Pharmacological action of Viagra.
 

Pharmachologic effect.

Sildenafil is a powerful selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5). The implementation of the physiological mechanism of erection is associated with the release of nitric oxide (NO) in the cavernous body during sexual stimulation. This, in turn, leads to an increase in the level of cGMP, subsequent relaxation of the smooth muscle tissue of the cavernous body and an increase in blood flow. Sildenafil does not have a direct relaxing effect on the isolated cavernous body in humans, but enhances the effect of NO by inhibiting PDE5, which is responsible for the breakdown of cGMP. Sildenafil is selective for in vitro PDE5, its activity against PDE5 exceeds that for other known phosphodiesterase isoenzymes: PDE6 - 10 times; PDE1 - more than 80 times; PDE2, PDE4, PDE7-PDE11 - more than 700 times. Sildenafil is 4,000 times more selective for PDE5 compared to PDE3, which is of paramount importance, since PDE3 is one of the key enzymes in myocardial contractility regulation. A prerequisite for the effectiveness of sildenafil is sexual stimulation. Sildenafil restores impaired erectile function under conditions of sexual stimulation by increasing blood flow to the cavernous bodies of the penis.

Efficiency.

The efficacy and safety of sildenafil was evaluated in 21 randomized, double-blind, placebo-controlled study of up to 6 months in 3,000 patients aged 19 to 87 years with erectile dysfunction of various etiologies (organic, psychogenic, or mixed). The efficacy of the drug was evaluated globally using an erection diary, an international index of erectile function (validated questionnaire on the state of sexual function) and a partner survey. The effectiveness of sildenafil, defined as the ability to achieve and maintain an erection sufficient for satisfactory sexual intercourse, has been demonstrated in all the studies performed and has been confirmed in long-term studies lasting for 1 year. In studies using a fixed dose, the ratio of patients who reported that therapy improved their erection was: 62% (dose of sildenafil 25 mg), 74% (dose of sildenafil 50 mg) and 82% (dose of sildenafil 100 mg), compared with 25 % in the placebo group. Analysis of the international index of erectile function showed that, in addition to improving erection, treatment with sildenafil also increased the quality of orgasm, allowed to achieve satisfaction from sexual intercourse and overall satisfaction. According to generalized data, among patients who reported improvement in erection with sildenafil treatment were 59% of patients with diabetes mellitus, 43% of patients undergoing radical prostatectomy and 83% of patients with spinal cord injuries (compared to 16%, 15% and 12% in the placebo respectively).


Dosing regimen.

For most patients, the recommended dose is 50 mg approximately 1 hour before sexual activity. Given the efficacy and tolerability, the dose may be increased to 100 mg or reduced to 25 mg. The maximum recommended dose is 100 mg. The maximum recommended frequency of use is 1 time / day. In case of renal failure of mild and moderate severity (CK 30-80 ml / min) dose adjustment is not required, in case of severe renal failure (CK <30 ml / min), the dose of sildenafil should be reduced to 25 mg. Since the elimination of sildenafil is impaired in patients with liver damage (for example, in case of cirrhosis), the dose should be reduced to 25 mg. Elderly patients dose adjustment is not required. Combined use with other drugs When combined with ritonavir, the maximum single dose of Viagra® should not exceed 25 mg, the frequency of use - 1 time in 48 hours. When used together with CYP3A4 isoenzyme inhibitors (erythromycin, saquinavir, ketoconazole, itraconazole), the initial dose of Viagra® should be 25 mg. To minimize the risk of postural hypotension in patients taking alpha blockers, the use of Viagra® should be started only after hemodynamic stabilization has been achieved in these patients. The feasibility of reducing the initial dose of sildenafil should be considered.

Sildenafil has a systemic vasodilating effect, leading to a transient decrease in blood pressure, which is not a clinically significant effect and does not lead to any consequences in most patients. However, before prescribing Viagra®, the doctor should carefully evaluate the risk of possible undesirable manifestations of the vasodilating action in patients with appropriate diseases, especially against the background of sexual activity. Increased susceptibility to vasodilators is observed in patients with obstruction of the excretory tract of the left ventricle (aortic stenosis, hypertrophic obstructive cardiomyopathy), as well as with rarely encountered multiple systemic atrophy syndrome, manifested by a severe dysregulation of blood pressure in the autonomic nervous system. Since the combined use of sildenafil and alpha-blockers may lead to symptomatic hypotension in individual sensitive patients, Viagra® should be used with caution in patients taking alpha-blockers. To minimize the risk of postural hypotension in patients taking alpha blockers, taking Viagra® should be started only after stabilization of hemodynamic parameters in these patients is achieved. It should also consider the feasibility of reducing the initial dose of Viagra®. It is necessary to inform patients about what actions should be taken in case of symptoms of postural hypotension.