Personalized Therapy in Pain Management: Where Do We Stand?

Abstract

Genomic variations influencing response to pharmacotherapy of pain are currently under investigation. Drug-metabolizing enzymes represent a major target of ongoing research in order to identify associations between an individual's drug response and genetic profile. Polymorphisms of the cytochrome P450 enzymes (CYP2D6) influence metabolism of codeine, tramadol, hydrocodone, oxycodone and tricyclic antidepressants. Blood concentrations of some NSAIDs depend on CYP2C9 and/or CYP2C8 activity. Genomic variants of these genes associate well with NSAIDs' side effect profile. Other candidate genes, such as those encoding (opioid) receptors, transporters and other molecules important for pharmacotherapy in pain management, are discussed; however, study results are often equivocal. Besides genetic variants, further variables, for example, age, disease, comorbidity, concomitant medication, organ function as well as patients' compliance, may have an impact on pharmacotherapy and need to be addressed when pain therapists prescribe medication. Although pharmacogenetics as a diagnostic tool has the potential to improve patient therapy, well-designed studies are needed to demonstrate superiority to conventional dosing regimes.

Prodrugs—from Serendipity to Rational Design

“…In addition, the threshold of experimental pain by codeine is increased in CYP2D6 EMs but not in PMs, who lack the activation machinery. However, evidence for impaired analgesic outcome in CYP2D6 PMs is sparse, and it has been postulated that large-scale studies will be needed to demonstrate genetically determined unresponsiveness to codeine analgesia (Smith, 2009;Stamer et al, 2010).…”

“…In one study, the proportion of tramadol nonresponders was increased in the CYP2D6 PM group compared with the patients with functionally active CYP2D6 alleles. Thus, there is evidence that CYP2D6 polymorphisms can influence the efficacy of codeine and tramadol analgesia, although in most trials, only a limited number of patients have been monitored (Stamer et al, 2010).…”

How polymorphisms of the cytochrome P450 genes affect ibuprofen and diclofenac metabolism and toxicity / Kako polimorfizmi gena citokroma P450 utječu na metabolizam i toksičnost ibuprofena i diklofenaka

“…Current guidelines on translating pharmacogenomics into clinical practice seem to bring some promise (3). It is important, however, to bear in mind that pharmacogenetics/pharmacogenomics is just a tool that has to be assessed with other relevant factors that may affect drug behaviour, including age, gender, comorbidities, and other concomitant drugs (63). This approach will improve treatment with NSAIDs while avoiding serious adverse effects.…”

Pharmacogenetics of nonsteroidal anti-inflammatory drugs

“…64 In addition, many agents comprising mainstream pharmacotherapy would benefit marginally from widespread pharmacogenetics testing because of the cost of the agents. However, certain NSAIDs (foe example, lumiracoxib) may have been able to positively affect patient care with the use of prospective genomic testing to aid in the identification of patients who had a variation in the HLA-DQA1*0102 allele, 32 preventing hepatic impairment and possible hepatotoxicity.…”