This is an old revision of the document!

Amiodarone

Amiodarone is a Class III antiarrhythmic with multi-class activity.

It blocks:

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

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

→ Dysrhythmias Module

Mechanism of Action

Primary action:

• Blocks potassium channels • Prolongs Phase 3 repolarization • Prolongs QT interval

Additional actions:

• Sodium channel blockade • Beta-blocking activity • Calcium channel blockade

Net Effect:

• Slows conduction • Prolongs refractory period • Suppresses automaticity

Unlike most QT-prolonging drugs, torsades risk is relatively low.

Indications

Atrial Fibrillation

• Rhythm control • Used when other agents fail

Ventricular Tachycardia / Ventricular Fibrillation

• Hemodynamically stable VT • Recurrent VT • Cardiac arrest (ACLS)

Heart Failure with Arrhythmia

• Preferred antiarrhythmic in HFrEF • Safer than Class IC drugs in structural heart disease

Pharmacokinetics

• Extremely lipophilic • Very large volume of distribution • Long half-life (weeks to months) • Slow onset and slow offset • Accumulates in tissues

Requires loading dose.

Effects persist long after discontinuation.

Major Toxicities

Amiodarone toxicity is multi-system.

Pulmonary: • Interstitial pneumonitis • Pulmonary fibrosis

Thyroid: • Hypothyroidism • Hyperthyroidism

Liver: • Elevated transaminases • Hepatotoxicity

Ocular: • Corneal deposits • Optic neuropathy (rare)

Dermatologic: • Photosensitivity • Blue-gray skin discoloration

Cardiac: • Bradycardia • QT prolongation (torsades uncommon)

Monitoring

Baseline and periodic:

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

Long-term therapy requires surveillance.

Drug Interactions

Amiodarone inhibits multiple CYP enzymes.

Can increase levels of:

• Digoxin • Warfarin • Other QT-prolonging drugs

Careful monitoring required.

Amiodarone vs Other Class III Agents

Sotalol: • Higher torsades risk • Renally cleared

Dofetilide: • Strict QT monitoring • Initiation in hospital

Amiodarone: • Most effective • Most toxic • Preferred in structural heart disease

Clinical Pearls

✔ Class III with multi-class activity ✔ Very long half-life ✔ Low torsades risk despite QT prolongation ✔ Multi-organ toxicity ✔ Preferred antiarrhythmic in HFrEF