If you suffer from chronic pain from conditions such as arthritis or sciatica and are looking for pain relief, chances are you have a bottle of either Advil® or Tylenol® in your medicine cabinet. Some people swear by Advil for pain management and denounce Tylenol as ineffective; others claim the opposite and swear by Tylenol. Some people encounter side effects from ibuprofen, others from acetaminophen. Why is this the case? The answer lies beneath your skin, within your genes. Knowledge of how your genetic makeup affects pain medication metabolism can be a powerful way to optimize your pain relief usage and dosage.
How does Advil work?
Ibuprofen, which is the active ingredient in Advil, belongs to a class of drugs known as nonsteroidal anti-inflammatory drugs (NSAID). This class of drug has wide ranging effects and is frequently used to reduce fever, inflammation and provide pain relief. Ibuprofen acts by binding to the cyclooxygenase enzymes (COX-1 and COX-2) which are encoded by the PTGS1 and PTGS2 genes. These enzymes function to convert arachidonic acid to prostaglandins, which are compounds within your body that are responsible for causing fever, pain and inflammation at the site of an injury. NSAIDs like ibuprofen temporarily block the function of COX-1 and COX-2 and by preventing prostaglandin production, these drugs block the inflammatory response and diminish the pain and fever associated with it.
Some side effects associated with ibuprofen are an increased risk of heart attack or stroke, stomach or intestinal bleeding, stomach ulcers, impaired kidney function, heartburn, nausea, dizziness and stomach cramps.
How does Tylenol work?
Acetaminophen is the active ingredient in Tylenol and is a proven analgesic (relieves pain) and antipyretic (reduces fever). It is used to treat a number of conditions, such as headaches, muscle pains, colds, fevers, backaches and arthritis. Acetaminophen increases the pain threshold by weakly and indirectly inhibiting the COX-1 and COX-2 enzymes and strongly inhibiting the more recently discovered COX-3 enzyme. Just like ibuprofen, acetaminophen acts as a pain reliever by decreasing prostaglandin production. Acetaminophen functions as an antipyretic by acting directly on the heat-regulating centers in the brain (specifically in the hypothalamus) to trigger vasodilation and sweating, which results in heat dissipation and a decrease in body temperature.
Some side effects associated with the use of acetaminophen include liver damage, nausea, pain in the upper stomach, itching, loss of appetite and jaundice.
Why do some people prefer Advil and others Tylenol and how does genetics play a role?
While ibuprofen (Advil) can start acting in as little as 30 minutes, it is also metabolized, inactivated and excreted by your body within 24 hours. Our genetic makeup encodes genes for enzymes that perform this drug metabolism. The CYP2C9 and CYP2C8 enzymes, encoded by the CYP2C9 and CYP2C8 genes respectively, are responsible for ibuprofen metabolism and break this drug down into products that are excreted in the urine. Similarly, acetaminophen (Tylenol) is metabolized and broken down by the CYP2E1 enzyme, which is encoded by the CYP2E1 gene.
Genetic variations in these drug metabolizing genes lead to varied responses in different people. People who carry mutations in the CYP2C9 or CYP2C8 ibuprofen-metabolizing enzymes that decrease their activity are considered “poor metabolizers” of Advil and clear this medication at a much slower rate than most of the population. Advil therefore remains in their system for a longer period of time and this is why Advil is a better pain reliever for these people than Tylenol. On the other hand, people with a mutation in the CYP2E1 acetaminophen-metabolizing enzyme clear Tylenol more slowly than Advil. People with these CYP2E1 variations are therefore poor metabolizers of acetaminophen and for them, Tylenol is a better pain reliever than Advil.
Your genetics also play a role in your response to other treatments for chronic pain
Other classes of drugs have been used in order to treat chronic pain. In addition to ibuprofen and acetaminophen, antidepressants, such as duloxetine and venlafaxine, have been shown to have some analgesic properties. Anticonvulsants, such as Gabapentin, can be prescribed for chronic pain treatment
Just like for Advil and Tylenol, each of these drugs are metabolized by enzymes and an individual’s genetic makeup plays a key role in determining that metabolic rate. There are many more examples of analgesic drugs where genetic differences lead to varying responses, including codeine, celecoxib, phenytonin, naproxen and diclofenac.
How can pharmacogenetics help me choose the right pain reliever?
People suffering from chronic pain often feel as though they are fighting a losing battle and may resort to extreme measures for relief. Managing chronic pain can be difficult and may require trying many different treatments, but scientific and medical advances have shown that pharmacogenetics and an understanding of the genetics of pain treatment metabolism can substantially improve pain management.
If you suffer from chronic pain such as from conditions such as arthritis or sciatic, your pain management can be greatly improved through genetic testing and personalized medicine. In concert with your team of medical professionals, a personalized pain management plan developed from drug response tests can reduce the time needed to select analgesic drugs that are effective for you, improve your pain relief, optimize dosage, and minimize your suffering. GeneYouIn’s PillCheckTM genetic test can help with your pain management by identifying any genetic variations that could affect your drug response and can help you answer the question “which painkiller is best for me, Tylenol/acetaminophen or Advil/ibuprofen?”. Click here to learn more about how genetic variations can affect your drug response, subscribe to our newsletter for updates and news about the genetics of drug response and follow us on Twitter and Facebook for the latest news on the genetics of pain management.