Phosphodiesterase type 5 inhibitors for erectile dysfunction

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Abstract
This is our first presentation of Great Drug Classes, and we start with a description of phosphodiesterase type 5 inhibitors and their use in erectile dysfunction. This is an in‐depth review of this class of drugs, offering the reader a description of how they work, in which conditions they may be particularly beneficial, and a comparison of the three different drugs. It is of necessity longer than the usual manuscript accepted for the BJU International, with a full list of references. The cyclic nucleotide signalling pathway mediates the smooth‐muscle relaxing effects of nitric oxide necessary for normal erectile function. Down‐regulation of this pathway is central to the pathophysiology of many forms of erectile dysfunction (ED), which is often associated with other chronic diseases (e.g. hypertension, type 2 diabetes mellitus) and treatments (e.g. certain drugs, radical prostatectomy). Conversely, selective inhibition of the enzyme that catalyses the degradation of cGMP (phosphodiesterase type 5, PDE‐5) promotes erectile responses to sexual stimulation. The successful launch and commercialization of the selective PDE5 inhibitor (PDE5I) sildenafil transformed the treatment of ED, not only by providing an effective, well tolerated oral ED therapy, but also by fostering greater candour about the problem among men. Sildenafil is highly effective in promoting erectile responses across a wide spectrum of severity and causes of ED, including patients with ED that is often refractory to treatment. The recent advent of vardenafil, which has the highest in vitro potency of all available PDE5Is, and tadalafil, which has a prolonged half‐life that may enable couples to have sexual activity with less planning, represent further advances. Other PDE5Is offering further potential improvements are under active investigation.