For Your Consideration: The Guide to Generic Viagra

Sildenafil citrate CanadaSildenafil citrate, the active ingredient of a far-famed Viagra and a range of other meds, is a preparation designed to eliminate erectile dysfunction symptoms, as well as combat pulmonary arterial hypertension. The preparation is primarily designed for males, and despite the confirmed effectiveness in women, the drug is not approved by FDA for use in females.

The preparation’s scope of action is narrowed to cGMP-specific phosphodiesterase type 5 inhibition – blocking the enzyme promoting cGMP degradation, which in its turn is handling the blood flow to the genitalia.

The preparation may cause mostly non-significant side effects: according to the Sider platform, aggregating publicly available side effects data, the most widely spread adverse reactions are headache (post-marketing research; observed in 4% – 49% of cases), nausea (postmarketing; 3 – 17% of cases) and flushing (1 – 16% of cases).

The medication is prescribed with caution to those diagnosed cardiovascular diseases.

Viagra should be refrained from in case of simultaneous nitrates treatment (e.g. isosorbide or nitroglycerin-based drugs). The co-administration may lead to an abrupt blood pressure drop with increasing risks of fatal outcome.

The invention of a revolutionary drug became possible due to the discovery of sildenafil citrate by Andrew Bell and his colleagues – David Brown and Nicholas Terrett, a team of scientists from Brand Company, in 1998. Since the release day the preparation maintains its global leadership position; in the US Viagra is ranked 42 in 2014 in terms of nationwide sales.

Indications for use: this is where it works perfectly

Sexual dysfunction

Sexual dysfunction

Viagra is primarily prescribed for elimination of erectile dysfunction (ED) symptoms: insufficient erection, premature ejaculation, sexual fatigue, inability to maintain/control erection and etc. The preparation is prescribed as a first line remedy in erectile dysfunction treatment, including the cases where patients are diagnosed diabetes mellitus and a variety of cardio-vascular problems (dosage correction is applied).

Pulmonary hypertension

Viagra enhances certain disease markers in those suffering from, although there’s strong evidence that it doesn’t impact the risks of lethal outcome or significant adverse reactions.

Antidepressants-provoked erectile dysfunction

The preparation is commonly used in those clinical pictures where erectile dysfunction is caused by reception of antidepressants.

Altitude sickness

Viagra is also prescribed to adjust risk factors in high-altitude pulmonary edema. This way or the other, there’s no clinical trials-based evidence on the impact on condition rate (according to the latest work, Update on High-Altitude Pulmonary Edema, 2008).

Clinical trials and efficiency overview

Clinical trials

Erectile dysfunction

The advent of sildenafil gave rise to a number of clinical trials in this area. As a result of numerous researches, ‘impotence’ was replaced with ‘erectile dysfunction’ term, which implies a potential correction of existing violations in the sexual sphere. Clinical studies of sildenafil led to the development of new diaries and questionnaires for the assessment of sexual function of men. Analysis of demographic indicators of the participants of large-scale clinical trials revealed risk factors for ED, which in turn contributed to the understanding of the mechanisms of its development. The evidence was accumulated that most cases of ED have the nature of somatic and psychological problems connected with lesions of vessels or nerves.

One of the largest meta-analysis of Viagra effectiveness combined data from 11 double-blind, placebo-controlled trials involving a total of more than 2,500 patients with ED. Within the trial group improved erections were reported of in 76% of patients versus 22% in the placebo group, which led to significant differences in the frequency of successful attempts at sexual intercourse – 66% and 26%, respectively. The efficacy of different dosages of the drug was 65% for the 25 mg, 74% for the 50 mg and 82% for the 100 mg. High efficacy of sildenafil was awarded in different age groups. In the category of patients younger than 65 years of effectiveness of the drug amounted to 77.6% versus 69.2% in the older age category. According to studies, the drug is effective compared with placebo in patients with ED, regardless of the reasons for its development and severity.

Despite the high effectiveness of the therapy of phosphodiesterase type 5 inhibitors, there remains a certain cohort of patients receiving this drug and having no impact. It is also clinically confirmed that the onset of action becomes significantly more noteworthy with the 5th and further intakes (up to 32% effectiveness difference).

Pulmonary hypertension

Let’s consider a study with 71% of patients with idiopathic pulmonary hypertension, and 25% of patients with pulmonary hypertension associated with connective tissue diseases. When prescribed in doses of 25-100 mg 2-3/daily, the drug caused hemodynamic improvement, increased exercise tolerance and contributed to an improvement of the functional class of the disease.

Generic Viagra’s (Know more) effectiveness is confirmed in a number of meta-analyzes that have demonstrated considerable effectiveness in comparison with prostacyclin analogues and endothelin receptor antagonists, according to a study Steele and authors. One-year survival rate when using sildenafil was 75.2%,comparable to that in the application of epoprostenol (78.4%), bosentan (77.8%), treprostinil (76.1%), Sitaxentan (75.8%) and beraprost (74.1%). sildenafil is indicated for the treatment of patients with pulmonary hypertension of 2nd and 3rd class. There is currently no data to support its use by patients with asymptomatic pulmonary hypertension.

The preparation should not be regarded as a drug of first choice for patients with severe disease (class 4, with the index test of 6-minute walking distance).

Sildenafil is generally well tolerated by the patients, including the long-term therapy, but with its appointment the doctor should assess the level of systemic blood pressure, and also confirm the patient is not taking concomitant medications that can enhance its hypotensive effect (nitrates, α-blockers).

