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Immunosuppressive therapy
Pichlová, Jitka ; Hrdina, Radomír (advisor) ; Nachtigal, Petr (referee)
Immunosuppressive therapy is used wherever it is necessary to inhibit unwanted immune system activity. Such clinical situations are the conditions accompanying organ transplantation and autoimmune diseases. The goal of immunosuppressive therapy is to reduce unwanted immune activity, ie to stay activated T and B lymphocytes. On the other hand, as little as possible to suppress non-specific cell immunity which mediate the immune response to various inflammatory stimuli, regardless of the specific antigen. Application of immunosuppressants is associated with an increased risk of infections of all types, and to otherwise rare. Moreover, an increased risk of developing lymphomas and other malignancies, therefore it is necessary to consider the benefits vs. risks of therapy. This work offers an overview of the substances used in immunosuppressive therapy. From the beginning they were non-specific cytotoxic agents (azathioprine, cyclophosphamide) and corticosteroids. Subsequently, it added ciclosporin A, tacrolimus, sirolimus and mycophenolate mofetil. Significant progress in immunosuppressive therapy has been achieved mainly by introducing polyclonal and monoclonal antibodies . Their use is generally achieved good clinical results and are well tolerated.
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Prodysrrhythmogenic effects of drugs
Péter, Bohuš ; Hrdina, Radomír (advisor) ; Tilšer, Ivan (referee)
The most common cardiac arrhythmia is atrial fibrillation. In most patients it is not the only heart disease. The main goal of therapy is to maintain a normal heart rhythm. This can be achieved by restoring the sinus rhythm or by controlling the ventricle response. The anticoagulation therapy may be needed to reduce the risk of tromboembolism. Several arrhythmias, including atrial fibrillation can be treated by a catheter ablation. This method is highly successful in treatment of supraventricular arrhythmias. The long-therm treatment of ventricular arrhythmias may require implantation of a cardioverter-defibrilator. Serious bradycardias are treated by permanent cardiac stimulation. The efficacy of pharmacologic treatment can be proved only in a clinical trial. Methods of preclinical identification of proarrhythmogenic substances are quite limited. Electrophysiology, drug effects, effects of genetic polymorphism can be studied mostly on models and preparations. Use of antiarrhythmics from groups IA and IB of the Vaughan Williams classification is now limited. Besides the beta blockers used in various indications, the antiarrhythmics from group III are most often used. It is likely that a new drug, dronedarone will be approved for treatment of atrial fibrillation. Positive effect on mortality, and in...
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The influence of pH on iron chelation
Hrabalíková, Jitka ; Mladěnka, Přemysl (advisor) ; Hrdina, Radomír (referee)
v angličtině Iron is one of essential elements which are necessary for life of cells. Many important processes are connected with it and its insufficiency can lead to cell death. Iron excess can be dangerous, too; such situation can be triggered not only by acute intoxication, but it appears also chronically due to genetic abnormalities (hereditary hemochromatosis) or by frequent blood transfusions during treatment of thalassaemia, sideroblastic anemia or myelodysplastic syndrome. Iron chelators are used to cure these pathological states, but there have been currently analysed for the treatment of tumors or acute myocardial infarction as well. In pathogenesis of both of these disorders, iron and change of pH play significant roles. In this study, influence of pH on iron chelation abilities of various substances (deferoxamine, synthetic chelator SIH, flavonoids and synthetic coumarin 7,8-dihydroxy-4- methylcoumarin) was measured with the use of ferrozine as an indicator. The stability of complex chelator - iron in various pH was also tested. It was found that chelation activity of all tested substances and the stability of iron- chelator complex is increased with increasing pH. Strong chelators SIH and deferoxamine kept their effectiveness within pH from 7.5 to 5.5, whereas chelating activity of...
