A patient with chronic stable angina is prescribed a transdermal nitrate patch for daily prophylaxis but develops tolerance within a week. What is the most effective strategy to prevent nitrate tolerance?
- A Provide a nitrate-free interval of 8-12 hours each day ✓
- B Switch to a different organic nitrate salt
- C Add a calcium channel blocker to counteract tolerance
- D Double the nitrate dose to overcome the tolerance
Correct answer: A. Provide a nitrate-free interval of 8-12 hours each day
Explanation
Nitrate tolerance develops due to depletion of sulphydryl groups required for bioactivation to nitric oxide, and counter-regulatory neurohormonal activation. A daily nitrate-free interval of at least 8-10 hours (usually at night when angina is less frequent) allows replenishment of SH groups and reversal of tolerance. Switching to a different organic nitrate does not help since all organic nitrates share this mechanism. Doubling the dose exacerbates tolerance without restoring efficacy.
Reference: KD Tripathi, Essentials of Medical Pharmacology, 8th ed.
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Written and medically reviewed by the StethoPrep medical team.