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Chapter: Basic & Clinical Pharmacology : The Alcohols

Alcohol-Drug Interactions

Interactions between ethanol and other drugs can have important clinical effects resulting from alterations in the pharmacokinetics or pharmacodynamics of the second drug.

Alcohol-Drug Interactions

Interactions between ethanol and other drugs can have important clinical effects resulting from alterations in the pharmacokinetics or pharmacodynamics of the second drug.

The most common pharmacokinetic alcohol-drug interactions stem from alcohol-induced increases of drug-metabolizing enzymes, as described. Thus, prolonged intake of alcohol without damage to the liver can enhance the metabolic biotransformation of other drugs. Ethanol-mediated induction of hepatic cytochrome P450 enzymes is particularly important with regard to acetaminophen. Chronic consumption of three or more drinks per day increases the risk of hepatotoxicity due to toxic or even high therapeutic levels of acetaminophen as a result of increased P450-mediated conversion of acetaminophen to reactive hepatotoxic metabolites (see Figure 4–4). In 1998, the Food and Drug Administration (FDA) announced that all over-the-counter products containing acetaminophen must carry a warning about the relation between chronic ethanol consumption and acetamin-ophen-induced hepatotoxicity.



In contrast, acute alcohol use can inhibit metabolism of other drugs because of decreased enzyme activity or decreased liver blood flow. Phenothiazines, tricyclic antidepressants, and sedative-hypnotic drugs are the most important drugs that interact with alcohol by this pharmacokinetic mechanism.

Pharmacodynamic interactions are also of great clinical signifi-cance. The additive CNS depression that occurs when alcohol is combined with other CNS depressants, particularly sedative-hypnotics, is most important. Alcohol also potentiates the pharmacologic effects of many nonsedative drugs, including vasodilators and oral hypoglycemic agents.


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Basic & Clinical Pharmacology : The Alcohols : Alcohol-Drug Interactions |


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