Pharmacological Groups Research Articles

Cytotoxic Effects of Phytomediated Silver and Gold Nanoparticles Synthesised from Rooibos (Aspalathus linearis), and Aspalathin.

The green chemistry approach has continuously been applied for the synthesis of functional nanomaterials to reduce waste, environmental hazards, and the use of toxic chemicals among other reasons. Bioactive natural compounds have been found great potential in this regard and are used to improve the stability, activity, and biodistribution of metal nanoparticles (MNPs). Aspalathin (ASP) from Aspalathus linearis (rooibos) has a well-defined pharmacological profile and functional groups capable of both reducing and capping agents in the synthesis of metallic nanoparticles (NP). This study provides the first report of the phytomediated synthesis of gold and silver nanoparticles (AuNPs/AgNPs) via ASP and the green rooibos (GR) extract. The study demonstrated a green chemistry approach to the biosynthesis of nanoparticles of GR-AuNPs, ASP-AuNPs, GR-AgNPs, and ASP-AgNPs. The results showed that GR and ASP could act both as reducing and stabilising agents in the formation of crystalline, with different shapes and dispersity of NPs in the ranges of 1.6–6.7 nm for AgNPs and 7.5–12.5 nm for the AuNPs. However, the ASP NPs were less stable in selected biogenic media compared to GR NPs and were later stabilised with polyethene glycol. The cytotoxicity studies showed that GR-AgNPs were the most cytotoxic against SH-SY5Y and HepG2 with IC50 108.8 and 183.4 μg/mL, respectively. The cellular uptake analysis showed a high uptake of AuNPs and indicated that AgNPs of rooibos at a lower dose (1.3–1.5 μg/mL) is favourable for its anticancer potential. This study is a contribution to plant-mediated metallic nanoparticles using a pure single compound that can be further developed for targeted drug delivery for cancer cells treatments in the coming years.

Фармацевтическое обеспечение синдрома зависимости вследствие употребления алкоголя среди участников боевых действий

Актуальность. По данным отечественных ученых, у 75% ветеранов боевых действий отмечаются симптомы, которые позволяют диагностировать психические и поведенческие расстройства вследствие употребления алкоголя. В Украине ежегодно почти 100 тысяч пациентов с алкогольной зависимостью становятся на учет в наркологические диспансеры. Цель исследования: Изучить фармацевтическое обеспечение синдрома зависимости вследствие употребления алкоголя (F 10.2) с определением параметров режима контроля среди участников боевых действий. Материалы и методы. Для достижения поставленной цели были использованы действующие международные и отечественные законодательные, нормативно-правовые и инструктивно-методические документы; научные источники; инструкции по применению лекарственных средств; Internet-ресурсы, которые были обработаны с применением нормативно-правового, документального, судебно-фармацевтического, сравнительного и графического методов анализа. Результаты. Согласованность принципов фармакотерапии синдрома зависимости от алкоголя (F 10.2) на международном и национальном уровнях определялась путем сравнительного анализа клинико-фармакологических групп лекарственных средств в таких нормативно-правовых документах: Drugs used in alcohol dependence EBM Guidelines 8.9.2017 (Latest change 8.9. 2017 Kaarlo Simojoki); приказ МЗ Украины № 681 от 21.09.2009 г. «Об утверждении клинических протоколов оказания медицинской помощи по специальности "Наркология"»; приказ МЗ Украины № 868 от 10.05.2018 г. «Об утверждении десятого выпуска Государственного формуляра лекарственных средств и обеспечения его доступности»; Постановление КМ Украины № 333 от 25.09.2009 г. «Некоторые вопросы государственного регулирования цен на лекарственные средства и изделия медицинского назначения», которым утвержден Национальный перечень основных лекарственных средств. Выводы. Изучено фармацевтическое обеспечение синдрома зависимости вследствие употребления алкоголя (F 10.2) с определением параметров режима контроля среди участников боевых действий. Проанализирована рубрификация кода F10.2 «Синдром зависимости вследствие употребления алкоголя» согласно МКБ-10, которая насчитывает 11 позиций. Систематизированы клинико-фармакологические группы лекарственных средств, которые используются для фармацевтического обеспечения синдрома зависимости вследствие употребления алкоголя среди участников боевых действий. На основании анализа нормативной базы определено, что в клиническом протоколе оказания медицинской помощи по специальности «Наркология» включены все исследуемые клинико-фармакологические группы лекарственных средств для фармакотерапии синдрома зависимости вследствие употребления алкоголя; в Государственном формуляре лекарственных средств отсутствуют сенсибилизирующие лекарственные средства; в Национальном перечне основных лекарственных средств отсутствуют 4 клинико-фармакологические группы: психоаналептики (антидепрессанты); сенсибилизирующие лекарственные средства; периферические вазодилататоры, производные g-аминомасляной кислоты (натрия оксибутират). Установлены параметры режима контроля лекарственных средств для фармакотерапии синдрома зависимости вследствие употребления алкоголя среди участников боевых действий. Указано, что специальный режим контроля имеют по классификационно-правовой группе 3 психотропные лекарственные средства (диазепам, натрия оксибутират и фенобарбитал), которые должны находиться в учреждениях здравоохранения на предметно-количественном учете. В сравнительном аспекте обоснованы особенности лицензирования оборота лекарственных средств в медицинских и аптечных учреждениях. Внедрение в деятельность учреждений здравоохранения данных относительно правового статуса лекарственных средств с учетом параметров их режима контроля обеспечит повышение уровня их правовой, информационной и физической доступности для врачей, провизоров и пациентов, а также надлежащую организацию порядка обращения таких лекарственных средств на этапах назначения, выписки, хранения, учета, контроля качества и отпуска в соответствии с требованиями действующего законодательства Украины.

