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Did you know DNA affects how you respond to pain medications?

Genetic guidelines to navigating the sea of pain medicines

A stubbed toe, a pricked finger or a mosquito bite might inflict you with fleeting moments of pain. A rub, a bit of pressure, or a scratch later, can help the feeling to pass, and you will have soon moved on. A root canal, or an appendectomy on the other hand calls for the ‘big guns’. Something in the lines of lidocaine or codeine that can numb the pain. In the middle of these two extremes are the over-the-counter pain relievers, such as Advil or Tylenol, and they will see you through the flu, an earache or a headache.

Most of us are quick to reach for painkillers, yet very rarely do we stop to consider their consequences. What if you could know the risks before you take a pain medication? Whether you are likely to overdose on fentanyl or if taking ibuprofen might lead to bleeding in the stomach? Pharmacogenomics can tell you just that, and all it takes is an analysis of your genes.

Our responses to medications depend on how they are processed in the body. Some drugs (e.g. codeine) have to be converted to an active form (morphine), before enabling pain relief. While the effectiveness of ibuprofen depends on how fast it is broken down. These processing steps make use of many enzymes, which means anything that can influence the activity of those enzymes will affect the quality of pain relief we receive from a medication. Pharmacogenomics identifies genetic variants that affect the function of these enzymes. These variants explain ~95% of the differing responses to pain medications. 

Cytochrome P450 (CYP450) is a class of enzymes found in the liver responsible for the break down of not only drugs, but also fats, hormones and toxins. Genetic variants of six members in this family have been implicated in the metabolism of pain medications. One of the best studied is CYP2D6. This enzyme metabolizes about a quarter of the prescription medications in use today, including some opioids. Over 100 variants of CYP2D6 are known, most of them either decreasing or completely abolishing the activity of the enzyme. Giving codeine (a medication activated by CYP2D6) to someone with little or no CYP2D6 activity will not give that person much, if any, pain relief.

On the other hand, there are variants associated with higher CYP2D6 activity. These ‘ultra-rapid metabolizers’ are more likely to overdose on opioids, because they activate the drugs much faster than normal. Both poor and ultra-rapid metabolizers are better off taking something like morphine or a non-opioid like ibuprofen for pain relief.

Cytochrome gene variants are not the only ones that affect metabolism of pain medications. TMPT is an enzyme that acts on Azathioprine, an immunosuppressant used to treat autoimmune diseases. People with TMPT gene variants have lower enzyme activity, so giving them standard doses of azathioprine can cause bone marrow toxicity. The MTHFR gene is another example where inheriting a variant can increase the risk of methotrexate toxicity. The MTHFR variant also reduces enzyme activity, so the chemotherapeutic agent sticks around longer in the body, increasing the risk of side effects. These are just a few of the many examples of genes that impact the efficacy of pain medications.

None of us plan to be sick, or deliberately choose to be in a situation that will cause us physical injuries and pain, yet we know life just happens. Just like a red bracelet on a patient’s wrist warns the doctors against administering penicillin, your pain medication genetic profile will make the choice of pain reliever much easier. 

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