Sildenafil with organic nitrates

Erectile dysfunction is a frequently encountered problem whose risk factors parallel those of coronary artery disease. Thus, many men desiring therapy for erectile dysfunction already may be receiving (or may require, especially if they increase physical activity) antianginal therapy. The combination of sildenafil and other phosphodiesterase 5 (PDE5) inhibitors with organic nitrate vasodilators can cause extreme hypotension. 

The phosphodiesterase type-5 inhibitors potentiate the hypotensive effects of nitrates in a proportion of patients, which might re-suit in potentiaiiy serious hypotension or even precipitate myocardiai infarction. Therefore, the concurrent use of sildenafil, tadalafil or vardenafil with organic nitrates (glyceryl trinitrate (nitroglycerin), isosorbide dinitrate, isosorbide mononitrate, etc.) is contraindicated. The concurrent use of nicorandil and all phosphodiesterase type-5 inhibitors is also contraindicated. 

Vasodilators are a group of dtugs, which relax the smooth muscle cells of the blood vessels and lead to an increased local tissue blood flow, a reduced arterial pressure and a reduced central venous pressure. Vasodilators reduce the cardiac pre-load as well as after-load and thereby reduce cardiac work. They are used in a variety of conditions including hypertension, cardiac failure and treatment/prevention of angina pectoris. Major groups are Ca2+-channel blockers (e.g. dihydropyridines), NO-donators (e.g. organic nitrates), K+-channel openers (minoxidil), phosphodiesterase inhibitors (e.g. sildenafil), Rho-kinase inhibitors (e.g. Y27632) or substances with unknown mechanism of action (e.g. hydralazine). Inhibitors of the... 

Webb DJ, Freestone S, Allen MJ, et al. Sildenafil citrate and blood-pressure-lowering drngs results of dmg interaction studies with an organic nitrate and a calcium antagonist. Am J Cardiol 1999 83 21C-28C. 

Sildenafil is contraindicated in patients who are taking organic nitrates, for their metabolism is blocked and severe and acute hypotension result. Patients with recent stroke or myocardial infarction or whose blood pressure is known to be < 90/50 mmHg should not use it. Sildenafil is a substrate for the P450 isoenzyme CYP3A4 (and to a lesser extent CYP2C9) which gives scope for interaction with inhibitors or inducers of this system. The metabolic inhibitors erythromycin, saquinavir and ritonavir (protease inhibitors used for AIDS), and cimetidine, for example, produce substantial rises in the plasma concentration of sildenafil. 

The combination of organic nitrates and sildenafil citrate (Viagra) can precipitate life-threatening hypotension in patients with angina (112). Sildenafil is a selective inhibitor of cyclic GMP-specific phosphodiesterase type 5, which causes smooth muscle relaxation and vasodilatation, and is an effective treatment for male erectile dysfunction. More than 3.6 million prescriptions have been issued as of August 1998, and so far there have been 69 deaths, 12 of which were attributable to the interaction with nitrates, as reported to the FDA. 

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