Alkohol, Alkoholismus und Arzneimittel

Abuse of alcohol (ethanol) and abuse of an increasing number of drugs (e.g. analgesics and sedatives) are among the outstanding social and medical problems of many industrialized countries including Switzerland. Since alcohol consumption has profound effects on both the pharmacokinetic and pharmacodynamic actions of a variety of drugs, the rational use of drugs in alcoholics is an increasingly difficult task and requires a thorough understanding of the physiologic, biochemical, pharmacologic and toxic actions of alcohol. Clinically the most important targets of alcohol action are the liver and the central nervous system (CNS), both of which are frequently involved in the mediation of potentially fatal interactions between drugs and alcohol. In practice the most important of these interactions include (a) inhibition of hepatic (cytochrome P450 dependent) drug oxidation by acute alcohol ingestion resulting in increased bioavailability of drugs that are predominantly excreted by hepatic metabolism, (b) inhibition of acetaldehydedehydrogenase by some drugs with production of an acute flushing reaction to alcohol, (c) increased sensitivity of the CNS to a variety of sedative drugs following acute alcohol ingestion leading to enhanced CNS toxicity of most psychoactive drugs, (d) stimulation of hepatic drug oxidation and decreased CNS sensitivity to sedatives after chronic alcohol abuse, thus explaining the "metabolic" and pharmacodynamic tolerance of these patients towards psychoactive agents, and (e) depressed drug metabolism and increased CNS sensitivity to sedative and hypnotic drugs in patients with cirrhosis of the liver. The mechanisms and practical consequences of the clinically most important influences of acute and chronic alcohol ingestion on the pharmacokinetics and the pharmacodynamic actions of drugs are outlined.