Нейропротекторная терапия глаукомы (обзор литературы)

This literature review presents data on neuroprotection in glaucoma. In neuroprotective therapy, it is desirable to use a comprehensive treatment that includes drugs of various pharmacological groups acting on different pathogenetic links of glaucoma optical neuropathy. One of the most promising areas of neuroprotection is the simultaneous combined effect of various physical factors (with mutual potency of their therapeutic action) and drug therapy, which increases the neuroprotective effect. However, treatment should be performed against the background of absolutely normalized intraocular pressure. Key words: glaucoma, glaucoma optical neuropathy, neuroprotection, drug therapy, normalized intraocular pressure.

ДОСЛІДЖЕННЯ СКЛАДУ ПРЕПАРАТІВ ДЛЯ ЛІКУВАННЯ ЗАХВОРЮВАНЬ ПОРОЖНИНИ НОСА

Drugs of group R01, according to the АTC- classification used in the treatment of diseases of the nasal cavity by composition and dosage form, were studied. The dependence of the therapeutic effect of drugs on the chemical structure of the active substance, possible combinations of active substances belonging to different pharmacological groups (sympathomimetics, corticosteroids, and antihistamines), which determine their specific effect on the human body, are analyzed. These active substances are found in both mono- and multi-component drugs. In combination drugs, other compounds of natural and synthetic origin are also used to enhance the therapeutic effect.

