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Prediction of the Antidepressant Effect of Ketamine Based on Clinical Parameters and Intoxication Phenomenology
Andrashko, Veronika ; Horáček, Jiří (advisor) ; Papežová, Hana (referee) ; Juřica, Jan (referee)
Background: ketamine is a rapid and potent antidepressant treatment, however no sufficient predictors for tailored treatment have been identified to date. The aim of the thesis was to identify possible clinical and phenomenological characteristics, associated with better antidepressant response in patients receiving ketamine. Materials and methods: data from 86 depressed patients from cohorts A (2010-2015) and B (2018-2022) were utilized. All patients underwent ketamine infusion and demographic as well as clinical assessment (severity of depressive symptoms, subjective and objective anxiety and anhedonia before and after ketamine application). In addition, an electrocardiogram was taken to assess heart rate variability in cohort A and blood pressure, heart rate, and altered state of consciousness scales were recorded in cohort B during ketamine intoxication. Results: in cohort A, the use of higher doses of benzodiazepines was associated with worse response at day 3 (p = 0.04) and day 7 (p = 0.02) after ketamine administration. Responders showed higher heart rate (p = 0.001) and differed from nonresponders in heart rate variability (p = 0.011). In cohort B, responders reached higher values od systolic (p = 0.003) and diastolic (p = 0.005) blood pressure during intoxication, but not higher heart...
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Novel bile acid derivatives as a promising therapeutic approach for liver and metabolic disorders
Štefela, Alžbeta ; Pávek, Petr (advisor) ; Vítek, Libor (referee) ; Juřica, Jan (referee)
IN ENGLISH LANGUAGE Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmacology and Toxicology Candidate: Mgr. Alžbeta Štefela Supervisor: Prof. PharmDr. Petr Pávek, PhD. Title of the doctoral thesis: Novel bile acid derivatives as promising therapeutic approach Bile acids (BAs) are amphipathic steroidal molecules that are traditionally known to facilitate intestinal digestion and absorption of lipids and fat-soluble substances. On top, the recent findings have revealed that they represent important signaling agents involved in the orchestration of lipid, glucose and energy metabolism and immune response. BAs exhibit these roles by activating intracellular nuclear receptors such as farnesoid X (FXR), pregnane X (PXR) vitamin D receptors. Furthermore, BAs act as endocrine signaling molecules and activate numerous biological cascades via a membrane G-protein-coupled receptor, termed TGR5. Therefore, the extensive modulation of BA scaffold underwent to identify compounds with specific targeting of above-mentioned receptors as a promising therapeutic approach for the treatment of various liver and metabolic disorders including cholestasis, biliary cirrhosis, nonalcoholic steatohepatitis or diabetes. The principal aim of this doctoral thesis was to investigate the structure...
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Novel bile acid derivatives as a promising therapeutic approach for liver and metabolic disorders
Štefela, Alžbeta ; Pávek, Petr (advisor) ; Vítek, Libor (referee) ; Juřica, Jan (referee)
IN ENGLISH LANGUAGE Charles University, Faculty of Pharmacy in Hradec Králové, Department of Pharmacology and Toxicology Candidate: Mgr. Alžbeta Štefela Supervisor: Prof. PharmDr. Petr Pávek, PhD. Title of the doctoral thesis: Novel bile acid derivatives as promising therapeutic approach Bile acids (BAs) are amphipathic steroidal molecules that are traditionally known to facilitate intestinal digestion and absorption of lipids and fat-soluble substances. On top, the recent findings have revealed that they represent important signaling agents involved in the orchestration of lipid, glucose and energy metabolism and immune response. BAs exhibit these roles by activating intracellular nuclear receptors such as farnesoid X (FXR), pregnane X (PXR) vitamin D receptors. Furthermore, BAs act as endocrine signaling molecules and activate numerous biological cascades via a membrane G-protein-coupled receptor, termed TGR5. Therefore, the extensive modulation of BA scaffold underwent to identify compounds with specific targeting of above-mentioned receptors as a promising therapeutic approach for the treatment of various liver and metabolic disorders including cholestasis, biliary cirrhosis, nonalcoholic steatohepatitis or diabetes. The principal aim of this doctoral thesis was to investigate the structure...
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Factors affecting drug distribution and elimination and their application in personalized pharmacotherapy.
Šíma, Martin ; Slanař, Ondřej (advisor) ; Juřica, Jan (referee) ; Tesfaye, Hundie (referee)
The aim of this dissertation thesis was to study the factors affecting drug distribution and elimination and to use these factors to individualize dosing. The work consists of three thematic areas: estimation of the volume of distribution and subsequent dosing of selected drugs (vancomycin, amikacin, phenobarbital) using body size descriptors; estimation of clearance and subsequent dosing of selected drugs (vancomycin, amikacin, phenobarbital, perindopril) using renal function status markers; and the impact of drug interactions on the distribution and elimination of phenobarbital. The thesis summarizes original papers on these topics. Individual pharmacokinetic parameters were calculated for each patient based on their demographic and clinical characteristics, dosing records and measured serum drug levels. The relationships between distribution volume/drug clearance and body size descriptors/renal functional status markers were examined by regression analysis. Vancomycin volume of distribution was best predicted by the total body weight. Loading dose of 10.7 mg/kg of total body weight was optimal in patients taking continuous vancomycin and would lead to reducing of median time to reach target concentrations from 17 to 1 hour. On the contrary, amikacin volume of distribution was most associated...
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