Current issues in pharmacy and medicine: science and practice

DFT analysis of the [3 + 2] heterocyclization reaction of ((1,2,4-triazole(1,3,4-oxadiazole)-3(2)-yl)methyl)thiopyrimidines

Yu. V. Karpenko — 2025-03-10

The article examines the mechanisms of the heterocyclization reaction using density functional theory (DFT) methods. A quantum-chemical analysis of the starting compounds, transition states, and products was conducted, with energy barriers and key reaction stages identified. Particular attention was given to the influence of electronic and steric effects on the stability of the resulting heterocycles. The application of solvent models (PCM) allowed for more realistic simulation of reaction conditions. The study’s findings provide a deeper understanding of chemical transformations in heterocyclic systems and can be utilized to optimize synthetic methods in medicine, agrochemistry, and materials science.

The aim of this work is to perform a DFT analysis of the heterocyclization reaction of ((1,2,4-triazole(1,3,4-oxadiazol)-3(2)-yl)methyl)thiopyrimidines and to evaluate the stability of the transition states, as well as the influence of substituents on the activation energy.

Materials and methods. ¹H and ¹³C NMR spectra were recorded on a Bruker AC-500 spectrometer (500 MHz and 125 MHz, respectively) in DMSO-d₆, using TMS as the internal standard (Agilent Technologies, Santa Clara, California, USA). LC-MS analysis was performed using an Agilent 1260 Infinity HPLC System equipped with a diode-array detector and proton ionization. Elemental analysis (C, H, N, S) was conducted on an ELEMENTAR vario EL cube, with sulfanilamide as the standard. Melting points were determined using the capillary method on a Stanford Research Systems Melting Point Apparatus 100 (SRS, USA). The reagents were sourced from Sigma-Aldrich (Merck). All calculations were performed using the molecular visualization program GaussView 5.0.8 and the Gaussian 09 Rev E.01 software package.

Results. This article presents the results of a study on the mechanisms of [3 + 2] and [4 + 1] heterocyclization for the synthesis of 1,2,4-triazole and 1,3,4-oxadiazole derivatives. The reaction stages are analyzed in detail, including the formation of intermediates and cyclization, culminating in aromatization and the formation of stable heterocyclic structures. Thermodynamic analysis was conducted using the Gaussian 09 software package, incorporating calculations of enthalpy, entropy, and Gibbs free energy in both the gas phase and ethanol medium. The resulting energy profiles illustrate the key stages of the reactions and define the temperature conditions required for their execution. Special attention is given to the role of the solvent and other factors influencing process efficiency.

Conclusions. The DFT analysis revealed that the [3 + 2] heterocyclization reaction for forming the 1,2,4-triazole ring proceeds through several sequential stages, with the cyclization stage being the most energy-intensive. The obtained thermodynamic parameters confirm the feasibility of the reaction at temperatures above 85 °C in the gas phase and 78 °C in ethanol solution. The heterocyclization mechanism involves a nucleophilic attack by the amino group of hydrazide, thiol-thiourea tautomerism, ring closure, and structure aromatization. The most significant energy transitions are associated with the activation of the thiourea group and the formation of a new heterocyclic bond.

Chromatography-mass spectrometric study of Arceuthobium oxicedri raw material

O. I. Panasenko — 2025-03-10

Arceuthobium oxycedri, M. Bieb., commonly known as dwarf mistletoe, is widespread in the Mediterranean region, parasitizing the branches of Juniperus oxycedrus as a host plant. Compared to white mistletoe, it is more aggressive. It exhibits antibacterial, antifungal, phytotoxic, cytotoxic, and insecticidal activities.

Aim. The study aimed to investigate the qualitative and quantitative composition of biologically active substances and the biological activity of the methanol extract of juniper dwarf mistletoe (Arceuthobium oxicedri, M. Bieb.) as a potential source of medicinal substances.

Materials and methods. The object of the study was the shoots and branches of juniper dwarf mistletoe collected during the fruiting phase. The qualitative and quantitative determination of components was carried out at the Department of Toxicological and Inorganic Chemistry, Zaporizhzhia State Medical and Pharmaceutical University.

Results. Chromatography-mass spectrometric analysis of juniper dwarf mistletoe identified 34 components, the main ones being γ-curcumin (20.405 %), cedrol (17.619 %), epimanoyl oxide (5.142 %), and humulene (3.893 %).

Conclusions. The data obtained indicate the significant value of juniper dwarf mistletoe as a source of biologically active compounds, providing a basis for further study to develop promising medicinal substances.

