Olomouc, Czech Republic
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Ehrmann J.,II. interni klinika gastro enterologicka a hepatologicka | Urbanek K.,Ustav farmakologie
Kardiologicka Revue | Year: 2014

Irritable bowel syndrome (IBS) and functional dyspepsia are the most common functional gut disorders. The main topic of the article is a summary review of the etiology and pathogenesis of this disease as well as its diagnostic procedures and treatment. Irritable bowel syndrome is characterized by abdomen pain with altered stool frequency or consistency. It is recommended that it be defined and classified according to the Rome III classification. The symptoms are induced by physiological aberrations (like dysmotility and visceral hypersensitivity) or by the mechanisms of the initial inflammation and neuroimmune interaction. This is also the focus of contemporary research. The etiology and pathogenesis, however, remain unclear and the therapy of the day remains at the level of decreasing the main symptoms: abdominal pain, constipation, diarrhea and psychological factors. Sulpiride, an antagonist of the D1 and D3 receptors, at a dose of 50 or 100 mg 3 times daily should be a first-choice treatment of IBS due to its anxiolytic and analgesic effects. The adverse effects of drugs for the treatment of IBS on the cardiovascular system are discussed in the last part of the article.


The medicinal product Relvar Ellipta is a new dry powder inhaler containing a new fixed combination of the inhaled corticosteroid fluticasone furoate (FF) and the selective ultra-long-Acting, 2-Adrenergic agonist vilanterol. The article summarizes the most interesting data from the preclinical development and phase I clinical evaluation of both molecules. Among the modern inhaled corticosteroids, FF has the highest affinity towards the glucocorticoid receptor. In preclinical testing in vitro and in vivo, the glucocorticoid activity of FF was stronger and it had longer duration than that of fluticasone propionate. The inhaled particles of FF dissolve very slowly bringing two major advantages. First, the pulmonary residence time is two-fold longer than that of fluticasone propionate making a once-daily inhalation possible and, second, the slower rate of absorption results in very low concentrations of FF in the blood. The safety profile of FF is further supported with the high velocity of hepatic elimination, biotransformation to inactive metabolites, negligible oral bioavailability and extensive binding to plasma proteins. Preclinical and clinical evaluation of vilanterol was able to document its improved pharmacodynamic characteristics in comparison to salmeterol. Namely, the intrinsic activity of vilanterol is higher and its effect has a more rapid onset and a longer duration. Both the extraordinary 2-selectivity and appropriate pharmacokinetic characteristics (fast hepatic elimination, conversion to inactive metabolites, short half-life, minimal oral bioavailability) are responsible for a favorable safety profile of vilanterol. The duration of action over 24 h following inhalation is ascribed to the high-Afinity binding of vilanterol to specific binding sites on the 2-receptor which enables its retention nearby and a repeated interaction with the receptors active site.


Bultas J.,Ustav Farmakologie
Casopis Lekaru Ceskych | Year: 2015

Mountaineering brings many health risks, one of which is mountain sickness. Its mildest form - acute mountain sickness - is mainly characterized by subjective symptoms (headache, loss of appetite, insomnia, weakness, nausea and rarely also vomiting). Advanced and life-threatening forms are characterized by tissue edema - cerebral or pulmonary high altitude edema. The common denominator of these acute forms is the low oxygen tension leading to hypoxemia and tissue ischemia. Sum of maladaptive or adaptive processes can modify the clinical picture. Underlying mechanisms of the chronic forms of pulmonary disease are the adaptation processes - pulmonary hypertension and polycythemia leading to heart failure. The only causal therapeutic intervention is to restore adequate oxygen tension, descend to lower altitudes or oxygen therapy. Pharmacotherapy has only a supportive effect. The prophylaxis includes stimulation of the respiratory center by carbonic anhydrase inhibitors (acetazolamide) antiedematous treatment with glucocorticoids (dexamethasone), increase lymphatic drainage of the lungs and brain by β2-agonists (salmeterol) or mitigation of pulmonary hypertension by calcium channel blockers or phosphodiesterase-5 inhibitors (sildenafil or tadalafil).


