Uloga farmakogenomike i interakcija lijekova u varijabilnosti učinkovitosti i sigurnosti primjene direktnih oralnih antikoagulansa

professional thesis

• Author: Marina Šandrk
• Mentor: Nada Božina (mentor)
• Committee member: Karmela Barišić (predsjednik povjerenstva)
• Committee member: Nada Božina (član povjerenstva)
• Committee member: Vesna Bačić Vrca (član povjerenstva)
• Granter: University of Zagreb; Faculty of Pharmacy and Biochemistry; Zagreb
• Defense date and country: 2023-02-24, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Pharmacy; Pharmacy

Abstract

Cilj istraživanja: Cilj ovog istraživanja je kritički osvrt na literaturne podatke koji se odnose
na utjecaj genskih varijanti na učinak i neželjene reakcije direktnih oralnih antikoagulacijskih
lijekova.
Materijali i metode: Za potrebe istraživanja i pisanja rada, od dostupnih baza podataka,
pretražene su baze podataka Medline i Pubmed prema ključnim riječima: direktni oralni
antikoagulansi (DOAK), dabigatran, rivaroksaban, apiksaban, edoksaban, farmakogenetika,
genski polimorfizmi CES1, CYP3A4, P-glikoprotein, MDR1/ABCB1, ABCB2. Odabrani
znanstveni članci obuhvaćaju sve dostupne članke iz područja farmakogenetike,
farmakogenomike DOAK-a u posljednjih 10 godina, uključujući originalne znanstvene članke
kao i pregledne radove koji zadovoljavaju tematiku rada. Također, u radu su prikazani
slučajevi iz kliničke prakse iz rutinskog testiranja u okviru obrade pacijenata u Kliničkom
bolničkom centru Zagreb u Odjelu za farmakogenomiku i individualizaciju terapije, uz
poštivanje svih etičkih načela.
Rezultati: Pregledom literature saznajemo da DOAK-i ovisno o metaboličkom putu stupaju u
interakcije sa određenim skupinama lijekova. Jednako tako, polimorfizmi prijenosnih
proteina i enzima utječu na pojavnost velikih štetnih događaja u vidu krvarenja.
Zaključak: Iako su novi oralni antikoagulansi sigurni lijekovi kod većine pacijenata, ipak
postoji određeni postotak pacijenata kod kojih je potrebna primjena s oprezom ovisno o
farmakogenetičkom profilu.

Abstract (english)

Objectives: The aim of this study was to critically review the literature data related to the
influence of genetic variants on the effect and adverse reactions of direct oral
anticoagulants drugs.
Material and methods: For research and writing, from the available databases, Medline and
Pubmed databases were searched by keywords: direct oral anticoagulants (DOAC),
dabigatran, rivaroxaban, apixaban, edoxaban, pharmacogenetics, gene polymorphisms
CES1, CYP3A4, P-glycoprotein MDR1 / ABCB1, ABCB2. The selection of scientific articles in
the search included all available articles in the field of pharmacogenetics,
pharmacogenomics of DOAC in the last 10 years, including original scientific articles and
review papers that meet the topics and objectives of the research set in the paper. This
paper also included cases from routine testing within the treatment of patients at the
Clinical Hospital Center Zagreb in the Department of Pharmacogenomics and
Individualization of Therapy, in compliance with all ethical principles.
Results: A review of the literature reveals that DOAKs interact with certain groups of drugs
depending on their metabolic pathway. Likewise, polymorphisms of transport proteins and
enzymes affect the occurrence of major adverse events in the form of bleeding.
Conclusion: Although new oral anticoagulants are safe drugs in most patients, there is still a
certain percentage of patients who require caution depending on the pharmacogenetic
profile.

• Keywords: direktni oralni antikoagulansi; DOAK; dabigatran; rivaroksaban; apiksaban; edoksaban; farmakogenetika; genski polimorfizmi CES1; CYP3A4; P-glikoprotein; MDR1/ABCB1; ABCB2
• Keywords (english): direct oral anticoagulants; DOAC; dabigatran; rivaroxaban; apixaban; edoxaban; pharmacogenetics; gene polymorphisms CES1; CYP3A4; P-glycoprotein MDR1 / ABCB1; ABCB2
• Language: croatian
• URN:NBN: urn:nbn:hr:163:706790
• 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: 2023-03-06 16:08:02