A Class III antiarrhythmic agent prolongs the action potential duration and QT interval primarily by which mechanism?

Explanation

## Class III Antiarrhythmics: Mechanism of Action **Key Point:** Class III antiarrhythmics work by **blocking potassium channels** (particularly delayed rectifier K^+^ channels), which delays Phase 3 repolarization and prolongs the action potential duration (APD) and QT interval. ### Mechanism: Potassium Channel Blockade **High-Yield:** Class III drugs inhibit outward potassium current during the repolarization phase: 1. **Normal repolarization:** K^+^ efflux through delayed rectifier channels (I~K~) rapidly restores resting potential 2. **With Class III blockade:** K^+^ channel inhibition → slowed K^+^ efflux → prolonged Phase 3 → increased APD and QT interval 3. **Electrophysiologic effect:** Increased refractory period → reduced ectopic activity and re-entrant arrhythmias ### Class III Agents and Their Targets | Drug | Primary K^+^ Channel Target | Secondary Actions | QT Prolongation | | --- | --- | --- | --- | | **Amiodarone** | Delayed rectifier (I~K~) | Na^+^ block, Ca^2+^ block, β-block | ✓✓✓ Marked | | **Sotalol** | Delayed rectifier (I~K~) | β-blockade | ✓✓ Moderate | | **Dofetilide** | Delayed rectifier (I~K~) | Selective K^+^ block only | ✓✓ Moderate | | **Ibutilide** | Delayed rectifier (I~K~) | Activates Na-Ca exchanger | ✓✓ Moderate | **Clinical Pearl:** Amiodarone is the most potent Class III agent because it blocks multiple ion channels (Na^+^, K^+^, Ca^2+^) plus β-adrenergic receptors — it is a "broad-spectrum" antiarrhythmic with properties of all four Vaughan-Williams classes. ### Contrast with Other Classes ```mermaid flowchart TD A["Antiarrhythmic Mechanism"]:::outcome --> B{"Which ion channel?"}:::decision B -->|"Na+ channels"|C["Class I: ↓ Conduction"]:::action B -->|"K+ channels"|D["Class III: ↑ APD & QT"]:::action B -->|"Ca2+ channels"|E["Class IV: ↓ AV nodal conduction"]:::action B -->|"β-adrenergic"|F["Class II: ↓ HR & AV conduction"]:::action D --> G["Delayed repolarization<br/>Prolonged refractory period"]:::outcome ``` **Mnemonic:** Class **III** = **I**nhibit K^+^ channels → **I**ncrease APD and QT interval. [cite:KD Tripathi 8e Ch 12]