Vega Pills is a potent selective inhibitor of cGMP-specific PDE-5.

Mechanism of action

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, the subsequent relaxation of smooth muscle tissue of the cavernous body and an increase in blood flow.

Vega Pills does not have a direct relaxing effect on the isolated cavernous human body, but enhances the effect of nitric oxide by inhibiting PDE-5, which is responsible for the disintegration of cGMP.

Selective Cobra 120 Vega Extra against PDE5 in vitro, its activity against PDE5 superior activity against other known PDE isoenzymes: PDE-6 — 10 times; PDE-1 more than 80 times; PDE-2, PDE-4, PDE-7 PDE–11 more than 700 times. Vegah Extra 120 Indication is 4000 times more selective for PDE-5 than PDE-3, which is crucial because PDE-3 is one of the key enzymes in the regulation of myocardial contractility.

A prerequisite for the effectiveness of Vega Pills is sexual stimulation.

Vega Pills restores impaired erectile function in conditions of sexual stimulation by increasing blood flow to the cavernous bodies of the penis.

Influence of Vega Pills on other drugs

Vega Pills is a weak inhibitor of cytochrome P450 — 1A2, 2C9, 2C19, 2D6, 2E1 and 3A4 ISOENZYMES (IC50 >150 µmol). When taking Vega Pills in recommended doses, its Cmax is about 1 µmol, so it is unlikely that Cobra Vega Extra can affect the clearance of the substrates of these isoenzymes.

Vega Pills increases the hypotensive effect of nitrates both with long-term use of the latter, and with their appointment for urgent indications. In this regard, the use of Vega Extra Cobra 130 Mg in combination with nitrates or nitric oxide donators is contraindicated. While taking α-adrenoblocker doxazosin (4 and 8 mg) and Vega 120 Mg (25, 50 and 100 mg) in patients with benign prostate hyperplasia with stable hemodynamics, the average additional decrease in sad/dad in the supine position was 7/7, 9/5 and 8/4 mm Hg.article, respectively, while in the standing position — 6/6, 11/4 mmHg, and 4/5.art. respectively. Reported rare cases of symptomatic postural hypotension in such patients, manifested in the form of dizziness (without fainting). In some sensitive patients receiving α-blockers, simultaneous use of Vega Pills can lead to symptomatic hypotension.

There were no signs of significant interaction with tolbutamide (250 mg) or warfarin (40 mg), which are metabolized by CYP2C9 isoenzyme.

Vega Extra Cobra (100 mg) has no effect on the pharmacokinetics of the HIV protease inhibitor, saquinavir, which is a substrate of CYP3A4 isoenzyme, at its constant level in the blood.

The simultaneous use of Sildenafil Tablets Vega Extra Cobra at equilibrium (80 mg 3 times a day) leads to an increase in the AUC and Cmax of bosentan (125 mg 2 times a day) by 49.8 and 42%, respectively.

Vega Extra 120 (50 mg) does not cause an additional increase in bleeding time when taking acetylsalicylic acid (150 mg).

Vega Pills (50 mg) does not increase the hypotensive effect of alcohol in healthy volunteers with Cmax of alcohol in the blood on average 0.08‰ (80 mg/DL).

In patients with hypertension, no signs of interaction of Vega Pills (100 mg) with amlodipine were found. The average additional reduction in blood PRESSURE in the supine position is 8 mm Hg.V. (systolic) and 7 mm Hg.V. (diastolic).

The use of Vega Pills in combination with antihypertensive agents does not lead to additional side effects.

The pharmacokinetics of Vega Pills in the recommended dose range is linear.

Suction. After intake of Vega Extra Cobra 130 Mg is rapidly absorbed. Absolute bioavailability averages about 40% (25 to 63%). In vitro Vega Pills at a concentration of about 1.7 ng/ml (3.5 nm) inhibits the activity of PDE-5 50%. After a single dose of Vega Pills 100 mg average Cmax free Vega Pills in plasma men is about 18 ng/ml (38 nm). Cmax when taking Signature Cobra Vega inside fasting is achieved for an average of 60 minutes (from 30 to 120 minutes). When taken in combination with fatty foods, the rate of absorption decreases: Cmax decreases by an average of 29%, and Tmax increases by 60 minutes, but the degree of absorption does not change significantly (AUC decreases by 11%).

Distribution. The average Vss of Vegah Extra 130 is 105 l. the Association of Vega Cobra 120 and its main circulating N-demethyl metabolite with plasma proteins is about 96% and does not depend on the total concentration of the drug. Less than 0.0002% of the dose of Vega Pills (an average of 188 ng) was found in sperm 90 minutes after taking the drug.

Metabolism. Vega Pills is metabolized mainly in the liver by the action of CYP3A4 isoenzyme (main pathway) and CYP2C9 isoenzyme (minor pathway). The main circulating active metabolite, formed as a result of N-demethylation of Vega Pills, undergoes further metabolism. The selectivity of this metabolite against PDE is comparable to that of Vega Pills, and its activity against PDE-5 in vitro is about 50% of the activity of Cobra Vega 120. The concentration of the metabolite in the blood plasma of healthy volunteers was about 40% of the concentration of Vega Cobra. N-demethyl metabolite undergoes further metabolism; its T1/2 is about 4 no.

Breeding. The total clearance of Sildenafil Vega Extra 120 is 41 l/h, and the final T1/2 — 3-5 h. After oral administration, as well as after I/V, Vega Pills is excreted as metabolites, mainly by the intestine (about 80% oral dose) and to a lesser extent by the kidneys (about 13% oral dose).

Cardiovascular complications

During the post-marketing use of Vega Pills for the treatment of erectile dysfunction, adverse events such as severe cardiovascular complications (including myocardial infarction, unstable angina, sudden cardiac death, ventricular arrhythmia, hemorrhagic stroke, transient ischemic attack, hypertension and hypotension) were reported, which had a temporary connection with the use of Vega Pills. Most of these patients, but not all of them, had risk factors for cardiovascular complications. Many of these adverse events were observed shortly after sexual activity, and some were observed after taking Vegah Extra 130 without subsequent sexual activity. It is not possible to establish a direct link between the reported adverse events and those or other factors.

Hypotension

Vega Pills has a systemic vasodilating effect, leading to a transient decrease in blood PRESSURE, which is not clinically significant and does not lead to any consequences in most patients. However, before prescribing Cobra Vega 120, the doctor should carefully assess the risk of possible undesirable manifestations of vasodilating action in patients with relevant diseases, especially against the background of sexual activity. Increased susceptibility to vasodilators is observed in patients with obstruction of the output tract of the left ventricle (aortic stenosis, GOCMP), as well as with the rare syndrome of multiple systemic atrophy, manifested by a severe violation of the regulation of blood PRESSURE from the autonomic nervous system.

Since the combined use of Vega Pills and α-blockers can lead to symptomatic hypotension in some sensitive patients, Vega Pills should be used with caution in patients taking α-blockers (see "Interaction"). To minimize the risk of postural hypotension in patients taking α-blockers, the drug Cobra Vega should be started only after achieving stabilization of hemodynamic parameters in these patients. It should also consider reducing the initial dose of Cobra Vega 120 Mg (see. "Dosage and administration"). The doctor should inform patients about what actions should be taken in case of symptoms of postural hypotension.

Vegah Cobra