LEVEL ASSESSMENT OF CONTROL OF BRONCHIAL ASTHMA IN ADOLESCENTS

Introduction. The problem of controlling bronchial asthma in adolescents remains relevant, and its monitoring is more difficult than in other age categories, since during the period of long-term remission the disease can be accompanied by signs of bronchial hyperreactivity to nonspecific irritants, and pulmonary ventilation disorders can have a «latent» character, persisting much longer than the clinical symptoms of the disease, which leads to tactical errors in determining the level of bronchial asthma control and is a risk factor for its progression. Aim: to develop a method for assessing the level of bronchial asthma control in adolescents, when there are no clinical, anamnestic and functional signs of insufficient control of asthma, by using a quality of life questionnaire and an additional bronchodilatory test. Materials and methods. The study included 43 adolescents with mild (41.9 %) and moderate (58.1 %) controlled bronchial asthma. To identify cases of «latent» bronchospasm, a bronchodilatory test with salbutamol was performed and the increase in forced expiratory volume in 1 second (FEV1) was calculated. In the case of an increase in FEV1 ≥ 12.0 %, the presence of «latent» bronchospasm was confirmed. If the increase in FEV1 turned out to be < 12.0 %, a questionnaire was performed using the Pediatric Asthma Quality of Life Questionnaire (PAQLQ) and if the value of the integral indicator of the overall quality of life PAQLQ ≤ 6.5 points, an additional bronchodilator test with a combined bronchodilator (fenoterol / ipratropium bromide). Results. The absence of changes in the initial levels of spirometric parameters was found in all 43 patients (FEV1 > 80.0 %). When carrying out a bronchodilatory test with salbatamol, 7 patients (16.3 %) with a positive response (increase in FEV1 ≥ 12.0 %) were identified, which indicated cases of «latent» bronchospasm and partial control of asthma, and 36 people (83.7 %) with a negative answer (increase in FEV1 < 12.0 %). Among 36 patients with an increase in FEV1 < 12.0 % in the test with salbutamol applied the PAQLQ questionnaire and identified 24 people or 66.7 % with an overall quality of life of ≤ 6.5 points, which reflected the negative impact of adolescents asthma on the quality of life and lack of complete asthma control. This was confirmed in 7 out of 24 people (29.2 %) in an additional bronchodilatory test with a combined bronchodilator, in which they gave a positive response (increase in FEV1 ≥ 12.0 %; r = -0.4, p = 0.02). The reasons for the decrease in the overall quality of life of ≤ 6.5 points in the remaining 17 adolescents were due to psychoemotional states or vegetative-vascular dysfunction, and not to the latent course of «latent» bronchospasm. As a result, among 43 adolescents, 14 patients or 32.6 % with «latent» bronchospasm were found. At the same time, the relative risk of a positive patient response to a bronchodilator test with a combined bronchodilator was 2.1 times higher than during a bronchodilator test with salbutamol (OR = 2.1, 95 % CI 1.1–7.0). Conclusions. Conducting bronchodilatory tests with bronchodilators of various pharmacological groups and questioning patients using the PAQLQ questionnaire on the quality of life makes it possible to establish cases of «latent» bronchospasm even with a negative response to salbutamol, when there are no clinical and anamnestic signs of insufficient asthma control and the FEV1 index exceeds 80.0 % of proper values. Keywords: adolescents, bronchial asthma, control, bronchospasm.

Pharmacological treatment after acute coronary syndrome: Baseline clinical characteristics and gender differences in a population-based cohort study

ObjectiveTo describe baseline socio-demographic and clinical characteristics and drugs prescribed for secondary prevention after a first episode of ACS and to assess differences between men and women. SettingPHC in Catalonia. Data source: SIDIAP (Information System for Research in Primary Care). ParticipantsPatients who suffered an ACS during 2009–2016 and followed-up in PHC centres of the Catalan Health Institute in Catalonia. InterventionsNot applicable. Main measuresSocio-demographic and clinical characteristics at baseline: sex, age, socioeconomic index, toxic habits, comorbidities, study drugs (prescribed for cardiovascular secondary prevention: antiplatelets, betablockers, statins, drugs acting on the renin–angiotensin system) and comedications. Results8071 patients included, 71.3% of them were men and 80.2% had an acute myocardial infarction. Their mean age was 65.3 and women were older than men. The most frequent comorbidities were hypertension, dyslipidaemia and diabetes and they were more common in women. Antiplatelets (91.3%) and statins (85.7%) were the study drugs most prescribed. The uses of all comedications were significantly higher in women, except for nitrates. The combination of four study groups was initially prescribed in 47.7% of patients and combination of beta-blockers, statins and antiplatelets was prescribed in 18.4%. More men than women received all recommended pharmacological groups. ConclusionWomen were older, had more comorbidities and received more comedications. Most patients were treated with a combination of four or three study drugs for secondary prevention. Men initiated more drug treatments for secondary prevention and dual antiplatelet therapy than women. EUPAS RegisterEUPAS19017.

Gastritis and dyspepsia: 2 names of one problem? Relations between predominant symptom and syndromal characteristics of upper GI disorders: results of a survey of physicians

Introduction. Chronic gastritis is one of the most common problems in gastroenterology and general medical practice. In this study, we tried to analyze the actions of therapists in relation to patients with symptoms of dyspepsia, to assess how different symptom complex affects the choice of therapy and the diagnostics.Aim. Identifying the process of a preliminary diagnosis by symptoms, determining the ability of physicians to differentiate clinical syndromes, and determining the approaches to empirical therapy at first visit and following the “test and treat” strategy aimed at identifying the H. pylori infection.Materials and methods. The study was conducted using the CAWI (Computer-assisted Web Interview) method. Each physician who agreed to participate in the study received a link to take the survey and independently entered the answers to the questions formulated by the researcher. The descriptions of three profiles of adult patients with suspected gastritis diagnosis who applied for the first time were suggested: 1) a patient with a pain syndrome and dyspepsia symptoms; 2) a patient with dyspepsia symptoms; 3) a patient with a pain syndrome.Results. The study involved 205 physicians from 33 cities of Russia. The most commonly assumed diagnosis was gastritis: 50% of responders suggested it for patient 1, 51% – for patient 2, and 40% – for patient 3. Despite the unambiguous description of the delayed motility symptoms in patients 1 and 2, the most commonly assumed diagnoses did not reflect the presence of a problem. At the same time, physicians did not conduct diagnostic tests for H. pylori infection in case of patients 1 and 3 with obvious symptoms of gastritis. In case of infection, physicians suggest prescribing eradication drugs to each patient, and the most popular pharmacological group suggested were PPIs (91%). However, every tenth physician suggested eradication without PPIs.Conclusion. The results of the survey indicate a lack of awareness among therapists about the symptoms of delayed motility. This leads to the symptomatic pharmacotherapy, which does not provide the rupture of pathogenetic mechanisms

