A 72-year-old man on digoxin for heart failure with atrial fibrillation is started on amiodarone for recurrent ventricular ectopics. Three days later he develops nausea, yellow-green visual disturbances, and bradycardia. Which mechanism explains this interaction?
- A Amiodarone displaces digoxin from plasma protein binding sites, raising free drug level
- B Amiodarone inhibits P-glycoprotein and reduces renal clearance of digoxin, raising its plasma level ✓
- C Amiodarone induces CYP3A4, accelerating digoxin metabolism
- D Amiodarone increases renal tubular secretion of digoxin
Correct answer: B. Amiodarone inhibits P-glycoprotein and reduces renal clearance of digoxin, raising its plasma level
Explanation
Amiodarone inhibits P-glycoprotein (P-gp) in the renal tubule, which is responsible for tubular secretion of digoxin. Inhibition of P-gp reduces digoxin clearance, causing plasma levels to rise by approximately 50-100%. The resulting digoxin toxicity manifests as GI symptoms (nausea, vomiting), visual disturbances (yellow-green halos, blurred vision), and bradyarrhythmias. Digoxin dose should be halved when amiodarone is added and levels monitored. Amiodarone is broadly a CYP inhibitor, not an inducer.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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