Fraser A G
Department of Medicine, University of Auckland, New Zealand.
Drug Metabol Drug Interact. 1998;14(3):123-45. doi: 10.1515/dmdi.1998.14.3.123.
H2-antagonists are commonly prescribed drugs and alcohol use is widespread in the community. Any possible interaction may be important because of the frequent co-administration of both drugs and the potential for unexpected impairment of pyschomotor function, in particular, driving skills. Hepatic ADH is the major site of alcohol metabolism. ADH is also found in the stomach, but it is uncertain whether gastric ADH is able to metabolise a significant amount of alcohol in vivo. Significant first-pass metabolism can be demonstrated at lower doses of alcohol, and if alcohol is given after meals. Varying degrees of extraction of alcohol from the portal circulation probably explains the data regarding first pass metabolism rather than gastric metabolism by gastric ADH. H2-receptor antagonists inhibit gastric ADH activity to a variable extent. If gastric metabolism of alcohol is negligible then this inhibition has no relevance. Given the uncertainty regarding a mechanism of interaction, only carefully conducted studies in controlled environments will answer the question. The large inter-subject variability of alcohol absorption means that any study which seeks to determine the effect of an H2-receptor antagonist on ethanol metabolism must have sufficient numbers. A cross-over design, with each subject acting as his own control, is preferable to avoid ascribing an effect to treatment rather than to chance. The alcohol dosing studies are reviewed and the results summarised according to dose of alcohol given. At a dose of 0.15 g/kg of alcohol, four commonly used H2-antagonists may cause a small increase in blood alcohol concentrations in certain conditions. This absolute increase is very small. The magnitude of effect is far less than the effect of taking a meal before alcohol. At doses of 0.3 g/kg and above the majority of evidence favours no interaction between H2-antagonists and alcohol. There is no interaction at doses that would be expected to impair psychomotor skills (above 25 mg/dl). There remains a question regarding the cumulative effect of repeated small doses of alcohol and further studies are required. The relationship between ethanol absorption and gastric emptying raises the possibility that the effects of H2-receptor antagonists observed at very low doses of alcohol may be due to the acceleration of gastric emptying by these drugs. This is an attractive hypothesis that explains many aspects of the debate, but studies of the effect of H2-antagonists on gastric emptying have been conflicting.
H2拮抗剂是常用药物，而饮酒在社会中很普遍。由于这两种药物经常联合使用，且可能意外损害精神运动功能，尤其是驾驶技能，所以任何可能的相互作用都可能很重要。肝脏乙醇脱氢酶（ADH）是酒精代谢的主要部位。胃中也发现有ADH，但胃ADH在体内是否能够代谢大量酒精尚不确定。较低剂量的酒精以及饭后饮酒时，可显示出显著的首过代谢。酒精从门静脉循环中不同程度的摄取可能解释了有关首过代谢的数据，而非胃ADH的胃代谢。H2受体拮抗剂在不同程度上抑制胃ADH活性。如果酒精的胃代谢可忽略不计，那么这种抑制就无关紧要。鉴于相互作用机制尚不确定，只有在受控环境中精心开展的研究才能回答这个问题。酒精吸收的个体间差异很大，这意味着任何旨在确定H2受体拮抗剂对乙醇代谢影响的研究都必须有足够的样本量。采用交叉设计，让每个受试者作为自己的对照，这样更可取，以避免将某种效应归因于治疗而非偶然因素。本文回顾了酒精给药研究，并根据所给酒精剂量总结了结果。给予0.15 g/kg酒精剂量时，四种常用的H2拮抗剂在某些情况下可能会使血酒精浓度略有升高。这种绝对升高非常小。其效应程度远小于饮酒前用餐的影响。给予0.3 g/kg及以上剂量时，大多数证据表明H2拮抗剂与酒精之间无相互作用。在预期会损害精神运动技能的剂量（超过25 mg/dl）下没有相互作用。关于重复小剂量酒精的累积效应仍存在疑问，需要进一步研究。乙醇吸收与胃排空之间的关系增加了一种可能性，即极低剂量酒精时观察到的H2受体拮抗剂效应可能是由于这些药物加速了胃排空。这是一个有吸引力的假设，解释了争论的许多方面，但关于H2拮抗剂对胃排空影响的研究结果相互矛盾。
