Drug Interactions: Classification and Systematic Approach

Interactions between drugs may result in favorable, toxic or no clinical effects. Generally classified in terms of proposed mechanism, drug interactions may be causal to physicochemical incompatibility, pharmacokinetic or pharmacodynamic interaction(s), combinations of each. Characterized by alterations in circulating unbound (tree) drug or its principal metabolic, pharmacokinetic interactions are secondary to modification(s) in absorption, volume of distribution, metabolism or excretion. Synergism, defined as two or more drugs acting upon receptor site(s) to produce additive or superadditive effects, or antagonism, defined by a shifting of the dose-response curve to the right indicating a diminution of effect after stimulation of a receptor site are pharmacodynamic interactions occurring without demonstrable alteration in plasma levels of the drugs. This article reviews these various types and mechanisms of drug interactions.