Final answer:
Concurrent use of nitrates and phosphodiesterase inhibitors like sildenafil is contraindicated, especially in patients with cardiac conditions due to the risk of severe hypotension. Sildenafil, initially investigated for heart conditions, was found effective for ED and is widely used, but its combination with nitrates can be life-threatening.
Step-by-step explanation:
Drug Interaction Between Nitrates and Phosphodiesterase Inhibitors
The concurrent use of nitrates and phosphodiesterase inhibitors, such as tadalafil and sildenafil, used for erectile dysfunction (ED) and pulmonary hypertension, is absolutely contraindicated. Nitric oxide (NO) released in the body acts as a ligand to induce relaxation of smooth muscles in the vasculature, including penile arteries, facilitating vasodilation and erection. However, phosphodiesterase type 5 (PDE5) inhibitors, which are designed to enhance this process and improve blood flow for treating ED, can lead to dangerously low blood pressure when taken with nitrates that also increase NO levels and promote vasodilation. This is particularly dangerous for individuals with cardiac disease taking nitrates, as this combination has been associated with reported fatalities.
In the 1990s, clinical trials for sildenafil as a treatment for hypertension and angina showed unsatisfactory results for heart conditions but led to the discovery of its effectiveness in treating ED. This led to the approval of sildenafil, marketed as Viagra®, which alongside similar drugs, now represents a significant market in ED treatments. Despite their effectiveness, their interaction with nitrates is hazardous and thus should be avoided by at-risk individuals, which include those suffering from cardiac conditions and using nitrate medication.