Pub Date : 2021-03-02DOI: 10.19163/2307-9266-2020-8-5-325-335
E. A. Muzyko, V. Perfilova, A. Nesterova, K. V. Suvorin, I. Tyurenkov
Maternal preeclampsia can bring about metabolic disorders in the offspring at different stages of ontogeny. Up to date, no ways of preventive pharmacological correction of lipid and carbohydrate metabolism disorders developing in different periods of ontogeny in the children born to mothers with this pregnancy complication, have been developed.The aim of the experiment was to study the effect of the gamma-aminobutyric acid derivative succicard (22 mg/kg) and its reference drug pantogam (50 mg) administered per os in the course of treatment in puberty (from 40 to 70 days after birth), on the parameters of lipid and carbohydrate metabolism in the offspring of the rats with experimental preeclampsia, in different periods of ontogeny.Materials and methods. To assess the activity of lipid and carbohydrate metabolism in the offspring, an oral glucose tolerance test was performed at 40 days, 3, 6, 12 and 18 months of age. The level of glycosylated hemoglobin was measured at the age of 6, 12, and 18 months, and the concentrations of total cholesterol, high-density lipoprotein cholesterol and triglycerides were tested at 40 days, 3, 6, 12, and 18 months of age.Results. The offspring of the rats with experimental preeclampsia, were found out to have lipid and carbohydrate metabolism disturbances during early (40 days and 3 months of age) and late (6, 12, and 18 months of age) ontogeny. In comparison with the offspring of healthy females, these disturbances were manifested by significantly higher levels of glucose revealed during the oral glucose tolerance test, by high glycosylated hemoglobin in males, and with elevated concentration of total cholesterol and triglycerides and a low level of high-density lipoprotein cholesterol in the negative control rats. Both the gamma-aminobutyric acid derivative succicard and its reference drug pantogam, reduced the negative effect of experimental preeclampsia on lipid and carbohydrate metabolism in the offspring in late ontogeny (6, 12 and 18 months of age). The effectiveness of succicard was either higher or comparable with pantogam.Conclusion. Thus, the negative impact manifestations of experimental preeclampsia on lipid and carbohydrate metabolism, are revealed in the offspring in early (40 days and 3 months) and late (6, 12 and 18 months of age) ontogeny. The gamma-aminobutyric acid derivative succicard reduces the negative effect of experimental preeclampsia. Based on this finding, the drug implies the possibility of the development of a safe and highly effective medicine for preventive correction of lipid and carbohydrate metabolism disorders in the children born to mothers with preeclampsia.
{"title":"EFFECT OF THE GABA DERIVATIVE SUCCICARD ON THE LIPID AND CARBOHYDRATE METABOLISM IN THE OFFSPRING OF RATS WITH EXPERIMENTAL PREECLAMPSIA IN EARLY AND LATE ONTOGENY","authors":"E. A. Muzyko, V. Perfilova, A. Nesterova, K. V. Suvorin, I. Tyurenkov","doi":"10.19163/2307-9266-2020-8-5-325-335","DOIUrl":"https://doi.org/10.19163/2307-9266-2020-8-5-325-335","url":null,"abstract":"Maternal preeclampsia can bring about metabolic disorders in the offspring at different stages of ontogeny. Up to date, no ways of preventive pharmacological correction of lipid and carbohydrate metabolism disorders developing in different periods of ontogeny in the children born to mothers with this pregnancy complication, have been developed.The aim of the experiment was to study the effect of the gamma-aminobutyric acid derivative succicard (22 mg/kg) and its reference drug pantogam (50 mg) administered per os in the course of treatment in puberty (from 40 to 70 days after birth), on the parameters of lipid and carbohydrate metabolism in the offspring of the rats with experimental preeclampsia, in different periods of ontogeny.Materials and methods. To assess the activity of lipid and carbohydrate metabolism in the offspring, an oral glucose tolerance test was performed at 40 days, 