Viagra Helps COPD Patients Control Pulmonary Blood Pressure

The drug sildenafil, popularly known as Viagra, may help people with chronic obstructive pulmonary disease control the illness-related blood pressure spikes in the heart's pulmonary artery, a new study found.

The medication, in addition to its use as a popular treatment for impotence, has already been approved by the U.S. Food and Drug Administration for the treatment of the chronic version of such blood pressure spikes, known as pulmonary arterial hypertension (PAH). The drug has been marketed specifically for this purpose under the trade name Revatio. Another drug -- bosentan -- is also approved for similar purposes.

The new research suggests that sildenafil may help all chronic obstructive pulmonary disease (COPD) patients -- even those not diagnosed with full-blown PAH -- who experience potentially dangerous pulmonary arterial blood pressure increases both at rest and following exercise.

The research was led by Dr. Sebastiaan Holverda of the department of pulmonary medicine at VU University Medical Center in Amsterdam, the Netherlands. Holverda and his VU colleagues were to present their findings Wednesday at a Salt Lake City meeting organized by the journal Chest.

According to the American Lung Association, COPD is actually a catch-all for two lung diseases that often strike in tandem -- chronic bronchitis and emphysema. In both cases, airflow is obstructed, impeding normal breathing.

Smoking is the leading cause of COPD, responsible for between 80 percent and 90 percent of all cases in the United States. More than 11 million Americans are estimated to have the illness, and more than 122,000 die from it each year. Women appear to be slightly more at risk than men.

There's no known cure for the disease, and medications primarily take aim at symptom relief and slowing the progressive disability the illness brings.

Pulmonary hypertension -- the incurable condition of continuous high blood pressure in the pulmonary artery located in the right ventricle of the heart -- is one of many serious complications that can strike COPD patients. PAH causes the artery, which is responsible for delivering blood from the heart to the lungs, to work harder than normal. A weakening of the heart muscle can ensue over time, increasing the risk of heart failure and even death.

The Dutch researchers noted that pulmonary hypertension is typically mild to moderate among COPD patients but is particularly aggravated while exercising.

Faced with the combined COPD-PAH threat, the Dutch team explored the potential benefit of treating at-risk chronic obstructive pulmonary disease patients with sildenafil both while at rest and during exercise. The drug works by shifting the activity of an enzyme called phosphodiesterase, reducing arterial blood pressure by dilating the smooth muscle of blood vessels that line the lungs. As these vessels expand, blood flow increases, the researchers explained.

The study authors focused on 12 patients who had been diagnosed with chronic obstructive pulmonary disease and were suspected of having PAH. Throughout the study, right heart blood pressure was tracked among all 12 patients by inserting a thin plastic tube into the pulmonary artery -- a procedure known as cardiac catheterization. Cardiac blood pressure was measured at rest and just after all the patients cycled for three minutes.

Then, the study participants were given 50 milligrams of oral sildenafil; 45 minutes later, resting and post-exercise blood pressure readings were taken again.

Holverda and his colleagues found that half the patients had PAH. But, both non-PAH and PAH patients experienced significant cardiac blood pressure increases when exercising.

Sildenafil appeared to control such increases after exercise, reigning in pulmonary blood pressure to markedly lower levels -- higher than at rest, but lower than non-medicated post-exercise readings. And, the non-PAH patients appeared to experience pulmonary blood pressure reductions after taking the drug, both while resting and exercising.

The authors concluded that the drug may help COPD patients -- whether they have developed PAH or not -- quickly control their pulmonary blood pressure in some situations.

Dr. Bartolome R. Celli, chief of pulmonary care at St. Elizabeth's Medical Center in Boston, applauded the Dutch study but called for more research.

"Pulmonary arterial pressure -- when it is elevated -- is a poor prognostic sign and reducing its levels should be of help," he said. "However, more testing is needed to see if those changes in pulmonary arterial pressure are translated into better clinical outcomes and not into any unwanted side effects."

