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The Contribution of Genetics, Environmental Factors and Demographics to the Side Effects of Opioid Pain Killers

Chicago — (June 20, 2012) 

A study in the July issue of Anesthesiology analyzes why some patients are more susceptible to problems caused by opioids, corner stone medications for the treatment of acute and chronic pain. The Stanford University study looked at the heritable component predisposing to opioid-related side effects, and was the first to address the relative roles of genetic, environmental and demographic factors in mediating problems associated with the use of opioid pain killers.

Each year in the United States, millions of patients are prescribed powerful and valuable opioid medications such as morphine, methadone and oxycodone. However, many problems are related to the use of these drugs, including the slowing or stopping of breathing, nausea, itching and addiction. In an effort to better identify and treat at-risk patients, researchers studied these adverse drug responses in pairs of identical and fraternal twins.

“One of the most basic questions we asked is to what extent genetic versus environmental factors determine individuals’ susceptibility to adverse opioid effects,” said study author Martin S. Angst, M.D.

Methodology and Findings
One hundred and twenty-one twin pairs participated in the study. The mu-opioid receptor agonist alfentanil and saline placebo were administered as target-controlled infusions under monitored laboratory conditions. Measured outcomes included respiratory depression, sedation, nausea, itching and drug liking and disliking. Demographic information was collected and aspects of mood and sleep were evaluated.

Findings indicated that genetic factors likely influence the degree to which study participants experience the side effects of nausea, slowed breathing and drug disliking. Genetic and shared environmental factors also are linked to how much a participant liked the opioid infusion. Drug disliking and liking could be linked to the individuals’ predisposition to become addicted to pain killers. Additional factors such as age, sex and psychological status also contribute to the likelihood of experiencing side effects.

“Our findings provide strong support to focus additional studies on the specific genetic makeup of individual patients who are more susceptible to adverse outcomes associated with opioid use,” said study co-author David J. Clark, M.D., Ph.D. “Since side effects are common among patients who use opioid medications, it will be beneficial to use such research to help at-risk patients avoid serious life-threatening complications.”

“The study is a significant step forward in efforts to understand the basis of individual variability in response to opioids and to eventually personalize opioid treatment plans for patients,” added Dr. Angst.

For more information, visit the Anesthesiology website at


Founded in 1905, the American Society of Anesthesiologists (ASA) is an educational, research and scientific society with more than 52,000 members organized to raise and maintain the standards of the medical practice of anesthesiology. ASA is committed to ensuring physician anesthesiologists evaluate and supervise the medical care of patients before, during and after surgery to provide the highest quality and safest care every patient deserves.

For more information on the field of anesthesiology, visit the American Society of Anesthesiologists online at . To learn more about the role physician anesthesiologists play in ensuring patient safety, visit Like ASA on Facebook , follow ASALifeline on Twitter and follow ASA on LinkedIn .



American Society of Anesthesiologists