Clinically Relevant Drug-Drug Interactions in Primary Care

Mary Carpenter, PharmD; Holly Berry, PharmD; Allen L. Pelletier, MD


Am Fam Physician. 2019;99(9):558-564. 

In This Article

Mechanisms of Drug-drug Interactions

Drug-drug interactions can be pharmacodynamic or pharmacokinetic. Pharmacodynamic interactions occur when two drugs that are taken concomitantly have either additive or canceling effects on the body. Pharmacokinetic interactions occur when a drug affects the absorption, distribution, metabolism, or excretion characteristics of another drug.[6]

Drug interactions based on altered metabolism are mostly attributable to effects on cytochrome P450 (CYP450) isozymes. Inhibition or induction of CYP450 drug metabolizing isozymes is the most common mechanism by which clinically important drug interactions occur. The most common isozyme is CYP3A4, followed by 2C19, 2C9, 1A2, 2E6, and 2D6. Drugs interacting with CYP450 isozymes can be classified as substrates, inducers, or inhibitors. Several drugs are substrates of transport-protein-complexes, such as P-glycoprotein (P-gp), which are expressed in hepatocytes and enterocytes, as well as in the epithelial cells of the renal tubules, the blood brain barrier, and the placenta. These transporters are subject to inhibition or induction that can elicit drug interactions.[6]