Pharmacological potential of 6,11-dihydro[1,2,4]triazolo[4’,3’:1,6]-pyrido[3,4-b]-5-carboxylic acid and its esters

S. O. Fedotov — 2025-03-10

The combination of the indole fragment, which demonstrates activity due to its aromatic structure, with the 1,2,4-triazole nucleus, which is characterised by chemical stability and the ability to form hydrogen bonds, creates a promising basis for the development of new therapeutic agents with improved properties. The active implementation of various modifications of indole and 1,2,4-triazole frameworks is aimed at optimizing the pharmacokinetic and pharmacodynamic characteristics of medicinal products. Due to their unique structural features and a wide range of biological activities, these compounds remain an attractive area of research for the development of innovative pharmaceuticals.

The aim of this work has been to preliminarily evaluate the potential of indole-containing 1,2,4-triazole derivatives as a basis for the development of biologically active substances.

Materials and methods. The selection of structures for in silico studies has been based on the results of the scientific literature analysis and the basic principles of organic chemistry, which allowed us to integrate known pharmacophore fragments in the condensed state rationally. To determine the safety and potential toxic effects of the studied compounds, in silico methods have been applied using the TEST (Toxicity Estimation Software Tool) software developed by the US Environmental Protection Agency. The online resource SwissADME has been used to analyse the physicochemical properties and pharmacokinetic parameters of the studied compounds. The molecular docking method, based on computational algorithms, has been used to predict and study interactions, including the identification of potential binding sites, estimation of energy parameters and spatial configuration of molecules. MarvinSketch 6.3.0, Hyper Chem 8, and AutoDock Tools-1.5.6 were used for creating ligand models. The enzymes had been prepared for analysis using Discovery Studio 4.0 and AutoDock Tools-1.5.6. Molecular docking was performed using Vina software, which provides modelling and evaluation of interactions between ligand and three-dimensional protein structure, considering their energy and spatial compatibility.

Results. The most favourable safety profile of in silico studies has been shown by 6,11-dihydro[1,2,4]triazolo[4’,3’:1,6]pyrido[3,4-b]-5-carboxylic acid. Instead, its iso-propyl and n-butyl esters require special attention due to their high level of toxicity and potential danger to the ecosystem and genetic integrity of organisms. Butyl-6,11-dihydro[1,2,4]triazolo[4’,3’:1,6]pyrido[3,4-b]-5-carboxylate demonstrates the widest range of interactions with lanosterol 14α-demethylase, peptide deformylase, cyclooxygenase-2 and, accordingly, a high potential for influence on these enzymes. On the other hand, ethyl-6,11-dihydro[1,2,4]triazolo[4’,3’:1,6]pyrido[3,4-b]-5-carboxylate is highly likely to affect the anaplastic lymphoma kinase. Similarly, 6,11-dihydro[1,2,4]triazolo[4’,3’:1,6]pyrido-[3,4-b]-5-carboxylic acid demonstrates a significant potential for binding to the mentioned kinase. All the structures submitted for the study demonstrate a high level of drug-like properties. Their ability to overcome all the filters associated with pharmacokinetic parameters, together with their high predicted bioavailability, indicates their suitability for oral dosage form development.

Conclusions. According to the results of the study, it has been found that 6,11-dihydro[1,2,4]triazolo[4’,3’:1,6]pyrido[3,4-b]-5-carboxylic acid and its esters demonstrate positive pharmacological potential for the creation of a biologically active substance.

Determination and analysis of the gene expression, involved in the differentiation and functioning of beta cells under the conditions of the development of experimental diabetes of the dexamethasone type (type 2 diabetes)

T. V. Ivanenko — 2025-03-10

According to the World Health Organization, the number of patients with diabetes is constantly increasing, making this issue relevant not only for medical science, but also for the healthcare system as a whole. The mechanisms of functioning and differentiation of beta cells of the pancreas have attracted significant scientific attention. Laboratory identification of the genetic mechanisms regulating these processes is crucial for understanding the molecular basis of the development of type 2 diabetes and for finding new approaches to its prevention and treatment.

The aim of the work is to identify and analyze a panel of genes, involved in the differentiation and functioning of beta cells under the conditions of the development of experimental type 2 diabetes.

Materials and methods. Analysis of the gene expression, involved in the differentiation and functioning of beta cells was performed using the real-time reverse transcription polymerase chain reaction method CFX-96 Touch™ (Bio-Rad, USA) using the RT2Profiler™ PCR Array Rat Diabetes kit (QIAGEN, Germany).

