Learning Objective
By the end of this section, learners should be able to describe the mechanism of action of Class III antiarrhythmic drugs and identify their clinical uses and major adverse effects in the treatment of atrial and ventricular arrhythmias.
Class III: K⁺ Channel blocker
Class III antiarrhythmic drugs act by blocking delayed rectifier potassium (K⁺) channels (I<sub>K</sub>), thereby slowing Phase 3 repolarization of the cardiac action potential.
Mechanism of Action
- ↓ Delayed rectifier K⁺ current (I<sub>K</sub>)
- Slows Phase 3 repolarization
- ↑ Action potential duration (APD)
- ↑ Effective refractory period (ERP)
- Prominent effects in:
- Purkinje fibers
- Ventricular muscle
Drugs
Dofetilide
-
Potassium channel blocker
Uses:
- Conversion of atrial fibrillation to normal sinus rhythm
- Maintenance of sinus rhythm in atrial fibrillation
Adverse Effects:
- Torsade de pointes
Amiodarone / Dronedarone
- Exhibits properties of:
- Class I
- Class II
- Class III
- Class IV
- ↑ APD and ERP in all cardiac tissues
Pharmacokinetics:
- Extensive tissue binding (large Vd)
- Half-life:
- Amiodarone: >80 days
- Dronedarone: ~24 hours
Uses:
- Broad spectrum: effective for both atrial and ventricular arrhythmias
Adverse Effects (Amiodarone):
- Interstitial pneumonitis
- Pulmonary fibrosis
- Phototoxicity
- Corneal microdeposits
- Hepatic necrosis
- Iodine-related effects:
- Blue-gray skin pigmentation
- Thyroid dysfunction
Sotalol
- Blocks delayed rectifier K⁺ channels → slows Phase 3
- Also a nonselective β-blocker:
- ↓ Heart rate
- ↓ AV nodal conduction
Uses:
- Life-threatening ventricular arrhythmias
Adverse Effects:
- Torsade de pointes
