- The Washington Times - Monday, October 31, 2005

The many warnings sounded of late about the adverse effects of certain prescription drugs are counterbalanced by a more positive trend: an increase in the number of so-called double-duty drugs — medicines that treat two medical conditions.

Their existence is well-known; many have a long history. For instance, a drug approved by the Food and Drug Administration in 1979 to treat high blood pressure also was found to be equally good at — and eventually approved for — treating hair loss. It is sold under the brand name Rogaine.

Wellbutrin is an antidepressant that has been found to help some patients who are trying to stop smoking. Viagra, another well-advertised brand, originally was thought to help reduce hypertension when investigators stumbled upon its better-known application: correcting erectile dysfunction.

The list of such drugs is long, and their generic names often resemble nothing so much as alphabet soup. They do not always provide clear clues to their primary application even when brand names “sound” justified. Terbutaline, for instance, is the generic name for an asthma drug often prescribed to help prevent contractions in pregnant women near term. AstraZeneca manufactures it under the brand names Brethine and Bricanyl.

Equally confusing to many people is the use of terms such as “off-label.” This refers to drugs that can be prescribed by doctors when research has shown the drug works for a certain condition other than one approved by the FDA. By law, the second use cannot be noted on the label; hence the name. Half or more of all prescriptions written are off-label.

A drug can be approved for one function while further studies are undertaken on its potential for another condition.

The generic drug misoprostal was approved by the FDA some years ago for treatment of ulcers, but alternative applications are still undergoing study in spite of its being known — and used — to induce labor by stimulating contractions of the uterus. It is sold under the brand name Cytotec.

Recent studies have shown that cholesterol-lowering statin drugs may help prevent bone fractures — a finding of special interest to older patients afflicted with osteoporosis. There are many types of statin drugs, and the latest study, published in the Sept. 26 issue of the Archives of Internal Medicine, does not make clear the dosages needed or time required for such treatment to be effective.

Such versatility doesn’t surprise pharmaceutical specialists, even if such dual-purpose uses can appear dramatic to a consumer.

“With some drugs, you are tempted to say, ‘What a leap of faith.’ Other times they are more obviously related,” notes Magaly Rodriguez de Bittner, associate dean for academic affairs at the University of Maryland School of Pharmacy and a spokeswoman for the American Pharmacists Association.

“We need to remember that drugs are chemical agents and not miracle pills,” she says, explaining how these substances work in the body.

“Drugs may affect a particular receptor among many similar receptors found in different parts or organs in the body. It’s like lock and key. If a drug is the key, you have to find the right lock or receptor that will produce a reaction. A lot of drugs are selective agents that target special receptors. They have a preference for one and affect others less. Nonselective agents, by contrast, can’t distinguish between the two.”

Advances in molecular biology are making it easier to develop so-called targeted drugs, she adds.

A label will give the primary indication for which the manufacturer has sought approval from the FDA, Ms. Rodriguez explains — meaning “the one that has produced the particular chemical effect that the FDA says is safe if used within specific parameters. Being chemical agents, that doesn’t mean there aren’t other effects.”

Discovery of a drug’s secondary use can come about in several ways. Clinical trials take place in a controlled environment with only a certain number of patients meeting certain criteria. When it comes on the market, a physician may find the drug works in other ways, too, because he or she treats a broader group of patients who have conditions other than the ones studied in the trials.

People using Wellbutrin as an antidepressant may have found they didn’t crave nicotine as much, and the drug eventually was approved for both uses.

Beta-blockers, Ms. Rodriguez points out, have been shown to prevent a heart attack by the way they work to reduce blood pressure. Some data also show that statins, which work on liver enzymes to decrease excessive

amounts of cholesterol in the

liver, may help prevent bone loss by simultaneously decreasing the amount of calcium lost.

“Often a drug will be used for one disorder and other symptoms will improve,” says Dr. Wayne Macfadden, U.S. medical director for AstraZeneca’s Seroquel, which the FDA approved for treating bipolarmania. Physicians used it off-label and then reported to the company that symptoms for depression improved as well. “We get inklings that way,” he says, calling the matter “an evolving science.”

Seroquel’s uses are related because both conditions refer to certain imbalances in the brain. Likewise, the antidepressant Prozac also was found to work for obsessive-compulsive disorders as well as other mental disturbances.

“A company may have an idea that a drug works for more than one thing, but it can’t do all the research at one time,” says Alan Goldhammer, a biochemist who is associate vice president for regulatory affairs at Phrma, the pharmaceutical trade association. “It will pick an area it thinks has the best, or earliest, chance of succeeding. They get approval for the first and continue to follow up for other indications.

“A lot of biotechnology drugs act on the immune system in various ways and tend to be effective against many kinds of diseases. The classic example is one of the first alpha-interferon drugs from about 20 years ago — a generic that acts on the immune system. They found it worked on five or six different diseases but was first approved for hairy-cell leukemia.”

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