Continuous transdermal nitroglycerin leads to loss of antianginal effect within 24 to 48 hours. Which prescribing strategy prevents this tolerance?

• A Providing a nitrate-free interval of 10 to 12 hours daily ✓
• B Doubling the patch dose every 48 hours
• C Adding a low-dose calcium channel blocker at bedtime
• D Switching to sublingual nitroglycerin used three times daily without interruption

Explanation

Nitrate tolerance develops rapidly with continuous exposure and is attributed to depletion of sulfhydryl groups needed for biotransformation to nitric oxide, along with oxidative stress and volume expansion. B daily nitrate-free interval of 10 to 12 hours restores responsiveness. Simply escalating the dose (option B) does not reverse tolerance, and uninterrupted frequent dosing of any nitrate formulation produces the same problem. This scheduling principle applies equally to patches and oral isosorbide preparations.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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