Health rising blog post, by Cort Johnson, 20 April 2018: Pain, Genes, Drugs and You: How Your Genetic Makeup May Be Keeping You in Pain
From Dr. Trescott’s lecture given to the Physician Partners of America: “Your Genes, Your Pain Drugs and You Or “Why Every Pain Physician Should be Testing Your Genes“
When the patient says, “This doesn’t work,” or, “I’ve been too sensitive,” or, “My mother had a terrible time with medicine X and I’ve had a terrible time with medicine X”, that should really tell you there’s likely to be a genetic problem there. Trescott
We know that many people with fibromyalgia and chronic fatigue syndrome respond very differently to drugs. A drug that works great for one person might have no effect in another person or even make another ill.
Why such variability? I’ve long assumed this meant that many people diagnosed with ME/CFS and FM actually have a different illness, but a recent lecture presented by the Physician Partners of America suggested that’s not necessarily true. It’s possible that underlying genetics or epigenetic changes which affect how our metabolism breaks down substances could play a role.
How you respond to a drug partly comes down to your genes. The human race is very variable genetically. A lot of that variability lies in small genetic variations called gene polymorphisms which can alter how effectively that gene works. These polymorphisms can have no effect or cause the gene to work less or more effectively.
Most people are normal – they have two “good” copies of a gene which allows them to metabolize substances properly. A significant number of people, however, have “good” and “bad” copies of a gene which can inhibit their ability to break down drugs. A smaller number of people (poor metabolizers) have two bad copies of a gene – they hardly break down some drugs at all.
Others with multiple copies of good genes (ultra-metabolizers) can find that even normal amounts of a drug can make them sick as they metabolize the drug into substances that cause harm. Rapid metabolizers of oxycodone, for instance, will produce high levels of oxymorphone, which causes nausea, sedation and other symptoms.
The pain field is a perfect place to look for genetic anomalies in drug metabolism because responses to pain drugs are all over the map. In fact, the process of producing a pain sensation is so complex that some despair of ever producing really effective pain drugs. Part of that complexity lies in the genes that produce the enzymes that break down pain drugs.
The lecturer, Andrea Trescott, MD, a well known pain researcher and doctor, provided a dramatic personal example of the effects a gene polymorphism can have. Her first clue that she might have some hidden genetic vulnerabilities came during a surgical procedure as she was giving birth when she was given Percocet. It had absolutely no effect on her pain.
That process repeated itself during an emergency dental procedure when she was given Percocet, once, twice, three times – and received no relief at all (nor experienced any side effects). She might as well have been eating sugar cubes.
A week later, she went back for another procedure and asked to be given Darvocet which knocked her pain levels out. Subsequently, she found out that genetic polymorphisms in her CYPD26 (or 2D6) gene left her unable to metabolize Percocet. (Ten percent of Caucasians are 2D6 deficient).
Years later, her son, who was also 2D6 deficient, was scheduled to have his wisdom teeth removed. Requesting that hydrocodone, which his genetic status suggested that he metabolized poorly, not be used, didn’t work. Stating that, “of course, he (the surgeon) blew me off”, her son got little relief from the hydrocodone, went back to the surgeon complaining of pain, and was labeled a drug seeker.
Take codeine. Codeine is inert – by itself it has no effects on pain – and has, like many opioid pain relievers, to be metabolized to morphine by the CYP2D6 enzyme to work. Morphine is then metabolized by another enzyme called UGT2B7 to M6G (morphine-6-glucuronide), which has pain-relieving properties. During that metabolic process, though, two other factors are released which can actually increase pain levels.
If you are not metabolizing codeine, you will get little relief from it. If you’re a super metabolizer taking large amounts of codeine, this could actually make your pain worse…
Read the full article for more information about drug metabolism and interactions, a gene called COMT and genetic testing to assess a patient’s response to a drug.