Class III antiarrhythmics (potassium channel blockers)

Mechanism of Action - The Potassium Block Party

• Primary Action: Block voltage-gated potassium (K+) channels, specifically the delayed rectifier current ($I_K$).
• Electrophysiologic Effect: This inhibition slows Phase 3 (repolarization) of the cardiac action potential.
• Net Result:
  • ↑ Action Potential Duration (APD).
  • ↑ Effective Refractory Period (ERP).
  • ↑ QT interval on EKG.

⭐ By prolonging the QT interval, these drugs create the electrophysiologic substrate for Torsades de Pointes (TdP), a potentially fatal ventricular arrhythmia.

Indications & Contraindications - Gatekeeper's Guide

• Indications (Atrial & Ventricular Arrhythmias):

  • Atrial fibrillation & flutter (maintenance of sinus rhythm)
  • Ventricular tachycardia (VT) & fibrillation (VF), especially life-threatening

• Contraindications & Cautions:

  • Congenital or acquired long QT syndromes
  • Severe sinus bradycardia or 2nd/3rd-degree heart block (without a pacemaker)
  • Concurrent use of other QT-prolonging drugs
  • ⚠️ Warning: High risk of Torsades de Pointes (TdP), exacerbated by hypokalemia or hypomagnesemia.

⭐ Amiodarone is uniquely broad-spectrum but carries significant non-cardiac toxicities (pulmonary fibrosis, thyroid dysfunction, hepatotoxicity), requiring careful monitoring.

Adverse Effects - The Toxicity Tango

• Amiodarone: Broad toxicity due to its iodine content and long half-life.

  • 📌 Mnemonic: Routinely check PFTs, LFTs, & TFTs.
  • Pulmonary: Chronic interstitial pneumonitis/fibrosis (most lethal).
  • Thyroid: Hypo- or hyperthyroidism.
  • Ocular: Corneal micro-deposits, optic neuropathy.
  • Hepatic: ↑ Transaminases, hepatitis.
  • Derm: Photodermatitis, blue-gray skin discoloration.
  • Neuro: Tremor, ataxia, neuropathy.
  • CV: Bradycardia, heart block, QT prolongation (lower TdP risk).

• Sotalol, Dofetilide, Ibutilide:

  • Major risk: Dose-dependent QT prolongation → Torsades de Pointes (TdP).
  • ⚠️ Risk ↑ with hypokalemia & hypomagnesemia.
  • Sotalol also has β-blocker effects (bradycardia, fatigue).

⭐ Exam Favorite: Amiodarone-induced pulmonary fibrosis is the most feared adverse effect. It requires baseline and periodic monitoring with chest X-rays and pulmonary function tests (PFTs).

Drug-Specific Profiles - Meet the K+ Crew

• Amiodarone:
  • Broad spectrum: Blocks K+, Na+, Ca²+ channels & β-receptors.
  • Very long half-life (weeks to months).
  • 📌 Mnemonic for side effects: "Check LFTs, PFTs, TFTs" (Liver, Pulmonary, Thyroid). Also corneal deposits, skin discoloration (blue-gray).
• Sotalol:
  • Also a non-selective β-blocker.
  • Dose-dependent risk of Torsades de Pointes (TdP).
• Dofetilide & Ibutilide:
  • "Pure" K+ channel blockers.
  • Used for chemical cardioversion of A-fib/A-flutter.
  • ⚠️ High risk of TdP; requires initiation with telemetry monitoring.

⭐ Amiodarone is lipophilic and accumulates in tissues, leading to its myriad of side effects, including pulmonary fibrosis, hepatotoxicity, and thyroid dysfunction.

• Primary MOA: Block potassium (K+) channels, which prolongs repolarization and the effective refractory period (ERP).
• Key ECG finding: ↑ QT interval, creating a major risk for Torsades de Pointes (TdP).
• Amiodarone is unique: exhibits properties of all four antiarrhythmic classes and has a very long half-life.
• Amiodarone's toxicities are widespread: pulmonary fibrosis, hepatotoxicity, thyroid dysfunction (hypo/hyper), and corneal deposits.
• Sotalol also has significant beta-blocking (Class II) activity.