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https://ptsldigital.ukm.my/jspui/handle/123456789/456156| Title: | Roles of MDR1 and OPRM1 gene polymorphisms on the pharmacodynamics of propofol-remifentanil Total Intravenous Anaesthesia (TIVA) in paediatric surgery |
| Authors: | Liew Yee (P104883) |
| Supervisor: | Mohd Makmor Bakry, Assoc. Prof. Dr. |
| Keywords: | Anaesthetic Analgesic Propofo Remifentanil Pharmacokinetics Universiti Kebangsaan Malaysia -- Dissertations Dissertations, Academic -- Malaysia |
| Issue Date: | 8-Aug-2022 |
| Description: | Anaesthetic and analgesic agents are imperative for a successful surgery and have a narrow therapeutic index. Gene polymorphisms are known to affect the pharmacokinetics and pharmacodynamics of drugs. Genetic variation of MDR1 and OPRM1 on the effects of these agents may affect the patients' clinical outcomes. This series of studies aimed to investigate the roles of multidrug resistance (MDR1) and muopioid receptor 1 (OPRM1) gene polymorphisms on the pharmacodynamics of propofol-remifentanil total intravenous anaesthesia (TIVA) in paediatric surgery. The first phase of the study involved a systematic review that summarised the effect of MDR1 (1236C>T, 2677G>T/A, and 3435C>T) and OPRM1 (118A>G) genetic variants on the pharmacological effects of anaesthetic and analgesic agents used in various surgical procedures. The result showed the effect of MDR1 gene polymorphism was inconclusive regarding anaesthetic, analgesic, and adverse effects of anaesthesia drugs whereas gene variant of OPRM1 118 A>G displayed weaker analgesic effect with a lower incidence of adverse effects. The next phase of the study involved data collection from Hospital Canselor Tuanku Muhriz. A total of 62 paediatric blood samples were collected to identify the prevalence of common polymorphisms in MDR1 (1236C>T, 2677G>T/A, and 3435C>T) and OPRM1 (118A>G) genes among paediatric patients. The DNA was extracted from the collected blood samples, the targeted DNA sequences were amplified via polymerase chain reaction and the genetic variants were identified using DNA sequencing. The allele and genotype distribution of MDR1 and OPRM1 polymorphisms were consistent with the Hardy-Weinberg equilibrium (p > 0.05) and comparable to those reported in other Asian populations. The final phase of the study was conducted to investigate the roles of MDR1 and OPRM1 gene polymorphisms on anaesthetic effects and adverse effects of propofol-remifentanil. The clinical data of paediatric patients including hemodynamic on anaesthesia, post-anaesthesia pain and sedation score, along with the occurrence of adverse effects were recorded and compared against the genetic data. Genetic polymorphisms in OPRM1 (118A>G) demonstrated plausible association with the efficacy and safety of propofol-remifentanil but not in MDR1 (1236C>T, 2677G>T/A, and 3435C>T) gene polymorphism. A larger prospective cohort is required to support the prospect of developing genetic profiles to make a recommendation based on genetic-guided dosing and monitoring of the adverse effect of propofol-remifentanil in paediatric patients. This may allow a tailored treatment regimen to an individual's specific pharmacokinetic or pharmacodynamics phenotype and complements the pre-existing anaesthesia clinical guidelines,Ijazah Sarjana Sains |
| Pages: | 165 |
| Publisher: | UKM, Kuala Lumpur |
| Appears in Collections: | Faculty of Pharmacy / Fakulti Farmasi |
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|---|---|---|---|---|
| ukmvital_130385+Source01+Source010.PDF Restricted Access | 2.88 MB | Adobe PDF |  View/Open |
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