3, 6, 12 and 18 months of age. The level of glycosylated hemoglobin was measured at the age of 6, 12, and 18 months, and the concentrations of total cholesterol, high-density lipoprotein cholesterol and triglycerides were tested at 40 days, 3, 6, 12, and 18 months of age.Results. The offspring of the rats with experimental preeclampsia, were found out to have lipid and carbohydrate metabolism disturbances during early (40 days and 3 months of age) and late (6, 12, and 18 months of age) ontogeny. In comparison with the offspring of healthy females, these disturbances were manifested by significantly higher levels of glucose revealed during the oral glucose tolerance test, by high glycosylated hemoglobin in males, and with elevated concentration of total cholesterol and triglycerides and a low level of high-density lipoprotein cholesterol in the negative control rats. Both the gamma-aminobutyric acid derivative succicard and its reference drug pantogam, reduced the negative effect of experimental preeclampsia on lipid and carbohydrate metabolism in the offspring in late ontogeny (6, 12 and 18 months of age). The effectiveness of succicard was either higher or comparable with pantogam.Conclusion. Thus, the negative impact manifestations of experimental preeclampsia on lipid and carbohydrate metabolism, are revealed in the offspring in early (40 days and 3 months) and late (6, 12 and 18 months of age) ontogeny. The gamma-aminobutyric acid derivative succicard reduces the negative effect of experimental preeclampsia. Based on this finding, the drug implies the possibility of the development of a safe and highly effective medicine for preventive correction of lipid and carbohydrate metabolism disorders in the children born to mothers with preeclampsia.","PeriodicalId":20025,"journal":{"name":"Pharmacy & Pharmacology","volume":"19 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"84668163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-03-02DOI: 10.19163/2307-9266-2020-8-5-345-353
D. Yakovlev, L. Naumenko, K. T. Sultanova, A. Spasov
Migraine and its comorbid conditions are pathogenetically associated with many factors, including hemorheological disorders. A class of drugs with a 5-HT2A antagonistic mechanism of action, is promising for the prevention and treatment of migraine attacks and concomitant pathologies.The aim of the research is to study and compare a hemorheological activity of anti-migraine drugs, antagonists of 5-HT2A receptors of cyproheptadine, and a new drug that completed preclinical studies of the 1-(2-diethylaminoethyl)-2-(4-methoxyphenyl)-imidazo[1,2-a]benzimidazole derivative of the RU- 31 compound.Materials and methods. The study of the hemorheological activity of the RU-31 compound and cyproheptadine, was carried out using an experimental model of rabbit blood hyperthermia in vitro. Pentoxifylline was used as a reference drug. In the course of the work, the parameters of blood viscosity, aggregation and deformability of erythrocytes were recorded.Results. It has been established that in the concentration of 1 μM, the RU-31 compounds reduce blood viscosity by 17% at high shear rates, which is comparable with pentoxifylline in the concentration of 100 μM on the activity level. In the concentration of 1 μM, cyproheptadine also causes a general tendency to reduce blood viscosity at high shear rates, being inferior in activity to the RU-31 compound and pentoxifylline. In the concentration of 1 μM, the RU-31 compound has a pronounced effect on the aggregation ability of erythrocytes in autologous plasma, reducing the aggregation rate by 70%, while the level of activity is not inferior to the drug compared to pentoxifylline in the concentration of 100 μM, and surpasses the drug cyproheptadine. For the RU-31 compound and cyproheptadine, no significant effect on the deformability of erythrocytes has been shown.Conclusion. The capacity of cyproheptadine and the RU-31 compound to influence the rheological properties of blood by reducing blood viscosity and aggregation of erythrocytes has been revealed.
