Alcohol and drug interactions.

Alcohol use is a serious health problem in the Czech Republic with significant impact on morbidity, mortality and pharmacotherapy. Approximately 15-18% of the population drink risky, and the combination of alcohol and drugs is common and often overlooked. Ethanol is metabolised predominantly in the liver by the enzymes ADH and CYP2E1. Chronic consumption induces CYP2E1, which might increase the production of toxic metabolites of some drugs. Ethanol acts on the CNS mainly through GABA, NMDA and adenosine receptors and affects ion channels, contributing to its CNS-depressant effects. Alcohol-drug interactions may be pharmacokinetic (e.g., alteration of absorption, induction or inhibition of enzymes) or pharmacodynamic (e.g., potentiation of hepatotoxicity, CNS depression, hypotension, hypoglycemia). A significant risk with several drugs represents so called disulfiram reaction. Alcohol may also increase neurotoxicity and the risk of seizures, especially when abruptly discontinued after chronic use. In the elderly population, an accumulation of risks plays a role: polypharmacy, altered pharmacokinetics and increased susceptibility to adverse effects. The combination of alcohol with immunomodulatory therapy may alter the immune response and increase the risk of infections. Interaction studies are limited by associated liver injury, small sample sizes, and variability in ethanol doses. Polymorbid elderly and patients with liver cirrhosis are at the highest risk.