Vol 8, No 4 (2020)


Pharmacodynamics of oral anticoagulants in patients with atrial fibrillation in the acute period of ischemic stroke

Petrov V.I., Gerasimenko A.S., Gorbatenko V.S., Shatalova O.V.


Background. Every fifth ischemic stroke is caused by a patient’s history of atrial fibrillation. Nowadays, direct and indirect oral anticoagulants are widely used to prevent thromboembolic complications in patients with atrial fibrillation. However, despite the prescription of this group of drugs, every year 1–2% of patients with atrial fibrillation have an ischemic stroke. In this situation, a number of questions take rise: if it is possible to carry out thrombolytic therapy in the patients who have been taking anticoagulants; if it is worth resuming anticoagulant therapy after a stroke; when exactly this should be done; and what drugs should be used to prevent another stroke.

The aim of this review was to summarize the available clinical guidelines and research results on the study of the anticoagulant therapy characteristics in patients with atrial fibrillation after an ischemic stroke.

Materials and methods. For this review, the information presented in the scientific literature from open and available sources, has been used. The information had been placed in the following electronic databases: PubMed, Scopus, Web of Science Core Collection, Cochrane Library, ClinicalTrials.gov; Elibrary, Cyberleninka, Google Academy. The covering period was 1997–2020.

The search queries were: “ischemic stroke + atrial fibrillation + anticoagulants”; “ischemic stroke + atrial fibrillation + direct oral coagulants” and “atrial fibrillation + ischemic stroke + warfarin” in both Russian and English equivalents.

Results and conclusion. Currently, the problem of the use of anticoagulants for the prevention of recurrent thromboembolic complications in patients with AF in the acute period of a stroke, is studied insufficiently. The difficulties are caused by the delivery of TLT in the patients who have been taking DOACs, first of all, due to the impossibility of an accurate assessment of the hemostasis state because of the unavailability of routine specific tests; and second, as a result of the lack of registered antidotes for most drugs, and their high costs. Besides, there are no RCTs dedicated to the study of the optimal time for the resumption or initiation of anticoagulant therapy in the acute period of an IS, and the optimal drugs for this group of patients. Most of the existing recommendations on these aspects, are based on the consensus of experts, and this fact indicates the need for further research in the area under review.

Pharmacy & Pharmacology. 2020;8(4):222-232
pages 222-232 views

Development of a solid dosage form with adsorption activity

Chirkova M.V., Gulyaev D.K., Chugunova M.P., Belonogova V.D.


Enterosorbents are produced in various dosage forms - powders, tablets, pastes, etc., some of them are also manufactured in the form of capsules. A water-soluble polysaccharide complex (WSPC) manifesting a pronounced adsorption activity, which determines the prospects for the development of dosage forms of sorbents, was obtained from the cones of European Spruce (Picea abies).

The aim of the work is to develop a solid dosage form with an adsorption activity based on a water-soluble polysaccharide complex from the cones of European Spruce (Picea abies).

Materials and methods. The samples of European Spruce (Picea abies) cones were collected on the territory of Ilyinsky district of the Perm Krai and used as plant raw materials. A water-soluble polysaccharide complex was obtained from the raw materials. In order to improve the technological properties of the substance, (WSPC) granulates were obtained. The granulates were hand-made by wet granulation. The adsorption activity of the obtained granules was determined by the ability to bind methylene blue.

Results. As a result of the experiment it has been established, that the WSPC substance of European Spruce (Picea abies) cones needs to be improved in its technological properties. Granulation of the substance led to an improvement in technological properties and an increase in the adsorption activity in most of the selected compositions. It has also been shown that increased moisture content of granulate decreases its adsorption activity. A direct dependence of the adsorption activity on the concentration of the granulating liquid (with the exception of some granulates) has been revealed, but no significant effect of the size of the granulate particles on the manifestation of the adsorption effect has been reported. According to the results of the study, a dosage form “Capsules” has been proposed for the compositions that showed the best results of the adsorption activity, and their biopharmaceutical evaluation was carried out according to the disintegration test.

Conclusion. Thus, a solid dosage form with an adsorption activity has been obtained. The study shows the prospects for further research on the preparation of the drug with an adsorption activity based on the water-soluble polysaccharide complex of European Spruce (Picea abies) cones.

Pharmacy & Pharmacology. 2020;8(4):233-241
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Study of the stability of the substance 3-[2-(4-phenyl-1- piperazino)-2-oxoethyl]quinazoline-4(3н)-one under stressful conditions

Gendugov T.A., Glushko A.A., Ozerov A.A., Shcherbakova L.I.


