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Sildenafil Citrate - Mechanism of Action

Medications are among the most important discoveries of humans. How a substance manipulates the body to offer relief of unpleasant symptoms or clear offending agents such as bacteria or viruses is simply amazing. In today’s article, however, we will be focusing on a slightly more intimate drug, which is also one of the most widely used medications in the world – sildenafil, commonly known as Viagra. Viagra is the branded version of sildenafil citrate that is produced by Pfizer. Many generic forms also exist, but they all contain the same active ingredient which is sildenafil (coming in its salt form, sildenafil citrate). Sildenafil exerts its effects by manipulating certain substances in the body to eventually result in a healthy erection that guarantees satisfactory sexual performance.

Erectile dysfunction is now known to affect 50% of men above the age of 40 years. Younger people may also be affected. If you have ED, there’s no point in learning to live with it and sacrificing your wonderful sex life because there is proven treatment.

If you are using sildenafil-based meds or you intend to use them someday, it is prudent to know how the drug works and the effects it produces on your body. Having this understanding will give you the ability to assess the risks and benefits of using sildenafil and any potentially dangerous consequences that can come with the concomitant use of other medications.

How Does Sildenafil Work?

When you take sildenafil citrate, what you expect is the super sexual power that you have been yearning for. Sildenafil achieves this by simply igniting reactions that cause increased blood flow to the penis.

Just like a balloon can fill with water, the penis fills with blood, increasing in size and getting stiffer. But unlike the balloon, the penis has thicker walls and many other supporting structures that make it very hard when you are sufficiently stimulated. For the penis to fill with blood, the blood vessels supplying it first dilate to increase the volume of blood that they can potentially accommodate. This dilation, or simply the expansion of the blood vessels is made possible by the release of some biochemical agents. cGMP, in particular, is the cyclic nucleotide that causes relaxation of blood vessel walls and the ultimate increase in blood flow to the penile erectile tissues, the corpora cavernosa.

The role of sildenafil citrate is to enhance the action of the chemical compound that facilitates blood flow to the penis, (cGMP). This is achieved by blocking the activity of an enzyme called PDE-5 which interferes with cGMP by breaking this facilitator of erection down.

The body has its natural way of initiating an erection and this is achieved by stimulation of the nervous system. But sometimes, the body’s natural mechanisms can fail due to some reasons, and this is why you might need intervention in the form of sildenafil or other similar medicines.

Mechanism of Action of Sildenafil Citrate: Diving into Details

Please, note that the paragraphs below might seem a bit too difficult for many as they include a lot of biological terms and stuff. Still, we strongly encourage you to read on – the biochemical processes behind human penis erection are very interesting. Besides, this info will help you understand how all ED meds including sildenafil work, so you no longer feel like Viagra is some magic potion from the medieval fairy tales.

Erection is a function of the parasympathetic nervous system. Interestingly, this is the same system that is responsible for urination, salivation, and lacrimation, just to mention a few. When one is sexually excited, the nerve terminals in the erectile tissue release nitric oxide, abbreviated as NO. Nitric oxide is made from an amino acid, L-arginine, by the enzyme NO synthase. The nitric oxide is then transported out of the nerve cells to the neighboring cells. In these cells, NO stimulates an enzyme called guanylate cyclase to produce cyclic guanosine monophosphate (cGMP) from Guanosine triphosphate (GTP). The cGMP is the compound that relays the message of the NO inside the cells of the erectile tissue, and it is termed as the second messenger in this context. The action of cGMP is to relax the smooth muscles of the blood vessels supplying the erectile tissue. Relaxation of these muscles leads to vasodilation, and this translates to increased blood flow into the penis which manifests as a hard erection.

An erection is a good thing but only if it is well controlled. The body has its way of terminating it. This is done by stopping the action of cGMP and the enzyme assigned this task is called phosphodiesterase (PDE)-5. When this enzyme comes to action, the blood vessels of the erectile tissue cease to dilate and regain their normal tone. This leads to a reduction in the volume of blood, and it is coupled to other mechanisms that end an erection.

Sildenafil citrate is a PDE-5 inhibitor. When it is present, it silences the action of phosphodiesterase 5 so that cGMP acts for longer and this is helpful in the treatment of erectile dysfunction because it sustains an erection to ensure sexual satisfaction.

When taken in the right doses, sildenafil citrate only causes an erection during sexual stimulation because this stimulation causes a release in NO.

Through its mode of action, sildenafil citrate can treat erectile dysfunction that results from various causes.

Sildenafil Citrate Contraindications

Based on how sildenafil citrate works, here is a glimpse at the most common contraindications to its use.

Sildenafil should not be administered by people who are using nitrates and organic nitrates because these meds’ mechanism of action is also based on the effects of nitric oxide, leading to dilation of blood vessels. When blood vessels dilate, there is reduced blood pressure because of an increased circulatory system volume. Therefore, concomitant use of sildenafil citrate with nitrates leads to a very low blood pressure that can be hazardous for one’s health or even life. Significant reduction in blood pressure also occurs when sildenafil is administered with antihypertensive medications such as calcium channel blockers.

Sildenafil should not be administered by people with cardiovascular diseases and by those in whom sexual activity has been contraindicated. The effect of hypotension caused by sildenafil can lead to dire consequences in this population.

Co-administration of sildenafil with other PDE-5 inhibitors such as vardenafil and tadalafil can enhance their effect further and lead to worse drops in the blood pressure. Furthermore, sildenafil should not be prescribed to people who are using cGMP stimulators such as Adempas and Riociguat because these also potentiate low blood pressure.

When used together with the antiretroviral agent ritonavir, the serum levels of sildenafil increase leading to the risk of adverse effects.

Sildenafil should also be used with caution in people with liver disease because it is metabolized by liver enzymes. In case of liver failure, the drug can accumulate to toxic levels.

Sildenafil is contraindicated for people who are allergic to sildenafil or any other component of the drug.

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