Farmakogenetika lajšanja pooperativne bolečine s tramadolom

Jeriha, Jakob (author), Dolžan, Vita (mentor)

Tramadol je centralno delujoč opioidni analgetik za lajšanje akutnih in kroničnih bolečin. Encimi CYP2D6, UGT2B7, ABCB1 in ABCC2 so ključni za presnovo in transport tramadola. Polimorfizmi v genih za te encime bi lahko vplivali na farmakokinetiko tramadola in s tem na odgovor na zdravljenje. Namen raziskave je bil preveriti pogostnost teh polimorfizmov in njihov vpliv na odgovor na zdravljenje pri bolnicah po operaciji raka dojke. Preverili smo hipotezi, da je pogostost neželenih učinkov pri slabih presnavljalkah CYP2D6 manjša kot pri hitrih ali ultrahitrih presnavljalkah in da imajo nosilke polimorfizmov ABCB1, ABCC2 in UGT2B7 večje tveganje za pojav neželenih učinkov kot preiskovanke brez polimorfnih alelov. Pri 113 preiskovankah smo s kvantitativnim PCR določili frekvence alelov CYP2D6: *3, *4, *5, *6, *10, *41 in *2xN, ABCB1 rs1128503, rs2032582 in rs1045642, ABCC2 rs2804402, rs717620 in rs2273697 in UGT2B7 rs7668258 in rs7668258, ter s statistično analizo preverili njihov vpliv na prekinitev zdravljenja in pojav neželenih učinkov. Bolnice homozigotne za polimorfni alel UGT2B7 rs28365063 GG so statistično značilno pogosteje prekinile zdravljenje zaradi neželenih učinkov. Vmesne in hitre presnavljalke CYP2D6 so statistično značilno pogosteje poročale o zaprtju (P=0,005). Vplivi ostalih preučevanih polimorfizmov na tveganje za prekinitev zdravljenja ali pojav neželenih učinkov niso bili statistično značilni.

• Language: Slovenian
• Keywords: tramadol, genetski polimorfizmi, CYP2D6, UGT2B7, ABCC2, ABCB1, neželeni učinki
• Work type: Master's thesis/paper
• Organization: BF - Biotechnical Faculty
• Year: 2019
• PID: 20.500.12556/RUL-110000
• COBISS.SI-ID: 5195855
• Publication date in RUL: 11.09.2019

Secondary language

• Language: English
• Title: Pharmacogenetics of postoperative pain management with tramadol

Abstract

Tramadol is a central-acting opioid analgesic for the relief of acute and chronic pain. CYP2D6, UGT2B7, ABCB1 and ABCC2 enzymes are crucial for the metabolism and transport of tramadol. Polymorphisms in the genes for these enzymes could affect the pharmacokinetics of tramadol and hence the response to treatment. The aim of the study was to determine the frequency of these polymorphisms and their impact on treatment response in patients following breast cancer surgery. We hypothesized that frequency of adverse events is lower in poor CYP2D6 metabolizers than in fast or ultrafast metabolizers and that ABCB1, ABCC2 and UGT2B7 polymorphisms confer to a greater risk of adverse effects than non-polymorphic allele . In 113 patients, the frequencies of CYP2D6 * 3, * 4, * 5, * 6, * 10, * 41 and * 2xN, ABCB1 rs1128503, rs2032582 and rs1045642, ABCC2 rs2804402, rs717620 and rs2273697 and UGT2B7 rs7668258 and rs7668258 were determined by quantitative PCR. Statistical analysis was used to assess the associations with treatment discontinuation and the occurrence of adverse events. Patients homozygous for polymorphic UGT2B7 rs28365063 GG genotype statistically significantly discontinued treatment due to adverse events more often. Intermediate and extensive CYP2D6 metabolizers statistically significantly reported obstipation more often (P = 0.005). The effects of other studied polymorphisms on the risk of discontinuing treatment or the occurrence of adverse events were not statistically significant.

• Keywords: tramadol, genetic polymorphism, CYP2D6, UGT2B7, ABCC2, ABCB1, adverse effects