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DRUG INTERACTIONS—PART I

The past several decades have witnessed a remarkable growth in our understanding of drug action and disposition within the intact organism. Awareness of the significant role which hepatic drug metabolizing enzymes play ill determining the duration and intensity of action of many drugs expanded prodigiously as a result of the fundamental research by Bernard B. Brodie and his co-workers at the National Institutes of Health. This achievement spurred the training of a new breed of pharmacologists devoted to the extension of these findings to man. Their insights, plus surveillance of prescribing habits, have generated concern over the frequency with which patients receive multiple medications concurrently. The possibility of interaction among these therapeutic agents increases in proportion to the number administered. In addition to prescribed drugs, the individual is also exposed to a host of environmental chemicals and over-the-counter preparations. All may alter drug action.
 Historically, drug interaction involves the prescribing of mixtures of ingredients, an approach which has deep-seated roots in medical tradition and psychological appeal for patient and physician. The appeal for the physician to prescribe not just one, but a combination of pharmacologically active ingredients, has been, and continues to be difficult to resist because of the inference that more drugs are necessarily better than few—a concept far from the truth.
 A widely accepted current definition of the word "drug" is "any biologically active substance." This encompasses both synthetic and natural substances. They may be administered or naturally occurring. Drug interaction may result not only among administered compounds but between an administered drug and endogenous substances.