Pharmacokinetics and pharmacodynamics of rebamipide. New possibilities of therapy: A review

The MedLine database contains 570 publications, including 71 randomized clinical trials and 6 meta-analyses on the rebamipide molecule in 2022. Indications for the use of rebamipide are gastric ulcer, chronic gastritis with hyperacidityin the acute stage, erosive gastritis, prevention of damage to the gastrointestinal mucosa while taking non-steroidal anti-inflammatory drugs, eradication of Helicobacter pylori. Currently trials are studying the efficacy and safety of the drug in gouty and rheumatoid arthritis, osteoarthritis, Sjgren's syndrome, bronchial asthma, vitiligo, atherosclerosis, diseases of the kidneys and liver; using in traumatology to accelerate bone regeneration; in ophthalmology to improve the regeneration of corneal epithelium; in oncology to reduce inflammatory changes in the oral mucosa after chemoradiotherapy. The review article is about the main pharmacokinetic and pharmacodynamic characteristics of rebamipide. A detailed understanding of pharmacodynamics and pharmacokinetics allows for individual selection of therapy based on the characteristics of the patient's body gender, age, comorbidities; choose the optimal route of administration and dosing regimen; predict adverse effects and drug interactions; be determined with new clinical indications

Pathogenetic role of tumor necrosis factor (TNF-α) for the development of peritoneal tuberculosis in an experiment

Currently tuberculosis is considered as a group of diseases united by one etiological factor. The pathogenesis of certain localizations of tuberculous inflammation, in particular peritoneum tuberculosis, hasn’t been sufficiently studied. The role of cytokine mechanisms in the development of the disease and the elaboration of non-sterile immunity requires further experimental studies, in particular the creation of a reproducible model on laboratory animals.The aim: to study the effect of TNF-α on the development of tuberculosis of the serous coat of the abdominal cavity, as well as to evaluate the possibility of modeling tuberculous peritonitis in laboratory animals using infliximab.Materials and methods. The studies were conducted on 18 male rabbits, which were simulated peritoneal tuberculosis by intra-abdominal administration of a suspension of Mycobacterium tuberculosis. 10 rabbits of the experimental group were intravenously injected with an infliximab solution and an iron (III) hydroxide sucrose complex intraperitoneally a day before infection.Results. In the control group of animals, tuberculosis either didn’t develop, or in a third of cases it affected only the pulmonary parenchyma, while proliferative processes prevailed. On the contrary, in animals with inactivated TNF-α, in 100 % of observations, tuberculous peritonitis was detected with associated lung damage and the predominance of alterative caseous processes.Conclusion. The created model of tuberculous peritonitis shows the leading role of TNF-α in the activation of macrophages, as well as in attracting cells to the site of infection. This is the primary signal necessary for the formation and stability of granulomas since the neutralization of this cytokine leads to a loss of control over the infection and the destruction of the granuloma with the development of destructive tuberculosis in the serous coat of the abdominal cavity

Влияние антагонистов α2-адренорецепторов на характеристики электроэнцефалограмм кроликов при введении дексмедетомидина

