ALCOHOL AND DRUG-INTERACTIONS

Interactions of ethyl alcohol with various drugs are common. Their consequences vary depending on the effects of the drugs concerned, the doses of drugs and alcohol given and their mode of administration. Pharmacokinetic interactions refer to altered tissue concentrations of alcohol or drugs or both and their metabolites which sometimes lead to serious toxic reactions. The kinetic interactions take place in the absorption or metabolism of alcohol or the drug, whereas significant interactions in their distribution phase are rare. Pharmacodynamic interactions refer to the combined actions, even serious ones, which primarily take place at the tissue (receptor?) level, with or without an important pharmacokinetic component of interaction. Acute substantial doses of alcohol given quickly tend to inhibit microsomal drug metabolism and thus enhance the effects of drugs. Chronic administration of of alcohol usually induces the synthesis of cytochrome P-450 isoenzyme II E1, thus accelerating the metabolism of its own and, depending on the circumstances, of various drugs as well. Reduced actions of the agents may then ensue. If the (toxic) effect of a drug (e.g., paracetamol) depends on the formation of active metabolites acute intake of alcohol may, paradoxically, reduce the drug effect, while chronic alcohol intake enhances it. Induction of hepatic enzymes by alcohol may affect the turnover of endogenous vitamins and hormones, or even produce carcinogenic substances. The groups of drugs significantly interacting with ethanol include: 1. The central nervous system depressants (hypnotics, opioids, psychotropic drugs, sedative H-1-antihistamines, anticonvulsants), the combined effects being mostly additive and without any important pharmacokinetic component; 2. Agents provoking antabuse reaction (disulfiram, carbimide etc.); 3. Vasodilating agents, which may lead to unexpected collapse; 4. Antidiabetic drugs (poor control of diabetes; antabuse reaction); 5. Coumarin anticoagulants (unstable kinetics during drinking spells); 6. Non-steroidal anti-inflammatory drugs (gastrointestinal toxicity, central interactions possible); The combined actions of groups 1 and 2 predominantly affect the nervous system and are discussed in detail, as are also some relevant aspects on the pharmacokinetics of alcohol.