AB028. Current status of pharmacotherapy for erectile dysfunction

Abstract: The advent of phosphodiesterase type 5 (PDE5) inhibition as oral therapy has significantly revolutionized both clinical and basic research in the area of erectile dysfunction (ED). Much of this progress is due to a better understanding in the last three decades of the various pathophysiological and cellular mechanisms contributing to ED. Apart from the three available PDE5 inhibitors viz., sildenafil, tadalafil and vardenafil globally at the turn of this century, four other PDE inhibitors have joined the armament in recent time; these include avanafil, lodenafil, mirodenafil and udenafil. All seven PDE inhibitors are effective therapies for the treatment of ED in men. There is no significant difference among them with respect to efficacy, safety profile and tolerability. As such, good safety profiles have widened the horizon in patient choice, selectivity and efficacy. With the ease of oral administration and better patient compliance, other measures of the past, including intracavernosal injections and non-pharmacological treatments have been relegated to second-line therapy for most patients with ED. But, PDE inhibitors as first-line oral therapies are effective in about 75% of male patients diagnosed with ED. Intracavernous injection (IC) therapy with PGE1 (alprostadil) for about 10% patient-usage in general is a well-known effective and well tolerated treatment for men with ED. It is also recommended as a second line therapy for ED along with urethral and topical PGE1. Transurethral PGE1 is less effective compared to IC PGE1. Also the transurethral dosage options are 125 to 1,000 µg, while the IC dosage options are 5 to 40 µg. The topical PGE1 (300 µg in 100 mg of the cream) is also less effective compared to IC PGE1. Topical cream is not approved in many countries as yet. Other existing vasoactive agents such as papaverine, and alpha adrenergic blockers and their combinations and the ever increasing number of other agents in the pipeline including nitric oxide donors, guanylate cyclase activators, potassium channel openers and Rho-kinase inhibitors with the potential to overcome some limitations of the existing measures offer significant promise of clinical application in refractory and resistant cases. The TriMix preparations usually contain PGE1, papaverine and phentolamine in formulation compounded in pharmacies. Several clinical studies have also tested the efficacy of yohimbine, L-arginine, cyclic adenosine monophosphate activators, melanocortin-stimulating hormone analogs, endothelin antagonists in addition to vasoactive intestinal polypeptide and calcitonin gene related peptide with variable success rates. Trazodone, a serotonin antagonist and reuptake inhibitor was shown to improve premature ejaculation and erectile function in psychogenic cases of ED. Cloning of inducible nitric oxide synthase has opened a new era in the use of gene therapy for ED and the day for stem cells therapy and autologous penile tissue implants is not too far. Thus, ongoing research worldwide will continue to define new roles for various modalities targeted at specific sites in the erectile pathway and these advances will ultimately enable the clinicians to make the most appropriate therapeutic or other selections for individual patients including possible permanent reversal of organic ED.

Keywords: Pharmacotherapy; erectile dysfunction (ED); phosphodiesterase type 5 inhibition (PDE5-I)