The humane treatment of laboratory animals is an integral part of good laboratory practice. It remains relevant to study the anaesthetic effects of various medicinal products helping to reduce pain and distress in laboratory animals.The aim of the study was to compare the effects of the α2 blockers proroxan and atipamezole on changes in electroencephalogram rhythm index ratios after dexmedetomidine administration.Materials and methods. The study used male Soviet chinchilla rabbits weighing 3.0±0.3 kg (n=12). Study animals received single injections of 100 μg/kg dexmedetomidine subcutaneously, 50 μg/kg atipamezole intramuscularly, and 170 μg/kg proroxan intravenously (equimolar to the dose of dexmedetomidine). The effects of these medicinal products were evaluated by pharmacoelectroencephalography. The authors recorded electroencephalograms using cup electrodes and a Neuron-Spectrum-1 8-channel encephalograph (Neurosoft, Russia)  with  a  bandwidth of 0.5–35 Hz and a sampling frequency of 500 Hz. The distribution of quantitative characteristics was checked for normality using the Shapiro–Wilk W test. The authors used one-way ANOVA with Dunnett’s post hoc test to evaluate the significance of differences for the normal distribution of quantitative characteristics; they used the nonparametric Kruskal–Wallis test with  Dunn’s  post  hoc  test  for the non-normal one.Results. Dexmedetomidine administration resulted in significant two-hour changes in the rabbit brain, and the authors observed an increase in the delta rhythm and     a decrease in the theta rhythm. At equimolar doses, atipamezole returned the ratios of the wave rhythm indices to the baseline values, whereas proroxan had no effect on the ratios.Conclusions. As demonstrated by the neutralisation of dexmedetomidine sedative and hypnotic effects, atipamezole can be used in veterinary for recovery from anaesthesia. Proroxan, on the contrary, is not effective in reversing the sedative effect of dexmedetomidine.Неотъемлемой частью надлежащей лабораторной практики является гуманное отношение к лабораторным животным. Актуальными  остаются  исследования  по изучению анестезирующего действия различных препаратов, позволяющих снизить болевой синдром и дистресс у лабораторных животных.Цель работы: оценка  влияния  α2-адреноблокаторов  пророксана  и  атипамезола на изменение отношения индексов ритмов  волн  электроэнцефалограмм при введении дексмедетомидина.Материалы и методы: в исследовании были использованы кролики-самцы линии Советская шиншилла массой 3,0±0,3 кг (n=12). Дексмедетомидин вводили однократно подкожно в дозе 100 мкг/кг, атипамезол — 50 мкг/кг внутримышечно, пророксан — 170 мкг/кг внутривенно (дозы эквимолярны дозе дексмедетомидина). Действие препарата оценивали методом фармакоэлектроэнцефалографии. Запись электроэнцефалограмм животных осуществляли с помощью чашечковых электродов с использованием 8-канального энцефалографа «Нейрон-Спектр-1» с полосой пропускания 0,5–35 Гц и частотой квантования 500 Гц. Осуществляли проверку распределения количественных признаков с использованием W-критерия Шапиро–Уилка. При нормальном распределении количественных признаков значимость различий оценивали с помощью однофакторного дисперсионного  анализа  ANOVA  с  post-hoc-тестом  по  Даннетту; при распределении, отличном от нормального, — с помощью непараметрического критерия Краскела–Уоллиса с post-hoc-тестом по Данну.Результаты: в результате введения дексмедетомидина наблюдали достоверное увеличение δ-ритма и снижение θ-ритма головного мозга кроликов на протяжении 2 ч. Введение атипамезола в эквимолярных количествах возвращало соотношение индексов ритмов к исходным значениям, эквимолярное введение пророксана не влияло на соотношение индексов ритмов волн.Выводы: атипамезол устраняет седативное и гипнотическое действие дексмедетомидина, что подтверждает возможность его применения в ветеринарной практике для вывода из наркоза. В свою очередь, применение пророксана с целью устранения седативного эффекта дексмедетомидина неэффективно

Pharmacotherapy treatment principles for insomnia

Pharmacotherapy of insomnia is an integral part of the treatment of this clinical syndrome. The range of drugs used for the treatment of sleep disorders is quite extensive, and not all of them are “true” sleeping pills”. Such pills often belong to the various classes of psychotropic medications. Advanced sleeping pills taken in compliance with the necessary rules provide the necessary sleeping effect without accompanied negative changes in the sleep structure and the quality of the subsequent waking. The domestic and foreign studies, the leading professional community guidelines (the Russian Society of Somanologists – 2016, the European Sleep Research Society – 2017, the American Academy of Sleep Medicine – 2017, the American College of Physicians – 2016) show that normalization of sleep in patients with insomnia by various methods, including pharmacotherapy, neutralizes its negative effects, improves the adaptive capacity of the individual and prevents the chronic sleep disorders with severe adverse effects

REMAXOL: MECHANISMS OF ACTION AND APPLICATION IN REAL CLINICAL PRACTICE. Part II

Окончание. Начало читайте в Томе 6, номере 2(28)-2016 г

EFFICACY OF REMAXOL AND ADEMETHIONINE IN EXPERIMENTAL LIVER DAMAGE CAUSED BY A COMBINATION OF RESERVE-SERIES ANTITUBERCULOSIS DRUGS AND ALCOHOL

