Amiodarone

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amiodarone hydrochloride

The hydrochloride salt of an iodine-rich benzofuran derivative with antiarrhythmic and vasodilatory activities. As a class III antiarrhythmic agent, amiodarone blocks the myocardial calcium, potassium and sodium channels in cardiac tissue, resulting in prolongation of the cardiac action potential and refractory period. In addition, this agent inhibits alpha- and beta-adrenergic receptors, resulting in a reduction in sympathetic stimulation of the heart, a negative chronotropic effect, and a decrease in myocardial oxygen demands. Amiodarone may cause vasodilation by stimulation of the release of nitric oxide and cyclooxygenase-dependent relaxing endothelial factors.

Mechanism of action of Amiodarone

Amiodarone (a" mee oh' da rone) is an iodinated benzofuran derivative that is a structural analogue of thyroid hormone. Amiodarone may interact with thyroid nuclear receptors, but its antiarrhythmic effects are believed to be mediated by its action in blocking membrane ion channels via perturbation of the lipid environment in the membrane bilayer. Amiodarone is highly lipophilic and is concentrated in many tissues and cells, including hepatocytes in the liver. It has a slow onset of action and a long but variable elimination half life (up to 6 months) and can accumulate in tissues including hepatocytes. Amiodarone is highly effective in suppressing ventricular arrhythmias and in maintaining sinus rhythm in patients with atrial fibrillation.

FDA approval information for Amiodarone

Amiodarone was first approved for use in the United States in 1985 and it is still widely used with several million prescriptions written yearly. Approved indications are limited to recurrent ventricular arrhythmias which have not responded to other available antiarrhythmics. Amiodarone is also used off-label for suppression of atrial fibrillation and maintenance of normal sinus rhythm after cardioversion.

Dosage and administration for Amiodarone

Amiodarone is available in tablets of 200 and 400 mg in generic forms and under the brand names of Cordarone and Pacerone. It is also available in solution for intravenous administration. Amiodarone is typically given in high loading doses of 800 to 1600 mg daily, either intravenously or orally until the arrhythmia is controlled, and as maintenance oral doses for long term therapy of 200 to 600 mg daily.

Liver safety of Amiodarone

Liver toxicity appears to be more common with higher doses.

US brand name

  • Cordarone
  • Nexterone

Side effects of Amiodarone

Amiodarone has multiple adverse side effects including fatigue, tremor, involuntary movements, poor coordination, peripheral neuropathy, nausea, vomiting, constipation, anorexia, visual disturbances, corneal deposits, skin discoloration and rash, photosensitivity, bradycardia, and worsening of arrhythmias. Uncommon side effects include pneumonitis, pulmonary fibrosis, optic neuropathy, blindness, thyroid dysfunction and liver injury.

List of antiarrhythmic agents:

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