Which drug combination should be avoided due to severe hypotension risk when used together?

• A. Nitrates with phosphodiesterase-5 inhibitors.
• B. ACE inhibitors with ARBs.
• C. Beta-blockers with calcium channel blockers.
• D. Nitrates with hydralazine.

Answer: (D)

The main idea is that some drug combos can cause dangerous hypotension because they magnify vasodilation. The classic risk is nitrates combined with phosphodiesterase-5 inhibitors (for example, nitroglycerin with sildenafil, tadalafil, or vardenafil). Nitrates trigger nitric oxide release, which increases cGMP and relaxes smooth muscle to dilate vessels. PDE-5 inhibitors prevent breakdown of cGMP, so when used with nitrates the result is an exaggerated drop in blood pressure. This combination can lead to severe hypotension, dizziness, syncope, and even ischemia if the blood pressure falls too much. So this pairing is contraindicated and patients are warned to avoid using them together. In contrast, nitrates with hydralazine is a combination sometimes used in heart failure management and is not avoided for hypotension risk; it’s monitored rather than categorically contraindicated.