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Pfizer Viagra


What is Viagra?

Let us start by saying that Viagra is the brand name of Sildenafil. This medication will relax blood vessel walls, allowing blood to flow to certain parts of the body. A Curious thing about this is that it started out as a treatment for pulmonary arterial hypertension but now is widely popular for its ED benefits. Another brand of drug, Revatio (contains the Sildenafil) is now used to treat pulmonary arterial hypertension.

When is Viagra used?

Erectile Dysfunction is translated by a defective blood flow into the penis. This will make your erection fail, or the situation where you cannot keep it long enough. If this happens, then other issues like decrease in sexual arousal, depression and relationship problems might occur. With Viagra you can turn the situation around. Its active ingredient (Sildenafil) will stimulate the penile blood vessels in order to expand and allow more blood to flow, thus maintaining a stronger and longer erection.

How to use Viagra?

Viagra is usually taken in pill form 30-60 minutes before any sexual activity. The blister packs contain four, eight or twelve tablets each. You should not take Viagra more than one time per day. Please keep in mind that the drug alone will not do a thing, sexual stimulation is always required. Also, you must respect the instructions regarding dosage and usage as well as your doctor’s advice. You should not take Viagra if you are not affected by ED. Please notice that Viagra is only intended to treat ED and not to increase penis size nor to increase your libido. This medication will only work together with sexual arousal. Consider Viagra as an important help to normal sexual life.

Dosage

This blue pill presents a singular diamond. You can check this on the package or after you talk to your doctors as he may advise otherwise. The strength is (either 25mg, 50mg or 100mg) and it is indicated on one side of the pill. The PFIZER brand name is present on the other side of the pill.

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An online doctor consultation means filling out a medical questionnaire. A registered EU doctor assesses your medical questionnaire and analize whether Pfizer Viagra is suitable and safe for you to buy. After approval, a prescription is issued and send to the registered EU pharmacy. You will receive your discretely shipped Pfizer Viagra pills within 3 business days.


Recent research demonstrates that 6% of all men (age between 18 to 55) experience erectile dysfunction. The numbers in men over 65 years is greater up to 60-70%. Medical tests were conducted with men who took Viagra and the results were the following: Viagra has, on average, a success rate of 82%; such can be used to say that Viagra works with 4 out of 5 men. It took around 12-37 minutes to achieve an erection. The duration differed from person to person.


Pfizer Viagra unboxing and instruction manual

How we are treated with Viagra?

Why Viagra can impair vision and hearing, why it is prescribed for newborns, why it is tested on women, how it helped hamsters get the Nobel Prize, and how nitric oxide participates in an erection.

Neurological disorders, hormonal disorders, diseases of the cardiovascular system, surgery, diabetes, multiple sclerosis, certain medications, alcohol or drug intoxication, and psychological problems can all cause erectile dysfunction (the term “impotence”, which it is often called, in a medical environment has already outlived itself). It is curious that the most famous drug for this condition was created for a completely different purpose.

A Cure for Hypertension Sandwich

Under such a description, the drug sildenafil, sold today under the brand name Viagra, as well as Vasan, Sildenafil "North Star" (yes, there is such a name, but not in the spirit of jade wands, but in honor of the manufacturer), Vizarsin, Dynamo, Maxigra , Potenzagra and Revazio. The medicine was developed in 1989 by employees of the Pfizer laboratory in the city of Sandwich (this small town in the British county of Kent was originally called Sondwic, which came from the words “sand” and “place to trade”, so now it’s better to translate it as “SoundVidge”, and not how to sandwich name). Scientists wanted to create a drug to improve blood flow in the myocardium with coronary heart disease and angina pectoris, as well as to combat high blood pressure (hypertension).

But their plans were not destined to come true: clinical studies have shown that sildenafil has virtually no power over cardiac blood flow. But here Pfizer employees recalled how, in their first clinical trials, they noticed a frequent side effect of the drug - spontaneous erections. So the idea came up to retrain the drug for the treatment of erectile dysfunction, and since it affects 31% of men aged 50-59 years, they attacked almost a gold mine.

