Caroline F Samer1, Valérie Piguet, Pierre Dayer, Jules A Desmeules. 1. Service de pharmacologie et toxicologie cliniques et Centre multidisciplinaire d'étude et de traitement de la douleur, Hôpitaux Universitaires de Genève, Genève, Suisse. Caroline.Samer@hcuge.ch
Abstract
OBJECTIVES: To evaluate the impact of certain genetic polymorphisms on variable responses to analgesics SOURCES: Systematic review, by means of a structured computerized search in the Medline database (1966-2004). Articles in English and French were selected. References in relevant articles were also retrieved. MAIN FINDINGS: Most analgesics are metabolized by CYP isoenzymes subject to genetic polymorphism. NSAIDs are metabolized by CYP2C9; opioids described as "weak" (codeine, tramadol), anti-depressants and dextromethorphan are metabolized by CYP2D6 and some "potent" opioids (buprenorphine, methadone or fentanyl) by CYP3A4/5. After the usual doses have been administered, drug toxicity or, on the contrary, therapeutic ineffectiveness may occur, depending on polymorphism and the substance. Drug interactions mimicking genetic defects because of the existence of CYP inhibitors and inducers, also contribute to the variable response to analgesics. Some opioids are substrates of P-gp, a transmembrane transporter also subject to genetic polymorphism. However, P-gp could only play a minor modulating role in man on the central effects of morphine, methadone and fentanyl. CONCLUSION: In the near future, pharmacogenetics should enable us to optimize therapeutics by individualizing our approach to analgesic drugs and making numerous analgesics safer and more effective. The clinical usefulness of these individualized approaches will have to be demonstrated by appropriate pharmacoeconomic studies and analyses.
OBJECTIVES: To evaluate the impact of certain genetic polymorphisms on variable responses to analgesics SOURCES: Systematic review, by means of a structured computerized search in the Medline database (1966-2004). Articles in English and French were selected. References in relevant articles were also retrieved. MAIN FINDINGS: Most analgesics are metabolized by CYP isoenzymes subject to genetic polymorphism. NSAIDs are metabolized by CYP2C9; opioids described as "weak" (codeine, tramadol), anti-depressants and dextromethorphan are metabolized by CYP2D6 and some "potent" opioids (buprenorphine, methadone or fentanyl) by CYP3A4/5. After the usual doses have been administered, drug toxicity or, on the contrary, therapeutic ineffectiveness may occur, depending on polymorphism and the substance. Drug interactions mimicking genetic defects because of the existence of CYP inhibitors and inducers, also contribute to the variable response to analgesics. Some opioids are substrates of P-gp, a transmembrane transporter also subject to genetic polymorphism. However, P-gp could only play a minor modulating role in man on the central effects of morphine, methadone and fentanyl. CONCLUSION: In the near future, pharmacogenetics should enable us to optimize therapeutics by individualizing our approach to analgesic drugs and making numerous analgesics safer and more effective. The clinical usefulness of these individualized approaches will have to be demonstrated by appropriate pharmacoeconomic studies and analyses.
Authors: C F Samer; Y Daali; M Wagner; G Hopfgartner; C B Eap; M C Rebsamen; M F Rossier; D Hochstrasser; P Dayer; J A Desmeules Journal: Br J Pharmacol Date: 2010-06 Impact factor: 8.739
Authors: C F Samer; Y Daali; M Wagner; G Hopfgartner; C B Eap; M C Rebsamen; M F Rossier; D Hochstrasser; P Dayer; J A Desmeules Journal: Br J Pharmacol Date: 2010-06 Impact factor: 8.739
Authors: Rajiv Balyan; Marc Mecoli; Raja Venkatasubramanian; Vidya Chidambaran; Nichole Kamos; Smokey Clay; David L Moore; Jagroop Mavi; Chris D Glover; Peter Szmuk; Alexander Vinks; Senthilkumar Sadhasivam Journal: Pharmacogenomics Date: 2017-02-17 Impact factor: 2.533