Репозиторий Университета

© Ima-Press Publishing House. All rights reserved. Objective: to investigate the efficiency of treatment for acute and subacute dorsalgia, by providing information to patients and by using nonsteroidal anti-inflammatory drugs (NSAIDs) without conducting physical therapy, reflexotherapy, and manual therapy. Patients and methods. A total of 140 patients (87 women and 53 men; mean age 50.7±17.6 years) with acute and subacute back pain were followed up. Out of them 127 (91%) patients were found to have nonspecific (musculoskeletal) pain; 13 (9%) had discogenic radiculopathy. All the patients were informed of the benign nature of the disease, the high probability of its rapid resolution, the feasibility of abandoning prolonged bedrest, and the lack of need for physical therapy, reflexotherapy, massage, and manual therapy. To reduce pain, the patients received meloxicam 15 mg/day orally or intramuscularly or first 15 mg/day intramuscularly and then orally. The investigators assessed pain intensity with the numerical rating scale and functional activity restrictions with the Roland-Morris disability (RMD) questionnaire. Results. After treatment, the visual analogue scale pain intensity scores decreased from an average of 6.4 to 1.0; the RMD scores dropped from 6.8 to 1.4 (p<0.001). The duration of treatment averaged 11.0±4.4 days. Comparison of different meloxicam dosage regimens showed no significant differences; a positive result was noted in all cases. No adverse events were observed during treatment. Conclusion. The investigation has shown the high efficiency of management in patients with acute and subacute dorsalgia, by providing information to patients (an education conversation), by using meloxicam, and by applying a personalized approach (treatment for concomitant diseases and conditions). Refusing physiotherapy, massage, acupuncture, and manual therapy substantially reduces the cost of treatment in patients with acute dorsalgia.

© 2018 Ima-Press Publishing House. All rights reservbed. The paper discusses the effects of drugs from different pharmacological groups on cognitive functions. It details the impact of drugs used to treat nervous system, cardiovascular, gastrointestinal, respiratory, and endocrine diseases on cognitive functions. It is emphasized that many drugs exert both negative and (less frequently) positive effect on cognitive functions, but it is especially pronounced in drugs used to treat nervous system diseases. There is evidence suggesting that different representatives of a number of pharmacological groups have no class effect on cognitive functions.

© 2018 Ima-Press Publishing House. Mental disorders (MDS) of the anxiety-depressive spectrum (ADS) and cognitive impairment (CI) substantially deteriorate the course and efficiency of therapy for rheumatoid arthritis (RA). There have been practically no studies on the impact of psychopharmacotherapy (PPT) for MDS on the efficacy of standard disease-modifying antirheumatic drugs (DMARDs) and biological agents (BAs). Objective: to investigate the impact of adequate PPT for MDS of ADS on the efficacy of DMARDs and BAs in patients with RA. Subjects and methods. The investigation included 128 patients (13% men and 87% women) with documented RA in accordance with the 1987 American College of Rheumatology (ACR) criteria. The patients' mean age was 47.4}0.9 years; the median duration of RA was 96 [48; 228] months. DAS28 averaged 5.34}0.17. 75.1% of the patients received DMARDs. The diagnosis of MDS was based on the ICD-10 codes, by applying a semi-structured interview and the Hospital Anxiety and Depression Scale. Changes in the pattern and severity of ADS were evaluated using the Hamilton Anxiety Scale and the Montgomery-Asberg Depression Rating Scale. Clinical and psychological procedures were used to diagnose CI. At baseline, ADS was detected in 123 (96.1%) patients: major depression in 41 (32.1%), minor depression in 53 (41.4%), and anxiety disorders in 29 (22.6%). CI was diagnosed in 88 (68.7%). PPT was offered to all the patients with MDS; 52 agreed to treatment and 71 refused. The following therapeutic groups were identified according to the performed therapy: 1) DMARDs (n = 39); 2) DMARDs + PPT (n = 43); 3) DMARDs + BAs (n = 32); 4) DMARDs + BAs + PPT (n = 9). The dynamics of MDS and the outcomes of RA were estimated in 112 (91.0%) and in 83 (67.5%) of the 123 patients at one-and five-year follow-ups, respectively. The efficiency of RA therapy was evaluated from the changes in DAS28 and SDAI. Results and discussion. One year later, the patients who had received the complete cycle of PPT and took DMARDs achieved a satisfactory effect twice more frequently (58.1 and 32.3%, respectively; relative risk (RR) = 0.53; 95% confidence interval (CI), 0.2-1.39; p = 0.024) and did not respond to therapy 3 times less often (21.0 and 58.1%, respectively; RR = 2.41; 95% CI, 0.87-6.71; p = 0.001) according to the EULAR criteria than those who had refused PPT. The patients with MDS who received DMARDs + PPT during one year were unresponsive to therapy significantly less frequently than those who received DMARDs and BAs without PPT (21 and 44.8%, respectively; RR = 0.6; 95% CI, 0.21-1.7; p = 0.029). After 5 years of follow-up, the probability of no response to RA therapy in MD patients who received only DMARDs was 3.6 times higher than in those who had PPT (66.7% and 10.4%, respectively; RR = 3.58; 95% CI 0.82-15.5; p < 0.001). The patients adequately treated with DMARDs and BAs for MDS according to the DAS28 showed 1.3-fold more frequently good and satisfactory results (100 and 76.2%, respectively; p = 0.14) than those who refused PPT, but these differences were not statistically significant because the DMARD+BA+PPT group was small. Five-year follow-up indicated that DAS28 remission was more common in the patients receiving DMARDs and PPT than in those who had DMARDs and no PPT (34.5 and 8.3%, respectively; RR = 1.79; 95% CI, 0.34-9.24; p = 0.024). DAS28 remission was somewhat more frequently observed among the patients receiving DMARDs, BAs, and PPT than among those taking DMARDs and BAs (33.3 19.0%, respectively; RR = 1.64; 95% CI, 0.28-9.57; p = 0.34), but these differences were insignificant. Remissions according to the 2011 ACR/EULAR criteria were achieved by only the patients having DMARDs and PPT (6.9% and 13.8% after 1 and 5 years, respectively). Conclusion. Adequate treatment of MDS in RA patients results in a significant increase in the efficiency of antirheumatic therapy.

