As many as 10 percent of people do not receive pain relief from opioids.
The pain was too intense to ignore. Sixteen years later, Tony Cirrincione still remembers it. He was on a weekend ski trip, and he staggered into the ski lodge, leaving his wife in charge of their son and the five other Cub Scouts they’d brought along. Wincing at the dull ache in his back, he tried to stretch away what had to a muscle cramp. But the bursts of pain grew only more intense, erupting at more frequent intervals. Soon he was in the emergency room in Chicago. Kidney stones that had him doubled over the triage station. Waiting for the prescription opioid Dilaudid (hydromorphone) to take hold. But it never did.
According to Genome Magazine, as many as 10 percent of people do not receive pain relief from opioids. That’s a staggering statistic in a country where more than 75 million people live with chronic pain. Many individuals, like Cirrincione, who don’t respond to certain prescription pain relievers have no idea why. But a type of genetic testing is bringing answers to a growing number of them.
It’s not only pain medications that are implicated. Gene variants could also interfere with about 100 to 150 of the 1,200 Food and Drug Administration approved prescription drugs on the market today. That may seem like a small number, but consider the burden of the conditions these drugs treat – depression, heart disease, among others. Some gene variants can render drugs useless. Others may mean a person needs a larger or smaller dose than the standard. Still other variants could put a patient at risk for potentially serious side effects. Genetic variability could explain some of the one million emergency room visits that adverse drug reactions cause every year.
Until recently, we took it for granted that risks of poor effectiveness or toxicity go hand in hand with taking medications. But the growing field of pharmacogenomics is turning that assumption on it head. Although genes won’t explain all of a patient’s variable responses to a medication, a pharmacogenomic test from a simple cheek swab could help predict a person’s individual response to a medication before the doctor ever writes the prescription.
Opioid pain medications work by attaching to receptors in the brain, spinal cord, gastrointestinal tract, and other organs to reduce the perception of pain. A number of variations in several different genes can affect how well these drugs work in a given person.
Variations in the CYP2D6 gene can make a person either a poor or an ultra-rapid metabolizer of certain opioids. Take codeine, for example. The body activates codeine by converting it into morphine, and it’s the morphine that delivers most of the pain relief. A poor metabolizer of codeine doesn’t convert the drug into morphine. A rapid metabolizer quickly converts a higher amount of codeine to morphine, putting the patient at risk for toxic levels in the bloodstream.
Including pain meds, CYP2D6 variants impact some 40 known medications, such as the metabolism of pimozide for Tourette syndrome and tetrabenazine for Huntington’s disease. As with many genes, such as those that code for eye and hair color, drug-related gene variants can be more prevalent in one subset of the population than another. Up to 10 percent of Caucasian people carry CYP2D6 variants that interfere with drug metabolism. Fewer than 1 percent of Asians carry the variants. In some African populations, carrier rates may be as high as 35 percent.
Not all opioids are metabolized by CYP2D6, though. That’s why poor metabolizers of one drug might benefit from a larger dose of that drug or a standard dose of a different drug. Rapid metabolizers might benefit from a lower dose, which would lower the risk of accumulating toxic levels of medication in the bloodstream. Or, like poor metabolizers, they might be better off with another drug.
FDA Warnings
The FDA requires pharmacogenomic warnings on the labels of about 100 drugs. In some cases, the label recommends that prescribers test for a particular gene variant before prescribing the drug.
Clinicians are hopeful, though, that the healthcare system will soon be more conducive to preventive pharmacogenomic testing and even provide informatics and financial support for it. “I think a lot of people’s minds will change in health institutions and insurance companies when you can prove that this pre-emptive genetic testing actually saves money in the long run by avoiding adverse events that are extremely expensive for the healthcare system,” said Stuart Scott, an assistant professor of genetics and genomic sciences at Mount Sinai Hospital Icahn School of Medicine in New York City.
The tide may be turning already. The American Society for Health-System Pharmacists predicts that most U.S. regions will have a formal hospital pharmacogenomics program within the next five years.
‘If you’re the person who can’t get any pain relief from that codeine that your dentist prescribes you, or if it’s your mother that’s crying in pain from osteoarthritis, you care about it a lot,” said Scott. ~ Genome Magazine
PGx Medical works with physicians, pharmacists and clinicians in Aging Services across the country educating and implementing pharmacogenomic testing.
For more information on pharmacogenomics, contact:
PGx Medical
info@pgxmed.com
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