Amiodarone prolongs the QT interval through potassium channel blockade (class III effect). Despite QT prolongation, amiodarone has a LOWER risk of torsades de pointes compared to sotalol. The most likely explanation is:
- A Amiodarone's class I sodium channel block reduces the upstroke amplitude, preventing re-entry
- B Amiodarone's active metabolite desethylamiodarone reverses QT prolongation
- C Amiodarone reduces heart rate through beta-blockade, shortening the absolute QT interval
- D Amiodarone blocks IKr and IKs uniformly, reducing transmural dispersion of repolarization ✓
Explanation
The risk of torsades de pointes from QT-prolonging drugs is driven by transmural dispersion of repolarization (TDR) — the difference in action potential duration between endocardial, midmyocardial (M-cells), and epicardial layers. Sotalol selectively blocks IKr, predominantly prolonging M-cell repolarization and increasing TDR. Amiodarone blocks both IKr and IKs (as well as multiple sodium and calcium channels), homogeneously prolonging all layers and thus reducing TDR despite increasing total QT. This electropharmacological 'uniformity' is the key reason amiodarone paradoxically has a lower torsades risk than other QT-prolonging agents. Desethylamiodarone is an active metabolite with similar effects, not a reversal mechanism.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.