Which statement describes the interaction between nitrates and PDE-5 inhibitors like sildenafil?

• A. Sildenafil has no interaction
• B. Sildenafil inhibits PDE-5; prevents breakdown of cGMP; severe hypotension with nitrates
• C. Sildenafil reduces nitrate tolerance
• D. Sildenafil enhances nitrates' effect without risk

Answer: (B)

The interaction being tested is that nitrates and PDE-5 inhibitors can cause dangerous, life‑threatening hypotension because they both amplify the same NO–cGMP pathway. Nitrates release nitric oxide, which activates soluble guanylate cyclase and raises cGMP in vascular smooth muscle, leading to vasodilation and lower blood pressure. PDE-5 inhibitors block the breakdown of cGMP, so cGMP stays around longer and its vasodilatory effect is amplified. When these are used together, cGMP can accumulate to a level that drops blood pressure severely, potentially causing fainting, chest pain, or ischemia due to reduced coronary perfusion. This is why the combination is contraindicated, and a washout period is recommended: avoid nitrates for at least 24 hours after sildenafil and about 48 hours after tadalafil. Statements suggesting no interaction or that there’s no risk are not correct.