The hepatic and endothelial protective effects of remaxol and S-adenosyl-L-methionine were studied on 24 male rats with liver damage caused by reserve-series antituberculosis drugs in combination with alcohol. The test agents were found to have a unilateral hepatoprotective effect in decreasing the blood levels of triglycerides, bilirubin, and alkaline phosphatase with a concurrent significant reduction in the manifestations of hyaline-drop and hydropic dystrophy of hepatocytes. Remaxol and ademethionine have the same endothelial protective activity manifested as normalization of an endothelium-dependent vasodilation response and endothelial dysfunction coefficient

Кашель при новой коронавирусной инфекции (COVID-19): рациональные подходы к фармакотерапии

Cough is one of the most frequent symptoms of the new coronavirus infection (COVID-19). It reduces the quality of life and contributes to the development of life-threatening conditions.Aim. This article analyzes modern approaches to the pharmacotherapy of cough in patients with the new coronavirus infection from the standpoint of pathogenetic justification of the use of drugs. The main mechanisms of cough development in COVID-19 presented in the literature are considered. The cough is associated with virus-induced damage to the epithelium and subsequent release of biologically active substances that irritate the afferent endings of the vagus nerve. Approaches to cough management in COVID-19 with the possible use of antitussive (central and peripheral action) and mucoactive drugs (expectorants, mucokinetics, mucolytics, mucoregulators) are addressed.Conclusion. Based on the literature data and pathogenesis, antitussive drugs play a crucial role in the treatment of cough in COVID-19.Кашель, при котором снижается качество жизни и развиваются жизнеугрожающие состояния, является одним из самых частых симптомов новой коронавирусной инфекции (НКИ) (COVID-19).Целью обзора явился анализ современных подходов к фармакотерапии кашля при НКИ с позиций патогенетического обоснования применения лекарственных препаратов. Рассмотрены представленные в литературе основные механизмы развития кашля при COVID-19, который связан с повреждением эпителия вирусом и последующим выделением биологически активных веществ, раздражающих афферентные окончания блуждающего нерва. Рассмотрены подходы к менеджменту кашля при COVID-19 с возможным применением противокашлевых (центрального и периферического действия) и мукоактивных препаратов (экспекторального, мукокинетического, муколитического, мукорегуляторного действия).Заключение. По результатам анализа данных литературных источников и известных механизмов патогенеза кашля установлено, что приоритетная роль в терапии кашля при COVID-19 отводится именно противокашлевым препаратам

SGLT2 Inhibitor Empagliflozin Modulates Ion Channels in Adult Zebrafish Heart

Empagliflozin, an inhibitor of sodium-glucose co-transporter 2 (iSGLT2), improves cardiovascular outcomes in patients with and without diabetes and possesses an antiarrhythmic activity. However, the mechanisms of these protective effects have not been fully elucidated. This study aimed to explore the impact of empagliflozin on ion channel activity and electrophysiological characteristics in the ventricular myocardium. The main cardiac ionic currents (INa, ICaL, ICaT, IKr, IKs) and action potentials (APs) were studied in zebrafish. Whole-cell currents were measured using the patch clamp method in the isolated ventricular cardiomyocytes. The conventional sharp glass microelectrode technique was applied for the recording of APs from the ventricular myocardium of the excised heart. Empagliflozin pretreatment compared to the control group enhanced potassium IKr step current density in the range of testing potentials from 0 to +30 mV, IKr tail current density in the range of testing potentials from +10 to +70 mV, and IKs current density in the range of testing potentials from −10 to +20 mV. Moreover, in the ventricular myocardium, empagliflozin pretreatment shortened AP duration APD as shown by reduced APD50 and APD90. Empagliflozin had no influence on sodium (INa) and L- and T-type calcium currents (ICaL and ICaT) in zebrafish ventricular cardiomyocytes. Thus, we conclude that empagliflozin increases the rapid and slow components of delayed rectifier K+ current (IKr and IKs). This mechanism could be favorable for cardiac protection