A patient using transdermal nitroglycerin continuously reports that the drug no longer relieves his angina after several days. The standard strategy to prevent this loss of efficacy is:

• A Increasing the patch dose progressively each week
• B Switching directly to high-dose intravenous nitroglycerin
• C Adding vitamin E to restore sulfhydryl groups permanently
• D Providing a daily 10 to 12 hour nitrate-free interval ✓

Explanation

Nitrate tolerance develops within 24 to 48 hours of continuous exposure. The accepted preventive measure is a daily nitrate-free interval of 10 to 12 hours, typically by removing the transdermal patch overnight. Proposed mechanisms include depletion of sulfhydryl donors, oxidative stress inhibiting mitochondrial aldehyde dehydrogenase, and volume expansion. Simply escalating the dose deepens tolerance without restoring efficacy, and intermittent dosing schedules are designed precisely to allow enzyme and sulfhydryl systems to recover.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.