Canadian Pharmacy Sildenafil PDE5 Inhibitor
Pharmacological class: drugs for erectile dysfunction treatment; PDE-5 inhibitors.
Pharmacological action: sildenafil is a potent selective cGMP-specific phosphodiesterase type 5 (PDE5) inhibitor.
Sildenafil has no direct relaxing effect on isolated cavernous body, but enhances NO effect by means of inhibiting PDE5, which is responsible for cGMP disintegration. Essential condition for Canadian Pharmacy Sildenafil PDE5 inhibitor effectiveness is sexual stimulation.
Sildenafil citrate, commonly known as Viagra, Revatio, etc., is a drug for erectile dysfunction and pulmonary arterial hypertension (PAH) treatment. Originally developed by British scientists, this drug was introduced into the market by American pharmaceutical company «Pfizer».
Viagra acts by inhibiting cGMP-specific phosphodiesterase type 5 – enzyme, that contributes to degradation of cGMP, which regulates blood flow to penis. Available since 1998, Canadian Pharmacy Sildenafil PDE5 inhibitor is primary means for erectile dysfunction treatment. Its main competitors in the market are medications Tadalafil (Cialis) and vardenafil (Levitra).
Sildenafil is mainly prescribed for erectile dysfunction treatment (inability to maintain erection necessary for sexual intercourse completion). At present time, the drug is used to treat erectile dysfunction, including patients with diabetes. Patients taking antidepressants may experience sexual frustration, as a result of either their disease or treatment. Research conducted in 2003 has shown that in such cases Canadian Pharmacy Sildenafil PDE5 inhibitor can improve male sexual function. As well as reports of 1999, this survey also shows that sildenafil improves sexual function at women taking antidepressants.
Sildenafil citrate is effective for treating rare disease – pulmonary arterial hypertension (PAH). Sildenafil weakens arterial walls, which leads to decrease in pulmonary arterial resistance and pressure. This reduces pulmonic ventricle of heart stress and improves right-sided cardiac insufficiency symptoms. Due to the fact that PDE-5 is primarily distributed in pulmonary smooth muscle arterial walls and penis, sildenafil selectively effects both these areas without causing vasodilation in other body organs.
«Pfizer» introduced an additional sildenafil registration to FDA, which was approved in June, 2005. To avoid confusion with Viagra, the drug was originally named Revatio, and issued in 20 mg white round pills.
Acosta’s Disease (Mountain Disease)
Sildenafil can be used for prevention and treatment of pulmonary edema associated with Acosta’s disease (mountain disease), which affects mainly alpinists. Although this effect was discovered only recently, sildenafil had already been used to treat this disease, particularly in situations when rapid descend was delayed for some reason.
During clinical tests most common sildenafil side effects were:
- hot flushes;
- nasal stuffiness;
- visual impairment, including photophobia and blurred vision.
Some patients complained on cyanopsia – a type of chromatopsia, when all objects acquire blue color. Some complained on blurred vision and loss of peripheral vision.
In July 2005, US FDA discovered that sildenafil in rare cases can cause visual impairment and a number of studies have confirmed the connection between sildenafil and occurrence of anterior ischemic optic neuropathy.
Rare but serious side effects include:
- severe arterial hypotension;
- myocardial infarction (heart attack);
- ventricular arrhythmias;
- blood stroke;
- elevated intraocular pressure;
- sudden hearing loss.
Basing on postmarketing reports in October 2007, FDA announced the necessity to include in labeling of all PDE5 inhibitors, including sildenafil, more prominent warning about potential risk of sudden hearing loss.
- administration of nitric oxide promoting agents, organic nitrites and such nitrates as nitroglycerin, nitroprussid sodium and amyl nitrite («poppers»);
- CvRF (cardiovascular risk factors);
- severe liver impairment (liver functional depression);
- severe renal impairment;
- hypotension (low blood pressure);
- blood strokes or heart attacks;
- hereditary degenerative amphiblestrodes disorders (including genetic amphiblestrodes phosphodiesterase disorders).
