Vol 10, No 2 (2022)


Activity modulation of various nitric oxide syntases as an approach to endothelial dysfunction therapy

Kurkin D.V., Abrosimova E.E., Bakulin D.A., Kovalev N.S., Dubrovina M.A., Borisov A.V., Strygin A.V., Morkovin E.I., Tyurenkov I.N.


Nitric oxide as a therapeutic approach to the treatment of cardiovascular diseases attracted the attention of researchers at the end of the 19th century. As a vasodilator, nitric oxide may be a unique therapeutic agent for the treatment of hypertension and, as a result, renal failure and left ventricular hypertrophy.

The aim of the article is to analyze the literature data on possible ways of modulating the activity of various nitric oxide synthases as an approach to the treatment of endothelial dysfunction.

Materials and methods. When searching for materials for writing a review article, such abstract databases as PubMed, Google Scholar, e-Library, etc., were used. The search was carried out on the publications for the period from 1990 to 2021. The following words and phrases were chosen as parameters for the literature selection: nitric oxide; NO synthase; endothelial dysfunction; NO synthase activator; NO synthase inhibitor.

The following words and phrases were chosen as parameters for the literature selection:

Results. The article presents the history of the nitric oxide discovery and its biological role, the process of its biosynthesis, as well as the isoforms of its synthesizing enzymes (NOS): neuronal – nNOS, endothelial – eNOS and inducible iNOS, and their role in normal and pathological physiology. The process of NOS uncoupling (its molecular mechanisms) has been considered as the basis of endothelial dysfunction.

The examples of the pharmacological correction (BH4, arginase inhibitors, statins, resveratrol) are presented. In addition, NO synthase activators (calcium dobesilate, cavNOxin, and some NOS transcription activators), as well as non-selective (L-NMMA, 1-NNA, L-NAME, ADMA, 546C88, VAS203) and selective (L-NIO, 7-nitroindazole, aminoguanidine, L-NIL, GW273629, GW274150, cavtratin) inhibitors of nitric oxide synthasehave been described.

Conclusion. Nitric oxide synthases continue to be promising targets for the development of agents that modulate their activity to correct various pathologies. As a therapeutic approach, modulation of the nitric oxide synthase activity can be implemented to treat endothelial dysfunction, which is the cause for complications of many diseases.

Pharmacy & Pharmacology. 2022;10(2):130-153
pages 130-153 views

Minimisation of risks associated with the use of pollen-based medicines, at the stage of pollen collection

Taube A.A., Buyanova T.A., Sakanyan E.I.


The aim of the study is the elaboration of Rules for Harvesting/Collecting of Pollen to minimize the risks associated with the use of pollen-based medicinal products.

Materials and methods. The following electronic resources were used in the study: PubMed, Medline, ScienceDirect, Web of Science, Scopus, Google Scholar, eLibrary, World Allergy Organization, Cochrane Database, Stallergenesgreer, Allergenscienceandconsulting, Pharmacopoeia, Fda.gov, fs.usda.gov, Ema.europa.eu. The analysis covered the period from January 1, 2010 until December 31, 2021.

Results. Currently, there are some general requirements for the quality of pollen in Russia, but there are no controls or standardised procedures for harvesting, drying, and purification of pollen. The USA and EU also lack established qualification programmes for pollen-collecting companies and/or individual pollen collectors. Regulatory authorities establish requirements only for visual control of raw materials or delegate responsibility to the manufacturer. The analysis of the existing regulatory documentation revealed lack of requirements for collection, storage, and processing of pollen used as the raw material for the production of allergen products. This calls for the elaboration of appropriate regulatory documents. The authors have compiled the Rules for Harvesting/Collection of Pollen, which include 6 parts. The Rules are intended for individuals directly involved in harvesting/collection of pollen, and contain requirements for pollen collectors, the process of pollen collection, documentation, storage, and transportation.

Conclusion. The authors have prepared the Rules for Harvesting/Collecting of Pollen, which include 6 parts. The Rules cover the whole process of pollen collection and all related processes. The implementation of this document will improve the process of pollen collection, thus reducing the risks associated with the use of pollen-based medicines. Further studies will assess the impact of the pollen quality on the safety of medicinal products.

Pharmacy & Pharmacology. 2022;10(2):154-163
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Comparative pharmacoeconomic analysis of long-acting lanreotide used in acromegaly therapy within conditions of the Russian Federation health care system

Krysanov I.S., Makarova E.V., Ermakova V.Y.


