Mechanisms of depressant drug action/interaction

Whereas the effects of individual psychotropic drugs depend upon drug type, route of administration, dose, and frequency of use, as well as unique subject (patient) variables, the actions achieved by two or more psychotropics taken concurrently are complicated by their influence upon each other. Interactions may be antagonistic, additive, or synergistic and are frequently predictable, given a basic understanding of the kinetic and dynamic characteristics for each drug. This knowledge should enable rational interpretation, therapeutic intervention, and possible prevention of polydrug toxicity. Classically, pharmacodynamic drug interaction is described in terms of common receptor activation or antagonism. This limited view is inadequate in the present context and should be broadened to encompass all of the mechanistic elements that initiate, transduce, and amplify neuronal membrane action. Thus, although psychotropic drugs may compete for a limited number of specific binding sites, as the opiates do, they may also interact through allosteric mechanisms and nonspecific modulation of the receptor environment or subsequent effector cell mechanisms. Drugs in the depressant class often act synergistically in these ways. Through consideration of nonreceptor mediated interaction, we can more fully appreciate the potentiation that occurs between seemingly unrelated substances (e.g., antihistamines and ethanol) and the ability or lack thereof to medically treat such interactions specifically. The pharmacokinetic determinants of drug action provide many opportunities for synergy between psychotropic drugs. Each process is a fertile substrate. Absorption from the gastrointestinal tract is sensitive to drugs that alter peristaltic motility and glandular secretion. Those that inhibit motility tend to delay the rate, if not the extent, of absorption and consequently reduce peak intensity and prolong duration of the psychotropic effect. Serum albumin binding can be a vital point of interaction for drugs with high intrinsic binding affinity (e.g., 98% for methadone); displacement of a small amount of bound drug by a competing substance may increase the free drug concentration severalfold and thereby potentiate its actions(s). Psychotropic drug effects would last for days and even weeks, were it not for the body's ability to synthetically alter drug molecule configuration. This process takes place primarily in the liver where oxidative reactions are frequently catalyzed by the mixed function oxidase system.(ABSTRACT TRUNCATED AT 400 WORDS)