Pharmacogenetics in palliative care

Analgesic, especially opioids, antiemetic and antidepressant drugs show marked interpatient variability in responses both efficacy and adverse effects. The cytochrome P450 2D6 poor metaboliser phenotype reduces the effects of some opioids, such as tramadol. However, in contrast, in ultrarapid metabolisers adverse effects are seen with codeine and the antidepressants, but enhanced efficacy to tropisetron. The efflux transporter p-glycoprotein located at the blood-brain barrier limits access of these drug classes to the brain; genetic polymorphisms in ABCB1 result in enhanced efficacy, but also adverse effects to many drugs used widely in palliative care. For opioids, a mu receptor polymorphism leads to reduced efficacy and for NSAIDs, CYP2C9 polymorphisms are associated with a higher risk of bleeding. Thus, a major source of interpatient variability in response to these major palliative care classes of drugs can be attributed to the patients’ genetic profiles that control their drug metabolism, transport out of the brain and target site. These might explain at the bedside why some of the drugs “don’t work” or “work too well”.Andrew A. Somogyihttp://trove.nla.gov.au/work/3843974