Making Medicine Safe (page 2 of 3)

Deadly Doses and the Gene Screen

An estimated 106,000 Americans die each year due to adverse reactions to medications, according to most recent research. Consider: Nearly half of all drugs on the market -- including painkillers such as codeine, cholesterol-lowering statins, and antidepressants such as Prozac and Paxil -- are processed by enzymes controlled by a family of genes known as CYP450.

Mutations in these genes can have very different results. Some people have multiple copies of a gene called 2D6. Dubbed "supermetabolizers," these people will, for instance, get no relief from codeine because it's broken down so fast it has no effect. Others -- more than 15 million Americans -- have two bad copies of 2D6, making them poor metabolizers. This was the case for nine-year-old Michael Adams-Conroy, who suffered from Tourette's syndrome and obsessive-compulsive disorder. He was put on Prozac, but his body was unable to metabolize the drug, which built up toxic levels. He eventually had a seizure and died. His genotype was learned only after his death.

"If you're taking Paxil or Prozac and you're one of the 7 of 100 people, you're going to build up high levels of drug in your system," says David Mrazek, a child psychiatrist who chairs the department of psychiatry and psychology at the Mayo Clinic in Rochester, Minnesota. "If you're an adult, you'll normally stop taking it because you'll have headaches and be sick to your stomach. But if you're a six-year-old and you've been told to take this drug, it's tougher to say, 'No, I feel lousy. I'm not going to take it.' "

Mrazek's clinic can now test patients who are candidates for Prozac and other antidepressants. Thanks to a device called a genetic chip, Mrazek can identify with 99.9 percent certainty the form of the gene people have and thus how well they'll be able to metabolize the drug.

"What we've done in the past is to try to choose a medication that we believe will be helpful and then watch and see what happens. And if there is a bad reaction, we try another," Mrazek says. "There are now 23 different medications that can be used to treat depression -- it's a staggering number." Using this trial-and-error process, he says, it could take months to find the right medication.

Warfarin is one of the 20 most commonly prescribed drugs in the country. Every year, some two million patients take it to prevent blood clotting and stroke. But about 40,000 of them develop major bleeding. "It's an effective drug," says Brian Gage, associate professor of medicine at Washington University in St. Louis. "But if you get too much, it can kill you."

Nearly one-third of Americans have a variation of a gene (known as 2C9) that causes them to be poor metabolizers of the drug. According to a 2002 study, these people are nearly two and a half times as likely to suffer serious, life-threatening bleeding. In another study of 369 warfarin patients published in January, Gage and his colleagues concluded that by testing patients in advance and adjusting their dosage, they could reduce the number of potential overdoses from 16 percent down to 6.5 percent. "There are hundreds to thousands of major bleeds each year attributable to this variation. They could be prevented if patients were genotyped," Gage says.

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