{"title":"HEMORHEOLOGICAL PROPERTIES OF THE 5-HT2A-ANTAGONIST OF THE 2-METHOXYPHENYL-IMIDAZOBENZIMIDAZOLE DERIVATIVE OF THE RU-31 COMPOUND AND CYPROHEPTADINE, IN COMPARISON WITH PENTHOXYPHYLLINE","authors":"D. Yakovlev, L. Naumenko, K. T. Sultanova, A. Spasov","doi":"10.19163/2307-9266-2020-8-5-345-353","DOIUrl":"https://doi.org/10.19163/2307-9266-2020-8-5-345-353","url":null,"abstract":"Migraine and its comorbid conditions are pathogenetically associated with many factors, including hemorheological disorders. A class of drugs with a 5-HT2A antagonistic mechanism of action, is promising for the prevention and treatment of migraine attacks and concomitant pathologies.The aim of the research is to study and compare a hemorheological activity of anti-migraine drugs, antagonists of 5-HT2A receptors of cyproheptadine, and a new drug that completed preclinical studies of the 1-(2-diethylaminoethyl)-2-(4-methoxyphenyl)-imidazo[1,2-a]benzimidazole derivative of the RU- 31 compound.Materials and methods. The study of the hemorheological activity of the RU-31 compound and cyproheptadine, was carried out using an experimental model of rabbit blood hyperthermia in vitro. Pentoxifylline was used as a reference drug. In the course of the work, the parameters of blood viscosity, aggregation and deformability of erythrocytes were recorded.Results. It has been established that in the concentration of 1 μM, the RU-31 compounds reduce blood viscosity by 17% at high shear rates, which is comparable with pentoxifylline in the concentration of 100 μM on the activity level. In the concentration of 1 μM, cyproheptadine also causes a general tendency to reduce blood viscosity at high shear rates, being inferior in activity to the RU-31 compound and pentoxifylline. In the concentration of 1 μM, the RU-31 compound has a pronounced effect on the aggregation ability of erythrocytes in autologous plasma, reducing the aggregation rate by 70%, while the level of activity is not inferior to the drug compared to pentoxifylline in the concentration of 100 μM, and surpasses the drug cyproheptadine. For the RU-31 compound and cyproheptadine, no significant effect on the deformability of erythrocytes has been shown.Conclusion. The capacity of cyproheptadine and the RU-31 compound to influence the rheological properties of blood by reducing blood viscosity and aggregation of erythrocytes has been revealed.","PeriodicalId":20025,"journal":{"name":"Pharmacy & Pharmacology","volume":"231 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"80259449","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-01-31DOI: 10.19163/2307-9266-2020-8-4-242-254
T. Gendugov, A. Glushko, A. Ozerov, L. I. Shcherbakova
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.
{"title":"STUDY OF THE STABILITY OF THE SUBSTANCE 3-[2-(4-PHENYL-1-PIPERAZINO)-2-OXOETHYL]QUINAZOLINE-4(3Н)-ONE UNDER STRESSFUL CONDITIONS","authors":"T. Gendugov, A. Glushko, A. Ozerov, L. I. Shcherbakova","doi":"10.19163/2307-9266-2020-8-4-242-254","DOIUrl":"https://doi.org/10.19163/2307-9266-2020-8-4-242-254","url":null,"abstract":"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.","PeriodicalId":20025,"journal":{"name":"Pharmacy & Pharmacology","volume":"31 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89562593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-01-31DOI: 10.19163/2307-9266-2020-8-4-255-262
V. M. Pokrovsky, E. A. Patrakhanov, P. Lebedev, A. V. Belashova, A. Karagodina, A. A. Shabalin, A. Nesterov, V. Markovskaya, M. Pokrovsky
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.
{"title":"ESTIMATION OF THE EFFICIENCY OF HORMONE-REGULATING SYNCHRONIZATION OF OVULATION IN FEMALE MICE","authors":"V. M. Pokrovsky, E. A. Patrakhanov, P. Lebedev, A. V. Belashova, A. Karagodina, A. A. Shabalin, A. Nesterov, V. Markovskaya, M. Pokrovsky","doi":"10.19163/2307-9266-2020-8-4-255-262","DOIUrl":"https://doi.org/10.19163/2307-9266-2020-8-4-255-262","url":null,"abstract":"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.","PeriodicalId":20025,"journal":{"name":"Pharmacy & Pharmacology","volume":"54 16 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"85809900","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-01-31DOI: 10.19163/2307-9266-2020-8-4-222-232
V. Petrov, A. Gerasimenko, V. S. Gorbatenko, O. Shatalova
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 anticoagu- lant 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 sourc- es, has been used. The information had been placed in the following electronic databases: PubMed, Scopus, Web of Sci- ence 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.
