Gamma-aminobutyric acid (GABA) became known as a potentially important chemical in the brain 50 years ago, but its significance as a neurotransmitter was fully found 16 years later. It is now known that at least 40 % of the inhibitory synaptic activity in the mammalian brain is accounted for by GABA. Аim. To analyze achievements in the study of the physiological and pharmacological role of GABA receptor subtypes, their potential applications in drug development and updated information on the clinical development of subtype-selective GABA receptor compounds. Results. The GABAA-receptor complex (GABA-RC) is ligand-gated ion channels with chloride conductance. These receptors contain α, β, and γ subunits, but δ, ε, θ, and ρ can be also present. The GABA binding site is located at the interface between α and β subunits where a number of important amino acids are also found. GABA-RC is sensitive to a wide range of drugs, e.g. benzodiazepines (BDZ), which are often used for their sedative/hypnotic and anxiolytic effects. Classical BDZ interact non-selectively with α1,3,5 βγ2 GABA-RС in the binding site located at the α+γ− interface. Conclusions. In addition to the potent and rapid pharmacotherapeutic action BDZ also possess some addictive potential (drug dependence), which appears after the interaction of molecules with α1-receptors. Using the selective targeting to separate subgroups not only the main effect of BDZ without side effects can be provided, but also one can use this approach in creating new analgesic medicines; we have demonstrated it on the example of propoxazepam (full agonist GABA-R).
The main principles of creating a quality system in modern laboratory diagnostics are: standardization of laboratory processes by developing standard operating procedures; general quality management of laboratory research based on the development and implementation of the requirements of international standards (according to ISO 15189: 2015 "Medical laboratories. Basic requirements for quality and competence"); quality control of all stages of the laboratory process through the implementation of the validation procedure. Aim. To develop a methodology for conducting validation procedures to assess the suitability of a biochemical method for determining the level of total cholesterol in biological fluids in the Clinical Diagnostic Laboratory of the Clinical Diagnostic Center of the NUPh. Materials and methods. The object of the study was a standardized method for determining the concentration of total cholesterol. The method was validated using the “Cholesterol Reagent Set” test kit and the standard sample “Chemical control. Reagent kit. Level 1 ", manufactured by High Technology, Inc. (USA) with known concentration. The measurements were carried out on an Express Plus automatic biochemical analyzer manufactured by Bayer Corporation, Germany. When processing the research results, descriptive statistics were used and a number of statistical evaluations were carried out. Results. A protocol and a validation report were developed at the Clinical Diagnostic Laboratory of the CDC NUPh to assess the suitability of the method for determining the concentration of cholesterol in biological fluids by the photometric enzymatic method on an automatic biochemical analyzer Express Plus (using reagents and control material manufactured by High Technology, Inc., USA). The validation characteristics of the method were determined: repeatability and reproducibility, correctness and uncertainty of measurements. Evaluation of the internal laboratory repeatability and reproducibility of this technique indicates the absence of gross errors in the operation of the instrument and statistically important differences in measurements. The assessment of the correctness of the method (carried out using the control material) proved that the systematic error is not significant (according to a given acceptance criterion). The expanded uncertainty calculation showed that the obtained values of the total cholesterol level can be considered accurate and reliable. Conclusions. Validation of the method for determining total cholesterol in human blood by the photometric enzymatic method has proven that this method has performance characteristics that correspond to the regulated ones, meets the established criteria, and the parameters measured with it correspond to the proper ones. Key words: validation, determination method, total cholesterol, repeatability and reproducibility, correctness and uncertainty of measurements
Chlorhexidine is an effective cationic antiseptic and disinfectant that has been used in medical practice for decades. It is generally recommended to use different concentrations of aqueous or alcoholic solutions of chlorhexidine for different therapeutic purposes. Objective. To determine the proportions of different chlorhexidine concentrations in medicines purchased by state and municipal organizations and to identify possible issue of chlorhexidine formulations utilization in the suboptimal or insufficient concentrations. Results. The vast majority of the chlorhexidine-containing medicines found in the State Register of Medicines of Ukraine are 0.05% solutions for external use, 0.05% gels for dental and urological use and vaginal suppositories (pessaries) with 16 mg of chlorhexidine in one dose. While the most common representatives of chlorhexidine-containing medicines abroad are solutions with a concentration of 4% and 2%, as well as mouthwashes with a concentration of 0.12%. The highest share - 96% - among the