Amiodarone: pharmacological profile, animal-model experimental data and clinical use. How important is the vasodilating effect?

Amiodarone, the major representative of class III antiarrhythmic agents, is widely used in the treatment of ventricular and hyperventricular arrhythmias, being specifically useful in the therapy of patients suffering from life threatening ventricular arrhythmias. The combination of antianginal and antiarrthythmic actions of amiodarone is an extremely significant advantage regarding the treatment of patients with chronic atherosclerotic cardiopathy, as heart rate disorders are frequently fatal in coronary heart disease and, reversely, a high percentage of cardiac arrhythmias are caused by coronary heart disease. Since 1980s, several experimental in vitro and in vivo data, as well as clinical studies, regarding both systematic and coronary circulation, support the vasodilative effects of amiodarone. We have previously showed that amiodarone in vitro exerts a vasodilator effect in isolated vessel tissue, mainly via the activation of intracellular calcium binding mechanisms, a fact that differentiates this agent from other coronary vasodilative drugs, such as calcium channel blockers, that affect extracellular calcium ions entrance. Thus, the vasodilative, antianginal and antiarrhythmic actions of amiodarone may be further enhanced by the simultaneous supplementation of calcium channel blockers via synergistic mechanisms, supporting the clinical use of such drug combinations. Finally, as amiodarone and noradrenaline have been reported to exert antagonistic actions, the application of amiodarone is particularly indicated in pathologic conditions characterized by the stimulation of sympathetic nervous system (sympathicotonia).