背景。每五分之一的缺血性中风是由患者的心房颤动史引起的。目前，直接和间接口服抗凝药物被广泛应用于房颤患者的血栓栓塞并发症预防。然而，尽管有这组药物的处方，每年仍有1-2%的房颤患者发生缺血性卒中。在这种情况下，出现了一些问题:是否有可能对服用抗凝剂的患者进行溶栓治疗;中风后是否值得恢复抗凝治疗;什么时候应该这样做;以及应该使用哪些药物来预防再次中风。本文综述了缺血性脑卒中后房颤抗凝治疗特点的临床指南和研究结果。材料和方法。在这篇综述中，我们使用了来自开放和可用资源的科学文献中的信息。这些信息被放置在以下电子数据库中:PubMed、Scopus、Web of science Core Collection、Cochrane Library、ClinicalTrials.gov;图书馆，赛博列宁卡，谷歌学院。调查期间为1997-2020年。搜索查询为:“缺血性卒中+房颤+抗凝剂”;“缺血性卒中+房颤+直接口服凝血剂”和“房颤+缺血性卒中+华法林”的俄文和英文等效版本。结果与结论。目前，对房颤患者在卒中急性期使用抗凝剂预防复发性血栓栓塞并发症的研究还不够充分。在服用doac的患者中，TLT的递送造成了困难，首先，由于无法获得常规的特异性检查，无法准确评估止血状态;其次，由于大多数药物缺乏注册的解毒剂，而且它们的成本很高。此外，目前还没有专门研究IS急性期恢复或开始抗凝治疗的最佳时间以及该组患者的最佳药物的随机对照试验。关于这些方面的大多数现有建议都是以专家的协商一致意见为基础的，这一事实表明需要在审查中的领域进行进一步的研究。
{"title":"PHARMACODYNAMICS OF ORAL ANTICOAGULANTS IN PATIENTS WITH ATRIAL FIBRILLATION IN THE ACUTE PERIOD OF ISCHEMIC STROKE","authors":"V. Petrov, A. Gerasimenko, V. S. Gorbatenko, O. Shatalova","doi":"10.19163/2307-9266-2020-8-4-222-232","DOIUrl":"https://doi.org/10.19163/2307-9266-2020-8-4-222-232","url":null,"abstract":"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 anticoagu- lant 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 sourc- es, has been used. The information had been placed in the following electronic databases: PubMed, Scopus, Web of Sci- ence 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.","PeriodicalId":20025,"journal":{"name":"Pharmacy & Pharmacology","volume":"1 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"83048004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-01-31DOI: 10.19163/2307-9266-2019-8-4-263-272
R. F. Cherevatenko, O. V. Antsiferov, S. Skachilova, M. Pokrovsky, V. Gureev, I. I. Banchuk, A. Banchuk, M. I. Golubinskaya, A. A. Syromyatnikova, I. S. Rozhkov, A. A. Mostovykh
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.
{"title":"THE SEARCH FOR NEUROPROTECTIVE COMPOUNDS AMONG NEW ETHYLTHIADIAZOLE DERIVATIVES","authors":"R. F. Cherevatenko, O. V. Antsiferov, S. Skachilova, M. Pokrovsky, V. Gureev, I. I. Banchuk, A. Banchuk, M. I. Golubinskaya, A. A. Syromyatnikova, I. S. Rozhkov, A. A. Mostovykh","doi":"10.19163/2307-9266-2019-8-4-263-272","DOIUrl":"https://doi.org/10.19163/2307-9266-2019-8-4-263-272","url":null,"abstract":"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.","PeriodicalId":20025,"journal":{"name":"Pharmacy & Pharmacology","volume":"66 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"79074696","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-01-31DOI: 10.19163/2307-9266-2020-8-4-273-284
I. Petrukhina, R. Yagudina, T. K. Ryazanova, V. Kurkin, S. V. Pervushkin, A. V. Egorova, L. V. Loginova, A. I. Khusainova, P. R. Blinkova
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”.
{"title":"ANALYSIS OF THE IMPLEMENTATION OF THE FEDERAL ASSURANCE PROGRAM OF SUPPORTING BENEFICIARIES WITH INDISPENSABLE MEDICINAL PREPARATIONS IN THE SUBJECTS OF THE RUSSIAN FEDERATION","authors":"I. Petrukhina, R. Yagudina, T. K. Ryazanova, V. Kurkin, S. V. Pervushkin, A. V. Egorova, L. V. Loginova, A. I. Khusainova, P. R. Blinkova","doi":"10.19163/2307-9266-2020-8-4-273-284","DOIUrl":"https://doi.org/10.19163/2307-9266-2020-8-4-273-284","url":null,"abstract":"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”.","PeriodicalId":20025,"journal":{"name":"Pharmacy & Pharmacology","volume":"161 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"76418115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-01-31DOI: 10.19163/2307-9266-2020-8-4-233-241
M. V. Chirkova, D. K. Gulyaev, M. Chugunova, V. D. Belonogova
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.
