Phosphodiesterase type 5 inhibitors (PDE5Is) are the first-line drugs in the management of erectile dysfunction (ED). However, over the past two decades tremendous efforts have been made to identify new clinical uses of PDE5Is beyond their roles in ED. Areas covered: Basic science articles, clinical trials, reviews, and meta-analysis published between 1996 and 2015 were searched using MEDLINE (PubMed interface) to collect the most relevant and impactful studies from our perspectives as practicing urologists. This review mainly focuses on the level one evidence-based clinical efficacy and drug-related toxicity of oral PDE5Is. In addition, drug discovery, pharmacokinetics and pharmacodynamics, potential use in other diseases, and future directions are discussed. Expert opinion: On-demand PED5Is for the treatment of ED has shifted toward chronic administration in a broad spectrum of conditions that are thought to be associated with endovascular health. Several studies have shown that PDE5Is may play a cardioprotective or neuroprotective role. Further studies are under way to verify beneficial effects of PDE5I in non-urological conditions.
Keywords: Erectile dysfunction; pharmacology; phosphodiesterase 5 inhibitors.