Results. According to the results of the PCR study, the activity of the studied genes, involved in the differentiation and functioning of beta cells can be divided as follows: Vapa – a gene with high expression, compared to the control group of animals, Glp1r, Hnf1b, Hnf4a, Inppl 1, Ins 1, Mapk 8, Neurod 1, Stxbp 1, Stxbp 4, Vamp 2, Vamp 3 – genes with low expression, compared to the control group of animals, Nfkb 1, Nsf, Rab4a, Stx 4, Stxbp 2 – genes, in which no changes were detected in the samples in relation to the control group of animals, Pdx 1, Pparg, Ptpn 1, Sod 2 – genes, whose expression was not detected.

Conclusions. The development of type 2 dexamethasone diabetes significantly (where ∆∆Ct <30) increases the expression of the Vapa gene by 2.81 times, compared to the control group of animals. During the development of type 2 dexamethasone diabetes, significantly (where ∆∆Ct <30) genes Glp1r showed a low expression by 5.71 times, Hnf1b by 7.45 times, Hnf4a by 16.06 times, Inppl 1 by 22.81 times, Ins 1 by 9.53 times, Mapk 8 by 2.07 times, Neurod 1 and Stxbp 4 by 3 times, Stxbp 1 by 28.46 times, Vamp 2 and Vamp 3 by 12 times in relation to the control group of animals. The expression of Pdx 1, Pparg, Ptpn 1, Sod 2 genes during the development of type 2 dexamethasone diabetes was not detected.

Structural-geometric and functional indicators of the heart in patients with multiple myeloma after anti-tumor treatment and COVID-19

B. B. Samura — 2025-03-10

Multiple myeloma is a severe hematologic malignancy characterized by aggressive progression. Over the last decade, the introduction of novel targeted therapies has significantly improved treatment outcomes. Despite these advancements, cardiovascular complications following antitumor therapy continue to pose a significant challenge, adversely affecting patient life expectancy.

The aim of the study was to assess the predictive role of regional myocardial contractile function indicators in identifying the risk of cardiovascular events in patients with multiple myeloma.

Materials and methods. The study included 107 patients who achieved regression of multiple myeloma after completing a course of antitumor therapy and did not experience disease progression during the entire observation period. All stages of the study were conducted in compliance with strict compliance with clinical trial regulations. The study participants were categorized into distinct groups based on whether they experienced cardiovascular complications during the follow-up period. To assess biomarkers, blood plasma samples were analyzed using the enzyme-linked immunosorbent assay (ELISA) method, which allowed for the quantification of circulating substances.

Results. A total of 65 cardiovascular complications were recorded among 29 patients, representing 27.1 % of the studied population. The spectrum of complications comprised 4 cardiovascular-related deaths, 15 arrhythmia episodes requiring treatment, and 8 ischemic events. Other notable incidents included 2 strokes, 4 cases of pulmonary embolism, and 2 instances of deep vein thrombosis. Moreover, 11 patients exhibited decompensation of pre-existing chronic heart disease, and 19 were hospitalized for cardiovascular pathologies.

The values of the parameter e’ were significantly lower than in the control group in patients with multiple myeloma by 17.6 % (p < 0.05), especially in the subgroup of patients with a history of symptomatic COVID-19, where the decrease was 23.5 % (p < 0.05). The lowest values of the E and E/A indices were observed in patients with a history of symptomatic COVID-19 compared to those who did not have this disease. Circular systolic myocardial strain was significantly lower in the multiple myeloma group compared to the control group by 38.1 % (p < 0.001), including the subgroup of patients with symptomatic COVID-19, where the reduction was 42.6 % (p < 0.001), and the subgroup without a previous infection, where the reduction was 38.5 % (p < 0.001).

Using univariate analysis, it was found that the highest relative risk of cardiovascular events was associated with: symptomatic COVID-19 (HR = 1.880; 95 % CI = 1.291–2.745, p = 0.009), chemotherapy with anthracyclines (HR = 1.493; 95 % CI = 1.014–2.040, p = 0.041), reduced longitudinal systolic myocardial strain (HR = 1.354; 95 % CI = 1.139–1.611, p = 0.008), chemotherapy with immunomodulating drugs (HR = 1.210; 95 % CI = 1.009–1.345, p = 0.048), and reduced circular systolic myocardial strain (HR = 1.171; 95 % CI = 1.056–1.297, p = 0.028). During multivariate analysis, the prognostic significance was preserved only for some factors: prior symptomatic COVID-19 (HR = 1.079; 95 % CI = 1.041–1.780, p = 0.025) and reduced longitudinal systolic myocardial strain (HR = 1.078; 95 % CI = 1.021–1.184, p = 0.032).