{"title":"DEVELOPMENT OF A SOLID DOSAGE FORM WITH ADSORPTION ACTIVITY","authors":"M. V. Chirkova, D. K. Gulyaev, M. Chugunova, V. D. Belonogova","doi":"10.19163/2307-9266-2020-8-4-233-241","DOIUrl":"https://doi.org/10.19163/2307-9266-2020-8-4-233-241","url":null,"abstract":"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.","PeriodicalId":20025,"journal":{"name":"Pharmacy & Pharmacology","volume":"3 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"74610509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-01-01DOI: 10.19163/2307-9266-2020-8-5-296-303
V. Semerikov, N. Yuminova, N. O. Postanogova, L. Sofronova
The aim. The article highlights the current state of the problem of mumps in the world and the Russian Federation.Materials and methods. The materials of the study were electronic resources WHO infection control, Cohrane, Elsevier, ScienceDirect, CDC infection diseases database, PubMed, eLibrary, CyberLeninka. The research methods were the analysis and generalization of scientific literature. The assessment is presented by the immunological structure of the population in different age groups to mumps (n = 593) in the study area (2018) according to the data of the Center for Hygiene and Epidemiology in the Perm Territory.Results. The spread of mumps is found to be widespread and uneven in different regions of the world in the form of sporadic cases and large epidemic outbreaks, despite the world practice of vaccine prevention of mumps. Analysis of the immunological structure to mumps in different age groups revealed a fairly high number of seronegative individuals (the largest number was found among adults aged 20–39 years) in the study area (2018). A decrease in the tension of post-vaccination immunity is the main cause for the emergence of an outbreak among the adult population, in addition to vaccination failures among vaccinated children. The immune defenses created by the vaccine strain do not have the same intensity and duration as with natural infection, and some genotypes of “wild” variants of the mumps virus can break through the immune barrier and cause disease. Antigenic differences between vaccine and circulating strains, low inoculation dose can weaken immunity and reduce the effectiveness of mass vaccine prevention.Conclusion. Ways of solving the problem were proposed to forestall an unfavorable epidemic situation with mumps.
{"title":"MUMPS: ACHIEVEMENTS, PROBLEMS AND WAYS OF SOLUTION","authors":"V. Semerikov, N. Yuminova, N. O. Postanogova, L. Sofronova","doi":"10.19163/2307-9266-2020-8-5-296-303","DOIUrl":"https://doi.org/10.19163/2307-9266-2020-8-5-296-303","url":null,"abstract":"The aim. The article highlights the current state of the problem of mumps in the world and the Russian Federation.Materials and methods. The materials of the study were electronic resources WHO infection control, Cohrane, Elsevier, ScienceDirect, CDC infection diseases database, PubMed, eLibrary, CyberLeninka. The research methods were the analysis and generalization of scientific literature. The assessment is presented by the immunological structure of the population in different age groups to mumps (n = 593) in the study area (2018) according to the data of the Center for Hygiene and Epidemiology in the Perm Territory.Results. The spread of mumps is found to be widespread and uneven in different regions of the world in the form of sporadic cases and large epidemic outbreaks, despite the world practice of vaccine prevention of mumps. Analysis of the immunological structure to mumps in different age groups revealed a fairly high number of seronegative individuals (the largest number was found among adults aged 20–39 years) in the study area (2018). A decrease in the tension of post-vaccination immunity is the main cause for the emergence of an outbreak among the adult population, in addition to vaccination failures among vaccinated children. The immune defenses created by the vaccine strain do not have the same intensity and duration as with natural infection, and some genotypes of “wild” variants of the mumps virus can break through the immune barrier and cause disease. Antigenic differences between vaccine and circulating strains, low inoculation dose can weaken immunity and reduce the effectiveness of mass vaccine prevention.Conclusion. Ways of solving the problem were proposed to forestall an unfavorable epidemic situation with mumps.","PeriodicalId":20025,"journal":{"name":"Pharmacy & Pharmacology","volume":"235 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"78704554","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2021-01-01DOI: 10.19163/2307-9266-2020-8-5-304-315
O. E. Antsiferova, M. P. Teleshchenko, Y. M. Tsuverkalova, M. Pokrovsky, V. Gureev, M. A. Zatolokina, A. V. Gureeva
