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Nitrate-PDE5 Inhibitor Interaction — EECC MCQ

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EasyCardiac PharmacologyNitrate-PDE5 Inhibitor InteractionEECC

A 60-year-old man with stable angina is treated with sublingual GTN for symptom relief. He is also taking sildenafil for erectile dysfunction. What is the critical interaction?

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Correct answer: C — Nitrates (GTN, ISDN, ISMN) are absolutely contraindicated with PDE5 inhibitors (sildenafil, tadalafil, vardenafil) due to synergistic vasodilation causing potentially fatal hypotension; a 24-48 hour washout is required

Nitrates donate nitric oxide (NO), which activates guanylyl cyclase to increase intracellular cGMP, causing smooth muscle relaxation and vasodilation. PDE5 inhibitors (sildenafil, tadalafil, vardenafil) inhibit the breakdown of cGMP. Combined use produces synergistic and potentially fatal vasodilation with profound hypotension. This is an ABSOLUTE contraindication. Timing: nitrates must not be given within 24 hours of sildenafil/vardenafil use, or 48 hours of tadalafil use (longer half-life). If a patient on a PDE5 inhibitor develops ACS requiring nitrate therapy, alternative anti-anginals (beta-blockers, calcium channel blockers) should be used. If severe hypotension occurs from this interaction, treatment includes IV fluids, phenylephrine (alpha-agonist), and Trendelenburg positioning.

Reference: BNF; ESC (2024): CCS Guidelines