Drug interactions with alcohol

Abstract

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.