A patient using a transdermal nitroglycerin patch around the clock reports that his anginal protection has faded despite continued therapy. What is the correct explanation and corrective measure?

• A Antibody-mediated neutralisation of the drug; rotate between nitrate classes
• B Receptor downregulation at muscarinic sites; double the patch dose
• C Induction of hepatic first-pass metabolism; switch to sublingual tablets
• D Tachyphylaxis from sulfhydryl group depletion; provide a daily nitrate-free interval of 8 to 12 hours ✓

Explanation

Continuous nitrate exposure depletes tissue sulfhydryl groups needed for biotransformation of nitroglycerin to nitric oxide, producing tolerance within 24 to 48 hours. The standard remedy is an asymmetric dosing schedule leaving an 8 to 12 hour nitrate-free interval each day so sulfhydryl stores recover. Doubling the patch worsens tolerance and headache. First-pass metabolism is irrelevant for transdermal delivery, and no immune mechanism exists.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.