Aversive and Reinforcing Opioid Effects: A Pharmacogenomic Twin Study | Anesthesiology. 2012 Jul | Free Full-text PMC article
The clinical utility of opioids is limited by adverse drug effects including respiratory depression, sedation, nausea, and pruritus. In addition, abuse of prescription opioids is problematic.
Gaining a better understanding of the genetic and environmental mechanisms contributing to an individual’s susceptibility to adverse opioid effects is essential to identify patients at risk.
While more and more studies are showing how frequently and thoroughly genetic differences affect patients, the CDC is denying all this science to arrive at arbitrary “standard” doses of opioids.
A classical twin study paradigm provided estimates for the genetic and familial (genetic and/or shared environment) contribution to acute adverse and affective opioid responses; all secondary outcomes of a larger data set. One hundred and twenty one twin pairs were recruited in a single occasion, randomized, double-blind and placebo controlled study.
Significant heritability was detected for
- respiratory depression (30%),
- nausea (59%) and
- drug disliking (36%).
Significant familial effects were detected for
- sedation (29%),
- pruritus (38%), [itching]
- dizziness (32%), and
- drug liking (26%).
Significant covariates included
- mood and
- drug liking and disliking, and
This study demonstrates that large scale efforts to collect quantitative and well-defined opioid response data are not only feasible but also produce data that are suitable for genetic analysis.
Genetic, environmental and demographic factors work together to control adverse and reinforcing opioid responses, but contribute differently to specific responses.
Addiction to opioids is heritable, and genetic studies have been designed to address the specific molecular underpinning.
While our study paradigm did not allow directly studying the complex clinical phenotype of opioid addiction, we were able to precisely measure acute reinforcing effects such as the liking and disliking of the drug.
- Liking in response to acute opioid administration is an established index phenotype to predict abuse potential, whereas
- Disliking upon first exposure is associated with lack of abuse
What this article tells us that is new
- The adverse effects of a steady-state alfentanil infusion were studied in 114 monozygotic and dizygotic twin pairs.
- Genetic effects were detected for decreased respiratory rate, nausea, and drug disliking.
- Genetic and/or shared environmental effects were detected for increased transcutaneous CO2, sedation, pruritis, dizziness, and drug liking.