Sildenafil

Sildenafil citrate is a drug used to treat male erectile dysfunction as well as pulmonary arterial hypertension (PAH). It is marketed under the names Viagra and Revatio, developed by Pfizer. Other pharmaceutical companies have also developed similar drugs to treat impotence and these are tadalafil (brand name Cialis) and vardenafil (Levitra). Tadalafil is in the clinical trial stages of treating pulmonary arterial hypertension.

Structure of Sildenafil

Discovery

Sildenafil was originally researched for use in treating hypertension and angina pectoris but was found to have little effect on angina, instead inducing penile erections. Due to this discovery, Pfizer decided to market sildenafil primarily for erectile dysfunction, but it was also released onto the market to treat PAH under another name – Revatio. It was approved by the FDA for use in 1998 and became the first pill to be approved for erectile dysfunction in the United States.

How it works

Viagra and Revatio work by relaxing the blood vessels in the penis and lungs respectively to increase blood flow in these areas. Revatio is used to improve the ability to exercise in people with PAH. Sildenafil acts as a selective inhibitor of cGMP specific phosphodiesterase type 5 (PDE5) which breaks down cGMP in the corpus cavernosum (erectile tissue) of the penis. cGMP is cyclic guanosine monophosphate released when NO binds to the enzyme guanylate cyclase, causing vasodilation in the corpus cavernosum leading to increased blood flow. Sildenafil has a similar structure to cGMP and can bind with the PDE5 leaving more cGMP for better erections. However, sildenafil should only work when there is sexual stimulation as the NO/cGMP system would not otherwise be activated^[1]. Revatio on the other hand works by relaxing the arterial wall, decreasing pulmonary arterial resistance and pressure. This then reduces the stress on the right ventricle of the heart and reduces right-sided heart failure.

Sildenafil is removed from the body by being broken down in the liver. Hepatic cytochrome p450 enzymes metabolise sildenafil to N-desmethylated sildenafil which is further metabolised. It is then excreted by the kidneys^[2].

Side effects

Sildenafil may cause some side effects, common ones include^[3] :

headache
heartburn
dizziness
difficulty falling asleep
muscle aches
sensitivity to light
changes in colour vision

Other more serious but less common side effects include priapism, hypotension, chest pains, and in some cases, strokes^[4].

Other uses

Recently, Sildenafil has been found to be useful in treating high altitute pulmonary edema in mountain climbers. It has also been used as a recreational drug, where users mix Viagra with ecstasy.

Research is still being done on sildenafil treating lower urinary tract symptoms (LUTS) and shows much promise as in theory it is thought that sildenafil relaxes the bladder neck/prostate smooth muscle.

Also, a National Institute of Health trial is currently underway to treat sickle cell anemia using sildenafil. It is hoped that sildenafil plus hydroxyurea will increase fetal haemoglobin in the patients blood by increasing the production of NO and hence prevent red blood cells from sickling^[5].

Nonreputable alternatives

Sildenafil is available by prescription from a doctor. However, the name Viagra is now so familiar, that it is easily available online. Users only have to fill in a web questionnaire (something like a web consultation) and be able to get it within a few days. It is advised not to trust such websites as many fake aphrodisiacs are now available. Some even claim to be the "herbal viagra" - a mixture of herbs and sildenafil. Taking this "fake viagra" could cause a life-threatening decrease in blood pressure especially in patients with diabetes, hypertension or other heart diseases as sildenafil interacts with nitrate-based prescription drugs used to treat chest pains^[5].