Conclusions. A decrease in circular and longitudinal systolic myocardial strain has prognostic value for the occurrence of cardiovascular complications in multiple myeloma treatment within 12 months after anticancer treatment. The prognostic significance of these indicators did not depend on the presence of cardiac infection in the anamnesis.

Obstetric and perinatal sequelae of labor in women with breech presentation

V. H. Siusiuka — 2025-03-10

The aim of the study is to characterise the somatic and obstetric and gynaecological anamnesis, as well as to assess the features of pregnancy, childbirth and newborns’ condition in women with breech presentation.

Materials and methods. The medical documents of 2980 patients with breech presentation in the period from 2022 to 2024 by materials of the Municipal Non-Commercial Enterprise “Zaporizhzhia Regional Clinical Children’s Hospital” of the Zaporizhzhia Regional Council were analysed. The study group included 65 histories of pregnancy and childbirth (primary accounting documentation form No. 096/o) and 68 newborn medical records (primary accounting documentation form No. 097/o). The used research methods were data from: obstetric, gynaecological, and somatic history; management of pregnancy, childbirth, initial assessment of newborns; results of newborn observation during their stay in the department of the hospital.

Results. When analysing medical records, breech presentation was diagnosed in 65 pregnant women (2.2 %). In 60 women with breech presentation, the delivery ended in a caesarean section (92.3 %), and in 5 (7.7 %) women with breech presentation, the delivery went through the natural birth canal. In the case of breech presentation, which accounted for 73.3 %, all pregnant women were delivered by caesarean section (88.6 % as planned, 11.4 % as urgent due to fetal distress). Other indications for caesarean section included: breech presentation of the first fetus in multiple pregnancy, uterine scar after caesarean section, pelvic ring deformity, HIV infection with a high viral load and premature detachment of a normally located placenta.

Conclusions. When analysing the anamnesis of women with breech presentation, the vast majority of extragenital pathology (76.9 %) was cardiovascular and endocrine diseases. An analysis of the course of gestation in women with breech presentation revealed that 40 % had such pregnancy complications as hypertensive disorders, pre- and post-eclampsia, anaemia, fetal distress, and premature rupture of membranes. Complications of the perinatal period accounted for 30.9 % (neonatal jaundice, congenital infections and parasitic diseases, neonatal encephalopathy, prematurity, etc.).

An analysis of prescriptions for coronary heart disease with comorbid conditions in health care institutions of Ukraine

N. A. Bilousova — 2025-03-10

Coronary heart disease (CHD) remains the leading cause of mortality among non-communicable diseases in Ukraine and is often accompanied by various comorbid conditions. Providing pharmaceutical care to patients with CHD and comorbid conditions requires a comprehensive approach that includes ensuring access to medications, supervising rational pharmacotherapy in accordance with domestic and international clinical guidelines, monitoring trends in medication consumption, optimizing the supply of medicines, and developing standards for pharmaceutical care during martial law and the post-war period.

Aim. The objective was to analyze the frequency of medication use by physicians of various specialties for patients with CHD accompanied by type 2 diabetes mellitus (T2DM) and chronic kidney disease (CKD). This was done to identify trends in medication consumption and to optimize the provision of essential medicines in the context of improving the population’s access to medicines during martial law.

Materials and methods. The study was based on an anonymous online survey of 788 physicians from 22 regions of Ukraine, conducted using Google Forms between June and September 2024. The survey was facilitated by the Department of Cardiology at the Shupyk National Healthcare University of Ukraine. The study employed statistical analysis, comparison, generalization, and retrospective methods, alongside clinical-epidemiological approaches, content analysis, and ABC-, VEN-, ATC/DDD-, and frequency analyses.

Results. The pharmaceutical component of CHD management was evaluated based on the frequency of drug prescriptions for pharmacotherapy of CHD with comorbid conditions, following the clinical protocol “Stable Coronary Heart Disease” and clinical guidelines from ESC, AHA, ADA, and KDIGO. Comprehensive ABC-, VEN-, ATC/DDD-, and frequency analyses were conducted to assess prescribing patterns and to optimize the supply of medications to pharmacies and healthcare institutions.

Conclusions. It was found that only 23.65 % of prescribed medications for the pharmacotherapy of CHD with comorbid conditions are covered under the “Affordable Medicines” reimbursement program. This limited coverage negatively impacts treatment adherence, restricts patient access to necessary medications, and hampers the achievement of optimal clinical outcomes. It is recommended to revise and expand the list of reimbursable medications for CHD with comorbid conditions in alignment with current legislation and clinical needs.

