Veronika Nikolaevna Khaziakhmetova

Background . Irrational use and improper disposal of medicines contribute to pharmaceutical pollution of the environment, highlighting the need for objective quantitative methods to assess the volume of unused drugs in clinically meaningful units. Objective . To evaluate the applicability of the ATC/DDD pharmacoepidemiological methodology for the analysis of expired and unused medicines collected from the public for safe disposal. Methods . From November 2022 to April 2024, a separate collection programme for unused and expired medicines was conducted in Kazan, Russian Federation. All collected medicines were classified according to the WHO ATC system, and DDD (Defined Daily Dose) values were assigned based on the WHO ATC/DDD Index 2024. Comparative analysis was performed using DDDs and mass of active substance (mg). Results . A total of 4,737 medicine packs were collected, corresponding to 1,213 brand names and 707 INNs. The ATC/DDD analysis included 2,793 packs (299 INNs). The highest number of defined daily doses was found in group C (Cardiovascular system) — 11,377.34 DDDs, and group A (Alimentary tract and metabolism) — 11,263.31 DDDs. The top individual substances included cholecalciferol, cyanocobalamin, prednisolone, folic acid, acetylsalicylic acid, and atorvastatin. Mass-based assessment (mg) showed a different distribution and did not reflect the clinical relevance of unused medicines. Conclusion . This is the first study to apply ATC/DDD analysis for quantitative assessment of unused and expired medicines collected from the public. The approach enables standardized evaluation of pharmacotherapy withdrawn from use, identifies drug classes most commonly wasted, and may serve as an additional tool for monitoring the rationality of drug prescribing and pharmaceutical environmental risk.

This article presents the results of a safety study of oral anticoagulants in surgical patients with polypharmacy. An analysis of medical records of inpatients receiving oral anticoagulants for the prevention of venous thromboembolic complications was conducted. Postoperative venous thromboembolism is one of the most common indications for the use of direct oral anticoagulants. Serious problems may arise during treatment and may be associated with age-related changes in the body, gender, and concomitant drug therapy.

The relevance of studying pharmacotherapy in the elderly is due to the global aging of the population and the associated medical challenges. Elderly people suffer from multiple chronic diseases (polymorbidity), which inevitably leads to the simultaneous use of multiple drugs (polypharmacy). More than 90% of people over 65 regularly take medications, and more than half take 5 or more at a time. Age-related changes in the body (decreased liver and kidney function, changes in body composition, sensitivity of the central nervous system and cardiovascular system) radically change the pharmacokinetics and pharmacodynamics of drugs, increasing the risk of their accumulation and toxicity. The combination of polymorbidity, polypharmacy, and altered drug response creates a high risk of dangerous drug interactions (up to 87% when taking 6+ drugs), frequent and severe adverse reactions (causing 10-17% of hospitalizations), and iatrogenesis. Additional complications include a limited evidence base for this group and a significant economic burden of complications. The employment of special tools (STOPP/START criteria) to optimize therapy and prevent irrational prescriptions is a prerequisite for ensuring safe and effective treatment of the elderly.

The widespread use of drugs during pregnancy has become an inevitable reality due to the deterioration of the health of women of reproductive age and the increase in the number of late births. However, the use of drugs during this period is associated with serious risks to the fetus. About 5% of congenital anomalies are associated with taking medications, which is explained by the difficulty of predicting their teratogenic effect based on research. Medicines pose the greatest danger during critical periods of pregnancy. In the first weeks after conception, they can lead to the death of the embryo, during the period of organogenesis (3-8 weeks) they can cause severe developmental defects, and in the later stages – disrupt labor and adaptation of the newborn. Particular caution should be exercised when prescribing antibiotics (tetracyclines cause dental hypoplasia, aminoglycosides – ototoxicity), NSAIDs (risk of premature closure of the arterial duct), antihypertensives (absolute contraindication for ACE inhibitors and ARBs), and hormonal drugs (estrogens and progestins in the first trimester provoke developmental abnormalities).

Pharmacotherapy in neonates and nursing mothers faces unique risks due to the physiological immaturity of the child's body. In infants, delayed drug clearance due to underdevelopment of cytochrome P450 enzymes and renal function can lead to accumulation of toxins even at standard dosages. For nursing mothers, the problem is aggravated by the fact that about 80% of drugs penetrate into breast milk, creating a risk of dysbiosis, allergies, other adverse reactions, and long-term developmental disorders in the baby. Peculiarities of pharmacokinetics in newborns aggravate the risks. Metabolism and excretion are also critically different: glucuronidation deficiency provokes chloramphenicol toxicity, and low glomerular filtration increases the half-life of furosemide by 8 times. Dosage errors increase hospitalization by 30%, and treatment of complications in premature babies can reach 5 million rubles per case. All this dictates the need to develop age-oriented protocols, take into account transplacental transfer of drugs, carry out strict monitoring during lactation, and create specialized dosage forms to protect the most vulnerable groups of patients.