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Pharmacotherapy of glaucoma
Konečná, Petra ; Hrdina, Radomír (advisor) ; Mladěnka, Přemysl (referee)
Charles University in Prague Faculty of Pharmacy in Hradec Králové Department of Pharmacology and Toxicology Candidate: Petra Konečná Supervisor: Doc. MUDr. Radomír Hrdina, CSc. Title of diploma thesis: Pharmacotherapy of glaucoma Glaucoma is one of the main causes of blindness in the world and its prevalence is progressively increasing. An early detection and an effective therapy are very important to prevent progression of this disease. Ways of treatment involve pharmacotherapy and laser or surgical interventions. The diploma thesis is concerned with pathophysiology, classification and detection of glaucoma. The main part focuses on a medical treatment, especially on individual groups of medications, which are used from the initial stage of the disease to maximally tolerated doses. Prostaglandin analogs, which are currently used as the first line of therapy and which are used with other medications in fixed or unfixed combinations, are described in detail. Glaucoma is unfortunately incurable but it is possible to prevent its exacerbation and an irreversible loss of sight. The thesis follows up and summarizes results from international studies dealing with an effect, an effectiveness and side effects of single groups of medications. The purpose was to organize new observations in one complex and...
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Pharmacotherapy of chronic obstructive pulmonary disease
Malinská, Eva ; Pourová, Jana (referee) ; Hrdina, Radomír (advisor)
CHARLES UNIVERSITY IN PRAGUE FACULTY OF PHARMACY IN HRADEC KRÁLOVÉ DEPARTMENT OF PHARMACOLOGY AND TOXICOLOGY CANDIDATE: EVA MALINSKÁ SUPERVISOR: DOC. MUDR. RADOMÍR HRDINA, CSC. TITLE OF DIPLOMA THESIS: PHARMACOTHERAPY OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE 2 ABSTRACT Topic: Chronic obstructive pulmonary disease (COPD) Autor: Eva Malinská Chronic obstructive pulmonary disease is one of the world significant cause of chronic morbidity and mortality. The main cause of COPD is continuous smoking of tobacco, together with other influences - like air polution, etc.. The proper and timely diagnosis of COPD leads to improvement of patient's life and reduction of complications such as pulmonary hypertension and other illnesses connected with it. To achieve satisfactory state , all patients need pharmacological treatment. Part of care for the patients should be regime measures, above all - smoking cessation. The pharmacotherapy in recent time prefers inhalation bronchodilators, possibly in combination with inhalation corticosteroids. Total cure of COPD is not possible yet. The course of the illness is not possible to stop, but it can be made slower and the symptoms can be minimalized. The base for successful treatment is co-operation of educated patient.
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New iron chelators and antioxidants in acute myocardial model / / infarction and oxidative stress-induced catecholamine / / - effect on the basic biochemical parameters
Mladěnka, Přemysl ; Hrdina, Radomír (advisor) ; Geršl, Vladimír (referee) ; Patočka, Jiří (referee)
I. SUMMARY Background: Iron is an essential element necessary for many physiological processes involving oxygen transport, DNA-synthesis and ATP-formation. The fate of iron in the organism is tightly regulated especially at the absorption and distribution level probably mainly due to lack of specific active iron excretion mechanism. Any derangement of iron homeostatis may lead to appearance of free (unbound or loosely bound) iron, which can catalyse reactive oxygen species (ROS) production by Haber-Weiss chemistry. Cardiovascular diseases, particularly coronary heart disease (CHD), remain notwithstanding recent scientific advances important therapeutic problem. The most serious form of CHD represents acute myocardial infarction (AMI). The pathophysiology of AMI involves in most cases initial ischaemic period caused by coronary blood flow derangement due to a thrombus formation. Ischaemia alters substantially tissue homeostasis with subsequent cytosolic free iron appearance. Reconstitution of coronary blood flow (reperfusion) represents the only way for myocardial tissue recovery although on the other hand, it is linked with a release of free redox-active iron in the circulation and formation of ROS both intracellularly as well extracellularly. Iron chelators are a large group of drugs with very...
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