Molecular genetics is on the guard of the law

L. I. Kucherenko — 2025-03-10

Molecular genetics is one of the key tools of modern medicine. With its help, scientists can study the structure and function of DNA, decode genetic codes, and develop new treatments. In the conditions of the modern world, where global crises, such as the war in Ukraine, occur more and more often, the role of molecular genetics goes far beyond standard medical tasks and becomes critically important for solving social, legal and humanitarian problems. Thus, molecular technologies have become an important tool both in the public health maintenance and in the human rights protection.

Aim. Study and optimization of methods of molecular genetic identification of a person using DNA analysis in forensic practice.

Materials and methods. The study is aimed at evaluating the effectiveness and accuracy of DNA analysis for solving identification tasks, as well as its application in the conditions of complex biological samples, which is important for ensuring the reliability of DNA expertise results in the context of forensics. At the first stage, a cytological examination is performed to identify cells with nuclei, after which DNA extraction is performed using proteinase treatment, phenol-chloroform purification, or the “Chelex” ion exchange resin method. The “Applied Biosystems” 7300 RealTime PCR Systems device is used to assess the quantity and quality of the isolated DNA, which allows to establish the state of the DNA for further analysis by the polymerase chain reaction (PCR) method. With the help of this method, which allows amplification of even minimal fragments of DNA, it is possible to obtain millions of copies of DNA, which enables its further study, even in the presence of trace amounts of biological traces. The obtained data are analyzed using the “Applied Biosystems” 3500 genetic analyzer, which has 8 columns and allows the simultaneous analysis of 8 objects and the four-channel “SeqStudio” genetic analyzer. This method helps to detail the length of DNA fragments and distinguish them by fluorescent labeling, which is used to build a DNA profile and establish kinship or identity.

Results. The results of the study confirm that the use of molecular methods allows achieving high levels of accuracy, reproducibility and reliability of data. This is especially important for complex cases where other methods cannot give the desired result. As a result, molecular technologies of DNA analysis have proven themselves as an effective method that allows not only to identify a person, but also to restore the chronology of events based on micro-traces of traces of biological origin, which significantly increases the accuracy and reliability of examinations, and helps in solving crimes.

Conclusions. The introduction of molecular technology into expert practice allows to perform the analysis of extremely small amounts of nuclear and mitochondrial DNA and thus to achieve the maximum effectiveness of researching the most complex biological objects to date: hair that has fallen out (one of the most frequently recovered objects from crime scenes); bone remains (including exhumed ones); mummified and dried tissues; cells of the epidermis. In the world, forensic DNA analysis is recognized as one of the most promising areas of development of forensic examinations, and its results are currently one of the most reliable pieces of evidence. This proves the relevance of research in the field of molecular biology and genetics, which are aimed at improving the methods of DNA analysis. The relevance of research is also due to the need to increase the accuracy and reliability of the obtained data, which is especially important when working with minimal biological samples or severely damaged materials.

Study of structural and mechanical properties of suppositories with bifonazole

T. V. Mielnyk — 2025-03-10

Currently, candidal vulvovaginitis is one of the most common infectious lesions of the mucous membrane of the vulva and vagina. The prevalence of this infection is one of the main reasons for impaired reproductive function and the development of pregnancy complications. In addition, this pathology is an important medical and social problem both for the healthcare system and for society, as it significantly reduces the quality of life of patients due to the manifestation of characteristic adverse symptoms. Treatment of candidal vulvovaginitis should be not only etiotropic, considering the species of the causative agent, but also pathogenetic. In addition, this pathology is an important medical and social problem both for the healthcare system and for society. As it significantly reduces the quality of life of patients due to the manifestation of characteristic adverse symptoms. Treatment of candidal vulvovaginitis should be not only etiotropic, considering the species of the causative agent, but also pathogenetic. One of the promising biologically active substances is bifonazole, which is an antifungal compound of the azole group with a wide spectrum of action. Based on complex physico-chemical, microbiological and biopharmaceutical research, the Department of Medicines Technology of the Zaporizhzhia State Medical and Pharmaceutical University developed a rational composition of the soft vaginal dosage form of bifonazole – suppositories containing 0.3 g of the active substance on a hydrophobic carrier.

The aim of this work is to study the rheological characteristics of the vaginal dosage form of bifonazole, depending on the temperature regime of the production process for the suppositories manufacture.

