Sildenafil belongs to a group of chemicals known as phosphodiesterase inhibitors, which are responsible for dilating blood vessels and reducing blood pressure. Over the years, sildenafil and its compounds been used to improve exercise ability and reducing clinical disease progression in patients with Pulmonary Arterial Hypertension (PAH).
Normally marketed under several trade names, Viagra as the most common used to treat erectile dysfunction, the oral formulation of sildenafil is a citrate salt of the compound Revatio (marketed by Pfizer). Known chemically as 1-[[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo [4,3-d] pyrimidin-5-yl)-4-ethoxyphenyl] sulfonyl]-4-methylpiperazine citrate, Revatio works by preventing the degradation of cyclic guanosine monophosphate (cGMP) in the lungs, which in turn releases the pressure off the right side of the heart, improving blood-flow.
How Revatio (Sildenafil citrate) Works
Phosphodiesterase (PDE) comprise a group of enzymes that including the common PDE5 that are distributed evenly along the arterial walls and smooth muscle cells across the lungs. Sildenafil works by inhibiting cGMP-specific phosphodiesterase type 5 (PDE5), which is responsible for hydrolysis in cGMP. Revatio blocks the catalytic sites of PDE5, which are responsible for binding to cGMP, by binding itself to those sites. This prevents metabolic breakdown of cGMP and increases its amount in the blood, ensuring regulation of calcium ion-channels and balancing calcium levels in the cytosol. Eventually, the process causes relaxation of the arterial muscles, reduction of arterial pressure, vasodilation and restoration of the normal blood-flow in and out of the heart.
Revatio (Sildenafil citrate) Clinical Trials
Revatio was first approved by the FDA for treatment of patients with PAH in June 2005. Later, in November 2009, the FDA approved Pfizer’s intravenous form. The approvals followed after a series of successful clinical trials with data suggesting the positive effects of the drug on PAH patients in improving their exercising abilities and slowing the rate of disease progression. However, in August 2012, the FDA ruled against using Revatio in children.
Dosage for Revatio ranges from 5mg to 20mg, depending on the patient’s condition and severity; three times daily, taken orally, at least 4-6 hours apart. If the patient is unable to consume the drug orally, doses from 2.5mg to 10mg can be administered via the intravenous route; three times daily then possibly increased per expert advice. Revatio may or may not be used in combination with other vasodilators, but clinical trials have not determined any significant improvement when used in combination therapy. Patients with other ailments like heart disease, renal or hepatic failure or bleeding disorders, should refrain from using the drug without expert opinion. Common adverse effects for Rveatio include flushing, redness, irritation, headache, dizziness, muscle pain and stomach upsets. If severe adverse effects that inlcude allergic reaction, convulsions, hearing loss, or edema occur, a doctor should be called immediately.
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