Rechtsmedizin

, Volume 21, Issue 3, pp 233–244

Pharmakogenetik in der Rechtsmedizin

CME Weiterbildung · Zertifizierte Fortbildung

Zusammenfassung

Die Pharmakogenetik beschäftigt sich mit den genetisch bedingten Unterschieden bei der Arzneimittel-, Drogen oder Giftwirkung und ist somit auch für die rechtsmedizinische Begutachtung von Bedeutung. Die häufigsten Sequenzvariationen in der Desoxyribonukleinsäure („deoxyribonucleic acid“, DNA) sind die „single nucleotide polymorphisms“ (SNP). Neben den metabolisierenden Enzymen, z. B. Zytochrom-P450- (CYP-)Isoenzyme, können Transportproteine oder auch Rezeptorproteine betroffen sein. Führen sie tatsächlich zu Änderungen in der Funktionalität der Proteine, kann es zu deutlichen interindividuellen Unterschieden in der Pharmakokinetik und Pharmakodynamik kommen. Aber auch Faktoren wie Komedikation, Alter, Geschlecht, Hormon- und Ernährungsstatus sowie Umweltfaktoren und Komorbidität sind von großer Bedeutung. Dies wird hauptsächlich durch Induktion oder Inhibition der Aktivität der Funktionsproteine bewirkt. Diese Interaktionen sind bei der Begutachtung ebenfalls zu berücksichtigen.

Schlüsselwörter

Einzelnukleotidpolymorphismus Pharmazeutische Präparationen Wirkstoffinteraktionen Zytochrom-P450-Enzymsystem Kodein 

Pharmacogenetics in legal medicine

Abstract

Pharmacogenetics deals with the differences in the effects of medicaments, drugs of abuse or poisons caused by genetic differences. It is also of importance for furnishing expert reports in legal medicine. The most common variations in deoxyribonucleic acid (DNA) sequences are single nucleotide polymorphisms (SNP). Metabolizing enzymes, e.g. cytochrome P450 (CYP) isoenzymes, as well as transport proteins and receptor proteins can also be affected. Significant interindividual differences in pharmacokinetics and pharmacodynamics can occur when the functionality of proteins is altered. However, factors such as comedication, age, sex, hormonal and nutritional status, as well as environmental factors and comorbidity are also of importance. This is mainly caused by induction or inhibition of functional proteins. These interactions must also be considered in the furnishing of expert reports.

Keywords

Single nucleotide polymorphism Pharmaceutical preparations Drug interactions Cytochrome P-450 enzyme system Codeine 

