What is Viagra?

Viagra (sildenafil citrate) is a medication made by Pfizer Pharmaceuticals, and is the first approved non-surgical treatment for erectile dysfunction (ED) that does not have to be either injected or inserted directly into the penis to achieve and maintain an erection. It was approved by the US Food and Drug Administration (FDA) for prescription sale at the end of March, 1998.

Development History of Viagra

Originally developed by Pfizer as a drug to help men who were suffering from chest pain, sildenafil citrate as a heart medication did not show promise and studies were stopped in 1992.

However, based on published information about some properties contained in sildenafil citrate, Pfizer researchers began to look at it as a treatment for erectile dysfunction. It was re-evaluated for its effect on the ability of men with ED to engage in sexual activity, and the ability to achieve and maintain erection sufficient for satisfactory sexual activity.

Eventually, 21 randomized, placebo-controlled clinical trials involving more than 3700 patients, ages 19 to 87 years, were held worldwide. The participants had varying degrees of impotence associated with the following:

• diabetes
• spinal cord injury
• history of prostate surgery
• no identifiable organic cause

Some patients also had coexisting illnesses, including hypertension and coronary artery disease.

The clinical trials found Viagra to be so effective, the FDA approved it only six months after submission, and without consulting an advisory committee of outside experts because there were no troubling questions and no significant side effects.

What are the General Precautions for Taking Viagra?

Healthcare professionals advise cautious optimism when considering using Viagra. Although data from the clinical trials are very promising, prospective patients must have realistic expectations. The drug is not an aphrodisiac, and does not change libido or desire. Viagra does not directly cause penile erection, but affects the response to sexual stimulation.

The FDA recommends that men follow these general precautions before taking Viagra:

• If you are taking medicines that contain nitrates, such as nitroglycerin, you should not use Viagra. The two taken together can lower blood pressure too much.
• Viagra should not be used by women or children.
• Have a complete medical history and physical examination to determine the cause of your erectile dysfunction.
• Men with medical conditions that may cause a sustained erection such as sickle cell anemia, leukemia or multiple myeloma, or a man who has an abnormally shaped penis may not be able to take Viagra.
• Tell your physician about all the medications you are taking - including over-the-counter ones - because there are medications known to interact with Viagra.
• Viagra's use in combination with other ED treatments has not been studied, therefore, its use in combination with other treatments is not recommended.

Possible Risks
Between March and November 1998, the FDA investigated more than 200 reported cases that involved death or serious illness. Many cases were eliminated because of unverifiable information. They concentrated on 130 deaths of men who had been prescribed the drug. Of these, "two men died from homicide and drowning; three had strokes; and 77 had cardiovascular events (41 with definite or suspected myocardial infarction, 27 with cardiac arrest, 6 with cardiac symptoms, and 3 with coronary artery disease). Cause of death was unmentioned or unknown for 48 cases."

The FDA acknowledged that number of deaths is a small percentage of the 6 million prescriptions written in that time period, and that "An accumulation of adverse event reports does not necessarily indicate that the adverse event was caused by the drug; rather, the event may be due to an underlying disease or some other factor(s)."

However, the FDA felt that label or enclosure information and warnings should be stronger. In November 1998, Pfizer revised the information in consultation with the FDA. The new labeling is intended to help make sure that consumers and doctors are fully informed about the:

• benefits and risks of using Viagra
• consideration that must be given to the cardiovascular status of patients prior to prescribing Viagra
• how to safely use Viagra

As with all approved medications, the FDA continues to monitor the safety of Viagra by carefully reviewing reports of death and other serious adverse events and will continue to evaluate the need for regulatory action.

Who Should NOT Take Viagra
According to FDA-updated information released in December 1998, the following people should not take Viagra:

• Men who are currently using medications that contain nitrates, such as nitroglycerin should not use Viagra because taken together they can lower blood pressure too much.
• Viagra should not be used by women or children.

Other FDA Warnings

Viagra was not studied in patients who have a history of the following conditions:

• heart attack, stroke, or life-threatening irregular heart rhythm within the last 6 months>
• very low and very high blood pressure
• heart failure or unstable chest pain
• certain eye disorders

Because of the blood pressure lowering effect of Viagra, your doctor will evaluate your overall medical condition to determine if this, in combination with sexual activity, could adversely affect your health.

