thumb|Chemical structure of [[sildenafil (Viagra), the prototypical PDE5 inhibitor]]
A phosphodiesterase type 5 inhibitor (PDE5 inhibitor) is a vasodilating drug that works by blocking the degradative action of cGMP-specific phosphodiesterase type 5 (PDE5) on cyclic GMP in the smooth muscle cells lining the blood vessels supplying various tissues. These drugs dilate the corpora cavernosa of the penis, facilitating erection with sexual stimulation, and are used in the treatment of erectile dysfunction (ED). Sildenafil was the first effective oral treatment available for ED. Because PDE5 is also present in the smooth muscle of the walls of the arterioles within the lungs, two PDE5 inhibitors, sildenafil and tadalafil, are FDA-approved for the treatment of pulmonary hypertension. As of 2019, the wider cardiovascular benefits of PDE5 inhibitors are being appreciated.
Medical uses
Phosphodiesterase-5 (PDE5) inhibitors such as sildenafil (Viagra), tadalafil (Cialis), vardenafil (Levitra), and avanafil (Stendra) are clinically indicated for the treatment of erectile dysfunction. Sildenafil and tadalafil are also indicated for the treatment of some subtypes of pulmonary hypertension, while tadalafil is also licensed for the treatment of benign prostatic hyperplasia.
Sildenafil, the prototypical PDE5 inhibitor, was originally discovered during the search of a novel treatment for angina. Studies in 2002 explored its potential for increasing neurogenesis after stroke, but clinical evidence for benefit in cerebrovascular diseases is currently lacking. PDE5 inhibitors are also contraindicated in patients with previous nonarteritic anterior ischaemic optic neuropathy and hereditary eye diseases. Back pain and muscle aches are also more common in patients taking tadalafil.
Since 2007 there has been evidence to suggest that PDE5 inhibitors can cause an anterior optic neuropathy, although the absolute risk increase is small. PDE5 inhibitors do not interact synergistically with other antihypertensive drugs. In 1986, Pfizer scientists at Sandwich, UK, started preclinical work on the development of a PDE5 inhibitor (later known as sildenafil citrate) for the treatment of angina.
Sildenafil, tadalafil, vardenafil and avanafil are the main agents marketed globally, although simmerafil, mirodenafil, udenafil, , and lodenafil are available in some countries.
Although all PDE5 inhibitors share the same mechanism of action, each agent has different pharmacokinetics and pharmacodynamics which affect how quickly it acts, how long its effects last, and its side effects. However, PDE5 inhibitors do not cause erections without sexual stimulation.
As well as their haemodynamic effects, PDE5 inhibitors have also been shown to have anti-inflammatory, antioxidant, antiproliferative, and metabolic properties in several experiments.