- Amiodarone is a potent antiarrhythmic medication widely used for the treatment and prevention of a variety of serious cardiac arrhythmias, particularly ventricular tachycardia, ventricular fibrillation, and atrial fibrillation.
- It is classified primarily as a Class III antiarrhythmic drug under the Vaughan-Williams classification system, due to its primary action of prolonging the cardiac action potential and refractory period by blocking potassium channels. However, amiodarone has multi-class effects, exhibiting additional actions consistent with Class I (sodium channel blockade), Class II (beta-adrenergic blockade), and Class IV (calcium channel blockade), making it one of the most complex and effective agents in arrhythmia management.
- Chemically, amiodarone is a benzofuran derivative with structural similarity to thyroxine and contains a high iodine content, which contributes to some of its unique pharmacokinetic and side effect profiles. The drug is highly lipophilic, leading to extensive tissue distribution and a remarkably long half-life—ranging from 20 to 100 days, depending on the duration of therapy. As a result, steady-state plasma concentrations may take weeks to achieve, and adverse effects may persist long after discontinuation.
- Pharmacodynamically, amiodarone inhibits repolarization by blocking voltage-gated potassium channels, which prolongs the QT interval on the electrocardiogram (ECG) and increases the refractory period of cardiac cells, reducing the likelihood of reentrant arrhythmias. It also slows conduction by inhibiting sodium channels and decreases heart rate and atrioventricular (AV) node conduction through noncompetitive beta-blockade and calcium channel inhibition. These combined effects make it effective in both supraventricular and ventricular arrhythmias, particularly when other treatments have failed or are contraindicated.
- Clinically, amiodarone is often used in life-threatening arrhythmias, especially ventricular fibrillation and hemodynamically unstable ventricular tachycardia, often in acute settings or advanced heart disease. It is also used as a rhythm control agent in patients with persistent or paroxysmal atrial fibrillation, particularly when catheter ablation is not feasible or in those with underlying structural heart disease.
- Despite its efficacy, amiodarone is associated with a wide array of potentially serious side effects, due to its accumulation in various tissues over time. Common adverse effects include pulmonary toxicity (e.g., interstitial pneumonitis and pulmonary fibrosis), thyroid dysfunction (both hypothyroidism and hyperthyroidism due to iodine content), hepatotoxicity, corneal microdeposits, photosensitivity, neuropathy, and skin discoloration (bluish-gray pigmentation in sun-exposed areas). Because of these risks, routine monitoring of pulmonary, hepatic, and thyroid function is essential during long-term therapy.
- Pharmacokinetically, amiodarone has an unusual profile: it is metabolized primarily by the CYP3A4 enzyme in the liver and has numerous drug interactions, including with warfarin, digoxin, statins, and other antiarrhythmics. Its long half-life and variable absorption complicate dosing and adjustments, especially when transitioning to or from other medications.
