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Methods for Predicting Drug Side Effects in Silico
Cicková, Pavlína ; Lexa,, Matej (referee) ; Berka,, Karel (referee) ; Provazník, Ivo (advisor)
Vývoj a výzkum léčiv je oblastí současné vědy, jejíž nedílnou součástí je i využití výpočetních metod. Z důvodu nákladnosti a časové náročnosti laboratorních přístupů, metody in silico sehrávají svou významnou roli. I přes rychlý vývoj výpočetních technik využívaných při vývoji léků, však není drtivá většina zkoumaných molekul v procesu vývoje úspěšná a do schvalovací fáze nepostoupí. Nejen proto se nejmodernější strategie návrhu potenciálních nových léčiv zaměřují na opětovné zkoumání již schválených léků a berou do úvahy i analýzu podobností. Tato práce popisuje vývoj a aplikaci souboru několika workflow, jež byl vytvořen v rámci analytické platformy KNIME a jež implementuje metody strojového učení za účelem predikce nežádoucích účinků léčiv. Součástí prezentovaných workflow je získání dat, jejich předzpracování, výpočet metrik podobností a provedení explorační analýzy. Následně je využito klasifikačních modelů k predikci specifických nežádoucích účinků léčiv. Tato predikce vychází z principů technik založených na podobnosti. K natrénování modelů rozhodovacích stromů pro predikci potenciální asociace nežádoucích účinků s léčivy byly využity strukturní a jiné podobnosti schválených molekul léčiv. Hlavní přínos práce spočívá především v přenositelnosti použitých metod. Soubor workflow je určen k využití jako vhodný nástroj k řešení výzkumných otázek ohledně podobnosti léčiv a jelikož analytická platforma KNIME poskytuje uživatelsky přívětivé grafické rozhraní, není nutné, aby měli uživatelé pokročilé zkušenosti v oblasti strojového učení nebo programování, aby mohli soubor navržených workflow v rámci této platformy pro své analýzy využít.
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Interaction of drugs used in gynecology and urology and their management
Kupka, Vojtěch ; Doseděl, Martin (advisor) ; Kostřiba, Jan (referee)
Interaction of drugs used in gynecology and urology and their management Author: Kupka Vojtěch Tutor: PharmDr. Martin Doseděl Ph.D., Department of Social and Clinical Pharmacy, Charles University in Prague, Faculty of Pharmacy in Hradec Králové Introduction: Drug interactions represent a serious health problem and they cause adverse drug effects and toxicity of drugs. Objectives: The goal of the thesis was to create an overview of possible drug interactions with drugs used in gynecological and urological practice. Methodology: From a theroretical introduction was selected registred drugs to 1 st January 2015 by State Institute for Drug Controle. Information about drug interactions were collected and collated from databases Vademecum Infopharm and Micromedex. From database Micromedex, the drug interactions were selected with quality of documentation "excellent" or "good". Pubmed database (www.pubmed.gov) with entering key words "basic drug", "drug interaction" and "interactive drug" was applied to create a current information. To complement the information was also gathered from magazines Practical Pharmacy and Clinical Pharmacology and Pharmacy. In case of not finding relevant information was drawn from the summary information of medicine (SPC). Results: The results were categorized into a research...
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Polymorphism of drug metabolizing enzymes as a potential target of prevention of serious treatment complications in neonates and infants
Hronová, Karolína ; Slanař, Ondřej (advisor) ; Paluch, Zoltán (referee) ; Hladík, Michal (referee)
Univerzita Karlova 1. lékařská fakulta Studijní program: Biomedicína Studijní obor: Preventivní medicína MUDr. Karolína Hronová Polymorfismus genů účastnících se v metabolismu léčiv jako potenciální cíl prevence závažných komplikací léčby u novorozenců a dětí Polymorphism of drug metabolizing enzymes as a potential target of prevention of serious treatment complications in neonates and infants Disertační práce- ABSTRAKT V ANGLICKÉM JAZYCE Školitel: prof. MUDr. Ondřej Slanař, Ph.D. Konzultant: MUDr. Pavla Pokorná, PhD. Praha, 2018 Abstract Background and aims: The safety of analgosedative drugs includes drug interactions, adverse effects, withdrawal syndrome and drug dependence are factors that significantly affect morbidity and mortality. Its prevention is critical for quality improvement of care in paediatric patients. The aim of the thesis was to evaluate the prediction of efficacy and safety of analgosedative drugs sufentanil, midazolam, tramadol and valproic acid in neonates and children based on the occurrence of selected pharmacogenetic biomarkers. The incidence of drug interactions of phenobarbital with other analgosedative drugs has also been evaluated. Methodology: The thesis is based on two studies conducted on Intensive and Resuscitation Care Unit of the Clinic of Paediatric and Adolescent...
