====== Amiodarone ====== 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. → [[cardio:arrhythmias:start|Dysrhythmias Module]] -------------------------------------------------------------------- ===== Mechanism of Action ===== 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. -------------------------------------------------------------------- ===== Indications ===== ==== Atrial Fibrillation ==== • Rhythm control • Used when other agents fail or are contraindicated ---- ==== Ventricular Tachycardia / Ventricular Fibrillation ==== • Stable monomorphic VT • Recurrent VT • Cardiac arrest (ACLS) ---- ==== Structural Heart Disease / HFrEF ==== • Preferred antiarrhythmic in systolic heart failure • Safer than Class IC agents in structural heart disease → [[cardio:heart_failure:start|Heart Failure Module]] -------------------------------------------------------------------- ===== Pharmacokinetics ===== • 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. -------------------------------------------------------------------- ===== Major Toxicities ===== 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) -------------------------------------------------------------------- ===== Monitoring ===== Baseline and periodic monitoring: • Chest X-ray • Pulmonary function if symptoms • Thyroid function tests • Liver function tests • ECG Long-term therapy requires structured surveillance. -------------------------------------------------------------------- ===== Drug Interactions ===== Amiodarone inhibits multiple CYP enzymes and P-gp. Can increase levels of: • [[cardio:arrhythmias:digoxin|Digoxin]] • [[anticoagulation:warfarin|Warfarin]] • Other QT-prolonging drugs Dose adjustments and monitoring are often required. -------------------------------------------------------------------- ===== Amiodarone vs Other Class III Agents ===== [[cardio:beta_blockers:sotalol|Sotalol]]: • Higher torsades risk • Renally cleared • Initiation monitoring required [[cardio:arrhythmias:dofetilide|Dofetilide]]: • Strict QT monitoring • Hospital initiation required Amiodarone: • Most effective • Lowest torsades risk among Class III drugs • Highest systemic toxicity burden -------------------------------------------------------------------- ===== Clinical Pearls ===== ✔ 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: → [[cardio:arrhythmias:start|Dysrhythmias Module]] → [[cardio:beta_blockers:sotalol|Sotalol]] → [[cardio:arrhythmias:dofetilide|Dofetilide]] → [[cardio:heart_failure:start|Heart Failure Module]] → [[cardio:intro:start|Return to Cardiovascular Modules]]