© 2018 Izdatel'stvo Meditsina. All rights reserved. This review summarizes the state-of-the-art in the problem of assessment of the safety of domperidone - a prokinetic and anti-emetic drug belonging to those most widely used in clinical practice. Special attention is devoted to the potential cardiotoxicity of domperidone, mechanisms of adverse effects development, and risk factors. For reducing the risk of development of dose-dependent side effects, new drugs have been created and used so as to maintain the active agent concentration in the blood plasma within the therapeutic range. Another method of increasing the efficacy and safety of domperidone treatment is based on the potentiation effect. An example is the use of domperidone in a fixed combination with omeprazole (Omez-DSR), in which a the prokinetic is present in a modified release form, which ensures uniform delivery of the acting agent into blood flow (without drug concentration +AJM-peaks+AJQ-related to increased risk of dose-dependent adverse drug reactions.

© Ima-Press Publishing House. All rights reserved. Objective: to investigate the effect of indapamide/perindopril fixed-dose combination (FC) on 24-hour blood pressure (BP) and cognitive functions in antihypertensive treatment-naive middle-aged patients with uncomplicated grade 1-2 essential arterial hypertension (EAH). Patients and methods. The open prospective study enrolled 25 patients (9 men and 16 women) aged 40-59 years with a diastolic BP of 90-109 mm Hg and/or a systolic BP of 140-179 mm Hg, as evidenced by routine measurements. As starting antihypertensive therapy, the patients received indapamide 1.25/perindopril 5 mg FC once daily in the morning; if necessary, after 2 weeks (if the routine blood pressure was ≥140/90 mm Hg) they took indapamide 2.5/perindopril 10 mg once daily in the morning. The follow-up period was 14-16 weeks. Before and at the end of the follow-up, the patients underwent 24-hour ambulatory BP monitoring (ABPM) and evaluation of cognitive functions using the Montreal Cognitive Assessment (MoCA), ten-words test (immediate and delayed word recall), verbal association test (literal and categorical associations), number connecting test (Trail making test (TMT), part A and numbers and letters connecting test (TMT) part B), and Stroop test. Results. At the end of the follow-up period, treatment with indapamide/perindopril fixed-dose combination showed a statistically significant reduction in BPs, as evidenced by routine measurements and ABPM (during 24-hour, and awake and sleep periods); a statistically significant cognitive improvement: an increase in the number of the so-called words in the ten-words test during both immediate (from 5.5±1.6 6.5±1.5 words; p=0.02 vs baseline) and delayed (from 6.2±1.7 to 7.4±1.4 words; p=vs baseline) recalls, a decrease in the performance time of TMT-B (from 112.6±42.5 to 90.4±28.4 sec; p=0.02) and Stroop test Part 3 (from 135.5±50.1 to 112.6±19.6 sec; p=0.02), and a larger number of called words in the categorical associations test (from 6.5±2.4 to 8.1±2.9 words; p=0.02). Conclusion. The results obtained indicate that in treatment-naive middle-aged patients with EAH, indapamide/perindopril fixed-dose combination assures an effective reduction in BPs, as evidenced by routine measurements and ABPM, also improves cognitive functions, particularly attention, information processing speed, semantic memory, cognitive flexibility, and short-term and long-term memory.

