Farmakogenetika klopidogrela

professional thesis

• Author: Andrea Plečko
• Mentor: Nada Božina (mentor)
• Committee member: Karmela Barišić (predsjednik povjerenstva)
• Committee member: Vesna Bačić Vrca (član povjerenstva)
• Committee member: Nada Božina (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; Zagreb
• Defense date and country: 2018-12-07, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Cilj istraživanja: Cilj rada je pregledno prikazati genetičke čimbenike koji utječu na
učinkovitost i sigurnost terapije klopidogrelom, a koji mogu omogućiti ljekarnicima lakše
savjetovanje i individualizaciju terapije.
Materijali i metode: U tu svrhu pretražena je znanstvena literatura, terapijske smjernice i
publikacije stručnih institucija i drugi izvori. Opisan je utjecaj genetičke varijabilnosti na
apsorpciju (gen ABCB1 ), metabolizam i aktivaciju (geni CYP2C19, CES1), mjesto djelovanja
(gen za receptor P2Y12 ) klopidogrela te utjecaj različitih varijanti ovih gena na ishod liječenja.
Rezultati: Studije pokazuju da nositelji neaktivnih alela CYP2C19 (*2 i*3) liječeni
klopidogrelom imaju manju koncentraciju aktivnog metabolita u plazmi i veću agregaciju
trombocita od homozigota za divlje alele gena CYP2C19. Intermedijarni i spori metabolizatori
putem enzima CYP2C19 liječeni klopidogrelom zbog akutnog koronarnog sindroma imaju
značajno veći rizik smrti, razvoja infarkta miokarda, moždanog udara i tromboze stenta od
brzih metabolizatora. Fenotip aktivnosti enzima CYP2C19 nezavisni je prediktor uspješnosti
terapije klopidogrelom u pacijenata s akutnim koronarnim sindromom i provedenom
perkutanom koronarnom intervencijom.
Zaključak: Rezistencija na klopidogrel jedan je od uzroka neuspješnog liječenja
aterotrombotičkih oboljenja. Genotipizacija CYP2C19 , uz ostale faktore rizika, može pomoći
u predviđanju odgovora na terapiju klopidogrelom, povećati uspješnost terapije i smanjiti
smrtnost.

Abstract (english)

Objectives: The goal of this thesis is to give an overview on the genetic factors that can
affect the efficiency and safety of clopidogrel therapy for the purpose of improving
pharmacists counseling and therapy individualization.
Materials and methods: To that end, scientific literature, therapy guidelines and
publications from relevant organizations and other sources has been reviewed. The impact
of genetic variability on absorption (ABCB1 gene), metabolism and activation (CYP2C19, CES1
gene) and biological activity (P2Y12 gene) of clopidogrel has been described. The relation
between these genetic variations and clinical outcome has also been described.
Results: Studies have shown that carriers of inactive CYP2C19 alleles (*2 and *3) have lower
plasma concentrations of active clopidogrel metabolite and higher on treatment platelet
aggregation compared to noncarriers of these alleles. Intermediate and poor CYP2C19
metabolizers treated with clopidogrel after acute coronary syndrome have significantly
higher risk of death, myocardial infarction, stroke and stent thrombosis. CYP2C19 phenotype
is an independent predictor of clopidogrel treatment outcome in patient with acute
coronary syndrome who underwent PCI.
Conclusion: Clopidogrel resistance is one of the causes of antithrombotic treatment failure.
CYP2C19 genotyping can help predict clopidogrel response, improve clinical outcome and
reduce mortality.

• Keywords: klopidogrel; famakogenetika; rezistencija; CYP2C19; ABCB1
• Keywords (english): clopidogrel; pharmacogenetics; resistance; CYP2C19; ABCB1
• Language: croatian
• URN:NBN: urn:nbn:hr:163:569129
• Study programme: Title: Clinical pharmacy; Study programme type: university; Study level: postgraduate specialist; Academic / professional title: sveučilišni/a magistar/sveučilišna magistra kliničke farmacije (sveučilišni/a magistar/sveučilišna magistra kliničke farmacije)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2019-04-30 13:49:05