A patient using transdermal nitroglycerin continuously reports that the drug stops relieving his angina within 24 to 48 hours of starting therapy. The mechanism underlying this loss of effect and the measure that prevents it are:
- A Receptor downregulation; rotate to a longer acting nitrate
- B Depletion of reduced sulfhydryl groups needed for NO generation; provide a daily 10 to 12 hour nitrate-free interval ✓
- C Accelerated hepatic first-pass metabolism; co-prescribe cimetidine
- D Reflex sympathetic activation; add propranolol
Correct answer: B. Depletion of reduced sulfhydryl groups needed for NO generation; provide a daily 10 to 12 hour nitrate-free interval
Explanation
Continuous nitrate exposure produces tolerance because bioactivation of nitrates to nitric oxide requires sulfhydryl-containing cofactors, which become depleted. An intermittent schedule providing a 10 to 12 hour nitrate-free interval each day restores responsiveness. Adding a beta-blocker does not reverse nitrate tolerance; it only blunts reflex tachycardia during nitrate use. First-pass metabolism applies to oral nitrates and is irrelevant to transdermal delivery, and cimetidine would inhibit rather than accelerate metabolism.
Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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