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Viagra is a new oral medication for the treatment of erectile dysfunction. He restores impaired erectile function and provides a natural response to sexual stimulation.
The physiological mechanism of erection of the penis involves release of nitric oxide (NO) in the cavernous body during sexual stimulation. Does viagra really work activates the enzyme guanylate cyclase, which leads to increased levels of cyclic guanosine monophosphate (cGMP), relaxation of corpus cavernosum smooth muscle and increase blood flow to the penis.
Sildenafil is a potent and selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5), which is responsible for the breakdown of cGMP in the cavernous body. Viagra has a peripheral effect on erections. Sildenafil has no direct relaxing effect on corpus cavernosum, but also actively enhances the relaxing effect of cheap viagra in uk on this tissue. When activated, the way NO / cGMP, which persist in sexual arousal, inhibition of PDE5 under the influence of sildenafil increases the levels of cGMP in the cavernous body. In this regard, for the manifestation of a favorable pharmacological effect of Viagra requires sexual stimulation.
In single dose of Viagra oral doses up to 100 mg in healthy volunteers, the drug did not cause clinically significant changes in ECG. The maximum decrease in systolic blood pressure in the prone position when using the online viagra order orally at a dose of 100 mg averaged 8.4 mm Hg. Art. The corresponding decrease in diastolic blood pressure in the prone position was 5.5 mm Hg. Art. Reduction in blood pressure due to vasodilating effects of sildenafil, probably by increasing the level of cGMP in vascular smooth muscle.
Viagra has no effect on visual acuity and contrast perception. Some patients at 1 h after dosing at 100 mg revealed a slight and temporary violation of color discrimination (blue / green) with the test Farnsworth-Munsell 100; 2 hours after taking the drug, these changes were absent. The proposed mechanism of violations of color vision see FDE6 oppression, which is involved in the transmission of light in the retina. Studies in vitro have shown that the effect of viagra results on FDE6 10 times inferior to its activity against PDE5.
Studies in vitro suggest that the activity of sildenafil against PDE5 10 -10 000 times higher than its activity against other isoforms of phosphodiesterase (PDE 1, 2, 3, 4 and 6). In particular, the activity of viagra price against PDE5 of 4 000 times greater than its activity against FDE3 – cAMP-specific phosphodiesterase involved in the reduction of the heart.
3.1.1. Additional information about clinical trials
Efficacy and safety of Viagra has been studied in 21 randomized, double-blind, placebo-controlled study lasting up to 6 months. Viagra used more than 3000 patients with erectile disorders of various outdated viagra (organic, psychogenic, mixed) aged 19 to 87 years. Effectiveness was determined on the basis of overall assessment, diaries, recording erections, assessing the international index of erectile function (IIEF, a questionnaire designed to assess sexual function), and survey partners.
The effectiveness of Viagra, which was estimated by the ability to provide advance preparation and conservation of an erection sufficient for sexual intercourse, was demonstrated in all over the counter viagra and persisted during long-term treatment (one year). When using fixed-dose proportion of patients reported improvement in erectile function, was 62% (25 mg), 74% (50 mg) and 82% (100 mg), while placebo – 25%. In addition to improving erectile function, IIEF analysis showed that treatment with Viagra improves as orgasm, satisfaction with sexual intercourse and overall satisfaction.
In all studies, the proportion of patients with diabetes mellitus, indicating improvement in the treatment of Viagra, accounted for 59% of patients after radical prostatectomy – 43% of patients with spinal cord injury – 83% (versus 16%, 15% and 12% of patients receiving placebo, respectively).
3.2. Pharmacokinetic properties
Suction
Viagra is rapidly absorbed. The concentration of drug in plasma after taking it inside an empty stomach reaches a peak within 30-120 min (average 60 minutes). Absolute oral negative effects viagra averages 41% (25-63%). Pharmacokinetics Viagra when administered in the recommended dose range (25-100 mg) is linear.
When you receive Viagra in combination with fatty food intake rate decreases; Tmax is increased by 60 min, and Cmax decreased by an average of 29%.
Distribution
The volume of distribution (Vss) Sildenafil at steady state an average of 105 liters, indicating that its distribution in tissues. Sildenafil and its major circulating N-desmetilovy metabolite approximately 96% bound to plasma proteins. Protein binding is not dependent on the total concentration of the levitra versus viagra.
In healthy volunteers who received Viagra (single dose of 100 mg), less than 0.0002% (average 188 ng) dose was found in semen after 90 min after administration.
Metabolism
Sildenafil is metabolized primarily by CYP3A4 (major route) and CYP2C9 (optional path) of the liver microsomal isoenzymes. The main circulating metabolite formed by the N-desmetilirovaniya Sildenafil. On the selectivity of action on PDE metabolite herbal viagra reviews with sildenafil, and its activity against PDE5 approximately 50% of the activity of the drug. Metabolite concentration in plasma is approximately 40% from those of sildenafil. N-desmetilmetabolit undergoes further metabolism; terminal during its half-life is about 4 hours
Withdrawal
The total clearance of sildenafil from the body is equal to 41 l / h and terminal elimination half-life – 3-5 hours after oral or intravenous administration of sildenafil is excreted as metabolites primarily in the faeces (approximately 80% of the administered dose) and to a lesser extent in cheapest viagra anywhere ( approximately 13% of the administered dose).
Pharmacokinetics in special groups of patients:
Seniors
In healthy elderly volunteers (65 years and older) sildenafil clearance was reduced, and the concentration of free drug substance in the plasma by approximately 40% higher than its guaranteed cheapest viagra in healthy young volunteers (18-45 years). However, analysis of safety data showed that age does not influence the frequency of adverse events.
Renal failure
In volunteers with mild (creatinine clearance 50-80 ml / min) and moderate (creatinine clearance 30-49 ml / min) renal insufficiency Viagra pharmacokinetics after a single oral administration (50 mg) did not change. In volunteers with viagra for sale without a prescription (creatinine clearance <= 30 ml / min) renal clearance of sildenafil decreased, which led to an increase in AUC (100%) and Cmax (88%) compared with those of volunteers, matched for age, which did not suffer a violation kidney function.