Bencova A.,Klinika Pneumologie a Ftizeologie | Antosova M.,Ustav Farmakologie | Kocan I.,Klinika Pneumologie a Ftizeologie | Rozborilova E.,Klinika Pneumologie a Ftizeologie
Studia Pneumologica et Phthiseologica | Year: 2014

The prevalence of chronic obstructive pulmonary disease (COPD) has been increasing both globally and in our country. It represents a serious problem because of its rising prevalence, morbidity, mortality and treatment costs. COPD is multi-component disease associated with several extrapulmonary manifestations which create conditions for development of comorbidities. Methods: A retrospective single-center study analyzing comorbidities in COPD patients hospitalized at the Clinic of Pneumology and Phthisiology, Jessenius Faculty of Medicine and University Hospital in Martin between 2007 and 2011. The data were sorted according to the involvement of organ systems and GOLD classification. The results were compared with similar studies performed worldwide. Results: The group comprised 994 patients. The most significant differences between genders were observed in musculoskeletal diseases, followed by mental disorders and gastrointestinal diseases, with female and male preponderance, respectively. The results and distribution of individual stages and comorbidities were expressed as absolute numbers and percentages and statistically analyzed. All results are shown in tables and graphs. Conclusion: The analysis showed that the most frequent comorbidity in COPD patients was cardiac diseases, with a prevalence twice that elsewhere in the world.


An advent of each new group of drugs associated with big expectations is inevitably followed by a period of critical evaluation. From the perspective of a gastroenterologist, a higher incidence of bleeding in the gastrointestinal tract associated with the use of some of the novel oral anticoagulants in comparison with warfarin is somewhat disappointing. Increased incidence of gastrointestinal haemorrhagic events was observed in both direct thrombin inhibitor - dabigatran, as well as some direct factor Xa inhibitors - xabans, specifically in rivaroxaban and edoxaban. In phase III clinical studies, the meta-analyses and analyses of registers has observed a relative increase in all bleeding events as well as major bleeding into the gastrointestinal tract of about a quarter to a half, but in absolute values the increase in the incidence is on average low, only 0.3%. However, for the individual drugs the absolute increase may be greater, e.g. in the case of rivaroxaban 1%. Given the fact that there are significant differences amongst individuals, rivaroxaban and dabigatran (at a dose of 2 × 150 mg) have a higher risk and the therapy with apixaban is not associated with a higher incidence of gastrointestinal bleeding, it is advisable for people at high risk of gastrointestinal bleeding to choose apixaban as the optimal anticoagulation therapy. The incidence of bleeding in the gastrointestinal tract is growing for a number of reasons, which increase the exposure to different drugs. These factors include in particular drug and food interactions, decreased renal functions, lower weight and some pharmacogenetic factors. Independently of the level of anticoagulants, the risk of gastrointestinal bleeding increases also the use of non-steroidal (even steroidal) anti-inflammatory drugs, infection with Helicobacter pylori or e.g. diverticulosis.


Direct oral anticoagulants (DOACs) are agents that have recently been introduced into clinical practice to replace warfarin. In addition to improved efficacy and safety, one of the anticipated benefits was the absence of the need for regular monitoring of coagulation parameters with the necessity of adjusting the doses on the basis of the obtained results. However, increasing need for quantitative determination of these substances in plasma in specific cases has been found. The gold standard for the essay of DOACs’ plasma concentrations is the LC-MS method. In daily practice, the use of indirect methods such as dTT for inhibitors of thrombin and chromogenic determination of anti-Xa for factor Xa inhibitors is more usual. So far, it has not been recommended for any DOAC that therapeutic drug monitoring should be performed repeatedly for dosage adjustment. Plasma concentrations measurements are used in cases such as suspected noncompliance, bleeding complications during treatment, the need for acute thrombolysis or surgical procedures. © 2015, Ambit Media a.s. All rights reserved.


