Amiodarone

Amiodarone is a class III antiarrhythmic agent that blocks voltage-gated potassium channels. It is used in the treatment of acute ventricular tachycardia and persisting ventricular fibrillation (VF) after unsuccessful defibrillation, as well as the long-term treatment of refractory supraventricular arrhythmia (atrial fibrillation). Since amiodarone has a very low negative inotropic effect, it can be used in patients with a reduced ejection fraction (EF). Side effects commonly involve the thyroid, liver, heart, eyes, and central nervous system. Pulmonary side effects, such as lung fibrosis and chronic interstitial pneumonitis, are rare but severe. Because amiodarone is a cytochrome P450 inhibitor, simultaneous administration of other drugs should be considered carefully to minimize the risk of interactions.

• Primary mechanism of action: antiarrhythmic effect via blockage of voltage-gated potassium channels → prolonged repolarization of the cardiac action potential
• Secondary mechanism of action: inhibits β-receptors and sodium and calcium channels → decreases conduction through the AV and sinus node
• Special uses: : only antiarrhythmic agent with (almost) no negative inotropic effect → use in patients with reduced EF

References:^[1][2]

Although amiodarone is an extremely effective antiarrhythmic drug, its side-effect profile limits its use primarily to short-term administration. Amiodarone accumulation in tissues can cause damage to the thyroid, lungs, nerves, skin, eyes, and heart.

"Am-IOD-arone" consists of approx. 37% iodine!

References:^[3][4]

We list the most important adverse effects. The selection is not exhaustive.

• Acute treatment (IV administration)
  • Second-line therapy for patients with ventricular tachycardia (VT) who are hemodynamically stable
  • Persistent VT after defibrillation
  • Pulseless ventricular fibrillation
  • Supraventricular tachycardia in patients with cardiac failure (LVEF < 40%)
• Long-term treatment (oral administration)
  • Rhythm control in refractory symptomatic atrial fibrillation (supraventricular arrhythmia) and underlying heart disease → restoration and maintenance of sinus rhythm

Amiodarone is the drug of choice for supraventricular arrhythmias in most heart failure patients (LVEF < 40%).
References:^[1][5][6][7]

• Severe sinus node dysfunction with marked sinus bradycardia
• Second- and third-degree heart block (except in patients with a functioning pacemaker)
• Hyperthyroidism and hypothyroidism
• Known allergy to iodine
• Pre-existing lung disease

References:^[8][9]

We list the most important contraindications. The selection is not exhaustive.

• Amiodarone is an inhibitor of cytochrome P450 enzymes (see principles of pharmacology) → reduced clearance of the following drugs:
  • Warfarin (risk of bleeding!)
  • Simvastatin (increased risk of rhabdomyolysis)
  • Digoxin
  • Cyclosporine
  • Flecainide, procainamide, quinidine
  • Sildenafil

References:^[1][8]

• Amiodarone is very lipophilic → accumulation of amiodarone in myocardium and muscles → long duration of action
• Metabolized in the liver by CYP3A4 with biliary excretion

References:^[8][10]