A patient using transdermal nitroglycerin continuously notices that its antianginal effect wanes after several days. The recommended strategy to prevent this loss of efficacy is:

• A Doubling the patch strength while keeping continuous wear
• B Adding isosorbide mononitrate at bedtime
• C Co-administering N-acetylcysteine indefinitely
• D Providing a 10 to 12 hour nitrate-free interval each day ✓

Explanation

Nitrate tolerance develops within 24 to 48 hours of continuous exposure, attributed partly to depletion of sulfhydryl groups needed for biotransformation of nitrates to nitric oxide and partly to volume expansion and oxidative stress. A daily nitrate-free interval of 10 to 12 hours restores responsiveness. Simply increasing the dose deepens tolerance rather than fixing it. Adding a long-acting oral nitrate adds to, rather than breaks, the continuous nitrate exposure driving tolerance.

Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.