Dr. Henry Baker Lecture Interaction of ethanol with drug toxicity.

The interaction of ethanol and drugs in complex. Ethanol interferes with the primary pharmacologic action of many drugs particularly other neuropharmacologically active agents. Ethanol is mainly a central nervous system depressant; sedatives such as the barbiturates tend to enhance these effects and stimulants tend to reduce them. The present review focuses not on this direct interaction but rather on indirect interaction relating to the metabolism of drugs. In that respect, acute and chronic effects of ethanol are usually opposite. Although there are some exceptions, generally, an acute dose of ethanol inhibits the metabolism of other drugs, most commonly through competition for an at least partially shared microsomal detoxification pathway, whereas chronic consumption enhances drug metabolism, often because of the induction of liver microsomal enzymes. Although the microsomal process usually results in detoxification of drugs, on occasion the opposite occurs, namely activation of the substrate to a more potent, hepatotoxic metabolite. The interaction of ethanol and drugs is further complicated by the fact that the "induction" of the microsomes after chronic ethanol consumption may be offset, at least in part, by the development of liver damage. In addition to some unique interactions characteristic of some specific drugs, the therapy of the alcoholic must take into account those general factors that determine the degree of interaction, such as blood level of alcohol present, duration of alcohol abuse, degree of liver disease, as well as pretreatment with other drugs and the state of nutrition which may affect the liver's capacity for detoxification.