The aim of the research was to study the stability of a new pharmaceutical substance 3-[2-(4-phenyl-1-piperazino)-2-oxoethyl]quinazoline-4(3Н)-one under stress conditions.

Materials and methods. The study was conducted in accordance with the recommendations of the ICH guidelines. The object of the study was a previously unknown derivative of quinazoline-4(3H)-one: 3-[2-(4-phenyl-1-piperazino)-2-oxoethyl]quinazoline-4(3Н)-one synthesized in Volgograd state medical university. The following laboratory equipment was used: HPLC chromatograph, HPLC-MS, centrifuge, electronic scales, pH meter, thermostat, laboratory filters.

The computational experiment was conducted on a computer with an Intel Xeon E3-1230 processor using the programs ORCA 4.1. and GROMACS 2019.

Results. The influence of the most unfavorable environmental factors, such as high temperature, light, oxidants, hydrolysis in acidic and alkaline environments, affect the stability of the test substance. The results of the computer-based stability prediction were confirmed by HPLC and HPLC-MS, and the degradation products of the substance under stressful conditions were determined. The conducted studies showed that the test substance is stable to UV radiation at the wavelength of 365 nm, at the elevated temperature (80°C), to the action of oxidants. But it is unstable to hydrolysis: in an alkaline medium of sodium hydroxide 1M, a break in the amide group occurs with the formation of 2-(4-oxoquinazoline-3-yl)acetic acid and 1-phenylpiperazine. And in an acidic environment, hydrochloric acid 1M is also destroyed, but it is significantly reduced, presumably due to the protonation and stabilization of tertiary nitrogen atoms in the molecule.

Conclusion. The conducted research makes it possible to conclude that the test substance 3-[2-(4-phenyl-1-of piperazino)-2-oxoethyl]quinazoline-4(3Н)-one is stable to aggressive environmental factors, with the exception of hydrolysis in an alkaline environment that will be further considered in the preparation of regulatory documents for this pharmaceutical substance.

Pharmacy & Pharmacology. 2020;8(4):242-254
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Estimation of the efficiency of hormone-regulating synchronization of ovulation in female mice

Pokrovsky V.M., Patrakhanov E.A., Lebedev P.R., Belashova A.V., Karagodina A.Y., Shabalin A.A., Nesterov A.V., Markovskaya V.A., Pokrovsky M.V.


The aim of the wok is to assess the efficiency of hormone-regulating synchronization of ovulation in female mice, to increase the number of simultaneously fertilized individuals and obtain their offspring in the planned time frame.

Materials and methods. The study was carried out on 180 female mice of three lines – CBA/lac, C57BL/6, BALB/c (n = 60), divided into three subgroups: intact (mating without confirmation of the estrous phase) (n = 20), cytological examination of vaginal secretions before mating with the determination of the estrous phase (n = 20), hormone-regulating synchronization of the estrous cycle with the introduction of progesterone (4.5 mg/100 g) on the 1st and prostaglandin F2α (0.083 mg/100 g) on the 7th day, once from the beginning of the experiment followed by immediate mating (n = 20). The planned date of delivery was considered the 22nd day from the moment of mating. The ovulation synchronization index (OSI) was assessed on the 14th day after mating.

Results. On the 14th day from the beginning of the experiment, the ovulation synchronization index in the intact groups of the CBA/lac, C57BL/6, BALB / c lines, was 25%, 25%, 40%, respectively. On the 14th day, the number of pregnant individuals admitted to mating after the established estrus by the method of cytological assessment of vaginal secretions according to OSI, was 65%, 60%, 75%, respectively. In the experimental groups, OSI was 80%, 75%, 100%, respectively. On the 22nd day, the number of delivered females of CBA/lac, C57BL/6, BALB/c lines in the intact group, was 3, 1, 3 individuals; in the control group – 10, 6, 9, and in the experimental group – 16, 15, 17, which is significantly higher than in the control and intact groups (p˂0.05).

Conclusion. Hormone-regulating synchronization of ovulation in female mice significantly increases the number of delivered individuals on the 22nd day, relative to those synchronized by estrus by 53%, and to intact groups by 85.5%. It has been revealed that an additional effect of hormonal synchronization of ovulation is an increase in the number of offspring by 120% in comparison with the control groups and by 390% in comparison with the intact groups. This method of timing planning of the offspring birth of the experimental animals reduces the time spent on preclinical studies of drugs for the following types of assessment of toxic effects: reproductive toxicity, embryotoxicity, teratogenicity, effects on fertility.

