Dronedarone

Atrial fibrillation is the most common type of arrhythmia that is caused by abnormal electrical activity in the atria. In atrial fibrillation, tachyarrhythmia, or fast heart rate, can either be paroxysmal (less than 7 days) or persistent (more than 7 days). Atrial fibrillation causes turbulent and abnormal blood flow through the heart chambers, leading to decreased the effectiveness of the heart to pump blood and an increased likelihood of thrombus formation within the atria which can ultimately dislodge and cause a stroke.

Dronedarone achieves heart rate and rhythm control in atrial fibrillation. In vitro, dronedarone decreased the maximum rate of the rise of an action potential in a concentration- and frequency-dependent manner. Cardiac action potentials are generated by ionic currents of multiple voltage-gated ion channels, including potassium, sodium, and calcium channels. Dronedarone is a multichannel blocker that meets the criteria of all four Vaughan Williams antiarrhythmic drug classes but the contribution of each of these activities to the drug's antiarrhythmic effect is unknown. Dronedarone inhibits rapid Na+ currents rate-dependently (class Ib), non-competitively antagonizes α– and β-adrenergic receptors (class II), blocks K+ outward currents (class III) and blocks slow Ca2+ inward currents (class IV). More specifically, it decreases delayed-rectifier K+ current (IKr), slowly activating delayed-rectifier K+ current (IKs), inward rectifier potassium current (IK1), peak Na+ current (INa) and L-type Ca2+ current (ICa (L)). Dronedarone ultimately increases refractory periods, decelerates cardiac conduction, and prolongs cardiac action potential and refractory periods.