Materials and methods. The study of the structural and mechanical characteristics of the suppository mass with bifonazole based on cocoa oil with the addition of 5 % emulsifier No. 1 was carried out using a rotary viscometer “Reotest-2” with a cylindrical device at a human body temperature of +37 °С and the temperature of the technological process of manufacturing the dosage form.

Results. They indicate the existence of a present structure in the suppository composition, that is evidenced by the decrease in effective viscosity simultaneously with the increase in deformation forces. The obtained data enable us to analyze the strength characteristics of the suppository mass and to calculate the main parameters of structural and mechanical studies, which allow us to conduct an objective assessment of the consistency studies of the system.

Conclusions. The consistent properties of the suppository mass with bifonazole based on cocoa oil with the addition of 5 % emulsifier No. 1 at human body temperature were studied. It was established, that it is a structured system with pronounced thixotropic properties, in which there is a uniform distribution of biologically active and auxiliary substances both at the time of manufacture and during use and long-term storage. It was found, that increasing the temperature of the suppository mass to +50 °С does not lead to a significant change in its structural and mechanical properties and transformation into a Newtonian system. Considering the obtained data, it was established, that the temperature regime for the manufacture of vaginal suppositories with bifonazole on a lipophilic basis (mixing, homogenization, pouring into molds) in the range of +50–55 °С creates sufficient fluidity of the mass for the unhindered implementation of the technological process and thixotropy of the suppositories, distribution of active and auxiliary substances in this dosage form.

The application of the concept of trust marketing in the study of price sensitivity to study the consumer value of topical antifungal agents in the dosage form “gel”

I. V. Bushuieva — 2025-03-10

The market of medicinal products in Ukraine tends to constant changes. The dynamics of the pharmaceutical market, especially in today’s conditions of uncertainty, completely depend on the income of the population. For the implementation of new trajectories of improvement of pharmaceutical care, there is a study of the processes of consumer preferences of the patient / buyer to the pharmaceutical product, followed by the formation of consumer values and price sensitivity.

The aim of the work was to determine the price sensitivity of consumers in order to establish the consumer value of topical antifungal agents in the medicinal form “gel”.

Materials and methods. The van Westendorp method (PSM – price sensitivity measurement) was used in the study. The material for conducting the study was the available information sources indicating the list of drugs for the prevention and treatment of mycosis of the feet in the soft dosage form “gel” with only antifungal activity and with antifungal activity and additional antibacterial action, azole derivatives (websites-aggregators: apteka24.ua/uk/, doc.ua, tabletki.ua, compendium.com.ua/uk/, likie.ua, liki24.com, helsi.me/liki) and the results of the responses of respondents-consumers based on processing of a previously created questionnaire.

Results. For each medicinal product with a gel dosage form with antifungal action only and with antifungal and additional antibacterial action, azole derivatives, we have built graphs of the cumulative distribution of respondents, calculated the point values of the minimum (MCP), maximum (MEP), optimal (OPP) and indifferent price (IDP) that respondents are willing to pay for an antifungal product. It was determined that, according to the generalized opinion of the respondents, the highest OPP and IDP and the corresponding range of acceptable prices (OPP-IDP) are for combined forms of medicines that have not only antifungal action but also additional antibacterial activity. At the second stage of the study, an intra-group price analysis was conducted. The respondents were divided into 2 groups based on the consumer income characteristic. The next stage of the study included an intra-group price analysis based on the consumer characteristic “sick / not sick”.

Conclusions. As a result of the analysis of the concept of trust marketing in the study of price sensitivity for the study of consumer value of antifungal topical agents in the gel dosage form with antifungal activity only and with antifungal activity and additional antibacterial action, azole derivatives, the price sensitivity of consumers was determined and lists of the most attractive studied drugs in terms of consumer value were formed.

Problematic aspects of staffing the domestic pharmacy segment in the context of pharmaceutical safety

N. O. Tkachenko — 2025-03-10

The aim of the work is to identify problematic issues of human resource potential in the domestic pharmacy segment from the point of view of pharmaceutical safety.

Materials and methods. The work used information search, critical and comparative analysis, online surveys, generalization and interpretation of results. The research materials were scientific publications on the researched issue, the results of an online survey of pharmacy employees during September – December 2024 using the Google Forms platform.