The aim of this study is to conduct a comprehensive pharmacoeconomic evaluation of the use of long-acting subcutaneous lanreotide gel compared to alternative drugs, for the treatment of acromegaly.

Materials and methods. Based on the literature data, a treatment model with a 1-year outlook was developed, a cost-effectiveness analysis (CEA) in pharmacoeconomics and a sensitivity analysis of changes in the model parameters were carried out. Direct medical costs for the annual therapy course were calculated. The data on the medicines costs were taken from the register of marginal prices of the State Register of Medicines.

Results. According to the unified Russian registry of the pituitary-hypothalamic tumors area, the achievement of remission in the acromegaly patients using lanreotide, a long-acting gel for a subcutaneous administration, compared to the long-acting octreotide, is 51% vs 24%. During the first year of treatment with octreotide, the total pharmacotherapy costs were lower than with lanreotide (RUB 225,496.07 vs RUB 574,451.84). According to the results of the cost-effectiveness analysis for one achieved case of remission, the advantage of using lanreotide over long-acting octreotide was revealed (RUB 1,251,870.56 versus RUB 1,431,005.31). The sensitivity analysis demonstrated the model’s stability to increases in the lanreotide price (up to +18%), decreases in the octreotide prices (up to –22%), increases in the transsphenoidal adenomectomy prices (up to +59%), and decreased lanreotide remission rates (up to –12%).

Conclusion. Although the treatment costs analysis showed lower total per year costs of the treatment with long-acting octreotide compared to lanreotide, the calculation of the cost-effectiveness ratio per remission showed that lanreotide had been superior to long-acting octreotide.

Pharmacy & Pharmacology. 2022;10(2):164-173
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Gender characteristics of adverse drug reactions development: experience of regional database analysis

Matveev A.V., Krasheninnikov A.E., Egorova E.A., Konyaeva E.I., Matveeva N.V.


The aim of the article is the gender characteristics study of the adverse drug reactions (ADRs) development based on the data of the notification forms registered in the regional database ARCADe (Adverse Reactions in Crimea, Autonomic Database), for the period from 2009 to 2018.

Materials and methods. The objects of the study were 6903 notification forms about adverse drug reactions recorded in the regional database called ARCADe (Adverse Reactions in Crimea, Autonomic Database) for the period from 2009 to 2018. The classification of drugs for separate pharmacological groups was carried out using the codes of the Anatomical Therapeutic Chemical (ATC) classification system of the World Health Organization (WHO) medicinal products, the instructions data of the State Registers of medicinal preparations used in the Russian Federation and Ukraine (for the cases registered before the entry of the Republic of Crimea into the Russian Federation).

Results. A general analysis of the number of cases of the adverse drug reactions (ADRs) development in patients of different genders made it possible to determine that 59.9% (4132 notification forms) of ADRs cases were observed in female patients; 37.7% (2602 cases) – in male patients. In 169 cards (2.4%), information about a patient’s gender was missing. The groups with the largest number of the registered cases of ADRs were antimicrobial agents for a systemic use (2864 cases, 41.5% of the total number of the ADRs registered cases), the drugs affecting the cardiovascular (811 cases, 11.7%) and nervous (734 cases, 10.6%) systems. In each of the presented groups, the incidence rate of ADRs in female patients exceeded that in men.

Conclusion. The study of the gender characteristics of the pharmacotherapy safety, carried out on the basis of the notification forms of the ADRs data registered in the Republic of Crimea, confirmed a higher likelihood of developing ADRs in female patients. This may be due to the peculiarities of the pharmacokinetics and pharmacodynamics of drugs in the female body, psychological factors, a more frequent use of drugs by this category of people. The implementation of the drug, taking into account specific features of each gender, can lead not only to better treatment outcomes, but also to increased patients’ compliance.

Pharmacy & Pharmacology. 2022;10(2):174-186
pages 174-186 views

Economic damage of pneumococcal vaccination absence as a risk factor for complications of chronic obstructive pulmonary disease

Orlova E.A., Dorfman I.P., Umerova A.R., Kantemirova B.I., Orlov M.A., Abdullaev M.A.


The aim of the article is the evaluation of the economic damage (ED) because of the absence of pneumococcal vaccination as a leading risk factor for the development of community-acquired pneumonia (CAP) and acute exacerbations of а chronic obstructive pulmonary disease (COPD).

