Structural Biochemistry/Viagra (Sildenafil Citrate)

Viagra (Sildenafil Citrate)

Sildenafil Citrate, more commonly known as Viagra, is a drug that is used to treat erectile dysfunction and pulmonary arterial hypertension (PAH). The main function of the drug is to inhibit the enzyme that degrades cGMP, a regulator of blood flow to the penis. The medical uses for Sildenafil Citrate are sexual dysfunction, pulmonary hypertension, and altitude sickness.

In 1998, the drug Viagra was introduce as an effective way to treat male erectile dysfunction (MED). It goes by the generic name of sildenafil citrate. It has quickly become one of the most popular and most prescribed drugs in the world. Its annual sales account for over a billion dollars each year. Sildenafil was synthesized by a group of pharmaceutical chemists working at Pfizer’s research facility in England. It was discovered by accident while attempting to produce a drug to treat coronary heart disease. It became the first oral treatment accepted by the FDA to treat MED.

Physical Properties

Sildenafil citrate is designated chemically as 1-[[3-(6,7-dihydro-1-methyl-7-oxo-3-propyl-1H pyrazolo[4,3-d]pyrimidin-5-yl)-4-ethoxyphenyl]sulfonyl]-4-methylpiperazine citrate. Sildenafil citrate is a white to off-white crystalline powder with a solubility of 3.5 mg/mL in water and a molecular weight of 666.7. Viagra (sildenafil citrate) is formulated as blue, film-coated rounded-diamond-shaped tablets

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  Step-by-step synthesis of Viagra

Mechanism

The mechanism of Viagra (sildenafil) in the body involves the protection of cyclic guanosine monophosphate (cGMP) from degradation by cGMP-specific phosphodiesterase type 5 (PDE5) in the corpus cavernosum of the male penis.

First, nitric oxide (NO) in the corpus cavernosum of the penis binds to guanylate cyclase receptors. This results in an increase of cGMP, which promotes vasodilation of the intimal cushions of the helicine arteries. Vasodilation of the intimal cushions allows for an increased blood flow into the spongy tissue of the penis, thus, causing the erectile tissue to expand and create an erection. Sildenafil is a potent and selective inhibitor of cGMP-specific phosphodiesterase type 5 (PDE5), which is responsible for degradation of cGMP in the corpus cavernosum. Once cGMP levels deplete, then the intimal cushions of the helicine arteries are not able to dilate to allow more blood flow. Without sexual stimulation, and therefore lack of activation of the NO/cGMP system, sildenafil should not cause an erection.

Alcohol

Ethanol and sildenafil cause similar reactions within the body. Therefore, doctors do not recommend consuming alcoholic beverages while taking the drug. Ethanol thins blood and dilates blood vessels which can cause dizziness, rapid heart rate, and low blood pressure. Sildenafil causes the same effect on the body which can cause a dramatic increase in the potential of suffering these effects.

PDE5 inhibitor

It belong to a family of drugs called PDE5 inhibitors. Sildenafil acts by inhibiting cyclic guanosine monophosphate(cGMP)-specific phosphodiesterase type 5, an enzyme which is responsible for degradation of cGMP in the corpus cavernosum in the penis. Nitric oxide in the corpus caverosum then binds to guanylate cyclase receptors, which leads to increased levels of cGMP, leading to smooth muscle relaxation. The molecular structure of sildenafil is similar to that of cGMP and acts as a competitive binding agent of PDE5 in the corpus cavernosum, resulting in more cGMP and better erections. Sildenafil is metabolised by liver enzymes and excreted by both the liver and kidneys. If taken with a high-fat meal, absorption is reduced; the time taken to reach the maximum plasma concentration increases by around one hour, and the maximum concentration itself is decreased by nearly one-third.

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  PDE5

Reactivity

This molecule is very sensitive to temperature and light therefore it has to be kept at room temperature between 15-30 degrees C away from moisture or heat. Also if exposed to prolonged period of time to light it can cause a molecular reaction.

Erectile dysfunction (ED)

Erectile dysfunction is a sexual dysfunction which is shown by the inability to maintain an erection of the penis during sexual intercourse. Because penile erection is a hydraulic effect of blood rushing into the penis and retained in sponge-like pores, erectile dysfunction is cause by circulatory mishap. One of the causes of ED is the modification of voltage-gated potassium channels, which play a major role in action potentials during depolarization. However, there are many other causes of ED such as diabetes, hormonal deficiencies, and neurological problems. Major drugs that are believed to cure ED are Viagra, Cialis, and Levitra and are under competition in the pharmaceutical market.

Treatment

According to a research, erectile dysfunction increases with passing age. Approximately 20% by the age of 60, though in the 21st century psychological factors such as (stress, depression and anxiety), medication, disease and injury is speeding up the process earlier then age. It is estimated than 70% of the population in United States suffer from erectile dysfunction due to an underlying disease like kidney condition. While smoking increases the chances by 50%. It was shocking to know that only 33% out of those only look for some advice or medical assistance, because this is the reason for 35% of the breakdown of relationships.

Effective treatment in such scenarios include injecting medication into the penis, changing one's lifestyle my reducing the amount of cigarette or alcohol consumed. Losing weight, and following an exercise regime that improves blood flow also helps. Vacuum pumps are also helpful since it encourages blood flow and makes the penis erect.

Side Effects

Halt taking viagra immediately if you present one or more of the following symptoms:

• hives
• difficulty breathing
• swelling on the face, lips, throat or tongue
• vision loss
• ring in the ear
• chest pain
• irregular heartbeat
• swelling in limbs
• shortness of breath
• vision changes
• penis erection for over 4 hours
• light headedness

Less serious conditions may include:

• stuffy nose
• headache
• memory problems
• upset stomach
• back pain

References

http://www.drugs.com/sfx/viagra-side-effects.html

Delar, Anthony. “Viagra with excessive use of alcohol may affect your erections negatively.” ArticleBiz.com. 2010. Sat. 20 Nov 2010.
http://www.articlebiz.com/article/532090-1-viagra-with-excessive-use-of-alcohol-may-affect-your-erections-negatively/

Wikipedia contributors. "Sildenafil." Wikipedia, The Free Encyclopedia. Wikipedia, The Free Encyclopedia, 18 Nov. 2010. Web. 22 Nov. 2010.
http://en.wikipedia.org/wiki/Sildenafil

“Viagra.” Drugs.com. 18 Oct. 2010. Sat 20 Nov 2010.
http://www.drugs.com/viagra.htm

Vollhardt, K. Peter C. “Organic Chemistry: Structure and Function.” Fifth Edition. W.H. Freeman and Company, New York 2007. Pg. 1176-1177