Pharmacy & Pharmacology. 2020;8(4):255-262
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The search for neuroprotective compounds among new ethylthiadiazole derivatives

Cherevatenko R.F., Antsiferov O.V., Skachilova S.Y., Pokrovsky M.V., Gureev V.V., Banchuk I.I., Banchuk A.Y., Golubinskaya M.I., Syromyatnikova A.A., Rozhkov I.S., Mostovykh A.A.


The aim of the study is to search compounds with neuroprotective properties among new ethylthiadiazole derivatives in simulated traumatic brain injury.

Materials and methods. The experiment was carried out on 78 white male rats 270±20 g line “Wistar” 5–6 months of age and 120 outbred sexually mature mice weighing 20±2 grams. The article describes the search for compounds with neuroprotective properties among new ethylthiadiazole derivatives under the codes LKHT 4–15, LKHT 10–18, LKHT 11–18, and LKHT 12–18 in experimental traumatic brain injury in rats. Acute toxicity of the compounds was studied. Pharmacological screening was performed using behavioral and neurological research methods. The McGraw stroke score scale modified by I.V. Gannushkina and the mNSS psychometric scale were used in the study. The open field and Rota-rod tests were used to assess the behavioral status of the animals.

Results. The compound-LKHT 12–18 at a dose of 50 mg/kg was detected as a leader. In pharmacological correction of pathology, this compound had the lowest percentage of fatality among the studied compounds (8%), the severity of neurological deficit was significantly reduced, the lowest scores and a higher level of motor activity of the limbs were registered. The number of rearing in the group of animals receiving the compound LKHT 12–18 at the dose of 50 mg/kg increased by 1.5 times, statistically significant (p<0.05) in comparison with the control group. Based on the results of the “Rota-rod” test, the total time of holding animals on the rod for 3 attempts was statistically significantly different in the groups administered with LKHT 12–18 derivatives (1.5 times longer) at the dose of 50 mg/kg compared with the control (p<0.05).

Conclusion. Based on the results obtained in this study, it is planned to study in more detail the compound LKHT 12–18 at the dose of 50 mg/kg.

Pharmacy & Pharmacology. 2020;8(4):263-272
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Analysis of the implementation of the federal assurance program of supporting beneficiaries with indispensable medicinal preparations in the subjects of the Russian Federation

Petrukhina I.K., Yagudina R.I., Ryazanova T.K., Kurkin V.A., Pervushkin S.V., Egorova A.V., Loginova L.V., Khusainova A.I., Blinkova P.R.


The aim of the research was to study the main indicative indicators of the implementation of the federal program “Provision of Essential Medicines” in 20 constituent entities of the Russian Federation based on the results of 2018 and 2019.

Materials and methods. The analyzed data were provided on the basis of the request cards specially designed by the health authorities of 20 subjects of the Russian Federation located in seven federal districts.

Results. It has been established that the funds allocated to the constituent entities of the Russian Federation, directly depend on the number of beneficiaries who retained the right to receive state social assistance in the form of a set of social services. These funds also correlate with the indicator “Population of the subject of the Russian Federation”. In all the studied constituent entities of the Russian Federation, more than 50% of the total number of people who retained the right to preferential drug provision in 2018–2019, asked for medical help as part of the program “Provision of Essential Medicines”. Herein, in the constituent entities of the Russian Federation, the average cost of one prescription amounted to 1,107.2 rubles in 2018 and 1,297.2 rubles in 2019. The estimated indicator “The average actual expenditures per 1 citizen entitled to state social assistance in the form of a set of social services, amounted to 1,723.0±90.2 rubles in 2018 and 1,526.8±80.5 rubles in 2019, which is higher than the approved input normative (823.3 rubles and 861.8 rubles in 2018 and 2019, respectively).

Conclusion. Thus, an excess of average actual expenditures per citizen entitled to state social assistance in the form of a set of social services, was notified over the standards established by the decrees of the Government of the Russian Federation. The revealed discrepancy between the normative and actual expenditures can also be an indirect confirmation of the fact that the most needy beneficiaries with chronic diseases remained in the program “Provision of Essential Medicines”.

Pharmacy & Pharmacology. 2020;8(4):273-284
pages 273-284 views

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