Literatur

  1. 1.
    Lazarou J, Pomeranz BH, Corey PN (1998) Incidence of adverse drug reactions in hospitalized patients: a meta-analysis of prospective studies. JAMA 279(15):1200–1205PubMedCrossRefGoogle Scholar
  2. 2.
    Schönhöfer PS, Lelgemann M, Maxen A, Wille H von (1998) Häufigkeit von Arzneimittelrisiken und Risikokommunikation. In: Hart D, Kemmnitz W, Schnieders C (Hrsg) Arzneimittelrisiken: Kommunikation und Rechtsverfassung. Nomos, Baden-Baden, S 109–120Google Scholar
  3. 3.
    Aktories K, Förstermann U, Hofmann F, Starke K (2004) Allgemeine und spezielle Pharmakologie und Toxikologie. Urban & Fischer, MünchenGoogle Scholar
  4. 4.
    Court MH, Duan SX, Hesse LM et al (2001) Cytochrome P-450 2B6 is responsible for interindividual variability of propofol hydroxylation by human liver microsomes. Anesthesiology 94(1):110–119PubMedCrossRefGoogle Scholar
  5. 5.
    Turpeinen M, Raunio H, Pelkonen O (2006) The functional role of CYP2B6 in human drug metabolism: substrates and inhibitors in vitro, in vivo and in silico. Curr Drug Metab 7(7):705–714PubMedCrossRefGoogle Scholar
  6. 6.
    Flockhart DA (2007) Drug interactions: cytochrome P450 drug interaction table, 2010. Indiana University School of Medicine. Ref Type: Online Source. Zugegriffen 01 November 2010Google Scholar
  7. 7.
    Mikus G, Bochner F, Eichelbaum M et al (1994) Endogenous codeine and morphine in poor and extensive metabolisers of the CYP2D6 (debrisoquine/sparteine) polymorphism. J Pharmacol Exp Ther 268(2):546–551PubMedGoogle Scholar
  8. 8.
    Kirchheiner J, Schmidt H, Tzvetkov M et al (2007) Pharmacokinetics of codeine and its metabolite morphine in ultra-rapid metabolizers due to CYP2D6 duplication. Pharmacogenomics J 7(4):257–265PubMedCrossRefGoogle Scholar
  9. 9.
    Yue QY, Alm C, Svensson JO, Sawe J (1997) Quantification of the O- and N-demethylated and the glucuronidated metabolites of codeine relative to the debrisoquine metabolic ratio in urine in ultrarapid, rapid, and poor debrisoquine hydroxylators. Ther Drug Monit 19(5):539–542PubMedCrossRefGoogle Scholar
  10. 10.
    He YJ, Brockmoller J, Schmidt H et al (2008) CYP2D6 ultrarapid metabolism and morphine/codeine ratios in blood: was it codeine or heroin? J Anal Toxicol 32(2): 178–182PubMedGoogle Scholar
  11. 11.
    Kang JM, Kim N, Lee DH et al (2008) Effect of the CYP2C19 polymorphism on the eradication rate of Helicobacter pylori infection by 7-day triple therapy with regular proton pump inhibitor dosage. J Gastroenterol Hepatol 23(8 Pt 1):1287–1291PubMedCrossRefGoogle Scholar
  12. 12.
    Evans WE, McLeod HL (2003) Pharmacogenomics – drug disposition, drug targets, and side effects. N Engl J Med 348(6):538–549PubMedCrossRefGoogle Scholar
  13. 13.
    Kosarac B, Fox AA, Collard CD (2009) Effect of genetic factors on opioid action. Curr Opin Anaesthesiol 22(4):476–482PubMedCrossRefGoogle Scholar
  14. 14.
    Nagashima M, Katoh R, Sato Y et al (2007) Is there genetic polymorphism evidence for individual human sensitivity to opiates? Curr Pain Headache Rep 11(2):115–123PubMedCrossRefGoogle Scholar
  15. 15.
    Rendic S, Di Carlo FJ (1997) Human cytochrome P450 enzymes: a status report summarizing their reactions, substrates, inducers, and inhibitors. Drug Metab Rev 29(1–2):413–580Google Scholar
  16. 16.
    Eichelbaum M, Burk O (2001) CYP3A genetics in drug metabolism. Nat Med 7(3):285–287PubMedCrossRefGoogle Scholar
  17. 17.
    Brauch H, Murdter TE, Eichelbaum M, Schwab M (2009) Pharmacogenomics of tamoxifen therapy. Clin Chem 55(10):1770–1782PubMedCrossRefGoogle Scholar
  18. 18.
    Niemi M, Backman JT, Fromm MF et al (2003) Pharmacokinetic interactions with rifampicin: clinical relevance. Clin Pharmacokinet 42(9):819–850PubMedCrossRefGoogle Scholar
  19. 19.
    Gasche Y, Daali Y, Fathi M et al (2004) Codeine intoxication associated with ultrarapid CYP2D6 metabolism. N Engl J Med 351(27):2827–2831PubMedCrossRefGoogle Scholar
  20. 20.
    Yin OQ, Lam SS, Lo CM, Chow MS (2004) Rapid determination of five probe drugs and their metabolites in human plasma and urine by liquid chromatography/tandem mass spectrometry: application to cytochrome P450 phenotyping studies. Rapid Commun Mass Spectrom 18(23):2921–2933PubMedCrossRefGoogle Scholar
  21. 21.
    Kroese M, Zimmern RL, Pinder SE (2007) HER2 status in breast cancer – an example of pharmacogenetic testing. J R Soc Med 100(7):326–329PubMedCrossRefGoogle Scholar
  22. 22.
    Grossniklaus D (2010) Testing of VKORC1 and CYP2C9 alleles to guide warfarin dosing. Test category: pharmacogenomic (treatment). PLoS Curr 2Google Scholar

Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  1. 1.Institut für RechtsmedizinUniversität ZürichZürichSchweiz

Personalised recommendations