Psychiatric Times 
November 2006 Vol. XXIII Issue 13
Sponsored by CME LLC for 1.5 Category 1 credits.
Original release date 11/06. Approved for CME credit through October 2007.
Educational Objectives
After reading this article, you will be familiar with:
- The role inhibitors, substrates, and inducers play in drug-drug interactions (DDIs)
- The 6 patterns associated with DDIs
- How to minimize the impact of DDIs
Psychiatrists, primary care physicians, neurologists, nurse practitioners, psychiatric nurses, and other mental health care professionals. Continuing medical education credit is available for most specialties. To determine whether this article meets the CE requirements for your specialty, please contact your state licensing board.
Dr Sandson is clinical assistant professor in the department of psychiatry at the University of Maryland Medical School and director of residency training at Sheppard Pratt Health System in Baltimore. He reports that he has no conflicts of interest concerning the subject matter of this article.
Coping with the issue of drug-drug interactions (DDIs) is one of the most challenging aspects of modern psychopharmacology. Psychiatrists are treating patients with medication regimens of ever-increasing complexity. Grappling with these regimens presents us with the daunting task of anticipating the myriad array of possible DDIs. While exhaustive tracking of all potentially significant DDIs is not currently considered the standard of care, that provides little comfort to the thousands of patients each year who suffer the clinical sequelae.1 Thus, it behooves the concerned clinician to master the essentials of this domain of pharmacotherapy.
CORE CONCEPTS
Before plunging into this topic, some terms need to be defined. Most drugs are metabolized and inactivated before excretion. Various enzymes catalyze these metabolic processes, most of which occur in the liver. The drugs whose metabolism is catalyzed by enzymes are referred to as substrates of the en zymes. Other drugs may be coadministered with these enzymatic substrates, and these drugs may im pair the ability of enzymes to catalyze the metabolism of their substrates. Such drugs are referred to as inhibitors.
Enzymatic inhibition may occur be cause the inhibitor binds so avidly to the substrate-binding site of the enzyme that it interferes with the ability of the substrate (or cosubstrate) to gain access to the enzyme for metabolism. This form of inhibition is termed competitive inhibition. Conversely, the inhibitor may bind to a nonsubstrate-binding site on an enzyme and impair the efficiency of that enzyme in performing catalytic reactions with its substrates. This form of inhibition is termed non competitive inhibition. On the other hand, there are drugs that induce the liver to increase production of enzymes. The greater quantity and availability of enzymes leads to more efficient metabolism of sub strates of these enzymes. Such drugs are termed inducers.
Aside from their opposite effects on drug metabolism, another important feature that distinguishes enzymatic inhibition from induction is the duration of these 2 processes. Once an inhibitor becomes bioavailable in the liver, inhibition is essentially in stantaneous. However, once an inducer is present, it takes the liver several days to weeks to produce clinically meaningful decreases in associated substrate blood levels.
