What interaction must be avoided when nitroglycerin is used in the presence of PDE5 inhibitors?

• A. Severe hypotension; avoid within 24-48 hours
• B. Enhanced vasodilation via cGMP
• C. No interaction
• D. Use within 12 hours

Answer: (A)

The key concept here is that combining nitrates with PDE5 inhibitors creates a dangerous drop in blood pressure due to excessive cGMP-driven vasodilation. Nitrates release nitric oxide, which boosts cGMP in vascular smooth muscle to cause dilation. PDE5 inhibitors prevent the breakdown of cGMP, so when a nitrate is present, cGMP accumulates more than normal. That synergy can lead to severe hypotension, which is why this interaction must be avoided for a period after taking a PDE5 inhibitor. In practice, the warning is to avoid nitroglycerin within about 24 to 48 hours after a PDE5 inhibitor, since residual effects can still provoke dangerous low blood pressure.