Materials and methods. The method of attributive statistics was used for the first time to assess the ED of the vaccination absence as an independent risk factor contributing to the development of CAP and COPD exacerbations in the Astrakhan region for the period of 2015–2019. To do this, at the beginning of the study based on the literature data, a relative risk of COPD complications associated with the absence of pneumococcal vaccination was determined. Using it as a risk factor, prevalence rates (a proportion of non-vaccinated patients with COPD), the population attributable risk (PAR) was calculated. Further, the annual economic damage (ED) from the development of CAP and COPD exacerbations was determined. To assess the cost-effectiveness of the COPD complications prevention, vaccination costs of newly registered patients were calculated and the ratio of these costs to the average annual ED was determined.

Results. A decrease in the non-vaccinated patients’ proportion corresponds to the decrease in the total ED from COPD complications: from 13.16 million rubles to 6.06 million rubles during the observation period. The calculations showed that due to the increase in the vaccinated patients’ proportion over a five-year observation period, the ED from the CAP development decreased by 2.1 times, from exacerbations of COPD – by 2.3 times. The vaccination costs of newly diagnosed COPD cases amounted to 0.63 million rubles. Thus, to prevent the annual ED of 3.24 million rubles, the sum for the state to spend, should be 5.2 times as small.

Conclusion. A study on the evaluation of the ED due to the risk factor (RF), the pneumococcal vaccination absence, showed that its elimination reduces the risk of acute COPD exacerbations and the development of CAP, as well the ED, as associated with them. Reducing the economic costs of the health care system with significantly lower vaccination costs, makes this preventive measure economically viable.

Pharmacy & Pharmacology. 2022;10(2):187-197
pages 187-197 views

Clinical and economic analysis of genetically engineered biologics consumption by patients with COVID-19

Petrov V.I., Ryazanova A.Y., Ponomareva A.V., Shatalova O.V., Levina Y.V.


The aim of the article is a comparative clinical and economic assessment of genetically engineered monoclonal antibodies against interleukins in infectious diseases facilities in Volgograd region, reassigned to treat COVID-19 patients.

Materials and methods. ABC analysis of the drug consumption in infectious disease facilities in Volgograd region in 2020 and 2021, cost-minimization analysis, and volume of consumption (standard dose per 1000 patients) for geneti- cally engineered monoclonal antibodies against interleukins, were performed on the basis of pharmacies dispensing drug reports on infectious diseases facilities, Russian State Register of maximum selling prices, and Russian guidelines for COVID-19 treatment.

Results. Only a small proportion of COVID-19 patients (43.6 standard doses per 1000 patients in 2020 and 137.8 per 1000 patients in 2021) received genetically engineered biologics in infectious disease facilities in Volgograd Region. Ne- vertheless, in the studied facilities, medical drug expenses on them exceeded from 20% in 2020 to 40% of the total inventory value in 2021. In mild COVID-19 patients with a high comorbidity index, netaquimab was the least expensive drug therapy and levilimab was the most expensive one. For moderate COVID-19, a standart recommended dose of sarilumab was the least expensive among the drugs used in the studied facilities, and anakinra was the least expensive drug among all the recommended GEBs. In severe and extremely severe COVID-19 courses, tocilizumab and sarilumab were less the least expensive among the GEBs used in the infectious disease facilities, and anakinra was the least expensive among all the recommended GEBs.

Conclusion. Accepting a possible equal effectiveness based on the currently available data, sarilumab is the least expensive for moderate COVID-19 and tocilizumab is the least expensive for severe and extremely severe COVID-19.

Pharmacy & Pharmacology. 2022;10(2):198-206
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Evaluation of antioxidant activity level of Actinidia arguta (Siebold et Zucc.) Planch. ex Miq. Plant raw material, grown in the caucasian mineral waters region

Pozdnyakov D.I., Adzhiakhmetova S.L., Vdovenko-Martynova N.N.


The aim of the study is the identification and evaluation of a new antioxidant activity in a potentially new medicinal raw material of Actinidia arguta folia.

Materials and methods. The total content of antioxidants was measured on a Tsvet Yauza-01-AA liquid chromatograph using the amperometric method. In parallel, the antioxidant activity of Actinidia arguta extracts was studied in vitro in the follo- wing dilution range: 62.5 µg/ml, 125 µg/ml, 250 µg/ml, 500 µg/ml and 1000 µg/ml. Herewith, DPPH, superoxide, and hydroxyl radical inhibitory properties of the analyzed samples were evaluated.