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Drug Information Centre service analysis IV. - drug interactions
Michálek, Georg ; Malá, Kateřina (advisor) ; Doseděl, Martin (referee)
Drug Information Centre service analysis IV. - drug interactions Author: Georg Michálek Supervisor: PharmDr. Kateřina Malá, Ph.D. Consultant: PharmDr. Petra Rozsívalová Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic Introduction: Drug information centre (DIC) of the Faculty of Pharmacy in Hradec Králové, Charles University, and University Hospital Hradec Králové was established in 1994. It provides drug information to healthcare professionals in the form of timely and accurate answers to drug-related enquiries, including drug interactions (DI). Aim: This study aimed to analyse enquiries related to DI processed by DIC from 2015 to 2020 and to solve three drug enquiries related to drug interactions. Methods: Quantitative and qualitative analysis of drug enquiries was carried out. Data was collected from individual enquiries related, but not limited to drug-drug, drug-herbal, and drug-disease interactions. The quantitative analysis based on descriptive statistical methods was performed on two levels: enquiry level and drug interaction level. On the enquiry level, ATC codes found in the enquiries were analysed and on the drug interaction level various parameters assigned to each DI were analysed, such as interacting components,...
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Drug Information Centre service analysis IV. - drug interactions
Michálek, Georg ; Malá, Kateřina (advisor) ; Doseděl, Martin (referee)
Drug Information Centre service analysis IV. - drug interactions Author: Georg Michálek Supervisor: PharmDr. Kateřina Malá, Ph.D. Consultant: PharmDr. Petra Rozsívalová Department of Social and Clinical Pharmacy, Faculty of Pharmacy in Hradec Králové, Charles University, Czech Republic Introduction: Drug information centre (DIC) of the Faculty of Pharmacy in Hradec Králové, Charles University, and University Hospital Hradec Králové was established in 1994. It provides drug information to healthcare professionals in the form of timely and accurate answers to drug-related enquiries, including drug interactions (DI). Aim: This study aimed to analyse enquiries related to DI processed by DIC from 2015 to 2020 and to solve three drug enquiries related to drug interactions. Methods: Quantitative and qualitative analysis of drug enquiries was carried out. Data was collected from individual enquiries related, but not limited to drug-drug, drug-herbal, and drug-disease interactions. The quantitative analysis based on descriptive statistical methods was performed on two levels: enquiry level and drug interaction level. On the enquiry level, ATC codes found in the enquiries were analysed and on the drug interaction level various parameters assigned to each DI were analysed, such as interacting components,...
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Polymorphism of drug metabolizing enzymes as a potential target of prevention of serious treatment complications in neonates and infants
Hronová, Karolína ; Slanař, Ondřej (advisor) ; Paluch, Zoltán (referee) ; Hladík, Michal (referee)
Univerzita Karlova 1. lékařská fakulta Studijní program: Biomedicína Studijní obor: Preventivní medicína MUDr. Karolína Hronová Polymorfismus genů účastnících se v metabolismu léčiv jako potenciální cíl prevence závažných komplikací léčby u novorozenců a dětí Polymorphism of drug metabolizing enzymes as a potential target of prevention of serious treatment complications in neonates and infants Disertační práce- ABSTRAKT V ANGLICKÉM JAZYCE Školitel: prof. MUDr. Ondřej Slanař, Ph.D. Konzultant: MUDr. Pavla Pokorná, PhD. Praha, 2018 Abstract Background and aims: The safety of analgosedative drugs includes drug interactions, adverse effects, withdrawal syndrome and drug dependence are factors that significantly affect morbidity and mortality. Its prevention is critical for quality improvement of care in paediatric patients. The aim of the thesis was to evaluate the prediction of efficacy and safety of analgosedative drugs sufentanil, midazolam, tramadol and valproic acid in neonates and children based on the occurrence of selected pharmacogenetic biomarkers. The incidence of drug interactions of phenobarbital with other analgosedative drugs has also been evaluated. Methodology: The thesis is based on two studies conducted on Intensive and Resuscitation Care Unit of the Clinic of Paediatric and Adolescent...
