What goes up must come down.

Viagra's glory story may be tainted--the potency pill doesn't mix well with protease inhibitors or recreational drugs

Before it even was introduced on the market, Viagra had achieved the kind of fame usually reserved for Hollywood superstars. As an easily used drug that can successfully treat male impotence, Viagra became the hottest topic in the media and provided an enormous boost to the stock of its manufacturer, Pfizer Inc., as doctors wrote tens of thousands of prescriptions in its first two weeks of availability alone. But now that the little blue pill is the Titanic of medications, doctors and mental health experts are warning gay men about the drug's potential downsides.

"I have never seen in my career a greater demand for prescriptions before a drug was released," says Gary R. Cohan, a physician at Pacific Oaks' Medical Group in Los Angeles. "There's a great demand, but there are a couple of interactions gay men need to know about."

However, dangerous side effects or not, doctors believe some men may rush to the drug without fully exploring whether they need it. "I would really caution people not to see it as a panacea but as something useful after they and their doctor work out what else is going on," says Kenneth Mayer, professor of medicine and community health at Brown University.

Viagra, treats impotence by acting on an enzyme that causes erections to subside. In men with erectile dysfunction, the enzyme is stronger than GMP, the body chemical that initiates erections. Viagra keeps the enzyme from breaking down GMP, letting it produce an erection without interference. Doctors recommend that patients take Viagra a half hour to an hour before sexual activity.

Within weeks of Viagra's introduction, AIDS Treatment News and the Gay and Lesbian Medical Association both issued alerts about potentially serious interactions between Viagra and other drugs. Their concern centered on two different circumstances during which the drug may be used: in combination with protease inhibitors and in combination with poppers, a class of recreational drugs used by some men to enhance sexual feeling.

Benjamin Schatz, executive director of the medical association, says Pfizer approached his group to discuss potential problems. "It speaks well for them," Schatz says. "Imagine a pharmaceutical company approaching a gay and lesbian medical group about something not HIV-related. On that level what they did is really important and should be applauded."

In the case of protease inhibitors, the drugs work on the same enzyme as Viagra. "Viagra is metabolized by the same enzyme that metabolizes 1protease inhibitors," Mayer says. "It's not thought that Viagra itself will influence the levels of protease inhibitors in the blood, but protease inhibitors, particularly ritonavir, can raise Viagra levels." Viagra also interacts with certain antibiotics, such as erythromycin.

Mayer says the potential side effects of the interaction are still unknown, although even at high doses Viagra does not seem to cause any long-term, serious medical problems. "Whether it translates into longer-lasting erections or more headaches is not clear," he says. "In the scheme of things, a protease inhibitor study is medically necessary, particularly when you're dealing with people who are otherwise doing well." Medical experts advise men taking protease inhibitors to limit their dosage of Viagra to 25 milligrams, half the normal suggested dose.

The issue is of particular concern because impotence is a common problem among men with HIV. Often the difficulty is caused by lowered levels of testosterone in the blood. "Viagra would probably work best in people with HIV-related erectile dysfunction if they are getting testosterone," Cohan says. "You first have to get the libido back, and then Viagra helps the blood flow to happen properly."

However, the causes of impotence are many. Viagra could make it easy to overlook some of the thornier issues, such as depression, that result in impotence. "It would be a shame if people don't see if something else is going on," Mayer says.

The other potential drug interaction of concern to gay men is with poppers, liquid nitrates that when inhaled cause blood pressure to drop and, for some, heighten sexual pleasure. Although the version of the drug widely used during the 1970s and '80s, amyl nitrate, can no longer be obtained legally, other versions have been enjoying increased popularity.

"Viagra is absolutely contraindicated with poppers," Cohan says. "It can cause the blood pressure to drop suddenly. Those are warnings I'm putting up in my exam rooms today." A dramatic drop in blood pressure could lead to fainting, shock, or even death. Mayer warns that other results would be less horrible but still painful: "You'd be well advised not to be standing up where your head might hit something sharp."

Often lost in the hoopla over Viagra is the fact that it is not an aphrodisiac. It cannot produce erections in the absence of desire, which is what releases GMP into the blood in the first place. Nor is there any evidence that it can promote greater staying power or more intense orgasms in men who have no problem getting an erection.

Nonetheless, the buzz about the drug has already made it a hot item on the black market, where pills go for about $16 each, roughly 60% more than the typical retail price of the drug. As a result, some health experts are concerned that gay men will turn to Viagra as a new recreational drug.

"I'm reluctant to stereotype gay men as a group, but there is a certain segment of the community where other drugs are abused in the context of sex," Schatz says. "So a drug that has a cultural reputation of enhancing sexual prowess could be abused in situations in which people are desirous of having multiple partners or greater staying power."

So far, the drug is too new to have had much of an impact on potential abusers. "It's kind of early," says David Schwing, director of Project Connect, the drug and alcohol program at the Lesbian and Gay Community Services Center in New York City. "It has not come to our attention at this stage of the game. People really don't come in and start talking a out these things immediately."

"There's always the opportunity for abuse, but at this point it hasn't come up," says Marc Malvin, a mental health clinician specializing in addiction at the Los Angeles Gay and Lesbian Center. "A little further down the line, we may see it come up more. It's something we have to be diligent about."

The primary concern is that some gay men will see Viagra as an antidote to the side effects of crystal meth, which arouses desire but can also cause impotence. The possibility that Viagra would restore potency could have a potentially disastrous impact on AIDS prevention.

"You will suddenly have a group of people who mercifully have not been able to be hypersexual and now would become quite potent," Cohan says. "That could be a problem. If it emboldens people to use more drugs, that's the last thing the community needs."

But Cohan says his bigger concern is the issue of dependence. "Men may be turning themselves into a subculture of pill poppers: to grow hair, to get erections, to keep HIV in check," he says. "The gay community has almost become the Valley of the Dolls. If they don't need the pill, they shouldn't be using it. I've had a number of patients with normal erectile function ask about Viagra because they think it may enhance it. Psychologically, people think they need to have the drug to have sex, and that's kind of sad."