title: Factors affecting the development of adverse drug reactions to β-blockers in hospitalized cardiac patient population.
abstract: 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.
authors.affiliation: Department of Pharmacotherapy, Faculty of Pharmacy, University of Montenegro; Clinical Trial Department, Agency for Medicines and Medical Devices of Montenegro, Podgorica, Montenegro.
authors.forename: Snežana
authors.initials: S
authors.lastname: Mugoša
authors.affiliation: Department of Pharmacology and Toxicology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac.
authors.forename: Nataša
authors.initials: N
authors.lastname: Djordjević
authors.affiliation: High Medical School "Milutin Milanković", Belgrade.
authors.forename: Nina
authors.initials: N
authors.lastname: Djukanović
authors.affiliation: Department of Pharmacology, Clinical Pharmacology and Toxicology.
authors.forename: Dragana
authors.initials: D
authors.lastname: Protić
authors.affiliation: Institute for Medical Statistics and Informatics, Faculty of Medicine, University of Belgrade, Belgrade.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Bukumirić
authors.affiliation: Department of Surgery, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.
authors.forename: Ivan
authors.initials: I
authors.lastname: Radosavljević
authors.affiliation: Clinic for Heart Diseases, Clinical Centre of Montenegro, Podgorica, Montenegro.
authors.forename: Aneta
authors.initials: A
authors.lastname: Bošković
authors.affiliation: Department of Pharmacology, Clinical Pharmacology and Toxicology; Department of Clinical Immunology and Allergy, Medical Center "Bežanijska kosa", Belgrade, Serbia.
authors.forename: Zoran
authors.initials: Z
authors.lastname: Todorović
keywords: CYP2D6; adverse drug reactions; pharmacogenetics; β-blockers