Mugoša Snežana, Djordjević Nataša, Djukanović Nina, Protić Dragana, Bukumirić Zoran, Radosavljević Ivan, Bošković Aneta, Todorović Zoran
Department of Pharmacotherapy, Faculty of Pharmacy, University of Montenegro; Clinical Trial Department, Agency for Medicines and Medical Devices of Montenegro, Podgorica, Montenegro.
Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac.
Patient Prefer Adherence. 2016 Aug 2;10:1461-9. doi: 10.2147/PPA.S108579. eCollection 2016.
The aim of the present study was to undertake a study on the prevalence of cytochrome P450 2D6 (CYP2D6) poor metabolizer alleles (*3, *4, *5, and *6) on a Montenegrin population and its impact on developing adverse drug reactions (ADRs) of β-blockers in a hospitalized cardiac patient population. A prospective study was conducted in the Cardiology Center of the Clinical Center of Montenegro and included 138 patients who had received any β-blocker in their therapy. ADRs were collected using a specially designed questionnaire, based on the symptom list and any signs that could point to eventual ADRs. Data from patients' medical charts, laboratory tests, and other available parameters were observed and combined with the data from the questionnaire. ADRs to β-blockers were observed in 15 (10.9%) patients. There was a statistically significant difference in the frequency of ADRs in relation to genetically determined enzymatic activity (P<0.001), with ADRs' occurrence significantly correlating with slower CYP2D6 metabolism. Our study showed that the adverse reactions to β-blockers could be predicted by the length of hospitalization, CYP2D6 poor metabolizer phenotype, and the concomitant use of other CYP2D6-metabolizing drugs. Therefore, in hospitalized patients with polypharmacy CYP2D6 genotyping might be useful in detecting those at risk of ADRs.
本研究的目的是对黑山人群中细胞色素P450 2D6(CYP2D6)慢代谢等位基因(*3、*4、5和6)的流行情况及其对住院心脏病患者群体中β受体阻滞剂发生药物不良反应(ADR)的影响进行研究。在黑山临床中心心脏病学中心进行了一项前瞻性研究,纳入了138例在治疗中接受过任何β受体阻滞剂的患者。使用基于症状清单和任何可能指向最终ADR的体征的专门设计的问卷收集ADR。观察患者病历、实验室检查和其他可用参数的数据,并与问卷数据相结合。在15例(10.9%)患者中观察到β受体阻滞剂的ADR。ADR的发生频率与基因决定的酶活性之间存在统计学显著差异(P<0.001),ADR的发生与CYP2D6代谢较慢显著相关。我们的研究表明,β受体阻滞剂的不良反应可以通过住院时间、CYP2D6慢代谢者表型以及其他CYP2D6代谢药物的联合使用来预测。因此,在接受多种药物治疗的住院患者中,CYP2D6基因分型可能有助于检测有ADR风险的患者。