GENETIC VARIABILITY OF PHARMACOKINETICS AND PHARMACODYNAMICS OF ANALGESICS (LAYERED MEDICINE)

Authors

  • Neamtu Monica University of Medicine and Pharmacy Iasi
  • Alexandru Vasincu
  • Daniela Ababei
  • Oana Arcan
  • Delia Bulea
  • Razvan Nicolae Rusu
  • Veronica Bild

Keywords:

analgesics, single nucleotide polymorphism, pharmacogenomics

Abstract

Pain therapy, the most widely spread disorder, tends more as other diseases, to administration of drug molecules targeted to the affected tissue at the right dose, or to the patient or patient groups (personalized medicine). A decisive determinant of this strategy is the genetic one, which is to some extent the basis of the variability of pharmacokinetic and pharmacodynamic response to analgesics in the patient population. The differences in action and response to analgesics are due in these cases to hyperfunctional or nonfunctional uni-nucleotide gene polymorphisms encoding enzyme-modified transport proteins or receptors involved in the biotransformation and dynamics of analgesics. Genomic testing increases therapeutic efficacy and avoids adverse effects especially in patients with long-term therapies.  

 

References

Blakey JD, Hall IP. (2011): Current progress in pharmacogenetics, British Journal of Clinical Pharmacology, 71,6:824-831

Buchsbaum MS, Davis GC, Bunney VE Jr. (1977): Nature , London, 270: 620-622, pmid: 339 110 (CrossRef, PubMed, Google Scholar)

Ciskowski C, Madadi P, Phillips MS, Lawres AE, Koren G.(2009): Codeine, ultrarapid metabolism genotype and post-operative death, New England J.Med. 361(8):827-828

Coller JK, Barrat DT, Dahlen K, Loennechen MH. et al.(2006): ABCB1 genetic variability and metadone dosage requirements in opioid-dependent individuals, Clin.Pharmacol.Therap.80:682-690

Covic M.(2012): Farmacogenomica: o speranţă pentru medicina personalizată, Rev.Viaţa medicală, 16(1162)

Eijkelkamp N, Heijnen KJ, Elsenbruch S, Holtman G. Et al. (2009): G-protein coupled receptor kinase 6 control post-inflamatory visceral hyperalgesia, Brain Behav. Immun. 23:18-26

Fergusson SS, Barak LS, Zhang J, Caron MG. (1996): G-protein- coupled receptor regulation: role of G-protein-coupled receptor kinases and arrestins, Canadian Journ.Physiol.Pharm.,74:1095-1110

Fujita K, Ando Y, Yamamoto W, Miya T. et al. (2010): Association of UGTB2B7 and ABCB1 genotypes with morphine-induced adverse drug reaction in Japanese pacients with cancer, Cancer Chemotherapy Pharmacology. 65:251-258

Goins WF,Cohen JB, Glorioso JC.(2012): Gene therapy for the treatment of chronic peripheral nervous system pain , Neurobiology of Disease, 48:55-270

Goodman Gilman A, Rall TW, Nies As, Taylor P (1992): The pharmacological Basis of Therapeutics, vol.I, VIII Edition, Mc Graw-Hill International Edit, Medical Series, pg.3 și 33

Kibaly C, Loh HH, Law P-Y.(2010): A Mechanisms Approach to the Development of gene Therapy for Chronic Pain, International Review of Cell and Molecular Biology, vol.327, ISSN 1937-6448

Kirchheiner J, Niccken K, Bauer M, Wong M-L, Licinio J. et al.(2004)- Pharmacogenetics of antidepressants and antipsichotics: the contribution of the allelic variation to the phenotype af drug response , Mol.Psichiatry 9: 442-473

Kirchheiner J, Sasse J,Maineke I, Roots I et al.(2003): Trimipramine pharmacogenetics after intravenous and oral administration in carriers of CYP2D6 fenotypes predicting poor, exiensive and ultrahigh activity, Pharmacogenetics,13:721-728

Lotsch J, Geisslinger G, Tegeder I. (2009)-Genetic modulation of the pharmacological treatment of pain, Pharmacology and Therapeutics 124:168-184

Marker CL, Stoffel M, Wickman K. (2004): Spinal G-protein-gated K+ channels formed by GIRK1 and GIRK-2 subunits modulate thermal nociception and contribute to morphine analgesia, Journ.Neurosci.24, 2806-2812