In 1996, the drug was patented (by the way, the patent will expire already in 2019, so Pfizer took the lead and released it's own generic, that is, a cheap copy of the drug). In 1998, the drug was approved by the American Food and Drug Administration (FDA), and in the same year, it was approved in Europe. Sildenafil has become one of the most famous examples. Redeveloped drugs and the first pill that can fight erectile dysfunction. This was much more convenient than administering the medicine with vacuum pumps, inserting suppositories (“suppositories”) into the urethra, suturing the capsules with it surgically, using injections, and especially making implants. How was the new substance so different from previous drugs in this group?

What is there in Viagra, chemically?

Chemically, sildenafil is correctly called 1 - [[3- (6,7-Dihydro-1-methyl-7-oxo-3-propyl-1H-pyrazolo 4,3-alpha- pyrimidin-5-yl) -4-ethoxyphenyl] sulfonyl] piperazine citrate, but mere mortals like you and me. The level of the drug in the blood reaches between 30 and 120 minutes after administration. Being absorbed by 40%, the drug is gradually destroyed by liver enzymes (mainly cytochrome P450 3A4, and to a lesser extent - cytochrome P450 2C9) and excreted in feces (80%) and urine. After 3-4 hours, half the dosage is already leaving the body.

Before that, he manages to play his main role - to block the action of enzymes called cGMP-specific phosphodiesterases. There are more than a dozen of them in us, which differ slightly in structure and “habitat”, but they all work on the same chemical reaction - they destroy the phosphodiester bonds that the cGMP or Cyclic guanosine monophosphate possesses. As you might guess, they were named for this, because in English these bonds will be phosphodiester bonds, and a lot of enzymes can boast the suffix "aza".

Cyclic guanosine monophosphate regulates the conductivity of channels in cell membranes through which charged particles (ions) move outward and inward. Changes in charge on different sides of the membrane help transmit electrical signals, without which the work of nerve and muscle cells is unthinkable. For example, when phosphodiesterase 5 (PDE 5) is activated, reacting to light on the retina of mammals, it also destroys cGMP, which causes hyperpolarization of the membrane of photosensitive cells, sending a signal from the eye to the brain.

CGMP molecules work throughout the body: they cause blood vessels to expand, are present in platelets, indicate the direction of growth of short processes of pyramidal neurons, and are produced in odor-responsive receptors. But it’s not so easy to take and slow down their splitting everywhere: we want to achieve an erection, but not damage the retina, not deafening, and not faint from critically lowered blood pressure. Therefore, a PDE blocking tablet should only work in certain parts of the body.

Fortunately, as we recall, there are a lot of types of phosphodiesterases, and as many as 11 of them prefer to cut phosphodiester bonds precisely at cGMP (and three of them practically do just that). As fashionistas like Chanel brand scents, cGMP-specific phosphodiesterases like sildenafil, but most of all, as in the case of famous perfumes, No. 5 is attractive to him. He likes PDE 5 drug ten times more than PDE 6, 80 times more PDE 1 and 700 times more than the rest (for example, PDE 4, which Drotaverinum is aimed at in No-shpa - we already wrote about it).

The fifth phosphodiesterase as a target for the treatment of erectile dysfunction is good because it is mostly produced in the cavernous bodies of the penis. In addition, there is a lot of it on the retina (for good reason we wrote about cGMP and vision). Phosphodiesterase 6 is also active there, the second in the "list of preferences" of sildenafil. Therefore, an overdose of Viagra can lead to color blindness - for example, one hero of an article in Retinal Cases began to see the world in red shades, because he received a toxic lesion of the retina, and the cones that are responsible for color perception were most affected.

There is PDE 5 in the lungs, so another frequent use of sildenafil in the treatment of pulmonary hypertension. However, in cases of impaired fetal development in the early stages of pregnancy, attempts to improve blood flow with this drug only harm unborn patients. The risk for them was shown by the study of the Medical Center of the University of Amsterdam, which had to be prematurely completed due to 11 cases of fetal death.

Say NO to bloody drams

But how is pelvic blood flow control directly related to male erection? The inner lining of the vessels, or endothelium, sensitively reacts to changes in the level of nitric oxide II, or NO (no, in the title there was no denial by caps), which in the body is considered a gaseous signaling substance. He “lives” in the blood for only a few seconds, but this time is enough to lead to the production of cGMP and to command the walls of the vessels to relax smooth muscles. expand, and because of this, the pressure decreases - as will happen if you drive the same amount of liquid with the same force into wider pipes.

