Sildenafil (Viagra), what is its mechanism of action?

Last week, talking to a patient who asked me whether or not he could use Sildenafil (Viagra), I was struck by something he told me, which coincides with other similar information told to me by another person who did not know that I was a doctor. It usually happens that when they know you are a doctor they will limit themselves to say some things in front of you, it is normal, I understand it, particularly I would not talk about some infrastructure in front of a civil engineer.

The funny thing is that both of them told me that what Viagra did was "make the blood more liquid" and for that reason more blood reached the virile member and in that way the erection was produced.

Well, nothing to do with that obviously, because it is not an anticoagulant. In this post I intend to explain the mechanism of action of this drug known as the blue miracle, and provide other information related to this drug that might surprise you. So I invite you to read on, what I have to say is sure to be of interest to you.

Sildenafil is a drug that is currently used mainly, or at least it is the best known use, to treat erectile dysfunction, however, that was not the use for which it was previously investigated or created.

Viagra was discovered by accident¹ by Pfizer's research team in 1991. Originally, they were investigating a treatment for high blood pressure and angina pectoris, but patients who tried the drug reported an unexpected side effect: an increase in erection.

Pfizer decided to target this side effect and develop the drug as a treatment for erectile dysfunction, which became Viagra and was approved by the FDA in 1998. And there is no doubt that from that moment things changed for many men...

But apart from the more well-known use of sildenafil, it is also used to treat pulmonary arterial hypertension in adults and children. It is even often used in newborns. PAHT is a disease in which the blood pressure in the pulmonary arteries is too high. Sildenafil dilates the pulmonary arteries (meaning makes them wider, so blood can flow better), which lowers blood pressure and improves exercise capacity in people with pulmonary arterial hypertension, interesting, don't you It seems?

^{Something similar happened with the discovery of penicillin, the first antibiotic discovered, which was entirely by accident..}

Well, the purpose of this post is not specifically to talk about how sildenafil is used, nor about side effects, but specifically about its main mechanism of action in the treatment of erectile dysfunction.

It is necessary, before understanding how it acts, to know how erection occurs in men.The biochemical mechanism behind a penile erection involves a series of reactions that occur in response to sexual stimulation, and they are as follows:

• Sexual stimulation: Upon receiving sexual stimuli, the nervous system sends signals to the nerves in the penis.

• Release of nitric oxide (NO): Sexual stimulation causes the release of nitric oxide (NO) in the corpora cavernosa of the penis.

• Activation of guanylate cyclase: NO activates guanylate cyclase, an enzyme in penile smooth muscle cells, which produces cyclic guanosine monophosphate (cGMP).

• ** cGMP:** Increased cGMP causes smooth muscle relaxation and dilation of the arteries in the penis, allowing increased blood flow to the corpora cavernosa and an erection.

• Maintenance of erection: cGMP maintains erection by inducing smooth muscle relaxation and preventing blood from flowing back into the corpora cavernosa.

• Degradation of cGMP: The degradation of cGMP is controlled by the enzyme phosphodiesterase type 5 (PDE5), which converts cGMP to guanosine monophosphate (GMP), allowing blood to flow back into the corpora cavernosa and decreasing erection.

I would like to make it known that for a normal erection to occur, all of these reactions must occur in a coordinated and efficient manner. Any problem at any point in this process can result in erectile dysfunction.

Free use image

Having understood the above, let's now talk about how Sildenafil facilitates erection in men, the mechanism of action is as follows:

• Phosphodiesterase type 5 (PDE5) inhibition: Sildenafil binds to and blocks the activity of the PDE5 enzyme, which allows cyclic guanosine monophosphate (cGMP) to accumulate in the corpora cavernosa of the penis.

• Increased cGMP: Increased cGMP causes smooth muscle relaxation and dilation of the arteries in the penis, allowing increased blood flow to the corpora cavernosa and an erection.

• Erection maintenance: cGMP maintains erection by inducing smooth muscle relaxation and preventing blood from flowing back into the corpora cavernosa.

It is important to note that sildenafil only helps achieve an erection in response to sexual stimulation. It has no effect on libido or the ability to ejaculate. In addition, a prior diagnosis and prescription is required to obtain the drug.

Pixabay/ Author: OneCoffeGuy

Basically this drug, like all drugs, acts at the molecular, i.e. biochemical, level, either by limiting a function of an enzyme or by increasing the function of an enzyme to increase the production or elimination of a particular chemical.

I know it can be difficult to visualize these processes, but I still hope you have a better idea, and that it has nothing to do with what might be popularly referred to as more liquid blood.

I also know that people are always looking for answers in the easiest or most understandable way, and it is respectable, but everything has an explanation, some we have no idea how they are produced, but in general, as far as drugs are concerned, if there are many things clear.

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This is a drug that must be administered under medical supervision, since it also affects the heart, the lungs and the vascular system, which means that it can produce a great risk for people if they use it without the minimum of care.

I appreciate if you have come this far, if you have something to add, you can leave it in the comments and that way we can all help each other.

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• Links consulted

• Erectile Dysfunction

• Diagnosis and treatment of erectile dysfunction– a practical update

• VIAGRA® (sildenafil citrate) Tablets

• MINI REVIEW, PHARMACOLOGY OF SILDENAFIL CITRATE