Arterial hypertension: modern advances in metabolomics

Early diagnosis and effective pharmacotherapy of arterial hypertension are urgent problems, a significant contribution to the solution of which can be made by metabolomics. The etiology of hypertension remains unknown for the majority of patients with high blood pressure; the diagnosis for 90% is defined as essential (primary) hypertension. This population is characterized by disturbance of the metabolic pathways of lipids, glucose, biogenic amines and amino acids, which may manifest with hyperlipidemia, hyperglycemia, and insulin resistance with the possible subsequent development of type II diabetes mellitus. The study of the metabolomic signature can provide a clue to the identification of biomarkers of hypertension and contribute to the effective development of preclinical diagnosis and identification of risk groups, as well as a more complete understanding of the etiological and pathogenetic mechanisms of increased blood pressure. Published studies indicate the existence of metabolome characteristic of hypertensive patients, distinguishing them from normotensive subjects. The most typical are changes involving amino acids, polyunsaturated fatty acids, carnitines, phosphatidylcholines, and acylglycerols.The variability of the response to antihypertensive therapy does not allow achieving effective control of blood pressure in a significant proportion of patients. The peculiarities of changes in the metabolome under the use of various pharmacological groups can be used to identify metabolite markers of the response to the main classes of antihypertensive drugs, as well as markers of the development of side effects of drug therapy. Thus, individualization of the pharmacotherapeutic approach based on pharmacometabolomics can significantly increase the efficacy and safety of antihypertensive therapy.This review aims to study the main groups of metabolites identified in published trials as predictors of the development of hypertension, as well as metabolite markers of response to antihypertensive therapy.

An Insight to Diagnosis and Management of Drug-induced Hepatotoxicity: An Overview

(ADRs) Adverse Drug Reactions are constitute and mutual chief health problem. Throughout the last period liver toxicity has remained one of the most recurrent reasons for pharmacovigilance protectionintelligences and the withdrawal from the marketplace of an accepted medicinal product. Liver is a mainorganelaborate in the systemic deposition and decontamination of exogenous and endogenous ingredients. Liver disfunction challenges not only health care specialists but also the pharmaceutical manufacturing and drug controlling agencies. (DILI) DrugInduced Liver Injury also mentioned as druginduced hepatotoxicity, formulae a main clinical problematic, which has developed the foremost cause of transplantation and acute liver failure in Western countries. Druginduced hepatotoxicity is one of the chiefreasons of chronic and acute liver disease. The Liver, a supreme organ is the Principal site for metabolism of nutrients and energy manufacture in the human body. It is also essential for elimination and metabolism of exogenous drugs and injuriousmaterials via kidney. Hepatotoxicity produced by a diversity of environmental contaminants, viruses, pathogenic micro-organism chemical and drugs agents may account for Several types of drug induced liver diseases are acute-dose reliant acute fatty infiltration, liver damage, cholestatic jaundice, active chronic hepatitis, liver granulomas, liver tumors, liver cirrhosis, liver tumors etc. Furthermore, there is no precisemanagement for hepatotoxicity, which is grounded on appending the assumed drug and treating symptoms. The most normallyconnected pharmacological groups are nonsteroidal anti-inflammatory analgesics (NSAIDs), antibiotics, anticonvulsantsand antidepressants. Druginduced liver injury has remained an adverse occasion, tough to recognize, treat and prevent; thus, the pharmacist interference can subsidize to the decrease of the harmfulbelongings in patient health. So, in this review we highlighted the pathogenesis, diagnosis and management of drug induced hepatoxicity.