Bultas J.,Ustav farmakologie | Karetova D.,II. interni klinika kardiologie a angiologie
Interni Medicina pro Praxi | Year: 2015

Currently, several oral anticoagulant drugs are available to treat and prevent thrombotic and thromboembolic states - warfarin, dabigatran, rivaroxaban, and apixaban. In a number of indications, there are options to choose from; at other times, the preference of one approach is more favourable - both in terms of higher efficacy and better safety, or sometimes the choice is limited to one anticoagulant only. An example when any anticoagulant can be chosen is the prevention of stroke in an otherwise uncompromised patient; when there is a high risk of thromboembolic stroke, dabigatran at a higher dose will most likely be preferred. By contrast, dabigatran cannot be used in the presence of moderate to severe reduction in glomerular filtration rate, and it is necessary to choose from xabans or, in terminal renal failure, warfarin is the only option. Similarly, dabigatran is not suitable in a patient with coronary involvement or a high risk of acute coronary event. However, in a patient with a higher risk of bleeding, particularly gastrointestinal bleeding, administration of apixaban or warfarin is an optimal option. With a higher risk of both cerebrovascular ischaemic event and gastrointestinal bleeding, apixaban is again most advantageous. In another indication, e.g. in thromboembolic event prophylaxis in patients after surgeries on major weight-bearing joints, rivaroxaban or apixaban are preferred. In the situation when an anticoagulant for treating acute phlebothrombosis is being chosen, it has to be taken into account whether we want to choose a one-drug strategy from the beginning - then rivaroxaben or apixaban is the option, or whether to initiate treatment with low-molecular-weight heparin and to administer an oral anticoagulant only in the subacute phase - then dabigatran or warfarin is the option. Other specific situations and reasons for preference are discussed in this review paper.


Methotrexate (MTX) is a conventional immunosuppressive drug of first choice in oral therapy of moderate-to-severe plaque psoriasis. Its use is comfortable and cost effective. The therapy improves the skin status according to the PASI score (psoriasis area and severity index) by 50% or more in up to 75% of patients. However, a high inter-individual variability in pharmacokinetics is one of the major factors responsible for either insufficient efficacy of the therapy or its premature discontinuation due to adverse effects of MTX. The review article critically evaluates the possible benefits of therapeutic drug monitoring (TDM) of MTX as a tool for personalized pharmacotherapy of psoriasis. Prospective clinical studies unraveled a relationship between the pharmacokinetics and the therapeutic effect of MTX. Recommendations on how to perform TDM were worked out and verified, which helped to improve the outcomes of the initial treatment phase (remission induction). Besides the individualization of MTX dosing, supplementation with folic acid was individually tailored only to patients with a proven folate deficit. © 2015, Ambit Media a.s. All rights reserved.


Sliva J.,Ustav farmakologie | Svacina S.,III. interni klinika
Interni Medicina pro Praxi | Year: 2016

The progress in the treatment of diabetes mellitus during last decade has been unprecedented, especially in the field of new oral antidiabetics. A high evidence of their effectiveness is needed for their successful clinical use as well as the evidence of their safety. In accordance to regulations of EMA and FDA, their cardiovascular safety has to be newly proven. Hence, the article summarizes most recent information from this topic, which was extensively discussed during last calendar year.


Karetova D.,II. interni klinika kardiologie a angiologie | Bultas J.,Ustav farmakologie
Kardiologicka Revue | Year: 2012

Warfarin has a long history as a golden standard in oral anticoagulation medication. In recent years, however, new anticoagulants have appeared, aspiring to take over the helm. Development has focused mainly on direct inhibitors of thrombin and direct inhibitors of Factor Xa. The greatest progress in the registration process has been achieved by dabigatran (Pradaxa®), followed by rivaroxaban (Xarelto®) and apixaban (Eliquis®). They are peroral agents with pointed effect, i.e. they block individual factors of the coagulation cascade - Factor Xa (xabans) and Factor II (gatrans), without any monitoring being necessary, but without any possibility to administer a specific antidote. They are already commonly used in the prevention of thromboembolic disease (TED) in orthopaedics and are starting to be administered as part of the prevention of systemic embolization in patients with atrial fibrillation. Registration for the purpose of treatment of acute venous thrombosis, pulmonary embolism and secondary prophylaxis of these events is approaching. Other molecules are currently at the stage of clinical trials (for instance, edoxaban, betrixaban, otomixaban).

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