Phosphodiesterase Inhibitor

Question 1

Sildenafil

Answer 1

• Atrial and brain natriuretic peptides (ANP and BNP) are polypeptide hormones that exert their effect by binding ANP receptors.
• These transmembrane receptors are linked to a guanylyl cyclase that converts guanosine 5′-triphosphate to cyclic guanosine 3′,5′-monophosphate (cGMP)
• cGMP then activates a downstream cGMP-dependent protein kinase, leading to relaxation of vascular smooth muscle and subsequent vasodilation
• Nitric oxide activates the same cGMP second messenger system by binding a cytosolic guanylyl cyclase.
• Penile erection is initiated by release of acetylcholine and nitric oxide (NO) from parasympathetic fibers, leading to a rise in intracellular cGMP and vasodilation of the arteries supplying the corpus cavernosum
• PDE inhibitor that decreases degradation of cgmp enhancing the effect of parasympathetic activation in erectile tissue
• because vasodilatory nitrates (NTG,ISMN) work by releasing NO, coadministration of sildenafil with nitrates can lead to excessive CGMP- induced vasodilation and severe hypotension