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ranolazine

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  • ranolazine is an antiischemic agent with novel mechanisms of action to decrease anginal frequency and to improve exercise capacity in patients with chronic stable angina.
    • basis for the improvement in myocardial ischemia appears to be inhibition of the late phase of the inward sodium current (INa) with consequent attenuation of intracellular calcium overload
    • at therapeutic concentrations, ranolazine also affects the delayed rectifier potassium current (IKr), which prolongs ventricular action potential duration (APD)
    • clinically, it has been observed in ambulatory ECG recordings from the MERLIN-TIMI 36 trial that ranolazine exerts significant antiarrhythmic effects, as evidenced by significantly fewer episodes of ventricular tachycardia
    • net effect in patients with chronic stable angina is a dose-related prolongation of the QT interval
      • therefore, for current clinical use, ranolazine is "contraindicated" in patients with preexisting QT prolongation and in combination with other QT-prolonging drugs due to concerns about possible proarrhythmias
      • shortening of action potential duration (and, possibly, antiarrhythmic effect) might be expected under conditions characterized by an abnormal increase in late INa: acute ischemia, some forms of long-QT syndrome type 3 (LQT3), and heart failure

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General Practice Notebook
General Practice Notebook
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