Novel data on opioid effect on breathing and analgesia

The most serious side effect of μ-opioid analgesics is the development of respiratory depression as this effect is potentially lethal. Recent genetic studies in mice revealed that opioid analgesia and respiratory depression are linked to one gene (Oprm) and consequently that the synthesis or discovery of a potent opioid analgesic without (respiratory) side effects is highly unlikely. Genetic studies in humans show that part of the variability in opioid analgesia and respiratory depression is related to one specific single nucleotide polymorphism (SNP): OPRM1:c.118A>G. However, the effect of this SNP is different for analgesia and respiration. Whereas homozygous carriers of the mutated allele (about 4% of the Caucasian population) display reduced analgesia and respiratory depression, heterozygous carriers (29%) display a reduction in analgesia only. Evidently, these latter individuals carry an increased risk for opioid respiratory depression. Due to the respiratory effects of opioids, some physicians underdose or abstain from using potent opioids in the treatment of pain. Currently, the best approach to reduce the chance of opioid-induced respiratory depression and reduce the fear of clinicians is education and applying the knowledge that we have on the pharmacokinetics and pharmacodynamics (and their link) of opioids and their antagonists (naloxone). The latter is important in case a patient needs to be treated for opioid overdose. Furthermore, application of data on the genetics of opioid effect and variability will allow individualization of opioid therapy, aimed at optimal analgesic efficacy and reduced toxicity. This will be possible in the near future.