Continuous transdermal nitroglycerin therapy loses its antianginal effect within 24 to 48 hours. The accepted strategy to prevent this tolerance is:

• A Adding a sulfhydryl donor such as N-acetylcysteine alone without any dosing change
• B Doubling the patch dose every third day
• C Providing a daily nitrate-free interval of 8 to 12 hours ✓
• D Switching to oral isosorbide mononitrate taken three times daily at even intervals

Explanation

Nitrate tolerance is attributed largely to depletion of sulfhydryl groups needed for biotransformation of nitrates to nitric oxide, along with volume expansion and oxidative stress. The standard preventive measure is an asymmetric dosing schedule creating a nitrate-free interval of 8 to 12 hours, typically overnight. Even-interval dosing of isosorbide mononitrate three times daily would itself produce tolerance, and simply adding a sulfhydryl donor does not reliably restore responsiveness.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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