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A Short History of Erectile Dysfunction and Viagra

11/19/2014
Defective Drugs
BY

A Short History

 

Viagra (sildenafil) was a breakthrough in the pharmaceutical world when it was first researched and released to the public. Never before had a pill been able to produce an erection. A groundbreaking (and likely very uncomfortable) presentation at the 1983 Urodynamics Society conference in Las Vegas by a Dr. Sir Giles Skey Brindley first demonstrated that erectile dysfunction could be treated through medicine rather than surgery. Penile implants were a popular surgical solution before the advent of drug therapy. Dr. Brindley, a psychiatrist, wasn’t satisfied with a surgical solution to what seemed like a simpler problem. At his infamous presentation, he tested papaverine (a chemical found in the opium poppy) and phentolamine which were injected directly into his penis.

Papaver somniferum (poppy bulb) showing the latex where papaverine can be derived.

Papaver somniferum (poppy bulb) showing the latex where papaverine can be derived.

Dr. Brindley used himself as a test subject and proudly displayed his results to the audience in the form of pictures and the effects of a very recent injection. You can imagine the effect he had on the audience. More importantly, Dr. Brindley opened the door to a new way of thinking about erectile dysfunction. Papaverine causes smooth muscle relaxation, and by injecting this chemical directly into the penis, Brindley had induced an erection. This finding is the key to understanding how Viagra and its drug cousins (Levitra and Cialis) work when ingested by patients. Dr. Brindley’s treatment, though slightly invasive, could induce an erection for 1 – 2 hours and could be used safely once a day and three times per week.

Even though Brindley showed that drug therapy could treat erectile dysfunction, the drug now known as Viagra was reportedly discovered by accident. Pfizer first discovered the chemical now known as sildenafil in the late 1980s.

The research team responsible for the discovery was first tasked with finding a chemical that might help expand blood vessels in order to treat angina, a common heart condition characterized by chest pain caused by decreased blood flow in the heart.

Pfizer’s researchers operated on a hypothesis that by selectively inhibiting an enzyme called PDE5, they might be able to produce the desired effect. Early tests showed that the first PDE5 inhibitor they produced (UK-92,480) only stayed in the body for a short time and had moderate effects on blood vessels. They did observe, however, that the chemical caused erections for several days after the initial dose. By tweaking the chemical to cause more immediate erections, history was made. The new drug was called Viagra and was patented in 1996. It was approved by the FDA in 1998 and became a hugely successful blockbuster drug, totaling $1.9 billion in sales in 2008. Even today, with the advent of generic drugs and other brand name competitors, like Cialis and Levitra, Viagra remains the #1 selling drug for erectile dysfunction.

Skin Cancer Risk

Viagra works by inhibiting the enzyme known as PDE5. This enzyme is prolific in vascular smooth muscle. Smooth muscle is spread throughout the body; in other words, it is not located only in the penis. Blood vessels are composed of smooth muscle. Even the eye is composed of smooth muscle. Viagra works by inhibiting an enzyme known for its constrictive properties. Basically, it works to lower blood pressure by “dilating” your blood vessels. The penis is full of blood vessels, and when the penis fills with blood, it becomes erect. However, PDE5 plays a very complicated role in the human body. Some researchers believe that by inhibiting PDE5, you may set off a chain reaction in the body that may affect and spread any melanoma cells you might have. Melanoma is a type of skin cancer, and can be incredibly deadly if not caught quickly.

How would Viagra cause skin cancer? It’s not believed that Viagra causes skin cancer at all. Rather, if you already have melanoma, Viagra, through its mechanism of action, can spread melanoma cells at a much higher rate than is normal. In other words, the melanoma becomes very invasive, very quickly. This can be deadly, and can eliminate certain treatment options that could be used if the melanoma was caught at an early stage. This is just a theory right now, but a recently released study in June of 2014 supports this theory of how Viagra could promote melanoma with real evidence.

For now, users of Viagra should consult with their doctors to discuss the known risks versus benefits of the drug to determine whether it is still beneficial in light of this latest safety concern. Also, those patients who are already at a high risk for developing melanoma or other skin cancers should also discuss this latest study with their prescribing physician.

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