这些药代动力学相互作用,还简要描述了酒精的一些其他与药物处方临床相关的效应。在我们能够确定是否存在任何酒精 - 药物相互作用之前,可能需要使用几种不同的研究设计。在志愿者中短期给予酒精是最常见的研究设计,但社交饮酒和长期适度饮酒的研究在某些情况下可能很重要。基于社区的研究可能会阐明任何相互作用的临床相关性。酒精可通过改变胃排空或肝脏代谢(通过诱导细胞色素P450 2E1)来影响药物的药代动力学。药物可通过改变胃排空和抑制胃酒精脱氢酶来影响酒精的药代动力学。本文综述了胃酒精脱氢酶在酒精首过代谢中的作用,并讨论了支持和反对酒精与H2受体拮抗剂之间任何潜在相互作用的论据。乙醛代谢的抑制可能会引起双硫仑样反应。酒精与处方药之间的药效学相互作用很常见,尤其是与苯二氮䓬类药物以及一些抗组胺药物的相加镇静作用;三环类抗抑郁药也可能发生其他相互作用。饮酒可能是正在治疗的疾病状态的一个促成因素,并且由于各种病理生理效应(例如口服降糖药导致糖异生受损和低血糖风险)可能使治疗复杂化。非甾体抗炎药与饮酒的联合使用会增加胃肠道出血的风险。