Martin N, Boomsma D, Machin G (1997): A twin-pronged attack on complex traits, Nat.Genet., 17: 387-392 (CrossRef, Pubmed, Google Scholar)

Mercer S, CoopA.(2011): Opioid Analgesics and P-glycoprotein Eflux Transporters: Apotential Systems-LevelContribution to Analgesic Tolerance, Curr Top Med Chem, 11(9):1157-1164

Mogil JS (1999): The genetic mediation of individual differences in sensitivity to pain and its inhibition, Proc.Natl.Acad.Sci. USA, 96 (14) 7744-7751 (https://doi.org/10.1073/.pnas.96.14.7744)

Muralidharan A, Smith TM. (2011): Pain, analgesia and genetics, Journ.of Pharmacy and Pharmacology, 63:1387-1400

Nishizawa D, Fukuda K, Kasai S, Ogai Y, Hasegawa J et al.(2014): Association Between KCNJ6 (GIRK2) Gene Polymorphism rs 2835859 and Post-operative Analgesia, Pain sensitivity and Nicotin Dependence, Journal of Pharmacological Sciences, 126:253-263

Oertel BG, Kettner M, ScholichK, Renne C, Roskam B et al. (2009): A common human opioid receptor variant diminishes the receptor signaling efficacy in brain regions processing the sensory information of pain, Journ.Biol.Chem. 284:6530-6535

Saland Lc, Chavez JB, Lee DC, Garcia RR, Caldwell KK. (2008): Chronic ethanol exposure increases the association of hippocampal mu-opioid receptors with G-protein –receptor kinase 2, Alcohol, 42: 493-497

Schiavone S, Neri M, Pomara C, Riezzo I. et al.(2017): Personalized medicine in the Paediatric Population: the Balance Between Pharmacogenethics Progress and Bioethics, Current Pharmaceutical Biotechnology, 18,3:253-262

Shabalina SA, Zaykin DV, Gris P, Ogurtsov AY et al. (2oo9): Expansion of the human mu-opioid receptor gene arhitecture: novel functional variants, Human Molecular Genetics, 18, 6:1037-1051

Smith SB, Marker CL, Perry C, Liao G. Et al. (2008): Quantitative trait locus and computational mapping identifies Kcnj9 (GIRK3) as a candidate gene affecting analgesia from multiple drug classes, Pharmacogenetics and Genomics, 18:231-241

Stamer UM, Lehnen K, Hothker F, Bayerer B, Wolf S. et al.(2003): Impact of CYP2D6 genotype on postoperative tramadol analgesia, Pain, 105:232-238

Stamer UM, Stuber F (2007)-The pharmacogenetics of analgesia, Expert Opin.Pharmacotherapy, 8(14): 2235-2245

Stamer UM, Zhang L, Stuber F.(2010): Personalized therapy in pain management: where do stand?, Pharmacogenomics, 11(6):843-864

Tang C, Shou M, Rushmore TH, Mei Q et al. (2001): In vitro metabolism of celecoxib, a cyclooxygenase 2-inhibitor by allelic variant forms of human liver microsomal cytochrome P450 2C9: correlation with CYP2C9 genotype and in vivo pharmacokinetics, Pharmacogenetics, 11: 223-235

Tyndale RF, Droll KP, Sellers EM (1997): Genetically deficient CYP2D6 metabolism provides protection against orale opiate dependence, Pharmacogenetics, 7(5):375-379

Wang GX, Zhang H, He FF, Fang XM. (2006): Effect of the CYP2D6*10 C188T polymorphism on postoperativ tramadol analgesia in a Chinese population, European Journal of Clinical Pharmacology.,62(11):927-931

Zhou SF.(2009): Polymorphism of human cyrochrome P450 2D6 and its clinical significance(Part II), Clinical Pharmacokinet.,48:761-804

CYP ALLELE Nomenclature Commitee (http://www.cypalleles .ki.se)

www.ncbi.nlm.nih.gov/SNP

Downloads

Published

2019-09-20

How to Cite

Monica, N., Vasincu, A., Ababei, D., Arcan, O., Bulea, D., Rusu, R. N., & Bild, V. (2019). GENETIC VARIABILITY OF PHARMACOKINETICS AND PHARMACODYNAMICS OF ANALGESICS (LAYERED MEDICINE). Journal of Experimental and Molecular Biology, 20(1-2), 7–14. Retrieved from http://www.jemb.bio.uaic.ro/index.php/jemb/article/view/32

Issue

Section

Reviews