Ranolazine : the newer but best drug for atrial fibrillation ! Buy one get three beneficial mechanism.

The most common arrhythmia is atrial fibrillation, but antiarrhythmic drugs in patients with heart failure are sparse, have major side effects (e.g. amiodarone), or are even contraindicated like flecainide.

       Newer studies  showed that Ranolazine not only inhibits late Na current but it may also act as an atrial selective peak Na current blocker.
The reasons for this include the fact that the half-inactivation voltage is more negative in atrial as compared with ventricular myocytes with a more depolarized resting membrane potential in atrial cells. The consequence is an increased fraction of inactivated Na channels at a given membrane potential. Accordingly, ranolazine produced a use-dependent depression of several Na channel parameters in atrial myocytes even at higher stimulation rates.
Ranolazine has antiarrhythmic effects due to an increase in atrial post-repolarization refractoriness resulting in depressed electrical excitability and impediment of arrhythmia initiation even at higher heart rates.

Post-repolarization refractoriness was calculatedwhen subtracting 75% of total monophasic action potential duration from the effective refractory period, and was suggested to be due to Na currents. Ranolazine also increased the action potential duration at any given pacing cycle length, attributed to its additional effects on the main repolarizing K current I Kr.. Perhaps surprisingly to some clinicians, the authors found an increased action potential duration in the atria of this heart failure model, although increased ventricular action potential duration in failing hearts is a well accepted hallmark. In atrial fibrillation, however, major known determinants of electrical remodelling include

       (i) reduced action potential duration; (ii) decreased L-type Ca current amplitude; and (iii) altered K currents, thereby favouring a re-entry mechanism, which are underlined by reduced effective refractory periods.

In addition, Nattel and Dobrev in a recent review stressed the importance of early and delayed afterdepolarizations and triggered activity associated with altered Ca handling, including spontaneous Ca release from the sarcoplasmic reticulum and diastolic overload. These proarrhythmogenic triggers have now been shown by several authors. Intracellular Ca and Na handling are closely coupled and therefore it is possible that both mechanisms exist in parallel. Alternatively, altered Na handling due to increased late Na current can contribute to cytosolic Ca overload through the Na/Ca exchanger and/or thus may lead to a transient inward current with delayed afterdepolarizations.. Finally, late phase 3 delayed and early afterdepolarizations as well as automatic beats serving as triggers were reduced in the presence of ranolazine.

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