Take a deep breath, all this is summarized in the diagram below: in response to a sexual stimulus, endothelial cells and non-adrenergic non-cholinergic neurons release nitric oxide, which enhances the work of an enzyme called guanylate cyclase. The latter turns GTP (one of the energy transfer molecules in the cell) into cGMP, which relaxes smooth muscles, causing an erection. But this process has a restraining mechanism: phosphodiester 5 breaks the phosphodiester bonds of cGMP, turning it into GMF. Sildenafil in the form of citrate interferes with the work of phosphodiesterase, helping erection in place, although it does not get to the cause, which may lie floors above this scheme. For example, if a patient with erectile dysfunction experiences nocturnal erections, the problem probably lies in the psychological plane.

Nitric oxide II was even used as a cure for erectile dysfunction because at the level of biochemistry, its lack is ultimately the root of the problem. Not surprisingly, in 1992, Science magazine proclaimed NO the "Molecule of the Year. "

But during an erection, the tissues do not look relaxed at all, rather, on the contrary. Nevertheless, the basis is not muscle tension, as you might have suggested, but the filling of special anatomical structures with blood - two cavernous bodies (corpora cavernosa). A third similar structure, the spongy body (corpus spongiosum), surrounds the urethra and is almost not filled with blood.

Circumference, Hardness, and Shnobel Prizes

How sildenafil works, in theory, is understandable. But let us return from excursions into biochemistry and physiology to real patients in clinical trials - all the more so, in the English-language database of medical scientific articles PubMed there are as many as 908 of them. More than a third of them are randomized, double-blind, placebo-controlled.

In most studies, there are about a hundred participants in the sildenafil and placebo groups (in one of the studies, for example, calculations are shown that for a statistical group there should be at least 70 people). For example, in a multicenter study of urologists from San Francisco, men from the drug group were twice as likely as men from the placebo group in the survey on the quality of their sex life, items describing the improvement of erection. Another article, based on five studies, shows that with a dose of 100 mg in two weeks it is easier to achieve an erection as solid as in a healthy person than with a dosage of 50 mg. At the same time, there were almost no differences in side effects. Another study showed that sildenafil improves an erection in men with unidentified dysfunction (that is, one that they themselves did not know about before the study).

Other works used objective methods of assessment - for example, the authors of a small study in 2010 applied plethysmography - measuring the circumference or volume of the penis (for the extravagant idea of ​​using postage stamps for such a procedure, the Nobel Prize was awarded last year ). They (not the Shnobelevka laureates, but the authors of the mentioned article, of course) found that the difference in effects in the group of the drug and placebo was 28%. By the way, this Nobel Prize is not the only one in a series of those that can be associated with sildenafil: for example, 2007 laureates proved that Viagra helps from jetlag. But you shouldn’t stock up on it yet, because experiments were carried out on hamsters.

We are not looking for the lungs but in vain

As many as three Cochrane Viagra reviews relate, oddly enough, pulmonary hypertension. So-called a group of diseases that increase the resistance of blood vessels of the pulmonary circulation. As a result, the blood is saturated with oxygen worse, and the patient suffers from shortness of breath, angina pectoris, fainting. Pulmonary hypertension can lead to earlier death due to right ventricular heart failure. Doctors try to cause vasodilation and the patient, using inhalation with nitric oxide or drugs with a similar effect, for example, sildenafil.

With pulmonary hypertension in newborns, this substance has been little studied: the authors of the 2017 Cochrane review found only five articles about trials totaling 166 infants worthy of consideration. Although the results can be considered positive, since sildenafil was superior to placebo, it is necessary to compare its safety with existing treatment methods.

Sildenafil is also prescribed for adults. However, for 2004, the authors of the review found only four articles matching the criteria. They talked about successful trials in 77 patients, but there was not enough information about the differences in the effect of the drug on different pictures of the disease, about side effects and about long-term use.

Finally, a very recent review of the effects of PDE5 inhibitors in nearly 3,000 patients dispelled doubts about pulmonary arterial hypertension, confirming the effectiveness of this group of drugs. The authors advise doctors to choose sildenafil, tadalafil or vardenafil depending on the individual characteristics of the patient's body and their side effects. But with pulmonary hypertension caused by heart problems, the benefit of the drug has not yet been proven.

