A patient using a transdermal nitroglycerin patch continuously develops loss of antianginal effect within 24 to 48 hours. The accepted strategy to prevent this tolerance is:
- A Increase the patch dose progressively
- B Provide a 10 to 12 hour nitrate-free interval each day ✓
- C Add oral isosorbide mononitrate at bedtime
- D Co-administer hydralazine
Correct answer: B. Provide a 10 to 12 hour nitrate-free interval each day
Explanation
Nitrate tolerance develops with continuous exposure and is attributed to depletion of sulfhydryl groups needed for biotransformation of nitrate to nitric oxide, along with volume expansion and oxidative stress. A daily nitrate-free interval of 10 to 12 hours restores responsiveness. Adding another long-acting nitrate worsens tolerance, and hydralazine co-therapy is relevant to heart failure regimens, not patch tolerance.
Reference: Katzung's Basic and Clinical Pharmacology, 16th ed.
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