Amiodarone

Common indications

• In the management of a wide range of tachyarrhythmias, including atrial fibrillation (AF), atrial flutter, supraventricular tachycardia (SVT), ventricular tachycardia (VT) and refractory ventricular fibrillation (VF). It is generally used only when other therapeutic options (drugs or electrical cardioversion) are ineffective or inappropriate.

 

Mechanisms of action

• Amiodarone has many effects on myocardial cells, including blockade of sodium, calcium and potassium channels, and antagonism of α- and β-adrenergic receptors. These effects reduce spontaneous depolarisation (automaticity), slow conduction velocity, and increase resistance to depolarisation (refractoriness), including in the atrioventricular (AV) node. By interfering with AV node conduction, amiodarone reduces the ventricular rate in AF and atrial flutter. Through its other effects, it may also increase the chance of conversion to, and maintenance of, sinus rhythm. In SVT involving a self-perpetuating (‘re-entry’) circuit that includes the AV node, amiodarone may break the circuit and restore sinus rhythm. Amiodarone’s effects in suppressing spontaneous depolarisations make it an option for both treatment and prevention of VT. The same rationale underlies its use in refractory VF, although there is little evidence from clinical trials to support this.

 

Important adverse effects

• In acute use, compared with other antiarrhythmic drugs, amiodarone causes relatively little myocardial depression, although it can cause hypotension during IV infusion. When taken chronically, it has many side effects, a number of which are serious. These include effects on the lungs (pneumonitis), heart (bradycardia, AV block), liver (hepatitis) and skin (photosensitivity and grey discolouration). Due to its iodine content (amIODarone) and structural similarities to thyroid hormone, it may cause thyroid abnormalities, including hypo- and hyperthyroidism. Amiodarone has an extremely long half-life. After discontinuation, it may take months to be completely eliminated.

 

Warnings

• Amiodarone is a potentially dangerous drug that should be used only when the risk–benefit balance justifies this. It should specifically be avoided in patients with severe hypotension, heart block and active thyroid disease.

 

Important interactions

• Amiodarone interacts with many drugs – too many to list here. Notably, it increases plasma concentrations of digoxin, diltiazem and verapamil. This may increase the risk of bradycardia, AV block and heart failure. The doses of these drugs should be halved if amiodarone is started.