A patient with stable angina is started on ranolazine. Its anti-anginal mechanism involves:
- A Inhibition of the late inward sodium current (late INa) in cardiomyocytes, reducing intracellular calcium overload ✓
- B Vasodilation of coronary arteries via NO-dependent sGC activation
- C Reduction in heart rate by blocking the If funny current in the SA node
- D Inhibition of fatty acid β-oxidation, shifting myocardial metabolism to glucose utilisation
Correct answer: A. Inhibition of the late inward sodium current (late INa) in cardiomyocytes, reducing intracellular calcium overload
Explanation
Ranolazine selectively inhibits the late inward sodium current (late INa) of cardiomyocytes. During ischaemia, enhanced late INa increases intracellular Na+, which drives the Na+/Ca2+ exchanger in reverse, loading cells with Ca2+. This calcium overload increases diastolic tension and impairs myocardial relaxation (diastolic dysfunction), worsening ischaemia. By inhibiting late INa, ranolazine reduces this calcium overload, improving diastolic relaxation and reducing anginal threshold without altering heart rate or blood pressure significantly.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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