Results. A list of problematic issues of personnel management in the pharmacy segment of the pharmaceutical sector of the healthcare industry was identified: pharmacies employ persons who do not have the right to participate in the provision of pharmaceutical care, since they do not have a pharmaceutical education; neglect by pharmacy management of the norms of law when applying for a job, choosing a position and documenting employment; high staff turnover; formation of work shifts in violation of labor legislation recommendations; an increase in the number of unprofessional obligations based on violation of ethical norms of the profession. It was found that the personnel policy of pharmacies for the majority of pharmaceutical specialists is not understandable, opaque, formal and not implemented. This causes rapid professional burnout, deterioration of the psychological state and pushes pharmaceutical specialists to change their field of activity, and also affects the quality of pharmaceutical care provided to the population in pharmacies. It was established that the top management of the health care and education and science systems, against the background of partial attempts to solve problems with the critical situation in pharmaceutical education, today lacks strategic plans regarding the staffing of the pharmaceutical sector of the health care industry. The issue of developing and implementing the Concept of Pharmaceutical Safety in Ukraine is actualized.

Conclusions. Based on the data set of an online survey of pharmacy employees, an analytical study of problematic issues of personnel potential in the domestic pharmacy segment was carried out and, based on its results, the prospects for the creation and implementation of the Concept of Pharmaceutical Safety in Ukraine were considered.

Staffing of perinatal care in Ukraine: dynamics and regional differences

T. M. Orabina — 2025-03-10

One of the key areas where staffing has a direct impact is perinatal care, which covers a range of medical services for mothers and newborns at different stages of pregnancy, childbirth and the postnatal period. Assessment of the dynamics of changes in the number of obstetricians and gynaecologists, as well as a study of regional imbalances in staffing, is necessary to identify problems and to develop measures aimed at solving them.

The aim of the study is a comprehensive analysis of the staffing of perinatal care in Ukraine, including an assessment of the dynamics of changes in the number and qualifications of obstetricians and gynaecologists in the period from 2015 to 2022, as well as the identification of regional disparities in the staffing of medical institutions.

Results. A significant decrease in the number of obstetricians and midwives, a decrease in the number of women per 1 obstetrician-gynaecologist, a decrease in the number of births per 1 obstetrician-gynaecologist and the number of newborns per 1 neonatologist, an increase in the number of women who were not under medical supervision during pregnancy, and an increase in the number of births outside the maternity ward were found in the frontline regions of Ukraine. In the period from 2015 to 2022, the ratio of obstetrician-gynaecologist to midwife decreased, which led to a decrease in the role of midwives in the provision of perinatal care and in the quality of patient care, and an increase in the proportion of caesarean sections in the total number of births.

Conclusions. The analysis of the dynamics of changes in the number of births, caesarean sections and the role of midwives indicates the need to improve human resources policy and optimise the resource provision of healthcare facilities. It is recommended to develop measures to improve staffing, training and implementation of effective management strategies to improve the quality of perinatal care in Ukraine.

Formation of a comprehensive rehabilitation program for patients considering the clinical and diagnostic features of the course of vertebral thoracic pain due to degenerative-dystrophic pathology of the thoracic spine

Ye. I. Maramukha — 2025-03-10

Aim. To determine the clinical and diagnostic features of the course of thoracic back pain syndrome, to investigate life quality data in patients with degenerative-dystrophic pathology of the thoracic spine (DDPS) depending on the indicators of vertebrodynamics in order to conduct differentiated kinesiotherapy technique.

Materials and methods. Rehabilitation measures were conducted for 124 patients with DDPS complicated by thoracalgia syndrome at the post-acute stage. All patients had a functional block of the 2nd degree in the thoracic spine. They were divided into two groups. The first group (n = 56) received basic rehabilitation, including drug therapy, massage, personalized therapeutic exercises, and physical therapy. The second group (n = 68) additionally underwent post-isometric and post-reciprocal muscle relaxation, mobilization techniques (K. Lewit, R. Maigne, V. Gubenko), and original kinesiotherapy methods tailored to vertebrodynamics indicators. The outpatient rehabilitation cycle lasted 14 days.

Results. Assessment of the effectiveness of patients treatment in the study groups before and after the rehabilitation measures according to the visual analogue scale for measuring pain intensity, the PainDETECT and LANSS scales for screening components of neuropathic pain in people with chronic pain, the Roland-Morris quality of life questionnaire and EQ-5D (EQ-5D-3L) indicate a statistically significant intergroup difference (p < 0.05) with higher quality of life and lower intensity of pain manifestations in patients of the 2nd group compared to patients of the 1st group. According to the results of the Spearman correlation analysis the progression of signs of mental disorders is directly proportionally associated with the intensity of manifestations of myofascial syndromes due to DDPS, as showed statistically significant relationships between the values of the results of the Spielberger anxiety and Montgomery–Asberg depression rating scales, on the one hand, and the integral indicator of the cumulative thoracic vertebral-mechanical index (Rs = +0.69 and +0.78 at p < 0.01 for all cases), confirming the important pathogenetic relationship between these pathological processes, which indicates the urgent need for rehabilitation measures according to generally accepted (A. Stoddard, K. Lewit) and optimized methods proposed by us to reduce anxiety-depressive disorders and normalize the mental state in general. According to the Pearson agreement criterion, patients with DDPS in the comparison group had significantly more frequently registered values of the five-component EuroQOL-5D system of more than 4 points (χ² = 11.63; p < 0.01).

