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    • Genes May Play Part in Opioid Side Effects (CME/CE)

    By Kristina Fiore, , MedPage TodayPublished: June 21, 2012Reviewed by Robert Jasmer, MD; Associate Clinical Professor of Medicine, University of California, San Francisco

    The respiratory depression and nausea often experienced by patients on opioid therapy appears to have some genetic component, researchers found.

    In a twin study, genetic effects accounted for nearly 60% of the response variance in nausea and 30% of the variance in respiratory depression, Martin Angst, MD, of Stanford University in Palo Alto, Calif., and colleagues reported on-line in Anesthesiology.

    “Our findings strongly encourage the use of downstream molecular genetics to identify patients who are more likely or less likely to benefit from these drugs — to help make decisions on how aggressive you want to be with treatment, how carefully you monitor patients, and whether certain patients are suitable candidates for prolonged treatment,” Angst stated in a statement.

    Opioids are a mainstay of pain management, but they carry side effects such as respiratory depression, sedation, nausea, and pruritus, as well as addiction.

    However, there have been few studies looking at the contributions of genetic and environmental factors to patient response to opioids.

    So Angst and colleagues conducted a twin study of 114 monozygotic and dizygotic twin pairs who were given either an infusion of saline placebo or alfentanil (Alfenta) — chosen for its quick onset and offset of action.

    They found that there was significant heritability for both respiratory depression and nausea, with genetic effects accounting for 30% and 59% of variance in response, respectively.

    Genetic factors also appeared to play a role in patients’ dislike of the drugs, accounting for 36% of the variance, the researchers reported.

    “Opioid disliking may constitute a useful and easily measurable index phenotype to assess the abuse potential of opioids in future research,” they wrote.

    There were other factors that were not necessarily found to be inherited, but still had a strong familial effect, which is due to shared genetic and environmental factors, the researchers said.

    These included sedation, pruritus, and dizziness, with familial effects accounting for up to 29%, 38%, and 39% of the variance in response, respectively.

    There was also a significant familial effect for drug liking, which accounted for up to 26% of response variance, they reported, noting that a “failure to detect heritability per se does not preclude relevant genetic effects.”

    Angst and colleagues also found that covariates such as age, sex, race, ethnicity, education, mood, and depression affected sedation, pruritus, drug liking and disliking, and dizziness. In particular, age was associated with greater respiratory depression and drug-induced slowing of cognitive speed, they found.

    Also, older age was associated with greater drug disliking, which is consistent with lower rates of opioid abuse in aging patients with chronic pain, they wrote.

    They concluded that genetic, environmental, and demographic factors “work together to control adverse and reinforcing opioid responses, but contribute differently to specific responses.”

    The researchers reported no conflicts of interest.

    joined MedPage Today after earning a degree in science, health, and environmental reporting from NYU. She’s had bylines in newspapers and trade and consumer magazines including Newsday, ABC News, New Jersey Monthly, and Earth Magazine. At MedPage Today, she reports with a focus on diabetes, nutrition, and addiction medicine.

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