The article is devoted to the problem of safety of anticoagulant use in patients with burn injury against the background of polypharmacy. A retrospective analysis of 100 medical records of inpatients in the burn department who received anticoagulants for the prevention of venous thromboembolic complications (VTEC) was conducted for the period from 2022 to 2023, in order to study the safety of using anticoagulants in burn department patients with polypharmacy. According to the analyzed data, in patients taking anticoagulants in prophylactic doses and receiving more than 3 drugs simultaneously, in addition to changes in some clinical and laboratory parameters and coagulogram parameters (a significant increase in the number of blood leukocytes by 18 % (p ≤ 0.002), alanine aminotransferase (ALT) by 61 % (p ≤ 0.0001), aspartate aminotransferase (AST) by 32 % (p ≤ 0.0001), international normalized ratio (INR) by 11 % (p ≤ 0.02), activated partial thromboplastintime (APTT) by 7 % (p ≤ 0.0001), there is an increase in the length of the patient's hospital stay by 7 days (by 85 %, p ≤ 0.00003), compared with those who received less than 3 drugs.

Cerebral edema is one of the most severe complications of various central nervous system (CNS) diseases, significantly affecting treatment outcomes. The use of glucocorticoids (GCs) in cerebral edema remains controversial despite their long history of application. We conducted a systematic analysis of 18 clinical guidelines (Russian and international) and 7 studies from PubMed (out of 33 identified). Significant heterogeneity in the evidence base for GCs use in cerebral edema of various etiologies was revealed. In traumatic brain injury, guidelines unanimously advise against GCs administration. For brain abscesses, GCs are recommended in cases of pronounced mass effect, despite contradictory meta-analysis results. In CNS tumors, GCs are indicated for symptomatic management of peritumoral edema, using minimally effective doses. GCs use is not recommended for hemorrhagic and ischemic strokes. The greatest variability in recommendations, with a substantial lack of evidence, is observed in infectious diseases. The efficacy of GCs varies significantly depending on the etiology of cerebral edema. A notable deficiency of high-quality randomized controlled trials (RCTs) with sufficient statistical power was identified, highlighting the need for standardized approaches to evaluate GCs use in different types of cerebral edema, considering individual patient characteristic.

Objective: to conduct a pharmacoeconomic evaluation of the rationality of prescribing medications and to analyze the frequency of prescribing potentially inappropriate medications to patients over 65 years old using the example of additional preferential drug provision.Material and methods. The analysis was based on registers of medications dispensed within the framework of additional drug provision over 2019–2021 period. We conducted an integrated study combining ABC/VEN analysis and the Beers criteria to assess the rationality of pharmacotherapy.Results. The analysis of the cost structure for medicines showed a positive trend in the distribution of categories V, E, N (vital, essential, nonessential) in A, B, C groups. In 2019, 13.7% of the budget was spent on the procurements of drugs of N category; in 2020, this indicator was 10.6%; and in 2021, the costs for the procurements of drugs of N category decreased to 2.6%. Expenditures for drugs in V and E categories increased from 86.3% to 97.4%. The prevalence of polypragmasy (prescription frequency of 5 or more drugs with different international nonproprietary names per patient for month) among patients over 65 years old reached 11% in 2019, 13% in 2020, and 1% in 2021. According to the Beers criteria, patients over 65 years old were prescribed potentially inappropriate drugs according to the Beers criteria in 12.03% of cases in 2019, in 10.84% of cases in 2020, and in 9.7% of cases in 2021.Conclusion. Due to comprehensive ABC/VEN analysis and the Beers criteria tool it was possible to evaluate the rationality of expenditures on additional drug provision over the period from 2019 to 2021, as well as the rationality of prescribing medications to patients over 65 years old. The use of Beers criteria enables to optimize pharmacotherapy in elderly patients.

The article discusses the process of management and control in matters of ensuring medication safety at the Republican Clinical Hospital of the Ministry of Health of the Republic of Tatarstan. Registration of adverse drug reactions is a mandatory measure for monitoring the safety of pharmacotherapy.

Relevance. Drug pollution of the environment is a global environmental problem of our time. Increased consumption of medicines directly affects the level of pollution of various ecosystems, including water resources. The insufficient efficiency of existing methods for treating wastewater from drugs leads to drug pollution of water bodies and requires studying the effect of ultra-low doses of drugs on the human body and animals. A non-steroidal antiinflammatory drug, diclofenac, was detected in surface water samples in Kazan at a concentration of 1×10−9 M.The purpose of this study is to study the presence of specific pharmacological effects of diclofenac detected in water samples in ultra-low doses in experimental models of pathological processes.Methods. The experiment used 21 male white laboratory mice, which were divided into three groups (each with 7 mice). For 4 days, mice were intragastrically injected with distilled water (control group), diclofenac solution 1×10−6 M (experimental group No. 1), diclofenac solution 1×10−9 M (experimental group No. 2). On the fifth day of the experiment, inflammation was induced by injecting carrageenan lambda (1 %, Sigma) subplantarly into the right hind paw in a volume of 0.05 ml. The amount of edema was determined using an IITC Life Science plethysmometer (USA).The results of an experimental study of the specific pharmacological activity of diclofenac showed that diclofenac in ultra-low doses of 0.32×10−3 mg per 100.0 g of weight is able to reduce the severity of acute inflammation caused by subplantar injection of carrageenan and to cause NSAID-associated gastropathy in mice.Conclusion. The obtained data likely indicate a potential risk of adverse effects from drug contamination of the environment with diclofenac, even in ultra-low concentrations.