A patient using a transdermal nitroglycerin patch continuously develops loss of antianginal effect within 24 to 48 hours. The mechanism responsible for nitrate tolerance is:
- A Depletion of sulfhydryl groups needed for conversion of nitrate to nitric oxide ✓
- B Downregulation of soluble guanylate cyclase receptors on vascular smooth muscle
- C Induction of hepatic cytochrome enzymes accelerating nitrate metabolism
- D Compensatory activation of the sympathetic nervous system overriding vasodilation
Correct answer: A. Depletion of sulfhydryl groups needed for conversion of nitrate to nitric oxide
Explanation
Organic nitrates require bioconversion to nitric oxide, a process that consumes free sulfhydryl (-SH) groups in vascular smooth muscle. Continuous exposure depletes these groups, so nitrate no longer generates adequate NO, causing tolerance. The practical consequence is a nitrate-free interval of 10 to 12 hours, typically by removing the patch overnight. Option B describes a related but less accepted mechanism; the classic teaching answer is sulfhydryl depletion. Hepatic enzyme induction is irrelevant because transdermal nitrate bypasses first-pass metabolism.
Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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