From the Guidelines
Amiodarone use is associated with effective arrhythmia control, but also significant extracardiac side effects, making it a second-line treatment option.
Effects of Amiodarone
- Antiarrhythmic effects: Amiodarone is an effective multichannel blocker, reducing ventricular rate and maintaining sinus rhythm in patients with atrial fibrillation (AF) 1.
- Extracardiac side effects: Amiodarone often causes significant extracardiac side effects, especially on long-term therapy, including thyroid abnormalities, pulmonary toxicity, hepatotoxicity, neuropathy, and insomnia 1.
- Proarrhythmia risk: Amiodarone is associated with a risk of proarrhythmia, including torsades de pointes, and requires monitoring of QT interval and TU waves 1.
- Dose and efficacy: Low-dose amiodarone (200 mg daily or less) may be effective and associated with fewer side effects than higher-dose regimens 1.
Clinical Use
- Atrial fibrillation: Amiodarone is considered a suitable alternative agent for heart rate control when conventional measures are ineffective, but its use is limited by potential toxicity 1.
- Ventricular arrhythmias: Amiodarone may be used to prevent recurrent ventricular arrhythmias, but its use is balanced by the risk of extracardiac side effects 1.
- Heart failure: Amiodarone has been associated with overall neutral effects on survival in patients with heart failure, but may be considered for antiarrhythmic therapy in select cases 1.
From the FDA Drug Label
Amiodarone is generally considered a class III antiarrhythmic drug, but it possesses electrophysiologic characteristics of all four Vaughan Williams classes. One of its main effects, with prolonged administration, is to lengthen the cardiac action potential, a class III effect. The negative chronotropic effect of amiodarone in nodal tissues is similar to the effect of class IV drugs. In addition to blocking sodium channels, amiodarone blocks myocardial potassium channels, which contributes to slowing of conduction and prolongation of refractoriness The antisympathetic action and the block of calcium and potassium channels are responsible for the negative dromotropic effects on the sinus node and for the slowing of conduction and prolongation of refractoriness in the atrioventricular (AV) node. Its vasodilatory action can decrease cardiac workload and consequently myocardial oxygen consumption
The effects of Amiodarone use include:
- Lengthening of the cardiac action potential
- Negative chronotropic effect in nodal tissues
- Blocking of sodium channels
- Blocking of myocardial potassium channels, contributing to slowing of conduction and prolongation of refractoriness
- Negative dromotropic effects on the sinus node
- Slowing of conduction and prolongation of refractoriness in the atrioventricular (AV) node
- Vasodilatory action, decreasing cardiac workload and myocardial oxygen consumption 2 2
From the Research
Effects of Amiodarone Use
The effects of Amiodarone use can be categorized into several areas, including its efficacy, safety, and side effects.
- Efficacy: Amiodarone is effective against a variety of arrhythmias, including ventricular and atrial arrhythmias 3, 4, 5. It has been shown to be superior to other drugs in some settings 4 and is currently the leading antiarrhythmic drug 4.
- Safety: Amiodarone has a relatively safe profile when used at the lowest effective dose 3. However, it can cause non-cardiac toxicity, including thyroid abnormalities, pulmonary fibrosis, and transaminitis 6, 5.
- Side Effects: The adverse effect profile of amiodarone is diverse, involving the cardiac, thyroid, pulmonary, hepatic, gastrointestinal, ocular, neurological, and dermatological systems 5. Common side effects include hypotension, bradycardia, and peripheral phlebitis 7.
Therapeutic Use
Amiodarone is used in the treatment of various cardiac arrhythmias, including:
- Ventricular arrhythmias: Amiodarone is effective in controlling hemodynamically stable VT, polymorphic VT, and wide-complex tachycardia of uncertain origin 7.
- Atrial arrhythmias: Amiodarone is used for ventricular rate control of rapid atrial arrhythmias in patients with severely impaired left ventricular function 7.
- Prevention of sudden cardiac death: Amiodarone may have a beneficial effect on mortality and survival in certain groups of patients with ventricular arrhythmias 5.
Monitoring and Contraindications
Regular monitoring is necessary to control the well-recognized adverse effects of amiodarone 5. Contraindications to the use of amiodarone include bradycardia, sinoatrial block, severe disturbances of conduction, second or third degree atrio-ventricular blocks, hypotension, severe respiratory failure, hepatocellular failure, and hyperthyroidism 7. Pharmacological interactions have been reported with several drugs, including HMG-CoA reductase inhibitors, class I antiarrhythmic agents, and other drugs that contribute to prolong QT interval 7.