Analysis of Adverse Reactions in Elderly Patients Based on Quantitative Methods of Signal Detection

A well-known problem in pharmacotherapy is an increased risk of adverse drug reactions (ADRs) in older as compared to younger patients. The Russian pharmacovigilance database includes a significant number of spontaneous reports of suspected ADRs in patients aged 65 and older. An increase in ADRs reporting makes it difficult to identify potential safety signals based on qualitative approaches only, which necessitates the use of statistical methods for signal detection based on disproportionality. The aim of the study was to assess the applicability of quantitative methods for signal detection and analysis of ADR risks in the elderly using the Russian spontaneous report database. Materials and methods: the study covered the reports on patients 65 years of age and older, which were submitted to the spontaneous report database from January 2008 until June 2018. The procedure recommended by the European Medicines Agency was used to identify potential statistical safety signals which were determined based on the following criteria: Reporting Odds Ratio, ROR—lower bound of the 95% confidence interval >1, number of cases ≥2; Proportional Reporting Ratio, PRR ≥ 2, Chi-square value χ 2 ≥ 4, number of cases ≥3, lower bound of the 95% confidence interval >1, number of cases ≥3. Results: 2231 potential statistical signals were identified. Of these, the vast majority of combinations of suspected drugs and ADRs were associated with known drug risks, and were not new safety signals for these drugs. The largest proportion of statistical signals was attributed to the following pharmacological groups: antiplatelet agents, cephalosporins, non-steroidal anti-inflammatory drugs, fluoroquinolones, angiotensin-converting enzyme inhibitors, metabolic agents, and indirect anticoagulants. Conclusion: the results obtained indicate the applicability and effectiveness of statistical methods based on disproportionality of reporting for the analysis of the Russian spontaneous report database in order to identify potential drug safety issues.

Search for the clinical effectiveness of Korean Tae-Geuk acupuncture therapy in chronic tension-type headache

BackgroundKorean acupuncture comes from the far-eastern tradition and has unique approaches to acupuncture point selection. ObjectivesThere are several types of acupuncture methods. Among these, Tae-Geuk acupuncture and Saam acupuncture adopt five phase characteristics, using five vital points. Cho-sun acupuncture regulates Qi using acupunctures and meridians according to the flow of Qi. In this project, the effects of Korean Tae-Geuk acupuncture on chronic tension-type headache (TTH) were examined. MethodsThis study is a randomized controlled study involving sham acupuncture (placebo acupuncture), and everything is clear except for the data processing phase. The purpose of the study; was to measure the safety and efficacy of Korean Tae-Geuk acupuncture in patients with chronic TTH. Groups used; acupunture + traditional pharmacological therapy, traditional pharmacological therapy only and placebo korean acupuncture + traditional pharmacological therapy groups. Seven treatment sessions were applied over a four-week period. Changes in pain and quality of life and side effects were examined during treatment and within 3 months after the completion of treatment. Results were evaluated by using the visual analog scale for pain and pain log records. ResultsKorean Tae-Geuk acupuncture is a more effective treatment than placebo and traditional pharmacological treatment in chronic TTH. Korea Tae-Geuk acupuncture showed significant improvement in clinically chronic TTH during treatment and in 3 months follow-up after treatment. ConclusionTae-Geuk acupuncture is a treatment branch of Sasang Constitution Medicine. Acupuncture points do not change according to acupuncture practitioner or disease.

Effects of a dance program on psychophysiological variables in hospitalized patients with depression: A mixed model approach

This study intended to examine the effects of two programs, pharmacological treatment vs. pharmacological treatment+Dance Program (DP), on the perception of self-efficacy, depression, and heart rate variability (HRV) in hospitalized patients with major depressive disorder (MDD); The primary caregiver's perception was also considered and recorded. The sample consisted of 27 patients (pharmacological=14 and pharmacological+DP=13) who were admitted to the IMSS Psychiatric Hospital, with a diagnosis of MDD. There was a significant increase in the perception of self-efficacy in the pharmacological+ DP group after treatment (Z = 3.19, p < .01), but not in the pharmacological group (Z = 0.126, p > .01). Regarding depression, a greater decrease was found in the pharmacological+ DP group. In HRV there were differences only in heart rate, showing a reduction due to the impact of the time factor and the time and group factor. As for the results of the interview with primary caregivers, their perceptions indicate that dance is an activity that can fortify the recovery process of their family members. In conclusion, a dance program of moderate to vigorous intensity in conjunction with pharmacological treatment reduces depressive symptoms and increases the perception of self-efficacy, resulting in a greater benefit for the recovery of depressive patients. Similarly, the primary caregivers involved in this study highlighted the importance of the dance program as an option to support the standard treatment of depression.