© 2018 Ima-Press Publishing House. All right reserved. The response rate to therapy for rheumatoid arthritis (RA) rarely exceeds 60%. Mental disorders (MDs) of the anxiety-depressive spectrum (ADS) and cognitive impairment (CI) substantially affect the evaluation of the efficiency of RA therapy. Adequate psychopharmacotherapy is one of the possible approaches to optimizing the treatment of RA. The factors influencing the efficiency of RA therapy with standard disease-modifying antirheumatic drugs (DMARDs) and biological agents (BAs) in combination with adequate psychopharmacotherapy have not been previously identified. Objective: to determine the predictors of response to therapy in patients with RA receiving DMARDs and BAs with or without adequate psychopharmacotherapy for ADS disorders. Subjects and methods. The investigation included 128 patients (13% men and 87% women) with a reliable diagnosis of RA. At baseline, 75.1% of patients received DMARDs; 7.8% - BAs. ADS disorders were detected in 123 (96.1%) patients. Psychopharmacotherapy was offered to all the patients with MDs; 52 patients agreed to treatment and 71 refused. The following therapeutic groups were identified according to the performed therapy: 1) DMARDs (n = 39); 2) DMARDs + psychopharmacotherapy (n = 43); 3) DMARDs + BAs (n = 32); 4) DMARDs + BAs + psychopharmacotherapy (n = 9). The changes of MDs symptoms and the outcomes of RA were assessed in 83 (67.5%) patients at five-year follow-up. The efficiency of RA therapy was evaluated with DAS28 (EULAR criteria). Predictors of response to therapy were determined using linear regression modeling. Results and discussion. At 5 years, 22 (26.5%) and 37 (44.6%) patients were recorded to show good and moderate responses to therapy, respectively; 24 (28.9%) patients were non-respondents. The linear regression model included 14 factors (p<0.001). The high values of DAS28 (β=0.258) at the inclusion; belonging to therapeutic groups 2 (β=0.267), 3 (β=0.235), and 4 (β=0.210), the absence of diabetes mellitus (β=-0.230), and experience in using glucocorticoids (β=-0.230) were associated with a high likelihood of response to therapy; high body mass index (β=-0.200) and long RA duration (β=-0,181), a high level of rheumatoid factor (β=-0.176), a history of myocardial infarction (β=-0.153), schizotypic disorder (β=-0.132), and extra-articular manifestations of RA (β=-0.106), and older age (β=-0.102) were related to a low probability of response. The area under the ROC curve for the model was 0.99 (p<0.001). Conclusion. BA therapy and psychopharmacotherapy, along with younger age, shorter duration and high activity of RA, a low level of rheumatoid factor, lower body mass index, the absence of diabetes mellitus, myocardial infarction, and extra-articular manifestations of RA in the history, schizotypic disorder, and experience in using glucocorticoids are associated with a greater likelihood of a good and moderate treatment response.

© 2018 Limited Liability Company KlinMed Consulting. All Rights Reserved. The article describes the definition of dementia, its diagnostic criteria, classification. Differences in the pathogenesis and clinical manifestations of different types of dementia are considered. The issues of interrelation of arterial hypertension and the risk of development of cognitive disorders and dementia in old and very old people are discussed in detail. Data on the effect of antihypertensive drugs of different groups on the risk of dementia and the state of cognitive functions are presented. The evidence base of dihydropyridine calcium antagonist amlodipine and thiazide-like diuretic indapamide-retard is discussed with respect to the prevention of dementia and cognitive decline and their beneficial effect on cognitive function in patients with arterial hypertension.

© 2018 Bentham Science Publishers. Background: Nitroproston is a novel prostaglandin-based compound modified by NO-donating groups with potential application in obstructive respiratory diseases such as asthma and obstructive bronchitis. Nitroproston has been extensively studied using various pharmacological models. Its biological stability is still uncertain. Objective: The aim of the present study was to evaluate Nitroproston stability in vitro, as well as to identify and characterize its major biodegradation products. Methods: The principal biodegradation products of Nitroproston were identified in vitro using liquid chromatography/ion trap – time-of-flight mass-spectrometry. The postulated structure of metabolites was confirmed using authentic reference standards. Rat, rabbit and human plasma and human whole blood samples were used for comparative in vitro degradation study. Nitroproston and its biodegradation products in biological samples were measured by liquid chromatography/triple –stage quadrupole mass spectrometry. Results: Nitroproston is rapidly hydrolyzed in rat plasma to generate glycerol-1,3-dinitrate and prostaglandin E2 . The latter can undergo conversion to cyclopentenone prostaglandins A2 and B2 . Thereby less than 5% of the parent compound was observed in rat plasma at the first moment of incubation. A similar pattern was observed for rabbit plasma where half-life (T1/2) of Nitroproston was about 2.0 minutes. Nitroproston biodegradation rate for human plasma was the slowest (T1/2 = 2.1 h) among tested species, occurred more rapidly in whole blood (T1/2 = 14.8 min). Conclusion: It was found that Nitroproston is rapidly hydrolyzed in rodent compared to human plasma incubations. Whereas Nitroproston is relatively stable in human plasma an enhanced hydrolytic activity was observed in whole human blood incubations. Extensive metabolism of Nitroproston in human whole blood was mainly associated with red blood cells. The observed interspecies variability highlights the need of suitable animal model selection for Nitroproston follow-up PK/PD studies.

