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Vliv genových polymorfismů na efektivitu farmakologické léčby deprese
MÍČKOVÁ, Dana
The bachelor thesis deals with the possible influence of genetic polymorphisms of selected cytochrome P450 (CYP) genes on the depression or other psychiatric diseases treatment. The treatment of psychiatric patients with psychotropic drugs often turns out to be unsatisfactory due to lack of effectivity or due to adverse drug reactions of psychiatric drugs. This means both a mental strain for the patient and social and economic impacts. One of many influences, participating on the unsatisfactory treatment, are the CYP gene polymorphisms, that result in the same (CYP) named enzymes activity, responsible for the metabolism of the respective drug. Mutation in these genes can cause both gain-of-function and reduced or loss-of-function of the respective enzymes and thus participate on the adverse drug reactions and/or lack of effectivity. The aim of the theoretical part of the thesis was to develop research on the topic of depressive disease, its history and methods of treatment. Moreover, to map the antidepressants prescribing practice in the Czech Republic during the last five years. Other aims were developing of an internet questionnaire for patients and test their genetic polymorphisms in the genes CYP2C19 and CYP2D6 (by the real-time PCR method with the melting curve analysis). Finally, to compare these results (questionnaires and test results) with each other with the aim of finding out whether there is a clear link between the detected type of metabolism and the patient's evaluation of the treatment, an/or whether it is possible to give some recommendations regarding treatment for specific patients.
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Ecotoxicological evaluation of selected psychotropic drugs
Hricová, Nikoleta ; Řezáčová, Veronika (referee) ; Zlámalová Gargošová, Helena (advisor)
This bachelor thesis done by literary research is about the issue of the occurence of psychopharmacs in the enviroment. Psychopharmacs such as antidepressants, anxiolytics, hypnotics, sedatives etc. belong to one of the most sold drugs around the world. The consumption of psychopharmacs is concerning and growing. Therofore their occurence in nature is also growing, which can negatively affect the ecosystems. Many studies confirmed the persistency of psychopharmacs in nature, their following bioaccumulation and ecotoxicity for the representatives of each ecosystem. This bachelor thesis describes possible ways of the drug’s intersection (penetration) in nature, the metabolism of psychopharmacs in the human body and the effectivity of their elimination in sewage tanks. This work also focuses on the occurence, stability, degradability and persistency of psychopharmacs in aquatic and in terrestrial enviroment. The consideration of risks in the occurence of psychopharmacs for the representatives of each ecosystems was processed by many ecotoxicological studies, which point out the danger of these substances. Based on this acquired knowledge, in the conclusion of this work, there was drafted a battery of ecotoxicological tests for the estimated effects of psychopharmacs.
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Embryotoxicity testing of psychopharmacs using the CHEST method
Pavlovič, Ondřej ; Peterka, Miroslav (advisor) ; Maňáková, Eva (referee)
Psychotropic drugs are commonly used group of pharmaceuticals, their main effect is to alter psychic condition, including mental diseases treatment. Symptoms of mental illnesses are more and more common, theref orenumber of patients diagnosed with mental illnes, and thus using psychotropics, is growing stronger. But using psychotropics during gestation is not without risks for mother and embryo itself. However, thanks to the absence of controlled human studies, the knowledge of emrbyotoxic effects of pschotropics is limited to casuistics, reported side effects and animal experimental studies. Many of those studies suggests emrbyotoxic potential of psychotropic drugs, on the other hand, others claim their safety. The goal of this thesis is to test at least some of them, using CHEST method, that allows us to observe direct effect of unmetabolized substance on chick embryo. In this thesis we tested selected psychotropics, very common antidepressant fluoxetine (prozac) and antipsychotic drug olanzapine, for embryotoxicity, using in ovo method CHEST with chick embryos as model organism. By bypassing the maternal organism and his metabolism, this method allows to observe direct effect of unmetabolized substance on chick embryo. Results revealed embryotoxic effect of fluoxetin in dosage 10-2 and 10-3 on 3rd and...
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Diabetes mellitus type 1 and depression. Psychopathology by somatic deseases
Komorousová, Jana ; Beran, Jiří (advisor) ; Lacigová, Silvie (referee) ; Jirák, Roman (referee)
Diabetes mellitus is a severe chronic life-long disease. The condition itself introduces a need for patient's lifestyle adjustment to the disease and a number of everyday therapeutic and diagnostic restrictions. Therefore, mental disorders are more common in diabetic patients than in the rest of the population. Biochemical and hormonal connections between mental disorders and diabetes mellitus represent another reason for their higher incidence in diabetic patients. Comorbid mental diseases can further negatively influence the course of diabetes. They are especially depression, anxiety disorders, eating disorders and cognitive disorders including dementia. Type 2 diabetes is also more common in patients with primary mental disease, as is e.g. schizophrenia and bipolar affective disorder. Regarding therapy, psychoactive drugs are used in diabetic patients. It is important to respect the specifics of the underlining disease during drug selection. The main factor for the selection of the medication is, apart of mental problems, the influence on body weight and blood glucose. Mental disorders can be also treated by psychotherapy and psychoeducation. Studies performed in diabetic patients with mental problems suggest the need for intervention in this area. The practical part of the work introduces a...
