Title Farmakogenetika rosuvastatina Title (english) The pharmacogenetics of rosuvastatin Author Janko Hrvoj Mentor Iveta Šimić (mentor)Committee member Nada Božina (predsjednik povjerenstva)Committee member Jasenka Markeljević (član povjerenstva)Committee member Iveta Šimić (član povjerenstva)Granter University of Zagreb Defense date and country 2014-07-15, Croatia Scientific / art field, BIOMEDICINE AND HEALTHCARE Scientific / art field, BIOMEDICINE AND HEALTHCARE Abstract Ateroskleroza je bolest u podlozi većine kardiovaskularnih bolesti. Posljedica je brojnih čimbenika, a jedan od glavnih je dislipidemija, koji dovode do oštećenja i promjena funkcije endotela arterija. Liječenjem se nastoji usporiti progresija ili postići regresija bolesti i u tome su danas najuspješniji statini. Statini su inhibitori HMG-CoA reduktaze, enzima koji je limitirajući korak u sintezi kolesterola. Smanjenom sintezom kolesterola u hepatocitima, utječu na koncentracije lipida u krvi, snižavaju razine LDL-a i triglicerida, a povisuju razine HDL-a. Lijekovi su koji se dobro toleriraju i imaju rijetke nuspojave. Nuspojave su posljedica djelovanja lijeka u mišičnim stanicama i mogu biti u rasponu od blagih, mialgija, pa do vrlo teških, rabdomioliza. Rosuvastatin je lijek nove generacije statina, koji zbog promjena u kemijskoj strukturi, ima veću lipofilnost i jači afinitet za ciljni enzim. Farmakološka svojstva mu se razlikuju od drugih statina, ima jači učinak na razine lipida u krvi i manji broj nuspojava, dokazano kroz brojne kliničke studije. Farmakogenetika je znanstvena disciplina koja proučava utjecaj gena na farmakološka svojstava lijeka, a polazi od toga kako su interindividualne razlike u farmakološkim svojstvima lijeka među pojedincima posljedica različitosti u genomu osoba. Povezujući određene genotipove s određenim fenotipovima omogućava prepoznavanje osoba u populaciji koje će imati različit odgovor na lijek (smanjeni učinak ili češće nuspojave). Takvim pojedincima će se temeljem smjernica moći individualno prilagoditi način uzimanja lijeka kako bi se provela uspješna farmakoterapija. Farmakogenetska istraživanja rosuvastatina utvrdila su gene koji utječu na farmakodinamiku (geni za HMG-CoA reduktazu, LDL receptor, KIF6 protein, proteine APOE, APOC1, APOC2, Lp(a) i CYP7A1) i gene koji utječu na farmakokinetiku rosuvastatina ( geni za SLCO1B1, ABCG2, CYP2C9 i CYP2C19). Osobe s polimorfizmom Rs2231142 na genu ABCG2 imaju rizik od viših koncentracija rosuvastatina u krvi od ostatka populacije i veću vjerojatnost pojave težih nuspojava.
Abstract (english) Atherosclerosis is a disease in the main of the most cardiovascular disease. It is a result of many factors, one of the major is dyslipidemia, which leading to damages and changes in arterial endothelial function. Treatment aims are to slow the progression or to regression of the disease. The most successful treatment to achieve this are statins. Statins are inhibitors of HMG-CoA reductase, the enzyme which is the limiting step in cholesterol synthesis. Reducing cholesterol synthesis in hepatocytes, they are affecting on lipids in blood plasma, lowering levels of LDL and triglyceride and increasing HDL levels. They are the drugs that are well tolerated and side effects are rare. Side effects are a consequence of drug activity in muscle cells and they can range from mild, myalgia, to the very serious, rhabdomyolysis. Rosuvastatin is a statin drug of a new generation. It has a higher lipophilicity and stronger affinity for the target enzyme. Pharmacological properties are different from other statins, it has a stronger effect on blood lipid levels and less side effects. This has been proved by numerous clinical studies. Pharmacogenetics is a scientific discipline that studies the influence of genes on the pharmacological properties of the drug. It bases on that interindividual differences in pharmacological properties are result of the genome diversity of people. By linking specific genotypes with specific phenotypes, it allows identification persons in the population that will have a different response to the drug (reduced effect or frequent side effects). Terapy of this individuals will be based on the guidelines, which will customize the way of taking the drug to conduct an effective pharmacotherapy. Pharmacogenetic study of rosuvastatin determine the genes that affect on the pharmacodynamics (genes for HMG-CoA reductase, the LDL receptor, KIF6 protein, APOE, APOC1, APOC2, Lp (a) and CYP7A1) and genes that affect on the pharmacokinetics of rosuvastatin (SLCO1B1, ABCG2, CYP2C9 and CYP2C19 genes). People with polymorphism Rs2231142 of the ABCG2 gene have a risk of higher concentrations of rosuvastatin in the blood than the general population and a higher chance of severe side effects.
Keywords
ateroskleroza
rosuvastatin
statini
farmakogenetika
Keywords (english)
atherosclerosis
rosuvastatin
statins
pharmacogenetics
Language croatian URN:NBN urn:nbn:hr:105:734409 Study programme Title: Medicine Type of resource Text File origin Born digital Access conditions Open access Terms of use Created on 2015-10-07 12:14:31