© The Author 2018. An in silico approach was adopted to identify potential cyclooxygenase inhibitors through molecular docking studies. Four potentially active molecules were generated by fusion of dopamine with ibuprofen or ketorolac derivatives. The binding mode of the considered ligands to cyclooxygenase-1 and cyclooxygenase-2 isoforms was described using Autodock Vina. Preliminary docking to full cyclooxygenase isoforms structures was used to determine possible binding sites for the described dopamine-derived ligands. The following more accurate docking iteration to the described binding sites was used to achieve better conformational sampling. Among the studied molecules, IBU-GABA-DA showed preferable binding to cyclooxygenase active site of cyclooxygenase-1, while IBU-DA bound to peroxidase site of cyclooxygenase-1, making these ibuprofen-comprising ligands a base for further research and design of selective cyclooxygenase- 1 inhibitors. Keterolac-derived ligands KET-DA and KET-GABA-DA demonstrated binding to both cyclooxygenase isoforms at a side pocket, which does not relate to any known functional site of cyclooxygenases and needs to be further investigated.

© 2018 Ima-Press Publishing House. All Rights Reserved. In 2015, the experts from various medical associations of Russia elaborated the clinical guidelines "Rational use of nonsteroidal anti-inflammatory drugs (NSAIDs) in clinical practice". These guidelines were drawn up to improve the use of NSAIDs, our country's most popular agents to treat pain in acute and chronic diseases. The main purpose of this paper was to reduce the frequency of potentially dangerous class-specific adverse events (AE) that may arise from the use of NSAIDs. To do this, the authors proposed a NSAID choice algorithm based on the assessment of risk factors for AE, the individual characteristics of various representatives of this drug group, and the possibility of prevention of AE. Since then, new data on the efficacy and safety of NSAIDs have been obtained. This has necessitated the revision and addition of a number of provisions in the 2015 guidelines. It seems that the new version of the guidelines, which has been drawn up based on the analysis of a large number of clinical and epidemiological studies, their meta-analysis, by taking into account the clinical experience and opinion of the world's leading experts, presents more fully the main aspects of the use of NSAIDs in real clinical practice. The guidelines are intended for physicians of all specialties.

Современная терапия, направленная на эрадикацию H.pylori, включает комплекс антисекреторных и антибактериальных препаратов, иногда препаратов висмута. Особенностью современных эрадикационных схем является четырнадцатидневное применение антибактериальных средств, назначаемых в высоких суточных дозах и избираемых преимущественно с учётом резистентности микроорганизма к кларитромицину и метронидазолу в соответствующем регионе. Однако каждый компонент эрадикационной схемы может иметь достаточно серьёзные неблагоприятные побочные реакции, а также влиять на биодоступность, биотрансформацию, выведение и потенцирование эффектов лекарственных препаратов, которые больной может принимать одновременно с антихеликобактерной терапией. В статье перечислены наиболее серьёзные и распространённые варианты лекарственных взаимодействий компонентов эрадикационных схем, дано описание механизма их развития, если таковой выяснен. До появления практических рекомендаций относительно профилактики лекарственных взаимодействий препаратов, включаемых в эрадикационные схемы, следует использовать общедоступные базы данных, содержащие сведения о таких взаимодействиях.

Современная терапия, направленная на эрадикацию H.pylori, включает комплекс антисекреторных и антибактериальных препаратов, иногда препаратов висмута. Особенностью современных эрадикационных схем является четырнадцатидневное применение антибактериальных средств, назначаемых в высоких суточных дозах и избираемых преимущественно с учётом резистентности микроорганизма к кларитромицину и метронидазолу в соответствующем регионе. Однако каждый компонент эрадикационной схемы может иметь достаточно серьёзные неблагоприятные побочные реакции, а также влиять на биодоступность, биотрансформацию, выведение и потенцирование эффектов лекарственных препаратов, которые больной может принимать одновременно с антихеликобактерной терапией. В статье перечислены наиболее серьёзные и распространённые варианты лекарственных взаимодействий компонентов эрадикационных схем, дано описание механизма их развития, если таковой выяснен. До появления практических рекомендаций относительно профилактики лекарственных взаимодействий препаратов, включаемых в эрадикационные схемы, следует использовать общедоступные базы данных, содержащие сведения о таких взаимодействиях.