Nitroglycerin with phosphodiesterase

Nitrovasodilators see Chapter 31) produce vasodilation by NO-dependent elevation of cychc GMP in vascular smooth muscle. The pharmacologic effects of sildenafil, tadalafil, and vardenafil result from inhibition of the type 5 cyclic nucleotide phosphodiesterase (PDE5) that hydrolyzes cyclic GMP to 5 GMP in the vasculature. Thus, coadministration of an NO donor e.g., nitroglycerin) with a PDE5 inhibitor can cause potentially catastrophic 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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