A patient stabilized on digoxin for atrial fibrillation is started on quinidine. Within days she develops nausea, confusion, and new ventricular bigeminy with a digoxin level of 4 ng/mL. The interaction responsible is:

• A Quinidine inhibits P-glycoprotein, reducing renal and biliary clearance of digoxin ✓
• B Quinidine displaces digoxin from skeletal muscle binding sites
• C Quinidine induces hepatic CYP3A4, increasing conversion to toxic metabolites
• D Quinidine reduces the volume of distribution by causing hypokalemia

Explanation

Digoxin is a substrate for the efflux transporter P-glycoprotein, which mediates its renal tubular secretion and intestinal efflux. Quinidine is a potent P-glycoprotein inhibitor, so digoxin plasma concentrations roughly double when the two are combined, requiring empiric digoxin dose reduction. The classic teaching point is that quinidine raises digoxin levels rather than sharing additive antiarrhythmic toxicity. Displacement alone explains only a minor transient rise, so it cannot account for sustained toxicity.

Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.