Viagra and women

In a female homologous (having the same origin) organ - the clitoris - when excited, an erection occurs according to the same biochemical mechanism. Only here are adjacent structures filled with blood, the so-called bulbs of vestibule, which are absent in men (and women do not have a spongy body). They, like the female homologs of the cavernous bodies, look as separate structures, but in the same way, they swell and become harder, filling with blood during excitement.

It is logical to assume that sildenafil will act on women who have similar problems. But such violations in women are much less obvious for diagnosis: even the 3D structure of the internal parts of the clitoris was mapped only at the beginning of the two thousandths. Nevertheless, in parallel with constant attempts to create a “female Viagra” in the form of tablets or substances for application to the vagina, ordinary Viagra was also repeatedly tested on representatives of the other half of humanity.

For example, in this review, 14 randomized controlled trials are examined that show that overall, women suffering from sexual arousal disorders and taking PDE5 inhibitors were more likely to report improvements than those taking a placebo.

In another randomized, double-blind, placebo-controlled study, 25 patients treated the vagina with a solution of the drug or placebo to reduce the pain of menstruation. On the pain scale, in the next four hours, women who used the drug felt better than those who used the dummy.

Although articles and reviews most often hint that PDE5 inhibitors may well help women, such studies are often fragmentary and scarce. We know very little about side effects in women, and in general, as in men, the problem may not be in the effects of phosphodiesterase 5, but at a different level. Therefore, it is better to listen to the advice of a review of scientists from the University of Ferrara, who recommend that you first diagnose the primary cause of female sexual dysfunction (although this is difficult), so as not to miss a serious systemic disease, and only if other drugs help, try this group of drugs.

Use of Viagra is not limited to only for erectile dysfunction

Viagra can indeed be considered an effective remedy for erectile dysfunction caused by various reasons (including unidentified ones). The effect of the medicine is confirmed by the patients themselves in specialized medical questionnaires, and direct measurements. The drug copes with erectile dysfunction in diabetes, and possibly with multiple sclerosis (although in the second case it is better to wait for the results of other studies). There is hope for patients with depression or those affected by the side effects of antidepressants.

But this is not the only purpose for which Viagra should be used. It is effective for pulmonary arterial hypertension and may even help newborns if the usual treatment is not available. But it’s dangerous for pregnant women to take it: there is a risk of impaired fetal development.

A combination of Viagra and a flu metastasis vaccine is being tested after removal of a cancerous tumor in the abdominal cavity. The results on mice are impressive: sildenafil does not allow PDE 5 to prevent the immune cells from attacking the intruder, and metastases fail to spread. However, even with successful trials, we will have to wait at least several years for this method to come into clinical practice.

And now about the dangers. The drug lowers blood pressure, so it can be dangerous for diseases of the cardiovascular system, as well as enhance the effect of other drugs (for example, nitrites and nitrates), which act in the same direction. Therefore, the combination of hypertension and Viagra is contraindicated. Caution should also be exercised for those patients who drink cimetidine or erythromycin.

An unusual warning is not to use the drug with grapefruit juice (this pharmacologically incredibly insidious citrus is worthy of a separate large article). Some protease inhibitors in grapefruit juice inhibit the action of cytochrome P450 3A4, which, as we wrote above, is responsible for the breakdown of the drug. Viagra supplementation with antiviral protease inhibitors (for example, drugs that inhibit the reproduction of HIV particles) can also have an unpredictable effect.

Finally - an important nuance: Viagra works only with sexual arousal (recall the scheme with NO). If there is no signal for excitation at all, increasing the dose to more than 100 mg per day is most likely pointless: sildenafil acts on the final chains of reactions, and not on their beginning. Therefore, you will not solve the problem, but the likelihood of side effects (for example, permanently damage vision or hearing loss ) will increase significantly.

It’s best to check for other reasons that could have caused the violation. Perhaps the examination will determine that you need hormone therapy, not Viagra at all, or that the drug should be supplemented with psychotherapy (the second idea, however, in a small sample, is supported by the Cochrane review ). For the same reasons, it is better not to use drugs from dubious suppliers, including liquid ones, since in them the dosage of the active substance is often exceeded. In the last paragraph, you will have to use all your care: according to Pfizer, the proportion of counterfeit goods reaches 80%, while such products may contain harmful impurities that affect the functions of the drug: printer ink, amphetamines, boric acid, and even rat poison.