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Nitrate Tolerance — EECC MCQ

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EasyCardiac PharmacologyNitrate ToleranceEECC

A 65-year-old man with stable angina on isosorbide mononitrate 60 mg modified-release daily reports that the medication initially provided excellent symptom relief but over the past 4 weeks has become less effective. He takes his tablet every morning at 8 AM. What is the most likely cause and solution?

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Correct answer: C — Nitrate tolerance; introduce a daily nitrate-free interval

Nitrate tolerance is a well-recognised phenomenon where continuous nitrate exposure leads to diminished efficacy within 24-48 hours, mediated by oxidative stress, neurohormonal activation, and depletion of sulfhydryl groups. The solution is to ensure a nitrate-free interval of 10-14 hours daily (typically overnight). For ISMN MR, this is achieved by once-daily morning dosing (which inherently provides a nitrate-free interval overnight). If the patient is also using GTN patches or short-acting nitrates that eliminate the free interval, these should be adjusted. Adding a second daily dose would worsen tolerance, not improve it. This is a pharmacological concept, not disease progression. Apply this conclusion only to the clinical circumstances stated, with appropriate specialist review, contraindication checks, shared decision-making and follow-up. Reassess if the physiology, treatment response or competing risk changes. The competing options would require a different haemodynamic profile, diagnosis, procedural indication or risk balance from the one described here.

Reference: BNF; ESC (2024): Guidelines for the Management of Chronic Coronary Syndromes: https://www.nice.org.uk/guidance/ng109/chapter/recommendations