The studies of the antioxidant activity with the determination of the activity of superoxide dismutase, glutathione peroxidase, catalase, the concentration of malondialdehyde and diene conjugates, have been conducted in vivo.

Results. When studying the antiradical activity (in vitro tests), it was found out that the highest radical-inhibiting activity comparable to the individual compound - quercetin, has the extraction from Actinidia arguta folia, obtained by the extraction with 40% ethyl alcohol. The IC50 value for the given extract in relation to DPPH; superoxide and hydroxyl radical, amounted to 537.6±23.924 µg/ml; 26.6±2.627 µg/ml and 72.6±3.264 µg/ml, respectively, which may indicate that this extract has redu- cing and radical scavenging properties. In parallel, the study of the total content of antioxidants in terms of quercetin and gallic acid has been carried out. It has also been found out that in the Actinidia arguta folia extract, obtained by the extraction with 40% ethyl alcohol, the content of the antioxidants is maximum.

Conclusion. The data obtained using the in vitro test were confirmed in the in vivo study, in which the course application of the Actinidia arguta folia extract, obtained by the extraction with 40% ethyl alcohol to the degree comparable to quercetin, contributed to an increase in the superoxide dismutase activity, a decrease in the lipid peroxidation products. The maximum content of antioxidants for Actinidia arguta folia was 0.73±0.007 and 0.47±0.005 mg/g in terms of quercetin and gallic acid, respectively. The extractant was 40% ethyl alcohol.

Pharmacy & Pharmacology. 2022;10(2):207-216
pages 207-216 views

Study of long-term clinical and pathogenetic effects of favipiravir-based anti-viral drug in patients with metabolic syndrome in post-COVID period

Radaeva O.A., Balykova L.A., Zaslavskaya K.Y., Taganov A.V., Bely P.A., Kostina Y.A., Negodnova E.V., Mashnina S.V., Bessheinov D.D., Iskandyarova M.S., Eremeev V.V., Chumakov N.M.


The article presents modern scientific data on long-term clinical and pathogenetic effects of the antiviral drug Areplivir (Favipiravir) in patients with metabolic syndrome in the post-COVID period.

The aim of the article is to study long-term cytokine-mediated (IL-6/sIL6r and LIF/sLIFr) pathogenetic effects of the favipiravir (Areplivir®) based drug on the incidence of complications in patients with metabolic syndrome in the post-COVID period.

Material and methods. With the approval of the local ethics committee at the N.P. Ogarevs Mordovia State University (Protocol No. 5 dated May 17, 2020) “An open prospective comparative study of the Areplivir® (Favipiravir) drug effectiveness in reducing the risk of complications in the post-COVID period in patients with metabolic syndrome” in the Republic of Mordovia was carried out.

The study included 190 metabolic syndrome patients who received the outpatient treatment for COVID-19 at Saransk polyclinics from February 2021 to March 2021. The case of COVID-19 was diagnosed in accordance with the current Temporary Guidelines for the prevention, diagnosis and treatment of the new coronavirus infection.

Results. The analysis of the metabolic syndrome patients’ follow-up within 1 year after undergoing COVID-19, revealed significant differences in the incidence of complications depending on the intake of the favipiravir based drug. The patients who were administrated with favipiravir at the early stage of infection, were characterized by lower serum levels of four members of the interleukin 6 family – IL-6 (IL-6, sIL6r and LIF, sLIFr) 10, 30 and 180 days after a clinical and laboratory recovery (p<0.001). The average statistical changes in the IL-6 /sIL6r system of the group administrated with favipiravir, were 90%, and they were higher than in the group not administrated with antiviral drugs. In the group of the patients administrated with favipiravir, there was a significant (p<0.001) positive dynamic of the sLIFr indicator, while in the comparison group, there was an increase in this indicator.

A protective effect of the early favipiravir use was characterized by a decrease in the frequency of cardiovascular complications, a 2.66-fold decrease in the risk of a stroke and the ACS in the post-COVID period.

Conclusion. The areplivir therapy in the acute period of coronavirus infection made it possible to timely reduce the viral load. It helps to correct the pro-inflammatory vector of the immune response at the post-COVID stage and, accordingly, reduces the risk of progression of atherosclerosis, transient cerebrovascular accidents with a cognitive decline, an endothelial dysfunction, and can be considered a secondary prevention of life-threatening cardiovascular complications.

Pharmacy & Pharmacology. 2022;10(2):217-228
pages 217-228 views

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