SILDENAFIL CITRATE

12.1 Mechanism of Action The physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. NO then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood. Sildenafil enhances the effect of NO by inhibiting phosphodiesterase type 5 (PDE5), which is responsible for degradation of cGMP in the corpus cavernosum. Sildenafil has no direct relaxant effect on isolated human corpus cavernosum. When sexual stimulation causes local release of NO, inhibition of PDE5 by sildenafil causes increased levels of cGMP in the corpus cavernosum, resulting in smooth muscle relaxation and inflow of blood to the corpus cavernosum. Sildenafil at recommended doses has no effect in the absence of sexual stimulation. Binding Characteristics Studies in vitro have shown that sildenafil is selec

Contraindications

• • 4 CONTRAINDICATIONS Administration of sildenafil tablets to patients using nitric oxide donors
• • such as organic nitrates or organic nitrites in any form. Sildenafil tablets was shown to potentiate the hypotensive effect of nitrates ( 4.1
• • 7.1
• • 12.2 ) Known hypersensitivity to sildenafil or any component of tablet ( 4.2 ) Administration with guanylate cyclase (GC) stimulators
• • such as riociguat ( 4.3 ) 4.1 Nitrates Consistent with its known effects on the nitric oxide/cGMP pathway [ see Clinical Pharmacology (12.1