Diffculties and ways to overcome them in selection of therapy for pain syndromes in patients with diabetes mellitus

Diabetes mellitus (DM) causes damage to various body systems, including the peripheral nervous system. The main variants of peripheral nerve damage in diabetes mellitus are considered. Information on the development of this kind of lesion, in particular, on the formation of neuropathic pain syndrome, is given. The therapeutic possibilities of drugs from various pharmacological groups for the treatment of patients with neurological complications of diabetes are analyzed.

Эффективность амбулаторного лечения артериальной гипертензии через призму качества жизни и гемодинамический фенотип пациентов

Актуальность. Эффективность амбулаторного лечения артериальной гипертензии (АГ) как совокупный результат — достижение целевого уровня артериального давления (АДцел) и приемлемый уровень качества жизни (КЖ) пациентов, а также влияние на него гемодинамического фенотипа, определяемого оригинальным методом количественного анализа связей параметров артериального давления (КАСПАД), не исследованы, что явилось целью данной работы. Материалы и методы. Обследованы 175 амбулаторных пациентов с АГ, средний возраст 60,0 (52,0–70,0) года, получавших длительную (3–12 лет) стандартную терапию антигипертензивными препаратами из основных групп лекарственных средств (ЛС). Оценивалось КЖ по русскоязычной версии опросника RAND-36; для определения гемодинамического фенотипа по КАСПАД использованы индивидуальные ряды величин АД (не менее 25), полученные при ежедневных домашних измерениях за 2–4 недели; проведен статистический анализ клинических и демографических признаков, их связей с КЖ и фенотипами. Результаты. Значимое ухудшение КЖ (физический компонент и общий уровень) отмечено с увеличением возраста, степени и кардиоваскулярного риска АГ, особенно при наличии хронических форм ишемической болезни сердца. КЖ у пациентов, не достигших АДцел, значимо ниже по большинству параметров, чем у достигших его лиц. Увеличение количества принимаемых ЛС сопряжено со снижением КЖ у лиц, достигших АДцел. Пациенты с гемодинамическим фенотипом D, независимо от фармакологической группы принимаемых ЛС и их количества, значимо реже достигают АДцел по сравнению с лицами с фенотипом H, а также имеют более низкое КЖ, еще более снижающееся при интенсификации медикаментозной терапии. Ингибиторы ангиотензинпревращающего фермента (ИАПФ) и блокаторы кальциевых каналов (БКК) были эффективны для достижения АДцел, в основном у пациентов с фенотипом H, но негативно влияли на КЖ: ИАПФ — при фенотипе H, БКК — при D. Бета-адреноблокаторы и диуретики существенно не влияли на КЖ. Предложена статистическая модель прогноза низкого общего уровня КЖ у пациентов с достигнутым АДцел на основе 5 клинико-демографических факторов. Выводы. Эффективность лечения АГ целесообразно оценивать по совокупности достижения АДцел и общего уровня КЖ не менее 60 баллов (по RAND-36). При назначении лечения следует учитывать гемодинамический фенотип: медикаментозную терапию всех пациентов с фенотипом D, а также лиц с фенотипом H при низком КЖ и недостигнутом АДцел необходимо дополнять комплексной реабилитацией с использованием немедикаментозных методов.

Rational mucolytic therapy in respiratory diseases: clinical interpretation of pharmacological properties for informed choice

Respiratory diseases remain a common group of diseases in the practice of general physicians and pulmonologists. Currently, there are various treatment protocols for patients with respiratory diseases, where one of the pharmacological groups is mucolytic drugs. They affect the physical and chemical properties of sputum by splitting complex mucins, which leads to its liquefaction. Indications for use of drugs of this group are clinical conditions, in which there is a cough with thick, viscous, difficult to detach sputum. The article discusses the possibility of treating several respiratory diseases with mucolytic therapy, provides a comparative characteristic of drugs of this pharmacological group. The clinical and pharmacological effects of erdosteine are discussed in detail: mucolytic, antioxidant, anti-inflammatory, immunomodulatory. These properties of the drug are extremely important in clinical practice conditions, because in addition to the mucolytic properties themselves, the patient has many adverse processes due to inflammation. All this is associated with additional damaging factors regarding the tissues and may also indicate an increased risk of complications. Thus, the multipurpose effects of the mucolytic erdosteine in various respiratory tract diseases are presented. In addition to acute respiratory viral diseases, the clinical experience of using erdosteine in chronic obstructive pulmonary disease is discussed in detail. The most important indicator to assess the effectiveness of drugs used in this disease is the reduction in the number of exacerbations per year and the severity of the course of the exacerbation. The conclusions, which are given according to the results of a number of studies, determine significant advantages in the use of erdosteine as mucolytic therapy.

