How Viagra works

Viagra is one of the best-known drugs of all time. Nearly every adult in America has heard of the drug and can tell you what it does. In the years since it was introduced in 1998, former Republican presidential nominee Bob Dole has served as a spokesman for the drug, manufacture of counterfeit pills has gone through the roof, and Viagra jokes are now a permanent feature of the pop culture landscape.

About “the little blue pill“:

Viagra- blue pill

It’s simple: When it works as intended, Viagra causes a man who is sexually stimulated to get an erection. How does Viagra do that? And why does Viagra work only if the man is sexually stimulated? For that matter, what causes an erection in the first place?

How Viagra works :

This is a fascinating story — it involves the technology of the human body and the techniques that scientists use to control its different parts with drugs. And in the case of Viagra, the story starts with the penis.

how viagra works

For many people, talking about the penis is tough. This area of the body is considered private and isn’t discussed publicly (well, not in polite company). However, the penis is simply a part of the male anatomy designed to accomplish a task, and we’ll treat it that way here.

In the case of the penis, there are actually two tasks that it handles:

When you want to move nearly any part of your body, you do it using muscles. Whether you’re moving your fingers, toes, arms or legs, muscles do the work. Even when you stick your tongue out, you do it using muscles:

You think about moving some part of your body.
The appropriate muscles contract.
That part of the body moves.
Muscles let you move your body voluntarily with precise control.

viagra-erection

The first real breakthrough in the treatment of erectile dysfunction came in 1983. Prior to that time, it was thought that erectile dysfunction — the inability to achieve an erection — was primarily mental.

That concept came crashing down at the 1983 American Urological Association meeting in Las Vegas when Dr. Giles Brindley injected his penis with the drug phentolamine. Following the injection, Brindley appeared on stage and dropped his pants to display one of the first drug-induced erections to the incredulous audience of urologists.

To understand how to make a penis-specific drug, think about the way blood flows in your body. Your body has just one pump — the heart. But different parts of the body need different amounts of blood at different times. For example, if you’re running a marathon, your body needs to send more blood to your arm and leg muscles, and it may want to cut most of the blood flowing to the stomach (and other nonessential organs) in order to save oxygen for the legs.

What your body needs, in other words, is a set of valves that it can use to increase and decrease blood flow to certain parts of the body — and your brain needs a way to control them.

Chemistry behind the ED

viagra-chemicals

When couples talk about having “chemistry” together, who knew it was such an accurate description?

The brain sends signals to NANC cells in the artery. The NANC cells release nitric oxide (NO). Nitric oxide acts as a signaling molecule and stimulates an enzyme called guanylate cyclase in nearby cells. The guanylate cyclase converts a chemical called GTP into another chemical called cGMP. cGMP causes muscles in the walls of the arteries to relax. This relaxation increases blood flow. Meanwhile, PDE is decomposing the cGMP and turning it back into GTP. There is a cycle — guanylate cyclase turns GTP into cGMP, and PDE turns cGMP into GTP. Nitric oxide turns the cycle on.

If you want to create a drug that increases blood flow to the penis, there are at least three ways to do it:

Increase the amount of nitric oxide produced in the penis

Increase the amount of cGMP produced in the penis in response to the nitric oxide
Eliminate the PDE in the penis so that the cGMP builds up instead of getting decomposed by the PDE
Viagra uses method No. 3 — it eliminates the PDE that is decomposing the cGMP, so cGMP builds up in the penis and has a larger effect on the artery walls. The greater the amount of cGMP, the greater the blood flow, and the greater the blood flow, the greater the degree of the erection.

Earlier, we talked about the enzyme PDE. To better understand its function, consider that an enzyme is a specially folded protein that can speed up a chemical reaction. (For example, the article How Cells Work describes the maltase enzyme.)

In the accompanying diagram, you see that maltose is made of two glucose molecules bonded together (1). The maltase enzyme is a protein perfectly shaped to accept a maltose molecule and break the bond

(2). The two glucose molecules are then released

(3). A single maltase enzyme can break more than 1,000 maltose bonds per second, and will only accept maltose molecules.

very few drugs work perfectly, and Viagra is no exception.

The first problem comes because Viagra happens to have a spillover effect. It blocks PDE5, but it also has an effect on PDE6. It turns out that PDE6 is used in the cone cells in the retina, so Viagra can have an effect on color vision.­ Many people who take Viagra notice a change in the way they perceive green and blue colors, or they see the world with a bluish tinge for several hours. For this reason, pilots can’t take Viagra within six hours of a flight.

Viagra is a hugely successful drug, so other drug companies of course want a piece of the action. They developed different chemicals to block the PDE5 enzyme and created two new drugs: Cialis (tadalafil) and Levitra (vardenafil). (There is another drug, Staxyn, with the same active ingredient as Levitra that has recently come onto the market. It’s an orally disintegrating tablet that isn’t interchangeable with Levitra, but chemically is much the same.)

Because Cialis and Levitra block the PDE5 enzyme, they work exactly the same way as Viagra. They help men who have trouble maintaining an erection because of blood flow problems, and they only work when the man is sexually aroused.

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