Friday, June 29, 2012

Genetic contribution of response to opioids

Opioids  are commonly prescribed for pain relief, yet many individuals suffer adverse side effects such as nausea, dizziness and sedation.

A study published in this month's Anesthesiology set out to establish the relative contribution of genetic and environmental factors in opioid response. 114 monozygotic and dizygotic twin pairs were recruited, and were given either alfentanil then placebo, or placebo then alfentanil. Significant heritability was shown for respiratory depression, nausea and disliking of the drug. Almost 60% of the variation in nausea response was attributed to genetic effects. Genetic effects also accounted for around 25% of the variance in disliking of the drug, and 30% of the variance in respiratory depression decreases. Genetic and/or environmental effects were attributed to liking of the drug, sedation, dizziness and pruritus.

Aversive and Reinforcing Opioid Effects: A Pharmacogenomic Twin Study. Angst M.S. et al. Anesthesiology. 2012 Jul;117(1):22-37. Read the article

PGx of opioids
Discovering the specific genetic variants behind these side effects may help identify patients most at risk before prescribing opioids...

Variants within the CYP3A5 and OPRM1 gene have been associated with alfentanil drug metabolism and dosage, respectively; view these variant annotations on PharmGKB.

To avoid toxicity, CPIC have published therapeutic dosing guidelines for codeine based on an individual's CYP2D6 genotype; view these dosing guidelines on PharmGKB.

Numerous genetic variants in many different genes have been associated with response to or dosage of methadone; view these variant annotations on PharmGKB.