procurements of chlorhexidine-containing medicines by state and municipal organizations is 0.05% aqueous solution for external use. Instructions for medical use of 0.05% aqueous chlorhexidine solution for external use contain indications that are not supported by international documents: WHO Model List of Essential Medicines and British National Formulary. Conclusions. The obtained results suggest probable cases of irrational use of chlorhexidine medicines in medical practice in Ukraine. The consequences of such cases are not limited to the failure to achieve therapeutic goals or to the development of nosocomial infection, but includes also the selection of chlorhexidine-resistant strains of microorganisms. Key words: chlorhexidine; assortment analysis; medicinal procurements study; suboptimal concentration; rational pharmacotherapy
Diseases of the respiratory system occupy an important place in the structure of morbidity in the population of Ukraine, being only second to diseases of the cardiovascular system in prevalence. Patients with a respiratory pathology make up a significant part of the pharmacy visitors. In most cases, at the first symptoms of such diseases, patients begin to be treated on their own with the help of non-prescription drugs, and quite often the first person they turn to is a pharmacist. A striking example of the effectiveness and safety of herbal medicine is the symptomatic treatment of cough as one of the most characteristic symptoms of the respiratory tract pathology. The use of herbal products with the antitussive, expectorant, mucolytic action has a long history, and currently it does not lose its significance. The clinical efficacy of herbal products is determined by the mechanism of their specific action, and the rational choice of the optimal drug taking into account the cause of the cough, its nature and the characteristics of the course of the inflammatory process in the respiratory organs, allows eliminating cough or effectively managing it. Bronchipret® is a herbal product of “Bionorica SE” company, which is one of the most studied and widely used in medical practice. The drug is indicated for the treatment of respiratory tract diseases accompanied by cough and sputum formation, including acute and chronic bronchitis. The main and well-studied pharmacological effects of Bronchipret® are secretolytic/mucolytic, anti-inflammatory, antiviral, antimicrobial and bronchospasmolytic ones. The pharmacological effects listed are due to a complex of biologically active substances (BAS) of such plants as the root of spring primrose, thyme herb, ivy leaf. All medicinal plants that make up the “active core” of the drug have a long history of their use in folk medicine. Moreover, their various beneficial effects on the human body in different diseases and conditions have been confirmed by empirical experience. The drug is produced in three dosage forms (drops, syrup, tablets), and it determines the targeting of its prescription to different categories of patients. The drug has a high evidence base and has been studied at the cellular and molecular levels. Conclusions. In the case of choosing a herbal medicine for responsible self-medication, drug consumers can rely on their own experience, but most of them trust the knowledge of a pharmaceutical professional, and this fact increases the pharmacist’s responsibility for the treatment prescribed. Therefore, it should be the choice of a drug with an optimal efficacy/safety ratio, which is determined from the standpoint of evidence-based medicine. It is precisely these requirements that the phytoneering drug Bronchipret® meets.
Providing the population of Ukraine with quality, effective and, at the same time, economically affordable medicines is a priority task of the healthcare system. Taking into account the relatively low cost of their development generic drugs are available to the majority of the country’s population; thus, bioequivalence studies are needed to obtain data on their efficacy and safety. Ukraine is currently in the process of harmonizing domestic regulatory requirements for generic drugs and conducting bioequivalence studies with global ones. Therefore, it is important to find out the differences in approaches to the registration of generics and studies of their bioequivalence in Ukraine and other countries. Another important aspect is to provide the policy of “transparency” of bioequivalence research results, which contributes to the use of better drugs. Aim. To analyze domestic and global approaches to the organization of the bioequivalence research and provide the policy of “transparency” of their results. Materials and methods. A comparative analysis of approaches to drug registration, requirements for generic drugs and bioequivalence studies and ways to provide the policy of “transparency” of their results in Ukraine, the United States and the European Union was conducted. Results. The analysis has revealed that the methods of registration of drugs in Ukraine, the United States and the EU are the same. Approaches to providing the “transparency” of the results of bioequivalence studies differ since in Ukraine the publication of such information is not mandatory and is at the discretion of pharmaceutical manufacturers. Conclusions. Domestic regulatory requirements for assessing generic drugs are harmonized with the world ones. Today, there is a need to introduce a mandatory requirement for the publication of bioequivalence studies, and it will contribute to providing an effective “transparency” policy.
