by Agent G

Created on: July 23, 2009

Sildenafil is the pharmaceutical name of a prescription medication used for both erectile dysfunction (ED) and pulmonary arterial hypertension (PAH). Sildenafil is marketed by Pfizer in the United States under the brand names Viagra when prescribed for ED and Revatio when prescribed for PAH. Sildenafil is the number one selling drug for ED in the world

Sildenafil for ED

The physiologic mechanism of erection of the penis involves release of nitric oxide (NO) in the corpus cavernosum during sexual stimulation. NO then activates the enzyme guanylate cyclase, which results in increased levels of cyclic guanosine monophosphate (cGMP), producing smooth muscle relaxation in the corpus cavernosum and allowing inflow of blood-resulting in an erection. Men who suffer from ED often have too much phosphodiesterase type 5 (PDE5) present.

Sildenafil helps prevent ED by selectively inhibiting cGMP-specific (PDE5) which is responsible for degradation of cGMP in the corpus cavernosum and thereby enhancing the effect of NO. When sexual stimulation causes local release of NO, inhibition of PDE5 by sildenafil causes increased levels of cGMP in the corpus cavernosum, resulting in smooth muscle relaxation and inflow of blood to the corpus cavernosum. Sildenafil at recommended doses has no effect in the absence of sexual stimulation.

Sildenafil belongs to a class of oral PDE5 inhibitors that treat ED that all have a similar mechanism of action. These agents include tadalafil (Cialis) and vardenafil (Levitra). While the mechanism action of these agents are similar to sildenafil they differ in duration and efficacy.

Sildenafil for PAH

Using the same mechanism of action, sildenafil is indicated for the treatment of PAH to improve exercise ability and delay clinical worsening. An oral dose of sildenafil increases cGMP within pulmonary vascular smooth muscle cells resulting in relaxation. In patients with pulmonary hypertension, this can lead to vasodilation of the pulmonary vascular bed and, to a lesser degree, vasodilatation in the systemic circulation

What is PAH?

Pulmonary arterial hypertension is a progressive, life-threatening disease that occurs when the pulmonary arteries (the arteries that connect the heart to the lungs) become constrained. This constriction inhibits blood flow to the lungs and increases strain on the heart causing the patient to become short of breath, fatigued, and experience chest pain. Untreated PAH may result in death. PDE5 inhibitors need to be taken daily in order to maintain proper blood flow between the heart and the lungs.

References

Revatio Prescribing Information. Pfizer. New York, New York. May 2009.

Viagra Prescribing Information. Pfizer. New York, New York. October 2007.

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