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New psychotropic drugs and their effect on developing embryo
Košťalová, Jana ; Maňáková, Eva (advisor)
In my diploma thesis, I researched the effect of mirtazapine on a developing embryo. Nowadays, new drugs are being developed and used for the treatment of depression. These drugs also include mirtazapine. The risk of using mirtazapine during pregnancy has not been documented yet and therefore it can not be used by pregnant women. These drugs are often very effective and well tolerated so it is very important to recognize the effect on a developing embryo. In our research, we used the method of CHEST (chick embryotoxicity screening test). We applied a dose of mirtazapine solution dissolved in DMSO to 4-day old chickens. The doses were 0.2µg, 0.15µg, 0.1µg, 0.05µg, 0.03µg in 3µl of the solution. As controls, we applied 3µl DMSO and 3µl destilled water. Embryos were being incubated for 5 days in an incubator and on the 9th day, we evaluated dead and malformed embryos and the spectrum of defects. From our observations, we have obtained the lethal dose, which was above 0.15µg and the dose that was equivalent to the LD50 - 0.05µg. Lower doses were safe, although these embryos were malformed. These malformations, however, were not statistically significantly different from the malformations occurring in controls. It is neccessary to continue and complete data for 2 -and 3-day old embryos, so that we cover all...
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The use of tryptophan depletion in the study of the mechanism of action of psychopharmaceuticals
Jirásková, Markéta ; Valeš, Karel (advisor) ; Telenský, Petr (referee)
Tryptophan depletion is a non-pharmacological and non-invasive method extensively used to investigate the role of serotonin (5-hydroxytryptamine in humans and animals. The method is based on reducing the availability of the essential amino acid tryptophan, the dietary serotonin precursor. As a precursor of serotonin, L-Tryptophan has a key role in the regulation of many physiological processes and, inter alia, in the pathology and pathophysiology of neuropsychiatric disorders and diseases. Despite the fact, that the method of tryptophan depletion has been applied in many experimental studies, the exact mechanism, by which tryptophan depletion inducted neurophysiological effects, remain unclear. Also, the protentional use of this method together with other drug coadministration has not been explored in detail yet. In this thesis, the most possible mechanisms of tryptophan depletion are discussed. Biochemical and behavioural effects of low dose of dizocilpine (0.1 mg/kg and 0.15 mg/kg) in animal model of tryptophan depletion are investigated as well. And finally, effects of administration of allopregnanolone and tacrine in model of tryptophan depletion with coadministration of MK-801 are studied. The results show that acute tryptophan depletion with prior starvation, not chronic depletion, caused...
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Ecotoxicological evaluation of selected psychotropic drugs
Hricová, Nikoleta ; Řezáčová, Veronika (referee) ; Zlámalová Gargošová, Helena (advisor)
This bachelor thesis done by literary research is about the issue of the occurence of psychopharmacs in the enviroment. Psychopharmacs such as antidepressants, anxiolytics, hypnotics, sedatives etc. belong to one of the most sold drugs around the world. The consumption of psychopharmacs is concerning and growing. Therofore their occurence in nature is also growing, which can negatively affect the ecosystems. Many studies confirmed the persistency of psychopharmacs in nature, their following bioaccumulation and ecotoxicity for the representatives of each ecosystem. This bachelor thesis describes possible ways of the drug’s intersection (penetration) in nature, the metabolism of psychopharmacs in the human body and the effectivity of their elimination in sewage tanks. This work also focuses on the occurence, stability, degradability and persistency of psychopharmacs in aquatic and in terrestrial enviroment. The consideration of risks in the occurence of psychopharmacs for the representatives of each ecosystems was processed by many ecotoxicological studies, which point out the danger of these substances. Based on this acquired knowledge, in the conclusion of this work, there was drafted a battery of ecotoxicological tests for the estimated effects of psychopharmacs.
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Ageing of the population and specific aspects of prescribing of hypnotics in older adults (II.)
Puldová, Karolína ; Fialová, Daniela (advisor) ; Kostřiba, Jan (referee)
Title: Ageing of the population and specific aspects of prescribing of hypnotics in older adults (II.) Student: Karolína Puldová, Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Czech Republic Supervisor: Assoc. Prof. Daniela Fialová, PharmD, Ph.D., Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové and Department of Geriatrics and Gerontology, 1st Faculty of Medicine and General Teaching Hospital, Prague, Czech Republic Introduction: World population is ageing and rational geriatric pharmacotherapy receives increasing attention. In seniors, rational pharmacotherapy is complicated by many risk factors, especially by physiological and pathological changes accompanying ageing, polymorbidity, polypharmacy, higher risk of adverse drug events, drug interactions and other risk factors. Particularly psychotropics belong to drug classes where rational prescribing in seniors often requires respecting of different rules. This diploma thesis focuses on specific aspects of irrational prescribing of hypnosedatives in ambulatory geriatric patients, particularly in the area of use of nongeriatric doses and nongeriatric lenght of therapy. Methodology: Data collection for this diploma thesis has been conducted between 2019-2020 years in the...
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