A patient using a transdermal nitroglycerin patch continuously around the clock notices complete loss of antianginal benefit within 48 hours. The phenomenon responsible, and the standard preventive measure, are:

• A Receptor downregulation, prevented by increasing the patch dose
• B Tachyphylaxis from sulfhydryl depletion, prevented by a daily 10 to 12 hour nitrate-free interval ✓
• C Enzyme induction of hepatic nitrate reductase, prevented by switching to oral isosorbide dinitrate
• D Plasma volume expansion from venodilation, prevented by adding a diuretic

Explanation

Continuous nitrate exposure causes tolerance through depletion of tissue sulfhydryl groups needed for biotransformation of nitrates to nitric oxide, along with oxidative stress and neurohormonal counter-regulation. A nitrate-free interval of 10 to 12 hours restores responsiveness and preserves antianginal efficacy through the waking hours. Simply escalating the dose deepens tolerance, and adding a diuretic addresses pseudo-tolerance only partially without restoring vascular responsiveness.

Reference: Katzung's Basic and Clinical Pharmacology, 15th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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