A 50-year-old woman on high-dose methadone maintenance therapy for opioid use disorder presents for preoperative evaluation before cholecystectomy. Her ECG shows a QTc interval of 520 ms. Which pharmacological property of methadone best explains this cardiac finding?

• A Methadone blocks cardiac hERG potassium channels prolonging ventricular repolarization ✓
• B Methadone enhances vagal tone causing bradycardia-dependent QT prolongation
• C Methadone blocks cardiac sodium channels widening the QRS complex
• D Methadone causes hypokalemia due to renal potassium wasting

Explanation

Methadone blocks the hERG potassium channel (IKr) in cardiac myocytes, delaying phase 3 repolarization and prolonging the QTc interval, which increases the risk of torsades de pointes, especially at higher doses. This is the established mechanism. Option B is not relevant to methadone. Option C describes sodium channel blockade, which widens QRS, not QT. Option D is incorrect as methadone does not cause hypokalemia.

Reference: Katzung Basic and Clinical Pharmacology, 15th ed.

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