PDE5 inhibitor

# Overview
A phosphodiesterase type 5 inhibitor, often shortened to PDE5 inhibitor, is a drug used to block the degradative action of phosphodiesterase type 5 on cyclic GMP in the smooth muscle cells lining the blood vessels supplying the corpus cavernosum of the penis. These drugs are used in the treatment of erectile dysfunction, and were the first effective oral treatment available for the condition. Because PDE5 is also present in the arterial wall smooth muscle within the lungs, PDE5 inhibitors have also been explored for the treatment of pulmonary hypertension, a disease in which blood vessels in the lungs become abnormally narrow.

# Indications
PDE5 inhibitors are clinically indicated for the treatment of erectile dysfunction. Sildenafil, one of the PDE5 inhibitors, is also indicated for the treatment of pulmonary hypertension, and the chemically related drugs tadalafil and vardenafil have been studied as other possible treatments for this disease.
Sildenafil, the prototypical PDE5 inhibitor, was originally discovered during the search of a novel treatment for angina. Recent studies are exploring its potential for increasing neurogenesis after stroke.

# Contraindications
PDE5 inhibitors are contraindicated in those taking nitrate medication. They are also contraindicated in men for whom sexual intercourse is inadvisable due to cardiovascular risk factors.

# Adverse reactions
The occurrence of adverse drug reactions (ADRs) with PDE5 inhibitors appears to be dose related. Headache is a very common ADR, occurring in >10% of patients. Other common ADRs include: dizziness, flushing, dyspepsia, nasal congestion or rhinitis.
On October 18, 2007, the FDA announced that a warning about possible sudden hearing loss would be added to drug labels of PDE5 inhibitors.
Other ADRs and their incidence vary with the agent and are listed in their individual pages.

# Drug interactions
PDE5 inhibitors are primarily metabolised by the cytochrome P450 enzyme CYP3A4. The potential exists for adverse drug interactions with other drugs which inhibit or induce CYP3A4, including HIV protease inhibitors, ketoconazole, itraconazole, and other anti-hypertensive drugs such as Nitro-spray (due to its capacity to diminish blood pressure).

# Examples
Sildenafil was the prototypical member of the PDE5 inhibitors. Two other agents, with their own advantages/disadvantages, are also available, and several other are in development.
- sildenafil
- tadalafil
- vardenafil

# Mode of action
Part of the physiological process of erection involves the release of nitric oxide (NO) in vasculature of the corpus cavernosum as a result of sexual stimulation. NO activates the enzyme guanylate cyclase which results in increased levels of cyclic guanosine monophosphate (cGMP), leading to smooth muscle relaxation in blood vessels supplying the corpus cavernosum, resulting in increased blood flow and an erection.
PDE5 inhibitors inhibit the degradation of cGMP by phosphodiesterase type 5 (PDE5), increasing bloodflow to the penis during sexual stimulation.
This mode of action means that PDE5 inhibitors are ineffective without sexual stimulation.

# Notes
-  Zhang, R. et al. Sildenafil (Viagra) induces neurogenesis and promotes functional recovery after stroke in rats. Stroke 33, 267580 (2002)
-  Jump up to: 2.0 2.1 2.2 Rossi S, editor. Australian Medicines Handbook 2006. Adelaide: Australian Medicines Handbook; 2006.
-  "FDA Announces Revisions to Labels for Cialis, Levitra and Viagra". Food and Drug Administration..mw-parser-output cite.citation{font-style:inherit}.mw-parser-output q{quotes:"\"""\"""'""'"}.mw-parser-output code.cs1-code{color:inherit;background:inherit;border:inherit;padding:inherit}.mw-parser-output .cs1-lock-free a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-limited a,.mw-parser-output .cs1-lock-registration a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-lock-subscription a{background:url("")no-repeat;background-position:right .1em center}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration{color:#555}.mw-parser-output .cs1-subscription span,.mw-parser-output .cs1-registration span{border-bottom:1px dotted;cursor:help}.mw-parser-output .cs1-hidden-error{display:none;font-size:100%}.mw-parser-output .cs1-visible-error{display:none;font-size:100%}.mw-parser-output .cs1-subscription,.mw-parser-output .cs1-registration,.mw-parser-output .cs1-format{font-size:95%}.mw-parser-output .cs1-kern-left,.mw-parser-output .cs1-kern-wl-left{padding-left:0.2em}.mw-parser-output .cs1-kern-right,.mw-parser-output .cs1-kern-wl-right{padding-right:0.2em}