Class III Antiarrhythmics - Ibutilide, Dofetilide

Summary

Dofetilide and Ibutilide are class III antiarrhythmic drugs that work by blocking potassium channels. Blocking potassium outflow in cardiac tissue extends the end refractory period, which can terminate arrhythmias and restore normal heart rhythm. This makes these drugs effective for rhythm control. One important adverse effect seen is QT prolongation, with increased risk of developing Torsades de Pointes.

Key Points

• Ibutilide and Dofetilide
  • Mechanism
    • Class 3 Antiarrhythmic
      • Along with Amiodarone, Sotalol, and Bretylium
    • Blocks Potassium (K+) channels
      • Prolongs phase 3 repolarization by blocking potassium outflow, mainly in non-nodal tissue
      • Increases AP duration and effective refractory period (ERP)
        • Prolonged QT creates risk for early after-depolarizations and Torsades de Pointes
  • Clinical Use
    • Atrial flutter/fibrillation
      • Used for cardioversion (e.g. rhythm control) and restoring of normal sinus rhythm
      • Current cardiology guidelines recommend rate control (class 2 or 4 antiarrhythmics) before rhythm control (cardioversion); therefore, these drugs should be given later in the course of therapy
    • Rarely used for ventricular tachycardia
      • Other class 3 antiarrhythmics (e.g. amiodarone) are preferred
  • Adverse Effects
    • Long QT (Torsades de Pointes risk)
      • All drugs that increase QT interval increase the risk of early after-depolarizations causing ventricular arrhythmias like Torsades de Pointes.