Erectile dysfunction and ED Treatment

PDE5

If you want to create a drug that increases blood flow to the penis, there are at least three ways to do it:

1. Increase the amount of nitric oxide produced in the penis
2. Increase the amount of cGMP produced in the penis in response to the nitric oxide
3. Eliminate the PDE in the penis so that the cGMP builds up instead of getting decomposed by the PDE

­Viagra uses method No. 3 — it eliminates the PDE that is decomposing the cGMP, so cGMP builds up in the penis and has a larger effect on the artery walls. The greater the amount of cGMP the greater the blood flow, and the greater the blood flow the greater the degree of the erection.

The reason that Viagra uses this technique is because of an interesting quirk of PDE.

It turns out that the human body has at least 11 different kinds of PDE that it produces. Only one of those kinds of PDE — PDE5 — is found primarily in the penis. Once scientists discovered this fact, the creation of Viagra®was relatively simple. All that Pfizer needed to find was a chemical that would selectively block PDE5 and nothing else. With the PDE5 blocked, cGMP could build up in the penis and increase the blood flow there without affecting other parts of the body.

If there were not a unique type of PDE found in the penis, we would not have Viagra today.

So how does Viagra block PDE5?

PDE5 is what is known as an enzyme. An enzyme is a specially folded protein that can speed up a chemical reaction. For example, the article How Cells Work describes the maltase enzyme. Maltase is shaped so that a maltose molecule can fit right in, and when it does, the maltase enzyme breaks the maltose molecule into two glucose molecules, as shown here:

PDE5 is an enzyme that accepts cGMP and breaks it down. Pfizer needed a chemical that would gum up PDE5 and keep it from doing its job. The chemical that Pfizer discovered is called sildenafil citrate. It fits right into the PDE5 enzyme and disables it.

Viagra contains sildenafil citrate packaged as a pill. When a man takes a Viagra pill, the sildenafil citrate flows throughout his body, but it really only affects the PDE5 enzyme in the penis. The drug stays in the bloodstream for about four hours, and then it is washed out of the blood by the liver and kidneys.

And that’s the end of the “how viagra works” for Penis and somemen:

• A man takes a Viagra pill.
• The sildenafil citrate enters his bloodstream and flows throughout his body.
• The sildenafil citrate attaches to the PDE5 enzyme in his penis and disables most of it.
• When the man becomes sexually aroused, the brain sends the normal message to the NANC cells in his penis, which produce nitric oxide as usual.
• The nitric oxide creates cGMP, which starts relaxing the arteries in his penis.
• Since the PDE5 has been disabled, the cGMP in the penis does not break down. Instead, it builds up and lets the arteries in the penis fully dilate.
• His penis inflates with blood, and the man gets a full erection.

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.

PDE5 inhibitors are clinically indicated for the treatment of erectile dysfunction. Sildenafil citrate, 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.

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).