Sildenafil citrate for pulmonary hypertension

Sildenafil is a drug used to treat two separate and distinct conditions: pulmonary hypertension and erectile dysfunction. These conditions are not otherwise associated with one another, and having one does not necessarily place you at increased risk of developing the other.

What is pulmonary hypertension?

Pulmonary hypertension refers to a condition where there is increased blood pressure (hypertension) in the pulmonary (lung) arteries. Do note that pulmonary hypertension is different to hypertension, which just means high blood pressure, and they are managed differently. Pulmonary hypertension (PH) is a life-threatening illness, in which the tiny arteries in your lungs become narrowed, blocked or destroyed, thereby raising pressure in the blood vessels of the lungs. Because of the heart and lungs’ anatomy, increased blood pressure in the lungs places increased pressure on the right-sided chambers of the heart, which can cause heart failure.

What are the causes?

Causes of PH include certain diseases of the lung and the heart.

Fibrosis, or interstitial lung disease, is a condition where the lungs become scarred. These stiffened lungs can cause decreased compliance of the pulmonary arteries thereby causing PH. Fibrosis can be caused by chronic exposure to certain allergens or chemicals (such as asbestos), blood clots in the lung, autoimmune conditions such as rheumatoid arthritis, scleroderma, and a number of other conditions.

Heart conditions include congenital heart disease, and conditions related to the left side of the heart, including mitral valve, aortic valve and left ventricular conditions.

Certain medications, HIV and sickle cell disease may also cause PH.

How it’s treated

For pulmonary arterial hypertension, there are 5 classes of drugs now available. These are endothelin receptor antagonists, soluble guanylate cyclase stimulators, prostacyclin analogues, prostacyclin receptor agonists, and phosphodiesterase-5 inhibitors. For chronic thromboembolic pulmonary hypertension, there is surgical removal of obstructing clots is the treatment of choice, or, for patients not suitable for surgery, a drug called riociguat, which is a stimulator of soluble guanylate cyclase. For patients with pulmonary hypertension due to left-sided heart disease or lung disease, prostacyclins, endothelin receptor antagonists, phosphodiesterase-5 inhibitors and guanylate cyclase stimulators have all been tried, with mixed results. A standard of care has yet to emerge.

Normally, blood vessels can open (dilate) to decrease blood pressure. This is managed biochemically by release into the bloodstream of nitric oxide and other cellular messengers, like cGMP.

A regulatory enzyme called PDE-5 reverses that process.

Sildenafil, one of the PDE-5 inhibitor drugs, keeps arteries as dilated as possible, maximising blood flow.

Other classes of drugs work in other ways, targeting different pathways, notably those involving endothelin and prostacyclin.

The bottom line

ED and PH are two separate and distinct conditions. Because of the similarity in the microscopic structure of the arteries of the penis and pulmonary arteries, both of these conditions are known to respond to sildenafil therapy.