Daily administration of phosphodiesterase type 5 inhibitors for urological and nonurological indications

Objectives: Although the discovery of phosphodiesterases (PDEs) was made soon after the identification of cyclic adenosine monophosphate nearly half a century ago, their true importance in medicine has taken many decades to be realised. The recognition of the important role PIDE enzymes play and the impact of altering intracellular cyclic nucleotide levels became significant for most urologists and clinicians in the early 1990s with the discovery of sildenafil, a PDE5 inhibitor (PDE5-I). Once approved around the world, on-demand use of PDE5-Is became the gold standard. Recently, the potential beneficial effects of PDE5-Is on the pulmonary, vascular, and other systems has led to examination of alternative dosing regimens. In this review, we have synthesised the available published peer-reviewed literature to provide a critical contemporary view of evolving indications for PDE5-Is and how alternative dosing regimens may impact on sexual and other functions. Methods: MEDLINE search of all peer-reviewed English literature for the period 1990-2007. Results: The plethora of articles detailing potential uses of PDE5-1 in multiple fields of medicine was uncovered. Use of alternative dosing regimens shows great promise across a number of clinical indications, including post-radical retropubic prostatectomy, pulmonary hypertension, endothelial dysfunction, and salvage of on-demand PDE5-1 nonresponders. Conclusions: Use of PDE5-1 on a daily basis may evolve into a major form of drug administration both for men with erectile dysfunction and for those with a myriad of other conditions shown to benefit from this approach.