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Study of interactions of antiviral drugs with intestinal drug efflux ABC transporters
Huličiak, Martin ; Červený, Lukáš (advisor) ; Vokřál, Ivan (referee)
Charles University Faculty of Pharmacy in Hradec Králové Department of Pharmacology & Toxicology Student: Martin Huličiak Supervisor: PharmDr. Lukáš Červený, Ph.D Title of diploma thesis: Study of interactions of antiviral drugs with intestinal drug efflux ABC transporters P-gp, MRP2 and BCRP are efflux transporters, members of the family of ATP binding cassette (ABC) transporters. These transporters are located on the apical membrane of the intestinal epithelium, where they may limit absorption of orally administered drugs. Study of drug interactions with/on intestinal efflux transporters is necessary to provide safe and effective treatment. The Caco-2 cell line is FDA recommended in vitro model of intestinal barrier and it is used for bidirectional testing of substrates and inhibitors of ABC transporters in preclinical research. However, this methodology has several shortcomings, so the need of introduction of new experimental models is increasing and the ex vivo method based on human or rat intestine is a promising option. Precision-cut intestinal slices (PCIS) represent a mini-model of the organ and contain all types of cells of the tissue. We used both in vitro model using Caco-2 cell monolayers for drug transport study and in our lab established ex vivo method of PCIS for accumulation study...
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Drug interactions of drugs used in thyroid diseases
Teťáková, Veronika ; Malý, Josef (advisor) ; Marešová, Helena (referee)
Drug interactions of drugs used in thyroid diseases Author: Veronika Teťáková1 Tutor: PharmDr. Josef Malý, Ph.D.1 1 Department of Social and Clinical Pharmacy, Charles University, Faculty of Pharmacy in Hradec Králové Introduction and objectives: Drug interactions are considered to be a significant aspect of pharmacotherapy that can lead to the potentiation of toxicity and side effects of drugs. However, their identification and adequate management of the use of drug combinations hampers a number of obstacles. The aim of this thesis was to summary information about the drug interactions of drugs used in thyroid diseases (levothyroxine, propylthiouracil, thiamazole) and to formulate articles describing the management of interactions in a clinical practice including information for the dispensation of these drugs. To compare the information presented in each database and to determine the degree of conformity between these sources. Methodology: Based on the use of numerous information sources (Micromedex, UpToDate, SPC, Stockley's Drug Interactions) lists of drug interactions of drugs used in thyroid disaeses were established. Information about these interactions were completed by findings from other sources (PubMed®, scientific reports, Google Scholar). The information presented in each of these...
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Interaction of drugs used in gynecology and urology and their management
Kupka, Vojtěch ; Doseděl, Martin (advisor) ; Kostřiba, Jan (referee)
Interaction of drugs used in gynecology and urology and their management Author: Kupka Vojtěch Tutor: PharmDr. Martin Doseděl Ph.D., Department of Social and Clinical Pharmacy, Charles University in Prague, Faculty of Pharmacy in Hradec Králové Introduction: Drug interactions represent a serious health problem and they cause adverse drug effects and toxicity of drugs. Objectives: The goal of the thesis was to create an overview of possible drug interactions with drugs used in gynecological and urological practice. Methodology: From a theroretical introduction was selected registred drugs to 1 st January 2015 by State Institute for Drug Controle. Information about drug interactions were collected and collated from databases Vademecum Infopharm and Micromedex. From database Micromedex, the drug interactions were selected with quality of documentation "excellent" or "good". Pubmed database (www.pubmed.gov) with entering key words "basic drug", "drug interaction" and "interactive drug" was applied to create a current information. To complement the information was also gathered from magazines Practical Pharmacy and Clinical Pharmacology and Pharmacy. In case of not finding relevant information was drawn from the summary information of medicine (SPC). Results: The results were categorized into a research...
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