The aim of the experiment was to determine the effectiveness of the combined use of trimetazidine and a purified micronized flavonoid fraction, as well as their combinations with methyldopa, in comparison with monotherapy with the same drugs in the correction of morphofunctional disorders arising in the conditions of experimental preeclampsia. An integrated/multimethodology approach is the most effective way of treatment for preeclampsia. Therefore, an urgent task of modern pharmacology is to study the effectiveness of new drugs when used in combinations, as well as the drugs included in the standards for treatment.Materials and methods. The study was carried out at the Research Institute of Pharmacology of Living Systems of Belgorod State National Research University. The experiment was performed on 200 female Wistar rats, weighing 250–300 g, in which an ADMA-like model of preeclampsia had been reproduced. To assess the degree of correction of emerging morphological and functional disorders, the following parameters were involved: blood pressure, a coefficient of endothelial dysfunction, microcirculation in the placenta, proteinuria, fluid contents in the greater omentum, morphometric indicators of placental tissues and fetal height and weight parameters.Results. The combined use of trimetazidine (Preductal® MB) 6 mg/kg and a purified micronized flavonoid fraction (Detralex®) 260 mg/kg, as well as their combination with methyldopa (Dopegit®) 86 mg/kg, leads to a more pronounced decrease in the blood pressure, compared with a decrease in the coefficient of endothelial dysfunction by 2.22, 2.19 and 1.94 times, respectively, in relation to “untreated” animals. There was an increase in microcirculation indices in the placenta by 2.35, 2.21 and 2.03 times, respectively. In addition, there was an improvement in morphological parameters in the placenta and fetuses.Conclusion. The results of the study showed a greater effectiveness of the combined use of the studied drugs in experimental preeclampsia compared to their monotherapy. This indicates the prospects for the use of trimetazidine and purified micronized flavonoid fraction in the complex therapy for preeclampsia and the need for further research in this direction.
{"title":"CORRECTION OF MORPHOFUNCTIONAL DISORDERS IN EXPERIMENTAL PREECLAMPSY BY COMBINED USE OF TRIMETAZIDINE AND PURIFIED MICRONIZED FLAVONOID FRACTION AS WELL AS THEIR COMBINATIONS WITH METHYLAMPSY","authors":"O. E. Antsiferova, M. P. Teleshchenko, Y. M. Tsuverkalova, M. Pokrovsky, V. Gureev, M. A. Zatolokina, A. V. Gureeva","doi":"10.19163/2307-9266-2020-8-5-304-315","DOIUrl":"https://doi.org/10.19163/2307-9266-2020-8-5-304-315","url":null,"abstract":"The aim of the experiment was to determine the effectiveness of the combined use of trimetazidine and a purified micronized flavonoid fraction, as well as their combinations with methyldopa, in comparison with monotherapy with the same drugs in the correction of morphofunctional disorders arising in the conditions of experimental preeclampsia. An integrated/multimethodology approach is the most effective way of treatment for preeclampsia. Therefore, an urgent task of modern pharmacology is to study the effectiveness of new drugs when used in combinations, as well as the drugs included in the standards for treatment.Materials and methods. The study was carried out at the Research Institute of Pharmacology of Living Systems of Belgorod State National Research University. The experiment was performed on 200 female Wistar rats, weighing 250–300 g, in which an ADMA-like model of preeclampsia had been reproduced. To assess the degree of correction of emerging morphological and functional disorders, the following parameters were involved: blood pressure, a coefficient of endothelial dysfunction, microcirculation in the placenta, proteinuria, fluid contents in the greater omentum, morphometric indicators of placental tissues and fetal height and weight parameters.Results. The combined use of trimetazidine (Preductal® MB) 6 mg/kg and a purified micronized flavonoid fraction (Detralex®) 260 mg/kg, as well as their combination with methyldopa (Dopegit®) 86 mg/kg, leads to a more pronounced decrease in the blood pressure, compared with a decrease in the coefficient of endothelial dysfunction by 2.22, 2.19 and 1.94 times, respectively, in relation to “untreated” animals. There was an increase in microcirculation indices in the placenta by 2.35, 2.21 and 2.03 times, respectively. In addition, there was an improvement in morphological parameters in the placenta and fetuses.Conclusion. The results of the study showed a greater effectiveness of the combined use of the studied drugs in experimental preeclampsia compared to their monotherapy. This indicates the prospects for the use of trimetazidine and purified micronized flavonoid fraction in the complex therapy for preeclampsia and the need for further research in this direction.","PeriodicalId":20025,"journal":{"name":"Pharmacy & Pharmacology","volume":"18 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2021-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87955124","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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