A Systematic Review on the Contribution of Artificial Intelligence in the Development of Medicines for COVID-2019

Background: COVID-2019 pandemic lead to a raised interest on the development of new treatments through Artificial Intelligence (AI). Aim: to carry out a systematic review on the development of repurposed drugs against COVID-2019 through the application of AI. Methods: The Systematic Reviews and Meta-Analyses (PRISMA) checklist was applied. Keywords: [“Artificial intelligence” and (COVID or SARS) and (medicine or drug)]. Databases: PubMed®, DOAJ and SciELO. Cochrane Library was additionally screened to identify previous published reviews on the same topic. Results: From the 277 identified records [PubMed® (n = 157); DOAJ (n = 119) and SciELO (n = 1)], 27 studies were included. Among other, the selected studies on new treatments against COVID-2019 were classified, as follows: studies with in-vitro and/or clinical data; association of known drugs; and other studies related to repurposing of drugs. Conclusion: Diverse potentially repurposed drugs against COVID-2019 were identified. The repurposed drugs were mainly from antivirals, antibiotics, anticancer, anti-inflammatory, and Angiotensin-converting enzyme 2 (ACE2) groups, although diverse other pharmacologic groups were covered. AI was a suitable tool to quickly analyze large amounts of data or to estimate drug repurposing against COVID-2019.

Prolyl Hydroxylase Inhibitors: a New Opportunity in Renal and Myocardial Protection.

Hypoxia, via the activity of hypoxia-inducible factors (HIFs), plays a crucial role in fibrosis, inflammation, and oxidative injury, processes which are associated with progression of cardiovascular and kidney diseases. HIFs are key transcription heterodimers consisting of regulatory α-subunits (HIF-1α, HIF-2α, HIF-3α) and a constitutive β-subunit (HIF-β). The stability of HIFs is regulated by the prolyl hydroxylases (PHDs). Specific PHD inhibitors (PHD-i) are being investigated as a therapeutic approach to modulate the cellular signaling pathways and harness the native protective adaptive responses to hypoxia. Selective inhibition of PHD leads to the stabilization of the HIFs, which is the transcriptional gatekeeper of a multitude of genes involved in angiogenesis, energy metabolism, apoptosis, inflammation, and fibrosis. PHD-i downregulate hepcidin, improve iron absorption, and increase the endogenous production of erythropoietin. Furthermore, this pharmacological group has also been proven to ameliorate ischemic injuries in several organs, opening a new and promising field in cardiovascular research.. In this review, we present the basic and clinical potential of PHD-i treatment in different scenarios, such as ischemic heart disease, cardiac hypertrophy and heart failure, and their interplay with other pharmacological agents with proven cardiovascular benefits, such as sodium-glucose cotransporter 2 (SGLT2) inhibitors.

Болезнь Крона у детей: актуальные аспекты диагностики и лечения согласно современным международным рекомендациям

В статье обобщены знания об эпидемиологических данных, клинических особенностях, современных принципах диагностики и лечения болезни Крона у детей на основе анализа литературных источников с использованием бумажных носителей и электронных баз данных PubMed, CyberLeninka, Web of Science, MedLine, The Cochrane Library. Обзор литературных источников по изучению данной патологии показывает, что на современном этапе диагностика воспалительных заболеваний кишечника, особенно у детей раннего возраста, все еще остается сложным вопросом. Обозначена проблема трудностей диагностического поиска вследствие не всегда типичного течения заболевания в детском возрасте. Приведены данные об особенностях клинического течения заболевания в зависимости от локализации патологического процесса. Автором также отдельно акцентирована важность ранней диагностики болезни Крона с целью проведения своевременного протокольного лечения и необходимость распознавания данной патологии уже на уровне первичной медицинской помощи. В статье также приведены данные Европейского общества детской гастроэнтерологии, гепатологии и питания и Европейской организации по изучению болезни Крона и колита относительно необходимого объема методов диагностики болезни Крона у детей согласно современным международным рекомендациям. Обзор освещает современные принципы лечения болезни Крона у детей, описаны основные фармакологические группы лекарственных средств, которые имеют доказательную базу эффективности в педиатрической практике. Особое внимание уделено роли полного энтерального питания как наиболее безопасного и достаточно эффективного направления стартовой терапии данной патологии у детей. В заключение автор освещает проблему дифференциальной диагностики воспалительных заболеваний кишечника в педиатрической практике.

