Is Your Medicine Right for Your Metabolism?
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A growing array of genetic tests is designed to help predict how people are likely to respond to many common medications, from antidepressants and antihistamines to pain relievers and blood thinners. The tests, which are controversial, look for tiny variations in genes that determine how fast or slow we metabolize medications.
Because of such gene variations, codeine, frequently prescribed to relieve pain, has little effect on as much as 20% of the population, while 2% of people have such a strong reaction that a normal dose can be life-threatening. About 25% of people can’t effectively absorb Plavix, a clot-busting drug, putting them at increased risk for a heart attack or stroke. Even everyday drugs such as Advil and Motrin, for pain relief, and Zocor, to lower cholesterol, can have widely varying effects.
Testing patients for gene variations could avoid some of the 700,000 serious drug reactions in the U.S. each year, some experts say. Proponents of the tests, which are done with a cheek swab, say they also could help doctors rely less on trial and error in choosing the right drug and the right dosage for individual patients.
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Alan Pocinki, an internist in Rockville, Md., says he orders gene testing for patients who have a history of unexplained symptoms or who haven’t gotten relief from drugs in the past. In many cases, he is able to find a better treatment based on their DNA, he says. “It makes a huge difference clinically among people I see every day.”
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Scientists have since discovered that about 75% of prescription and over-the-counter drugs depend on a handful of liver enzymes to be absorbed and eliminated from the body. Minor variations in the genes that regulate those enzymes are very common—95% of people have at least one. People who get two impaired copies of an enzyme gene—one from each parent—are likely to be “poor metabolizers” and absorb drugs so slowly that even a normal dose can become toxic. “Intermediate metabolizers”—with one impaired and one normal gene—allow drugs to build up in the body and over time can cause side effects. People sometimes get extra copies of enzyme genes, which can make them “ultrarapid metabolizers” of some drugs and flush them out of the body so fast they have little effect.
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http://www.wsj.com/articles/is-your-medicine-right-for-your-metabolism-1457982384
Many common medications can affect people differently depending on minor variations in the genes that regulate key enzymes. The variations can make people metabolize certain drugs either more slowly or rapidly than normal. Some examples:
DRUGS
Pain relievers codeine or oxycodone, including Tylenol 3 and Percocet
ENZYME PATHWAY AT WORK
CYP2D6
IMPACT
A standard dose can have little effect in up to 20% of people, while as many as 2% can have a life-threatening reaction.
DRUGS
Blood thinner Plavix (clopidogrel) and acid reducers Prilosec (omeprazole) and Prevacid (lansoprazole)
ENZYME PATHWAY AT WORK
CYP2C19
IMPACT
Up to 15% of people metabolize these drugs very slowly, resulting in a higher effective dose and greater risk of side effects.
DRUG
Blood thinner Coumadin (warfarin)
ENZYME PATHWAY AT WORK
CYP2C9
IMPACT
People with some gene variants have twice the risk of severe bleeding, but other factors are involved and population percentages are unclear.
DRUG
Cholesterol reducer Zocor (simvastatin)
ENZYME PATHWAY AT WORK
SLCO181
IMPACT
Up to 40% of people have impaired ability to metabolize this drug, giving them increased risk of muscle pain and other side effects.
Source: Clinical Pharmacogenetics Implementation Consortium
