Linnoila M, Mattila M J, Kitchell B S
Drugs. 1979 Oct;18(4):299-311. doi: 10.2165/00003495-197918040-00003.
Ethanol and drugs can affect each other's absorption, distribution, metabolism, and excretion. When ingested together, ethanol can increase drug absorption by enhancing the gastric solubility of drugs and by increasing gastrointestinal blood flow. However, high concentrations of ethanol induce gastric irritation causing a pyloric spasm which in turn may delay drug absorption and/or reduce bioavailability. The 'quality' of the alcoholic beverage, independent of its ethanol content, can contribute to altered absorption of a drug. Ethanol is not bound to plasma proteins extensively enough to modify drug distribution. However, serum albumin levels in chronic alcoholics may be abnormally low so that some drugs, e.g. diazepam, have an increased volume of distribution. In addition to the amount ingested, the duration of regular intake determines the effect of ethanol on drug metabolism. Acute intake of ethanol inhibits the metabolism of many drugs but long term intake of ethanol at a high level (greater than 200g of pure ethanol per day) can induce liver enzymes to metabolise drugs more efficiently. At the present time there are no accurate means, with the possible exception of liver biopsy, to clinically predict the capacity of an alcoholic to metabolise drugs. Several drugs can inhibit the metabolism of ethanol at the level of alcohol dehydrogenase. Individual predisposition determines the severity of this drug-ethanol interaction. During its absorption phase, ethanol inhibits the secretion of antidiuretic hormone and is also able to induce increased excretion of a drug through the kidneys. However, chronic alcoholics with water retention may show reduced excretion of drugs via this route. At the pharmacodynamic level, ethanol can enhance the deleterious effects of sedatives, certain anxiolytics, sedative antidepressants and antipsychotics and anticholinergic agents, on performance. Mechanisms of lethal interactions between moderate overdoses of ethanol and anxiolytics/opiates/sedatives are poorly understood. On the other hand, certain peptides, 'nonspecific' stimulants, dopaminergic agents and opiate antagonists can antagonise alcohol-induced inebriation to a significant degree.
乙醇和药物会相互影响对方的吸收、分布、代谢及排泄。同时摄入时,乙醇可通过增强药物在胃中的溶解度以及增加胃肠道血流量来提高药物吸收。然而,高浓度乙醇会引起胃部刺激,导致幽门痉挛,进而可能延迟药物吸收和/或降低生物利用度。酒精饮料的“品质”,与其乙醇含量无关,也可能导致药物吸收改变。乙醇与血浆蛋白的结合程度不足以影响药物分布。然而,慢性酗酒者的血清白蛋白水平可能异常低,以至于某些药物,如地西泮,分布容积会增加。除了摄入量外,规律摄入的持续时间也决定了乙醇对药物代谢的影响。急性摄入乙醇会抑制许多药物的代谢,但长期大量摄入乙醇(每天超过200克纯乙醇)可诱导肝酶更有效地代谢药物。目前,除了肝活检可能是个例外,没有准确的方法在临床上预测酗酒者代谢药物的能力。几种药物可在酒精脱氢酶水平抑制乙醇代谢。个体易感性决定了这种药物 - 乙醇相互作用的严重程度。在吸收阶段,乙醇会抑制抗利尿激素的分泌,还能促使药物经肾脏排泄增加。然而,有水肿的慢性酗酒者经此途径的药物排泄可能会减少。在药效学层面,乙醇可增强镇静剂、某些抗焦虑药、镇静性抗抑郁药、抗精神病药和抗胆碱能药物对机体功能的有害影响。中度过量乙醇与抗焦虑药/阿片类药物/镇静剂之间致命相互作用的机制尚不清楚。另一方面,某些肽、“非特异性”兴奋剂、多巴胺能药物和阿片拮抗剂可在很大程度上对抗酒精引起的醉酒状态。