How to take Viagra to achieve the maximum performance

How to take Viagra

The drug is designed for oral administration; the original preparation comes in tablet form, while numerous generic may also come in oral jelly, soft tablet and even powder and capsule forms. For a majority of patients 50 mg per 24 hours (the maximum allowed number of takes is limited to 1). The onset of action in Canadian Generic Viagra www.mycanadianpharmacyrx.com/generic-viagra is individual; however, it takes 40-45 minutes on average for the preparation to start working. Therefore, it is recommended to take the drug an hour before anticipated sexual intercourse. As a rule, non-tablet forms typically demonstrate faster onset of action, but in either event, the correction of consumption time should be made after 4-6 intakes. In the event of insufficient efficiency and tolerability the dosage can be adjusted up to 100 mg or decreased to 25 mg. The maximum daily dose must not exceed 100 mg exceeding the dosage doesn’t result into a more prominent effect, plus the risk of adverse reactions is greatly increased.

The dosing regimen in the elderly implies adjustments. In case of renal insufficiency, mild to moderate with creatinine clearance of 30-80 ml/min the dose adjustment is required, with severe renal insufficiency (creatinine clearance).

Сo-administrative treatment

When combined with ritonavir, the maximum single dose should not exceed 25 mg with the multiplicity of application not exceeding 1 intake per 48 hours. In combined treatment with CYP3A4 inhibitors (erythromycin, saquinavir, ketoconazole, itraconazole, etc.), the initial dose of Viagra should exceed 25 mg as well. To cut down the possible postural hypotension risks in those taking alpha-blockers, Viagra is recommended to be prescribed only after hemodynamic stabilization (the initial dose of sildenafil should be picked up carefully and start from the minimum possible one).

The impact of sildenafil in long term treatment

sildenafil in long term treatment

Perhaps, the most controversial issues of modern treatment ecology is the reasonability of long-term PDE-5 inhibitors therapy. Long-term efficacy of sildenafil was investigated by F. Montorsi et al., in a series of studies that included 2618 polls in patients taking the drug for 3 years. Overall, 96% of respondents were satisfied with the treatment, and only 1.6% have stopped taking it due to low efficiency.

The possibility of long-term use of the drug can not only be aimed at the preservation of erectile function, but also at partial normalization of lower urinary tract symptoms. The impact of sildenafil on lower urinary tract symptoms was studied by K. Sairam. After 1 and 3 months after treatment a significant decline in the international scale of evaluation of symptoms in diseases of the prostate and improved Quality of Life index were observed. Respectively, the degree of improvement in erectile function was confirmed. The most common reasons for these changes are the improvement of blood circulation in the pelvis and the normalization of exocrine function of the prostate gland through the regular emptying of gland ducts.

The constant use of small doses of sildenafil appears to be very promising in the treatment of diseases associated with impaired endothelial function. In addition to the main therapeutic effect it strengthens the blood supply to the corpora cavernosa – sildenafil may improve the microcirculation in various organs. Endothelial dysfunction is regarded as one of the early stages of pathogenesis of atherosclerotic vascular lesions.

The impact of sildenafil on endothelial function of coronary and brachial arteries was studied in several trials. Sildenafil at a dose of 25 to 100 mg was associated with improvement in endothelial function in patients with heart failure, diabetes, coronary heart disease and smokers. It is shown the evidence on the ability of the drug to eliminate tobacco-related short-term deterioration of endothelial function. In this regard, prolonged use of phosphodiesterase inhibitors is not only harmless, but also very useful from the viewpoint of prevention of atherosclerosis.

In patients with heart failure, long-term use of sildenafil in addition to the correction of endothelial dysfunction and coronary arteries of the shoulder, also led to an improvement in pulmonary hemodynamics, and had a mild antiplatelet effect. Combined intake of sildenafil and the ACE inhibitor ramipril in this group of patients was accompanied by potentiation favorable effect of both drugs on endothelial function.

The possibility of addiction to the drug has been well-studied too. El-Galley and colleagues have interviewed 82 patients by phone two years after the appointment of a sildenafil. 41 respondent (59%) has continued to take the drug, 37% have increased the initial dose due to lower efficiency and 17% of patients have stopped taking the drug due to low efficiency. Laboratory tests do not confirm the presence of the effect of addiction when taking sildenafil. Thus, the existing data doesn’t support the presence of habituation effect with long-term treatment.

Sildenafil citrate in women: a panacea without approval?

Sildenafil citrate in women

Viagra is basically designed for males and approved by FDA for use in males only. However, the medication has been successfully used in females too. There’s even clinical evidence of it, such as research University of New Mexico School of Medicine in Albuquerque. The details on a breakthrough clinical research have been published in American Medical Association Journal in 2008.

A group of researchers lead by professor Nurnberg was targeting the beneficial effect of Viagra and Generic Viagra in treatment of sexual dysfunction in females triggered by antidepressant remedies. As a result, 72% of women were able to achieve orgasm with Viagra against the background of 20% women in the control group taking placebo.

Harry Croft MD, a research group participant, admits that the problems with sexual function is regularly observed in a fraction of women taking antidepressants; and the beneficial action of Viagra is manifested in shorter timeframes to achieve orgasm and improved satisfaction.

The study involved 98 women participants taking antidepressants, 37+ years old. The participants were divided into 2 groups taking placebo and Viagra. The treatment started with 50mg of the preparation, increased up to 100mg in the course. Antidepressant history was no less than 4 weeks course and well-pronounced troubles with health. 72% successful cases in Viagra treatment and 28% no improvement was the result of the research. The side effects reported of had mostly mild nature: 43% of Viagra group members admitted increased headaches (against 27% result in placebo group).

The research was kicked off due to a grant issued by Brand Company, Viagra manufacturer which raises certain concerns as for the results fairness. This way or the other, these are just the results that give some ground for ‘off-label’ Viagra use, which is certainly neither covered by insurance and nor recommended by specialists.

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