Drug Interactions and the Cytochrome P-450 Enzymes

Abstract

The catabolism of drugs by the cytochrome P-450 enzymes is germane to the understanding of drug interactions. This is true for the allergist and all prescribing physicians. These data go beyond the well known toxicity of theophylline, as well as terfenadine and astemizole. Genetically, these naturally occurring enzymes can vary from 10- to 30-fold. The addition of a strong inhibitor or inducer of these enzymes multiplies the toxicity or deletes the effective action of many drugs. It is also important to know the effects of these inhibitors or inducers on substrates other than theophylline and terfenadine. Some substrates are naturally occurring hormones, chemicals in our environment, and carcinogens, including cigarette smoke. Some of these same agents may also act as inhibitors or inducers for other enzymes. This paper explains the genetic derivation of these various enzymes, and how they work. The nomenclature for these enzymes, both old and new, is included. Methods of determining titers of each enzyme in different patients are also described. In the future, the knowledge of a patient's genetically derived enzyme profile will allow us to tailor drug doses precisely, instead of the current standard of "start low, go slow." For the present, knowledge of the many drug interactions cited is essential for any practicing physician, primarily to avoid problems, but also to treat problems by using inducers (and occasionally inhibitors) as antidotes.