Pharmacogenetics in palliative care.
Response to analgesics, anticancer pharmacotherapy and pharmacotherapy of other cancer related symptoms vary broadly between individuals. Age, disease, comorbidities, concomitant medication, organ function and patients' compliance may partly explain the differences. However, the focus of ongoing research has shifted towards genomic variants of phase I and II drug metabolizing enzymes with one important goal being an individual dose adjustment according to a patient's genotype. Polymorphisms of the cytochrome P 450 2D6 influence the metabolism of many drugs including the analgesics codeine, tramadol, hydrocodone and oxycodone, as well as the metabolism of tricyclic antidepressants and the anticancer drug tamoxifen. Other candidate genes such as (opioid)-receptors, transporters and other molecules important for pharmacotherapy in pain management are discussed. Although pharmacogenetics as a diagnostic tool has the potential to improve patient therapy, study results are often equivocal and limited by small sample sizes and often by their retrospective design. Well designed studies are needed to demonstrate superiority of pharmoacogenetics to conventional dosing regimes.
Kleine-Brueggeney
Maren
M
Department of Anaesthesiology and Pain Therapy, Inselspital, University Hospital Bern, Freiburgstr., 3010 Bern, Switzerland. maren.kleine-brueggeney@insel.ch
Musshoff
Frank
F
Stuber
Frank
F
Stamer
Ulrike M
UM
D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000701:Analgesics, Opioid / Q000493:pharmacokinetics; D000929:Antidepressive Agents, Tricyclic / Q000493:pharmacokinetics; D018931:Antineoplastic Agents, Hormonal / Q000493:pharmacokinetics; D002394:Catechol O-Methyltransferase / Q000235:genetics; D019389:Cytochrome P-450 CYP2D6 / Q000235:genetics; D014644:Genetic Variation; D006801:Humans; D009369:Neoplasms / Q000150:complications; D010146:Pain / Q000188:drug therapy / Q000209:etiology; D010147:Pain Measurement; D010166:Palliative Care; D010597:Pharmacogenetics; D017450:Receptors, Opioid, mu / Q000235:genetics; D058831:Serotonin 5-HT3 Receptor Antagonists / Q000493:pharmacokinetics; D013629:Tamoxifen / Q000493:pharmacokinetics
C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000701:Analgesics, Opioid; D000929:Antidepressive Agents, Tricyclic; D018931:Antineoplastic Agents, Hormonal; C485764:OPRM1 protein, human; D017450:Receptors, Opioid, mu; D058831:Serotonin 5-HT3 Receptor Antagonists; D013629:Tamoxifen; D019389:Cytochrome P-450 CYP2D6; D002394:Catechol O-Methyltransferase