proarrhythmic

Proarrhythmia refers to drug-induced arrhythmia or worsening of existing arrhythmias, a serious adverse effect of antiarrhythmic drugs. Class I drugs (sodium channel blockers: flecainide, propafenone, quinidine) and Class III drugs (potassium channel blockers: amiodarone, sotalol, dofetilide) are most proarrhythmic. Mechanisms include: (1) Altered refractoriness leading to re-entry; (2) Triggered activity from early afterdepolarizations (EAD) or delayed afterdepolarizations (DAD); (3) QT prolongation from Class III effects creating EAD substrate; (4) Slowed conduction allowing re-entrant circuits. Risk factors for proarrhythmia: female sex, hypokalemia, hypomagnesemia, bradycardia, structural heart disease (cardiomyopathy, prior MI), renal/hepatic dysfunction (reduced drug clearance), drug interactions (inhibiting cytochrome P450 metabolism), and high drug doses. Torsades de pointes is a specific proarrhythmic presentation with Class I/III drugs causing QT prolongation—polymorphic ventricular tachycardia with twisting QRS axis on ECG. Acute MI survivors with reduced EF treated with Class I drugs (flecainide, encainide) have increased mortality despite suppressing premature ventricular contractions (CAST trial—seminal evidence). On boards: always check QTc when prescribing QT-prolonging drugs; avoid in hypokalemia; use with caution in structural heart disease. Amiodarone, despite Class III effects and QT prolongation, is less proarrhythmic than other Class III drugs due to concomitant Class I, II, and IV effects. Management of proarrhythmia: discontinue offending drug, correct electrolyte abnormalities, use overdrive pacing or IV magnesium for torsades, and avoid re-challenging with same drug.