Which medication class is contraindicated with PDE-5 inhibitors due to risk of hypotension?

• A. Beta-blockers
• B. ACE inhibitors
• C. Nitrates
• D. Calcium channel blockers

Answer: (C)

The main idea here is a dangerous interaction between two types of vasodilators that boost nitric oxide signaling. PDE-5 inhibitors work by blocking the breakdown of cGMP, the molecule that relaxes vascular smooth muscle, so they enhance vasodilation. Nitrates provide an external source of nitric oxide, which also raises cGMP. When these two are used together, they produce a synergistic drop in blood pressure that can be severe and life‑threatening, leading to dizziness, fainting, or even heart problems. That is why nitrates are contraindicated with PDE-5 inhibitors.

Other drug classes listed can lower blood pressure or interact additively with PDE-5 inhibitors, but they do not carry the same universal contraindication. You might monitor or adjust therapy if these are used in combination, but they’re not categorically avoided like nitrates are with PDE-5 inhibitors.