Could a widely used treatment for depression be a remedy for osteoporosis?

Researchers have discovered that the drug Prozac also increases bone mass, at least in adult mice.

"Treating animals for six weeks with Prozac resulted in an increase in trabecular bone mass," said study lead author Ricardo Battaglino, assistant member of the staff in the department of cytokine biology at the Forsyth Institute in Boston. "It was a pretty significant 60 percent increase."

Trabecular bone is one of two main types of bone and makes up most of the spongy interior of the majority of bones.

Although it's way too early to advocate popping Prozac to reverse or stop bone loss, experts say it's a tantalizing lead for future research.

"For several reasons, people need to be cautious because fluoxetine [the generic name for Prozac] has central nervous system effects," said Dr. Grant Mitchell, chief of psychiatry at Northern Westchester Hospital Center in Mount Kisco, N.Y. "But it is interesting that current treatments for bone loss in osteoporosis do not take this approach, so the idea that we could at some point have another approach to reducing bone loss or even rebuilding new bone is actually exciting. Having more options would be great."

The study, which was funded by the U.S. National Institute of Dental and Craniofacial Research, is expected to be published in an upcoming issue of the Journal of Cellular Biochemistry.

Previous research, some of it by the same team, had found that serotonin receptors were commonly expressed on the surface of bone cells. Serotonin receptors govern the entry of serotonin -- a molecule that helps transmit signals between neurons and is implicated in anxiety and depression -- into cells.

Prozac is a member of a group of antidepressants called "selective serotonin reuptake inhibitors" (SSRIs) that act on this receptor.

The fact that these receptors populated bone cells "was surprising for us," Battaglino said, "because we were taking bone cells and serotonin, two molecules that apparently didn't have much to do with each other."

The next question was whether Prozac, which has an effect on serotonin, also exerted an influence on bone cells and, ultimately, bone mass.

For this study, laboratory mice were treated with Prozac for six weeks. The investigators were specifically interested in seeing if the drug stimulated new bone formation under normal conditions and if it blocked bone loss caused by inflammation or by loss of estrogen after taking out the ovaries.

Prozac both spurred the formation of new bone under normal conditions and reversed overall bone loss triggered by inflammation.

The drug was administered both systemically (like taking a pill) and locally (directly to the bone), and the effects were observed with both delivery methods, the researchers reported.

"They developed a way to deliver locally to the bone, which makes more sense," Mitchell pointed out. "The idea there would be to avoid the [potential] brain effects."

Oddly, a prior study using Prozac found that the drug actually hindered bone growth. The discrepancy may have been due to the way bone mass or density was measured and also to the fact that it involved children, not adults, Battaglino said.

In the new study, Prozac was not effective in female mice without circulating estrogen (i.e. after their ovaries had been removed). In those cases, Prozac "did not prevent bone loss associated with estrogen deficiency," Mitchell said. "It looks like, to be effective in relation to bone loss, Prozac needs to be in the presence of estrogen." This has implications for women moving into menopause who lose estrogen and have an increased risk of osteoporosis, he said.

The findings need to be replicated and, of course, tried in humans, but, given the number of people taking Prozac, the implications could be enormous.

"Fluoxetine is one of the most widely prescribed psychoactive drugs in this country and most likely the world, and it's been like that for at least 15 or 20 years," Battaglino said. "From the public health point of view, this would be pretty relevant."

The jury is still out on whether other SSRIs -- such as Celexa, Paxil and Zoloft -- might have the same effect on bone, Battaglino added, since similar tests on those drugs haven't yet been performed.

"This could be a class effect for SSRIs," he said. "However, it is known that in addition to blocking the serotonin transporter, Prozac can target other molecules -- for instance, some nicotinic acetylcholine receptors and even some serotonin receptors. So, this effect could be specific for Prozac. The experiments will have to be done to answer the question."