Conclusions. Against the background of the course treatment, more than 90 % of patients with clinical manifestations of DDPS at the thoracic level achieved reliable positive results (significant reduction in pain syndrome, increased range of motion in blocked vertebral-motor segments, improved quality of life indicators).

Harmonization of pharmaceutical legislation of the European Union and its member states in the context of legal liability: problematic aspects of the relationship and development prospects

O. H. Aleksieiev — 2025-03-10

The issue of legal liability in the pharmaceutical sector is one of the key topics of modern legal regulation of healthcare. In the countries of the European Union (EU), where the pharmaceutical industry has reached a high level of development, this issue is becoming particularly relevant.

The aim of the work is to establish the main problematic aspects of harmonizing EU pharmaceutical law with national sectoral legislation. To analyze examples of law enforcement and the experience of the EU.

Results. The insufficient level of legislative coherence is proven. The analysis showed that discrepancies between the national legislation of individual countries and European regulations create significant challenges in implementing uniform quality standards for medicines. This complicates the effective fight against drug falsification and ensuring transparency of the pharmaceutical market. The role of legal liability is emphasized. Legal liability in the pharmaceutical sector performs an important regulatory function, contributing to the protection of patients’ rights and ensuring justice in cases of violation of norms. However, the level of its implementation largely depends on the harmonization of the legislative framework and clear mechanisms for bringing it to justice. It has been confirmed that the harmonization of national legislation with European standards (in particular Directive 2011/62/EU and Regulation 2016/161) is a necessary condition for increasing the effectiveness of control over the circulation of medicinal products. The implementation of drug verification systems, mandatory labeling and digital tracking tools is of particular significance.

Conclusions. Harmonization of national and European legislation in the pharmaceutical sector is a key condition for ensuring effective control over the circulation of medicinal products and protecting patients’ rights. Strengthening legal responsibility, the implementation of digital tools and the harmonization of legal norms will contribute to the fight against the falsification of medicines and the creation of a transparent market.

The potential of 1,2,4-triazole derivatives as antioxidant agents (literature review)

V. O. Salionov — 2025-03-10

1,2,4-Triazoles are important compounds in organic and pharmaceutical chemistry, which are known for their high reactivity and biological activity. They show a wide range of pharmacological properties with minimal toxicity. A promising area of research is the use of 1,2,4-triazole derivatives as antioxidants. 1,2,4-Triazoles are notable for their ability to neutralize free radicals and other reactive oxygen forms, which can damage cells and tissues.

Aim. The aim of this work is the antioxidant activity data analysis of new 1,2,4-triazole derivatives in recent literature. Based on the results of the research, conclusions will be drawn regarding the prospects for further work in the search for potent synthetic antioxidants.

Materials and methods. The data search was conducted using scientific databases (PubMed, Scopus, Google Scholar). The material for the study consisted of publications reporting new 1,2,4-triazole derivatives exhibiting antioxidant activity. The study employed methods of information search, analytical, descriptive and generalization techniques.

Results. In the analysis of scientific literature 1,2,4-triazole derivatives with antioxidant activity were characterized. To determine the prospects for developing new potentially effective drugs based on 1,2,4-triazole with clearly directed antioxidant action, scientists are conducting in vitro and in silico studies. Synthesized 1,2,4-triazole derivatives could serve as a foundation for new drugs aimed at preventing or treating cancer, heart diseases, as neuroprotective agents, and for slowing down the aging process, due to their antioxidant properties. Based on the study of available information, it was established that the Ukrainian market is insufficiently saturated with domestically produced 1,2,4-triazole-containing drugs exhibiting antioxidant properties.

Conclusions. The literature review of the antioxidant activity of new 1,2,4-triazole derivatives revealed that chemical modification of the triazole fragment at various positions and with different pharmacophores significantly enhances antioxidant activity. The obtained data clearly correlate with the results of computer-based drug prediction (in silico) and in vitro studies. Analysis of the results demonstrates the potential for further investigation of the antioxidant properties of 1,2,4-triazole derivatives to develop original and effective antioxidant drugs.