Final answer:
The major concern about drug interactions with nitrates is severe hypotension when taken with PDE inhibitors like sildenafil, which can lead to cardiovascular collapse and other serious health issues.
Step-by-step explanation:
A major concern about drug interactions with nitrates is the risk of severe hypotension (low blood pressure) when nitrates are taken in combination with phosphodiesterase inhibitors (PDE inhibitors), such as sildenafil (Viagra). Nitrates, like nitroglycerin, are used to treat heart conditions by releasing nitric oxide (NO), which causes vasodilation and restores blood flow to the heart. However, PDE inhibitors also promote vasodilation by stopping the degradation of cGMP, a molecule that helps dilate blood vessels. When combined, these two types of drugs can cause an excessive drop in blood pressure, leading to cardiovascular collapse and other serious health complications. Deaths have been reported in patients with cardiac disease who were taking nitrates and also used PDE inhibitors, highlighting the danger of this interaction.