A patient with chronic stable angina reports that his sublingual nitroglycerin no longer provides adequate pain relief despite taking it regularly throughout the day. Which pharmacological strategy best prevents nitrate tolerance?
- A Administering a higher continuous dose
- B Providing a 10 to 12 hour nitrate-free interval ✓
- C Adding a beta-blocker
- D Switching to a calcium channel blocker
Correct answer: B. Providing a 10 to 12 hour nitrate-free interval
Explanation
Continuous nitrate exposure leads to tolerance, primarily due to neurohormonal activation and free radical generation. The standard strategy to prevent this is a daily nitrate-free interval of 10 to 12 hours, typically overnight, to restore vascular responsiveness. Increasing the dose does not overcome tolerance and only increases the risk of side effects.
Reference: Goodman and Gilman's The Pharmacological Basis of Therapeutics, 14th ed.
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