Answer: The ability for opioid medications to stop pain depends on certain liver enzymes, among other factors.
Opioid painkillers, such as morphine, are commonly used in the clinic. These drugs work by blocking the sensation of pain through activating brain circuits that communicate with the spinal cord. When recovering from a major surgery, a patient might be given a morphine drip or a pill containing a slow release oxycodone. Both morphine and oxycodone are opiate drugs.
For many people, opioids are effective at blocking pain; they are the most effective analgesic drugs that are currently available. However, these drugs do not always work for everyone. Some people can take morphine and not experience a strong painkiller effect. For these people, a non opioid painkiller, such as ibuprofen or aspirin, may be more effective.
There are several possible reasons why this may happen.
Genetics of opioid processing enzymes
In a health care setting, it may be preferable to treat the patient with a less potent opioid medication, which may have lower addiction potential. Hydrocodone and tramadol fit this category, and are sometimes referred to as first-line opioids.
After these drugs enter the bloodstream, they are processed by enzymes in the liver. One of the key enzymes used in opioid metabolism is a form of the cytochrome P450 called CYP2D6. When this enzyme interacts with hydrocodone or tramadol, it creates a byproduct with significant opioid activity. These byproducts actually have a stronger ability to bind to and interact with the opioid receptors than the original compound. Due to random variations in genetic sequences, some people have a version of the CYP2D6 enzyme that is less effective. For these people, a higher dose of the opioid is needed before they experience the same degree of analgesia (Impact of CYP2D6 Pharmacogenomic Status on Pain Control Among Opioid‐Treated Oncology Patients).
Closely related is another liver enzyme called UGT2B7. Morphine is processed by the UGT2B7 enzyme into two different compounds. One of them, called M3G, has no activity at the opioid receptors. If a person has a genetic mutation in the UGT2B7 gene, they may process morphine into M3G quicker, meaning that morphine exists for less time in the blood. Another result of the morphine metabolism is a different chemical called M6G, which is actually a better analgesic than morphine. Mutations of the enzyme may again influence a person’s response to opioids.
These genetic components are entirely out of a person’s control.
Previous exposure to opioids leading to tolerance
When a person is exposed to a drug repeatedly, they may develop a tolerance. Tolerance is a change of the body where a person needs to take more drug to experience the same effect. People can develop tolerance if they use opioid drugs recreationally, whether it is heroin or a prescription.
Tolerance happens at the level of receptors. Opioid painkillers bind to receptors throughout the nervous system. When a person regularly takes opioid drugs, the cells expressing the receptors may downregulate the receptors, making them less sensitive to other opioids. So, when a person is given more opioid painkiller, the downregulated receptors makes it so the person needs a higher dose to experience the same degree of analgesia.
