Role of pharmacogenomics in pain therapy: Focus on opioids

Abstract

Analgesics, especially opioids, show remarkable inter-individual variability in both efficacy and adverse effect profile. There are many factors that contribute to this variability, including renal and liver function, co-morbidity and concomitant medications. Another source of interpatient variability in response to analgesics is the patients' genetic profile that controls their drug metabolism, drug transport out of the brain and target site activity. The cytochrome P450 2D6 poor metaboliser phenotype reduces the effects of some opioids, such as tramadol. In contrast, in ultrarapid metabolisers, adverse effects are seen with codeine and antidepressants. The efflux transporter p-glycoprotein located at the blood brain barrier limits the access of these drug classes to the brain. Genetic polymorphisms in ABCB1 result in enhanced efficacy, but also increased adverse effects to many drugs used widely in palliative care. For opioids, a mu receptor polymorphism leads to reduced efficacy and for Non Steroidal Anti-inflammatory Drugs, CYP2C9 polymorphisms are associated with a higher risk of bleeding. These genetic factors might explain why some drugs 'don't work' or 'work too well' in routine clinical practice.