Sildenafil citrate, a selective phosphodiesterase type 5 inhibitor: urologic and cardiovascular implications.

Erectile dysfunction (ED) occurs in varying degrees in an estimated 20 to 30 million American men and is associated with adverse effects on quality of life; particularly personal well-being, family and social interrelationships. Research into ED has focused primarily on the physiologic mechanisms of corpus cavernosum smooth muscle relaxation, and penile erection as the end result of smooth muscle relaxation. These processes are mediated by cholinergic, nonadrenergic, noncholinergic (NANC, e.g., nitric oxide), vasoactive intestinal peptide (VIP), and potentially calcitonin gene-related peptide (CGRP) containing nerves. Release of nitric oxide following sexual stimulation from non-adrenergic, non cholinergic nerves and vascular endothelium activates guanylyl cyclase and induces intracellular cGMP synthesis. In turn, cGMP results in lowering intracellular concentrations, inhibits contractility of the penile smooth muscle, and induces an erectile response. Phosphodiesterase type 5 (PDE 5) is the predominant enzyme responsible for cGMP hydrolysis in trabecular smooth muscle. Activation of PDE 5 terminates NO-induced, cGMP-mediated smooth muscle relaxation, and subsequent penile flaccidity. Sildenafil citrate is a potent PDE type 5 reversible and selective inhibitor which blocks cGMP hydrolysis effectively. FDA approval of sildenafil citrate as the first oral agent for ED in males has resulted in significant interest. We discuss the clinical and pharmacologic properties of sildenafil citrate as well as the urologic and cardiac implications.