EXPERIMENTAL STUDY OF TOXIC PROPERTIES OF VMU-2012-05 DRUG – ORIGINAL NON-NUCLEESIDE INHIBITOR OF HIV-1 REVERSE TRANSCRIPTASE

Antiretroviral therapy is currently the main component of treatment for HIV patients. The development of new, more effective and safer drugs is an urgent task.The aim of the research is to study the toxic properties of the finished dosage form (FDF) VMU-2012-05, a non-nucleoside reverse transcriptase inhibitor (1-[2-(2-benzoylphenoxy)ethyl]-6-methyluracil) for the HIV-1 infection treatment in single and repeated enteral administrations.Materials and methods. The study of toxic properties in single administrations was carried out on outbred mice; the drug was administered at the limiting dose of 2000 mg/kg (by reference to the active substance). For 90 days, in repeated daily administrations, the toxic properties were studied in rats of both sexes at the doses of 0 mg/kg (placebo), 9 mg/kg (1 HTD), 45 mg/kg (5 HTD), 90 mg/kg (10 HTD). The toxic properties were also studied in rabbits of both sexes within a 28-day administration at the doses of 0 mg/kg, 4 mg/kg (1 HTD), 20 mg/kg (5 HTD), 40 mg/kg (10 HTD); the recovery period 30 days. Clinical observations and examinations, body weight registrations, physiological and clinical laboratory studies were carried out during the experiment. At the end of the administration period (50% of animals) and at the end of the recovery period, a pathological examination was performed.Results. The LD50 of the drug is more than 2000 mg/kg. In the repeated administrations, the no observed adverse effect level (NOAEL) has been established. For rats, it is 9 mg/kg (1 HTD), for rabbits – 4 mg/kg (1 HTD). According to the results of the experiments carried out on rabbits and rats, the main target organ of the drug toxic effect is the liver. According to the data obtained in the study on rats, a toxic effect on the organs of the male reproductive system has been manifested (hypoplasia of the spermatogenic epithelium). Under the conditions of the experiment, the test drug had no effect on the gastrointestinal tract.Conclusion. The results have manifested a favorable safety profile of the drug, not inferior to the ones of a similar pharmacological group used in clinical practice; it can be considered a promising drug candidate for the HIV-1 infection treatment.

PHARMACOTHERAPY OF PSORIASIS SUPPORT WITH ANTIPHOSPHOLIPID SYNDROME: ABC/VEN ANALYSIS OF ANTI-VIRAL DRUGS

The aim was to research the pharmacotherapy of psoriasis with antiphospholipid syndrome based on ABC/VEN analysis of antiviral drugs. The materials of the study were the clinical and pharmacological groups for pharmacotherapy of psoriasis on the background of antiphospholipid syndrome. Regulatory, documentary, marketing, pharmacoeconomic, ABC/VEN research methods were used. Studied the clinical and pharmacological groups of the most drugs INN for basic pharmacotherapy of psoriasis have diagnostic codes of ATC classification L "Antineoplastic and immunomodulatory agents" and code M "Agents affecting the musculoskeletal system". In the article, the results of share of different medical forms of drugs for pharmacotherapy of psoriasis with antiphospholipid syndrome were shown. Matrix of the consolidated ABC-VEN analysis of drugs for pharmacotherapy of psoriasis with antiphospholipid syndrome was developed during the research. Shown the relevance and necessity of the chosen research topic because of a review of the scientific literature on epidemiology and pharmacotherapy. Marketing research of medicines were determined by assortment, country of origin, dosage forms, and registration certificates. Estimated that in the A/E categories, drugs coincide and are in a niche with an affordable share (17.04%). In terms of priority for pharmacotherapy of psoriasis on the background of antiphospholipid syndrome, a matrix of the combined ABC/VEN analysis was developed. The results of the study provide an opportunity to make administrative and managerial decisions in determining the pharmacotherapy of psoriasis with antiphospholipid syndrome to improve the use pharmaceutical provision for patients with systemic autoimmune diseases.