Composition and Application of the drug Sildenafil

Clinical and pharmacological group: A drug for the treatment of erectile dysfunction. PDE5 inhibitor
Pharmaco-therapeutic group: Erectile dysfunction treatment agent, the PDE-5 inhibitor
pharmacologic effect

Selective inhibitor of acycloguanosine monophosphate (cGMP) -specific PDE5. PDE5, responsible for the breakdown of cGMP, is contained not only in the cavernous body of the penis but also in the vessels of the lungs.

Restores impaired erectile function and provides a natural response to sexual arousal. Sildenafil does not have a direct relaxing effect on the corpora cavernosa, but actively enhances the relaxing effect of nitric oxide on this tissue. With sexual arousal, the local release of NO under the influence of sildenafil leads to inhibition of PDE5 and an increase in the level of cGMP in the corpus cavernosum, resulting in relaxation of smooth muscles and increased blood flow in the corpus cavernosum.

As a PDE5 inhibitor, sildenafil increases the content of cGMP in the smooth muscle cells of the pulmonary vessels and causes them to relax. In patients with pulmonary hypertension, taking sildenafil leads to vasodilation of the lungs and, to a lesser extent, other vessels. If you want to find Sildenafil for sale you should visit erectile meds store online shop with a wide variety of ED pills with sildenafil citrate.

Sildenafil is selective for PDE5 in vitro. Its activity against PDE5 exceeds the activity against other known PDE isozymes: PDE6, which is involved in the transmission of a light signal in the retina of the eye - 10 times; PDE1 - 80 times; PDE2, PDE4, PDE7-PDE11 - more than 700 times. The activity of sildenafil against PDE5 is more than 4000 times higher than its activity against PDE3, a cAMP-specific PDE involved in cardiac contraction.

Sildenafil can cause mild and transient color discrimination (blue/green). The supposed mechanism of color vision impairment is the inhibition of PDE6, which is involved in the process of light transmission in the retina. In vitro studies have shown that the effect of sildenafil on PDE6 is 10 times less than its activity against PDE5.

Pharmacokinetics

After oral administration, sildenafil is rapidly absorbed. The absolute bioavailability averages 40% (25-63%). After a single oral administration in a dose of 100 mg, Cmax is 18 ng / ml and is achieved when taken on an empty stomach for 30-120 minutes. When taking sildenafil in combination with fatty foods, the rate of absorption decreases; Тmax increases by 60 minutes, and Cmax decreases on average by 29%. The Vd of sildenafil in an equilibrium state averages 105 liters. Sildenafil and its main circulating N-desmethyl metabolite are approximately 96% bound to plasma proteins. Protein binding is independent of the total concentration of sildenafil. Less than 0.0002% of the dose (average 188 ng) was found in semen 90 minutes after taking sildenafil.

Sildenafil for sale is metabolized mainly by the action of microsomal liver isoenzymes CYP3A4 (main pathway) and CYP2C9.

The main circulating metabolite, which is formed as a result of the N-demethylation of sildenafil, undergoes further metabolism. In terms of the selectivity of the action on PDE, the metabolite is comparable to sildenafil, and its activity against PDE5 in vitro is approximately 50% of the activity of sildenafil itself. The concentration of the metabolite in plasma is approximately 40% of that of sildenafil. N-desmethyl metabolite undergoes further metabolism; it's terminal T1 / 2 is about 4 hours.

The total clearance of sildenafil from the body is 41 l / h, and T1 / 2 in the terminal phase is 3-5 hours. After oral administration, sildenafil is excreted as metabolites mainly in the feces (approximately 80% of the dose) and to a lesser extent in the urine ( approximately 13% of the dose). You can buy sildenafil online on erectilemeds store without any risk.

In elderly patients (65 years and older), the clearance of sildenafil is reduced, and the concentration of the free active substance in the plasma is approximately 40% higher than its concentration in young (18-45 years) patients.

In renal failure mild (CC 50-80 ml/min) and moderate (CC 30-49 ml/min) severity, the pharmacokinetic parameters of sildenafil after oral administration of a single dose (50 mg) do not change. In severe renal failure (CC ≤ 30 ml/min), the clearance of sildenafil decreases, which leads to an approximately two-fold increase in AUC (100%) and Cmax (88%) compared with those in patients with normal renal function in patients of the same age group.

In patients with cirrhosis of the liver (class A and B on the Child-Pugh scale), the clearance of sildenafil decreases, which leads to an increase in AUC (84%) and Cmax (47%) compared with those with normal liver function in patients of the same age group ...

Indications of active substances of the drug Sildenafil

Treatment of erectile dysfunction characterized by an inability to achieve or maintain an erection of the penis sufficient for satisfactory intercourse.

Pulmonary hypertension.