Opioids can be angels or devils. When used properly, these medications can provide relief from severe acute pain, such as what you could experience after a surgery or from cancer. However, opioids can also have devastating consequences, including addiction, overdose, and death.
There are some ailments for which opioids are not a good treatment option—most notably, chronic pain (i.e. lower back pain that someone has had for years). “This is because while they are excellent analgesics, people develop tolerance quickly, so they end up needing higher and higher doses to maintain the same effect,” says Kathleen Brady, MD, PhD, Vice President of Research at the Medical University of South Carolina, and a Genomind Advisory Board Member.
This is one of the ways that opioids have the potential for abuse and the development of an addiction. “Many people get euphoric from opioids and end up taking more than prescribed, for longer periods than they are prescribed for, so it is particularly important to take exactly as directed and for as short a period of time as possible,” she says.
What Determines Opioid Addiction
Becoming addicted to opioids isn’t a given. Most patients don’t set out to misuse or abuse opioids, but between 8% and 12% of patients will go on to develop an opioid use disorder, according to the National Institute on Drug Abuse.
How your body metabolizes opioids plays a role in whether they will have a pain-relieving effect, or induce a toxicity. Opioids are cleared through the body the same way all medications are—through a process of absorption, distribution, metabolism, and elimination.
READ MORE: How Your Body Metabolizes Medications
Understanding how your body may process opioids can help decrease your risk for opioid harm. Here is what you should know before taking an opioid.
- How opioids are metabolized.
Most drugs, including many opioids, are metabolized through a family of enzymes in the liver called cytochrome P450 system (CYP450). The opioids that are metabolized by CYP450, for instance, include codeine, hydrocodone, oxycodone, methadone, tramadol, and fentanyl. So when they are taken along with other drugs that are also mediated by the same pathways, there is the potential for a dangerous interaction, Dr. Brady explains.
Whether you have variations of these enzymes as part of your genetic makeup can be revealed through tests such as Genomind Professional PGx Express. The results of this test can help your doctor determine how your body metabolizes medications that involve CYP450 enzymes. Genomind can provide you and your doctor with this information, which we call Rx MetaTypeTM, to help inform choices of medication and dosing.
- The metabolism of other drugs you might be taking.
Drug interactions are also an important concern, especially when you consider this: “Individuals with opioid use disorder and/or chronic pain often have depression and are prescribed antidepressants, so interactions between antidepressants and opioids are important,” Dr. Brady says.
One common significant drug-drug interaction involves the concurrent use of opioids and benzodiazepines—a prescription sedative that’s commonly used to treat anxiety or insomnia. Both opioids and benzodiazepines sedate users and suppress breathing, as well as impair cognitive functions. Both classes of these drugs now contain “black box warnings” about using these two together.
Concurrent use of antidepressants and opioids can also be a problem, although the National Institute on Drug Abuse doesn’t have a strong warning about these.
For instance, serotonin reuptake inhibitors, which are a type of antidepressant, exert a variety of effects on the CYP450 enzyme system. “Both fluoxetine and fluvoxamine …can be associated with decreased metabolism of opioids.” Dr. Brady says. “While fluoxetine has not been associated with clinically important increases, fluvoxamine has been reported to result in significantly increased methadone plasma concentrations.”
She says that while there have not been reports of adverse drug interactions with other serotonin reuptake inhibitors, such as sertraline and citalopram, both are associated with inhibiting parts of the CYP450 system—so they could theoretically increase opioid levels.
The FDA requires labeling on over 200 medications to include pharmacogenetic biomarker information due to specific actionable gene-drug associations. Make sure you discuss these and any other medications that you are taking with your doctor, as well as information that your Genomind Rx MetaTypeTM card reveals about potential gene-drug interactions you could experience.
- The health of your kidneys and liver.
Opioids go through a first-pass metabolism in your liver, before circulating throughout your body (where they cross cell membranes to reach target tissues). Impaired kidney and liver function can affect opioid metabolism, but do not contribute to the development of, or risk for, opioid addiction. “People with impaired liver or kidney function will generally be more sensitive to opioids because of impaired metabolism and excretion, so lower doses of opioids should be used,” Dr. Brady says.
- Your vitals.
Age, sex, and ethnicity can all factor into how certain opioids are metabolized by your body, requiring a dose adjustment or change in the opioid that’s prescribed. Older patients may have a harder time clearing codeine, fentanyl, morphine, and oxymorphone from their bodies. In addition, the older you are, the more likely you are to be taking multiple medications.
Gender plays a role in certain opioids. For example, in women, oxycodone and hydromorphone concentrations are 25% higher than in men for the same standard dose.
Finally, your ethnicity can be associated with genetic variants that can affect opioid metabolism and drug interactions. Understanding how your body metabolizes medications based on genetic variants can help you and your doctor choose appropriate treatment. For example, Asian or African-American populations are more likely to have a genetic variant of the CYP2D6 enzyme that affects the way they metabolize codeine and hydrocodone.
Genetic tests, such as Genomind’s Professional PGx Express, can help identify genes that determine how a drug is metabolized by your body and, as a result, help your health care provider determine a treatment tailored to you.