Is there an interaction between H2-antagonists and alcohol?

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.