A patient with stable angina is given ranolazine as add-on therapy. The anti-ischemic mechanism of ranolazine is best described as:

• A Activation of soluble guanylate cyclase to increase cGMP and vasodilate coronary arteries
• B Inhibition of fatty acid beta-oxidation, shifting cardiac metabolism toward glucose oxidation
• C Inhibition of the late sodium current (late INa) in cardiomyocytes, reducing intracellular Na+ and secondary Ca2+ overload during ischemia ✓
• D Blockade of L-type calcium channels in coronary smooth muscle producing vasodilation

Explanation

Ranolazine selectively inhibits the late (persistent) inward sodium current (late INa) that is abnormally augmented during myocardial ischemia. Excess late INa causes intracellular Na+ accumulation, which secondarily inhibits Na+-Ca2+ exchange (NCX), leading to Ca2+ overload, mechanical dysfunction, and arrhythmias. By reducing late INa, ranolazine decreases ischemia-related Ca2+ overload and myocardial oxygen demand without significantly lowering heart rate or blood pressure. Earlier models proposed metabolic shift via partial fatty acid oxidation (pFOX) inhibition, but current evidence favors late INa inhibition as the primary mechanism.

Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.

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Written and medically reviewed by the StethoPrep medical team.