Amiodarone is a Class III antiarrhythmic with multi-class electrophysiologic effects.

It blocks:

• Potassium channels (Class III) • Sodium channels (Class I) • Beta receptors (Class II) • Calcium channels (Class IV)

Because of this broad activity, amiodarone is highly effective for both atrial and ventricular arrhythmias.

→ Dysrhythmias Module

Primary effect:

• Blocks potassium channels • Prolongs Phase 3 repolarization • Prolongs action potential duration • Prolongs QT interval

Additional effects:

• Sodium channel blockade → slows conduction • Beta-blocking activity → reduces sympathetic drive • Calcium channel blockade → slows AV node

Net Effects:

• Slows conduction • Increases refractory period • Suppresses automaticity

Despite QT prolongation, torsades risk is relatively low compared to other Class III agents.

• Rhythm control • Used when other agents fail or are contraindicated

• Stable monomorphic VT • Recurrent VT • Cardiac arrest (ACLS)

• Preferred antiarrhythmic in systolic heart failure • Safer than Class IC agents in structural heart disease

→ Heart Failure Module

• Extremely lipophilic • Very large volume of distribution • Accumulates in fat and tissues • Long half-life (weeks to months) • Requires loading dose

Effects may persist long after discontinuation.

Amiodarone toxicity is multi-system.

Pulmonary: • Interstitial pneumonitis • Pulmonary fibrosis (most serious long-term risk)

Thyroid: • Hypothyroidism • Hyperthyroidism

Liver: • Elevated transaminases • Hepatotoxicity

Ocular: • Corneal microdeposits • Optic neuropathy (rare)

Dermatologic: • Photosensitivity • Blue-gray skin discoloration

Cardiac: • Bradycardia • QT prolongation • Torsades (rare compared to other Class III agents)

Baseline and periodic monitoring:

• Chest X-ray • Pulmonary function if symptoms • Thyroid function tests • Liver function tests • ECG

Long-term therapy requires structured surveillance.

Amiodarone inhibits multiple CYP enzymes and P-gp.

Can increase levels of:

• Digoxin • Warfarin • Other QT-prolonging drugs

Dose adjustments and monitoring are often required.

Sotalol: • Higher torsades risk • Renally cleared • Initiation monitoring required

Dofetilide: • Strict QT monitoring • Hospital initiation required

Amiodarone: • Most effective • Lowest torsades risk among Class III drugs • Highest systemic toxicity burden

✔ Class III with multi-class activity ✔ Extremely long half-life ✔ Low torsades risk despite QT prolongation ✔ Multi-organ toxicity ✔ Preferred in structural heart disease and HFrEF ✔ Requires routine monitoring

Related:

→ Dysrhythmias Module → Sotalol → Dofetilide → Heart Failure Module → Return to Cardiovascular Modules