Ranolazine reduces anginal episodes without affecting heart rate or blood pressure. Its primary anti-ischaemic mechanism is:
- A Selective inhibition of fatty acid oxidation, shifting myocardial substrate utilisation to glucose
- B Blockade of mitochondrial permeability transition pore during ischaemia-reperfusion
- C Inhibition of the late inward sodium current (late INa) in ischaemic cardiomyocytes, reducing intracellular Na+ and secondary Ca2+ overload ✓
- D Activation of AMP-kinase, increasing glucose uptake in ischaemic myocardium
Correct answer: C. Inhibition of the late inward sodium current (late INa) in ischaemic cardiomyocytes, reducing intracellular Na+ and secondary Ca2+ overload
Explanation
During ischaemia, the late INa channel (a persistent activation of the Na+ channel) becomes abnormally active, causing intracellular Na+ accumulation. This raises intracellular Ca2+ via the Na+/Ca2+ exchanger, causing diastolic dysfunction. Ranolazine selectively inhibits this late INa, reducing intracellular Ca2+ overload without affecting heart rate or blood pressure. Earlier studies proposed partial fatty acid oxidation inhibition, but late INa blockade is the established mechanism.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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