Viagra may cause a rare but serious condition of prolonged erection (priapism). It is important to contact your health care provider immediately if your erection lasts longer than 4 hours. Men for whom sexual activity is inadvisable may not be good candidates for Viagra.

What are the side effects of Viagra?

In the clinical trials, when Viagra was taken on an as-recommended and as-needed basis, the following adverse events were reported:

• headache - 16 percent with Viagra; 4 percent with the placebo
• flushing - 10 percent with Viagra; 1 percent with the placebo
• indigestion - 7 percent with Viagra; 2 percent with the placebo
• nasal congestion - 3 percent with Viagra; 2 percent with the placebo
• urinary tract infection - 3 percent with Viagra; 4 percent with the placebo
• mild and temporary visual changes (blue/green color perception changes, light perception changes, and blurred vision) and also increased sensitivity to light or blurred vision. - 3 percent with Viagra; 0 percent with the placebo
• diarrhea - 3 percent with Viagra; 1 percent with the placebo
• dizziness - 2 percent with Viagra; 1 percent with the placebo
• rash - 2 percent with Viagra; 1 percent with the placebo

Side effects that occurred less than 2 percent included respiratory tract infection, back pain, flu syndrome, and arthralgia.

How does Viagra work?

The erection of the penis involves release of nitric oxide (NO), a chemical that is normally released in response to sexual stimulation, in the corpus cavernosum of the penis.

• Nitric oxide then activates an enzyme called guanylate cyclase, which, in turn, results in increased levels of cyclic guanosine monophosphate (cGMP).
• This produces smooth-muscle relaxation in the corpus cavernosum and allows the inflow of blood.
  
  [There are three types of muscles: smooth, cardiac, and striated. Smooth muscles are those that are involuntary in action and are found principally in internal organs.]
• Viagra (sildenafil citrate) has no direct relaxant effect on the human corpus cavernosum.
• Instead, sildenafil enhances the effect of nitric oxide (NO) by inhibiting phosphodiesterase type 5 (PDE5).
• PDE5 is responsible for degradation of cGMP in the corpus cavernosum, which causes the penis to become flaccid, or relaxed.
• When sexual stimulation causes local release of NO, sildenafil inhibits PDE5, which, in turn, causes increased levels of cGMP in the corpus cavernosum. This results in continued smooth-muscle relaxation, allows for inflow of blood to the corpus cavernosum, and erection of the penis.
• Sildenafil at has no effect in the absence of sexual stimulation.

Viagra for Men with Heart Disease

Viagra has received another approval for its use among men with severe coronary artery disease. The approval, the result of a study recently published in the New England Journal of Medicine, opens the door for discussion among physicians and heart patients wishing to take the medication.

With millions of men in the United States experiencing erectile dysfunction, and the overlap of risk factors often contributing to heart disease, the researchers felt there was a need to determine if the use of sildenafil was dangerous to heart patients. The risk factors for both erectile dysfunction and heart disease include older age, high blood pressure and cholesterol levels, and diabetes.

The study involved 14 men who ranged in age from 61 to 72 years of age. The men all suffered from severe coronary artery disease with nearly half of the participants also suffering from hypertension and diabetes. (Please note the small sample size used for this study.)

The men all had heart conditions stable enough to discontinue nitrate medication for at least 24 hours prior to the study. It is recommended that individuals undergoing nitrate therapy, often prescribed to manage the symptoms of angina pectoris or chest pain caused by coronary heart disease, should not take Viagra. The combination of the two medications can increase the risk of hypotension, which is potentially fatal.

The participants were given Viagra and then carefully monitored. Measurements of their arterial blood pressure, pulmonary capillary, and pulmonary artery pressures were recorded, as well as their heart rate and cardiac output.

The results found that there were no significant changes in coronary blood flow, heart rate, or cardiac output. The researchers also found slight reductions in systemic vascular resistance and pulmonary vascular resistance.

The study's authors conclude that Viagra does not negatively affect men diagnosed with severe coronary artery disease. In addition, the researchers were able to find a positive reaction with the drug improving the men's coronary blood flow reserve.

This is not the first time the medication has received the green light for use among heart patients. The American Heart Association also supports Viagra use if the patient's heart condition is stable and they are not undergoing treatment involving the use of nitrates.

Always consult your physician for more information.