Late Sodium Current Blocker (Ranolazine)
Mechanism of Action
Ranolazine represents a new class of antianginal drugs. It blocks late inward sodium currents in cardiomyocytes. In the ischemic myocardium, late inward sodium currents contribute to an elevation in intracellular sodium, which leads to an increase in intracellular calcium through the sodium-calcium exchanger. Calcium overload in ischemic cells leads to impaired relaxation, which increases ventricular diastolic wall stress and end-diastolic pressure. This causes mechanical compression of the microcirculation within the wall of the ventricle, which impairs coronary blood flow during diastole and therefore worsens ischemia, particularly in the subendocardial regions. By blocking late inward sodium currents, calcium overload and diastolic wall stress are reduced, leading to improved coronary blood flow. It is possible that other mechanisms may contribute to the antianginal effects of ranolazine. Unlike other antianginal drugs, such as beta-blockers and calcium-channel blockers, ranolazine has no clinically significant effect on heart rate or arterial pressure.
Therapeutic Indication and Administration
Ranolazine was approved by the FDA in 2006 as a treatment for chronic angina. It is available as an extended release oral compound and is dosed twice daily. Ranolazine may be used along with other antianginal drugs such as nitrates, beta-blockers and calcium-channel blockers.
Side Effects and Contraindications
Ranolazine prolongs the QT-interval by inhibiting outward potassium (delayed rectifying) currents during phase 3 of the cardiac action potential, and therefore is contradicted in patients with prolonged QT-intervals because this can lead to torsade de pointes and ventricular tachyarrhythmia. Constipation, nausea, dizziness and headaches are among the more common side-effects. More information on ranolazine can be found at www.rxlist.com.