Nitrates, organic with phosphodiesterase

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... 

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. 

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. 

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