PDE5 Inhibitors: A New Tool In The Hands Of Urologists

Main Category: Urology / Nephrology
Article Date: 27 Jun 2008 - 9:00 PDT

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ORLANDO, FL (UroToday.com) - Professor Montorsi gave the SIU lecture on PDE5 inhibitors. He discussed the molecular mechanisms of PDE5 inhibitors. The nitric oxide pathway was reviewed. PDE5 inactivates cGMP to 5'-GMP. The effects of PDE5 inhibitors last beyond their half-lives, suggesting a cellular memory effect. This may be due to other phosphorylation actions or retention in the vascular tissues. The concentration of PDE5 inhibitors over time changes due to binding to other molecules in the cell. In a rat model, sildenafil treatment resulted in upregulation of muscarinic receptors. He showed that daily dosing in clinical trials supports these observations.

PDE5 inhibitors are used for other problems such as BPH are reported. NOS levels are decreased in the prostate and this is also mediated by Rho-kinase and PDE5 inhibitors can change this. PD5 is also found at high levels in the bladder. Thus 3 clinical trials were performed, but while symptoms improved, flow-rates did not.

PDE5 inhibitors are also used in the treatment of priapism. Nitrous oxide (NO) bioactivity is downregulated and cGMP is not degraded and accumulates in tissues. Treating priapism patients with daily morning low-dose PDE5 inhibitors decreased episodes of priapism in 6 of the 7 pilot patients studied.

For premature ejaculation, 83% of clinical trials have shown benefit. The combination of paroxitene with sildenafil was superior to paroxitene alone. There are some limitations to the study designs, but this treatment may improve patient outcomes.

Regarding infertility, PDE5 inhibitors improve sperm motility but causes premature acromsome reaction. Sildenafil improved motility, while tadalafil decreased the motility. The different PDE5 inhibitors have not been compared in a prospective, randomized fashion and the doses used were high. The endpoint of live births was not used.

He also mentioned that sildenafil may provide benefit to women with sexual dysfunction, but this is not yet clearly known.

PDE5 inhibitors can have side effects that must be understood.

Presented by Francesco Montorsi, MD, at the Annual Meeting of the American Urological Association (AUA) - May 17 - 22, 2008. Orange County Convention Center - Orlando, Florida, USA.

Reported by UroToday.com Contributing Editor Christopher P. Evans, MD, FACS

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