Recently Canadian Pharmacy Sildenafil PDE5 inhibitor gained popularity among young people. Trade sildenafil name – «Viagra» – is widely accepted in popular culture, the drug is associated with erectile dysfunction treatment, which leads to its recreational use. The reason is that people believe that the drug increases libido, improves sexual function or enlarges their penis permanently. Studies on Viagra recreational use are limited, but it is assumed that the drug has little effect on sexual function, in case when patient doesn’t suffer from erectile dysfunction. One study has shown that 25 mg dosage intake doesn’t cause any significant changes in erection quality, but reduces resting period between sexual intercourses. This study also registered a significant effect in control group receiving placebo.
Individual recreational sildenafil and other PDE-5 inhibitors use is especially spread among drug addicts. Sildenafil is sometimes used as a neutralizer of other, often illegal, substances effects. In attempt to lessen common erectile dysfunction side effect, some people combine this drug with methylenedioxymethamphetamine (MDMA, ecstasy), other stimulants or opiates, such combinations are known as «Sextasy» or «Rockin’and Rollin’». Taking sildenafil together with amyl nitrite is especially dangerous and potentially fatal.
Sildenafil (Viagra) Analogues
Acetildenafil (hongdenafil) is a structural sildenafil analogue and is one of PDE-5 inhibitors, referring to «herbal» aphrodisiacs, sold without prescription. This analogues class has passed no strict testing, unlike drugs such as Canadian Pharmacy Sildenafil PDE5 inhibitor, and thus, has unknown side effects.
There have been made attempts to ban this drug, but the process was slowed down, because in spite of laws prohibiting new drugs, still there are primarily prohibited analogues of illegal drugs, not drugs, sold by prescription. However, at least one court case has led to product withdrawal from sale. US FDA has banned numerous products which packages revealed Eurycoma longifolia content, but, in fact, containing sildenafil analogues. The manufacturers of these medications usually claim that they just changed their products names.
Mechanism of Action
Sildenafil action mechanism includes cyclic guanosine monophosphate (cGMP) protection from cGMP-specific phosphodiesterase type 5 (PDE-5) disintegration in cavernous body. Nitric oxide (NO) in penis cavernous body binds with guanylate cyclase receptors, which leads to cGMP level increase, and then – to smooth muscles of helicine arteries intimal thickening relaxation (vasodilation). This relaxation leads to vasodilation and increases blood flow into penis spongy tissue which causes erection.
Sildenafil is a potent and selective cGMP-specific phosphodiesterase type 5 (PDE-5) inhibitor, which is responsible cGMP degradation in cavernous body. Sildenafil molecular structure is similar to cGMP and acts as a competitive agent binding PDE5 in cavernous, which leads to cGMP increase and causes erection. Without sexual stimulation, and, as a result, without NO/cGMP system activation, Canadian Pharmacy Sildenafil PDE5 inhibitor does not cause erection.
Sildenafil is metabolised by liver enzymes and excreted through liver and kidneys. At fatty foods reception sildenafil absorption decreases. Time required to reach maximal concentration in plasma increases by about one hour, and maximal concentration is reduced by nearly a third.
Sildenafil (Viagra) History
Learn interesting fact from Viagra history:
Sildenafil (UK-92, 480 compound) was synthesized by a group of pharmacists working at «Pfizer» research center Sandwich, Kent, England. Originally it was studied as a means to treat arterial hypertension (high blood pressure) and cardiac angina (ischemic heart disease symptom).
The first clinical sildenafil tests were carried out in Morrison hospital in Swansea. In first phase of clinical tests under of Ian Osterloh supervision, it was suggested that the drug had little effect on cardiac angina disease and can cause penile erection. «Pfizer» therefore decided to sell the drug as means for erectile dysfunction treatment, rather than cardiac angina.
The drug was patented in 1996, approved for use for erectile dysfunction treatment by US FDA in March 27, 1998. Sildenafil became the first medicine, administered orally, approved for erectile dysfunction treatment, and later in the same year, the drug was released for sale in the United States. The drug has been met with stunning success. Annual Viagra sales reached its peak in 2008, and made 1934 million dollars.
British press claimed that Peter Dunn and Albert Wood were the real inventors of the drug, which was opposed by «Pfizer» company. Their names were mentioned in patent application, but original patent for drug synthesis belongs to Terretu Nicholas and Peter Ellis. Read this article revealing the research of Pfizer concerning Viagra.