Farmakogenetika tiopurinskih lijekova

master's thesis

• Title (english): Pharmacogenetics of thiopurine drugs
• Author: Ana-Marija Jelčić
• Mentor: Nada Božina (mentor)
• Committee member: Silvija Čuković-Čavka (predsjednik povjerenstva)
• Committee member: Jasenka Markeljević (član povjerenstva)
• Committee member: Nada Božina (član povjerenstva); : NB094
• Granter: University of Zagreb; School of Medicine; Zagreb
• Defense date and country: 2015-07-15, Croatia
• Scientific / art field, discipline and subdiscipline: BIOMEDICINE AND HEALTHCARE; Clinical Medical Sciences; Clinical Pharmacology and Toxicology

Abstract

Tiopurinski lijekovi azatioprin (AZA), 6-merkaptopurin (6-MP) i 6-tiogvanin (6-TG) primjenjuju se za liječenje malignih bolesti, reumatskih bolesti, dermatoloških stanja, upalnih bolesti crijeva i nekih poremećaja imunološkog sustava. Aktivni metaboliti tiopurina djeluju kao purinski antagonisti i inhibiraju sintezu endogenih purina, DNA, RNA i nekih koenzima. Tiopurini imaju relativno malu terapijsku širinu, pa je vrlo važno razumjeti metabolizam lijeka u organizmu i njegovu široku interindividualnu varijabilnost. Gotovo trećina bolesnika ne odgovara na primjenu tiopurina, a 20-25% bolesnika koji počnu uzimati lijek razvije neki oblik nuspojava. Jedan od važnih rizika koji vodi razvoju toksičnosti pri primjeni tiopurinskih lijekova, najčešće u vidu mijelosupresije, je genetski polimorfizam enzima važnih u metabolizmu tiopurina: tiopurinmetiltransferaze (TMPT), ksantin-oksidaze (XO) i inozin-trifosfat-pirofosfataze (ITPA). Prije primjene tiopurinskih lijekova potrebno je odrediti aktivnost tiopurinmetiltransferaze (TPMT) radi optimiziranja terapije, što je sada rutinska obrada u mnogim zemljama. Toksičnost i nuspojave kod interakcije tiopurina s drugim lijekovima treba također uzeti u obzir.

Abstract (english)

Thiopurine drugs azathioprine (AZA), 6-mercaptopurine (6-MP) and 6-thioguanine (6-TG) are used to treat malignancies, rheumatic diseases, dermatologic conditions, inflammatory bowel diseases and other immune regulation disorders. Active metabolites of thiopurines act as purine antagonists and inhibit endogenous protein synthesis, synthesis of DNA, RNA and some coenzymes. Thiopurine drugs have a relatively narrow therapeutic index and it is very important to understand their metabolism in the body as well as the wide interindividual variability. Almost one third of patients do not respond to thiopurines, and 20-25% of patients who start taking them develop some form of side effects. One of the important risk factor that may lead to toxicity, most often myelosuppression, is the genetic polymorphism of the enzymes which are involved in the metabolism of the thiopurines such as thiopurine methyltransferase (TPMT), xanthine oxidase (XO) and inosine triphosphatase pyrophosphatase (ITPA). Pretreatment determination of thiopurine methyltransferase (TPMT) status to optimize dosage before commencing thiopurine therapy is now a routine in many countries. Toxicities and adverse events resulting from drug-drug interactions should also be taken into account with thiopurine drugs.

• Keywords: tiopurinski lijekovi; genetski polimorfizam; tiopurinmetiltransferaza (TMPT); ksantin-oksidaza (XO); inozin-trifosfat-pirofosfataza (ITPA)
• Keywords (english): thiopurine drugs; genetic polymorphism; thiopurine methyltransferase (TPMT); xanthine oxidase (XO); inosine triphosphatase pyrophosphatase (ITPA)
• Language: croatian
• URN:NBN: urn:nbn:hr:105:169099
• Study programme: Title: Medicine; Study programme type: university; Study level: integrated undergraduate and graduate; Academic / professional title: doktor/doktorica medicine (doktor/doktorica medicine)
• Type of resource: Text
• File origin: Born digital
• Access conditions: Open access
• Created on: 2016-04-08 08:40:04