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Functional dizziness (FD) is the most common form of chronic dizziness, accounting for up to 20% of all cases of chronic dizziness and is diagnosed in 40% of patients referred to specialized clinics. This article discusses the pathogenesis, clinical manifestations and diagnostic features of FD. An overview of standard and new methods of drug therapy and methods of vestibular rehabilitation for patients with FD is provided. Experts conclude that FD, currently defined as persistent postural perceptual dizziness (PPPD), is the most common cause of chronic non-rotational dizziness. PPPD is thought to be multifactorial; central and peripheral vestibular disorders, anxiety disorders and traumatic brain injury are noted as possible precipitating causes. The diagnosis of PPPD is based on the presence of a feeling of unsteadiness or non-rotational dizziness occurring more than half of the days over a period of three months or longer, when other possible causes of dizziness have been ruled out. When managing a patient with PPPD, it is necessary to inform the patient about the nature of the disease, provide a patient with an education program and apply psychotherapy and vestibular rehabilitation methods. The use of buspirone prolonged-release tablets (Vespirate®) and vestibular rehabilitation in clinical practice is discussed.

The issues of diagnosis and treatment of hypertension (HTN), as well as the prevention of its complications, are an urgent problem in cardiology. On June 21, 2023, the Journal of Hypertension published guidelines on HTN from the European Society of Hypertension (ESH), which were first presented to the public at the annual European Hypertension Meetings on June 24, 2023 in Milan. This publication describes the highlights and key updates of the guidelines and outlines its clinical significance. Russian experts also discussed current problems of pathogenesis, diagnosis and treatment of HTN.

Scientific relevance. Being the main class of medicinal products for dyslipidaemia treatment, statins are widely used in clinical practice in various patient populations. However, statins can cause statin-associated muscle symptoms (SAMS), which are the most frequent and, in some cases, even life-threatening adverse reactions associated with these medicinal products.Aim. The study aimed to perform a systematic review of the epidemiology, classification, and physiological pathogenesis of SAMS, risk factors for this complication, and clinical guidelines for primary care physicians regarding the identification and treatment of patients with SAMS.Discussion. SAMS is an umbrella term that covers various forms of myopathies associated with satin therapy. According to the published literature, the prevalence of SAMS varies considerably and may depend on the study design, inclusion criteria, and the medicinal product used. SAMS has multiple putative pathogenic pathways that include genetically determined processes, abnormalities in mitochondrial function, defects in intracellular signalling and metabolic pathways, and immune-mediated reactions. The main known risk factors for developing SAMS include high-dose statins, drug–drug interactions, genetic polymorphisms, female sex, older age, Asian race, history of kidney, liver, and muscle disease, and strenuous physical activity. Given the lack of universally recognised algorithms for diagnosing SAMS, clinicians should consider the clinical presentation and the temporal relationship between statin therapy and symptoms. Other factors to consider include changes in muscle-specific enzyme levels and, in some cases, the results of blood tests for antibodies to 3-hydroxy-3-methyl-glutaryl-coenzyme A reductase.Conclusions. To ensure the safety of statin therapy, it is essential to raise clinicians’ awareness of the risk factors for SAMS, indicative clinical and laboratory findings, and the need for dynamic patient monitoring, including the involvement of clinical pharmacologists.

Objective: to evaluate the pharmacokinetic parameters, safety and tolerability of Vespireit® (INN buspirone), prolonged-release tablets, 15 mg (JSC “Valenta Pharm”, Russia), which is being developed as a drug for the treatment of functional vertigo, in healthy volunteers with a single oral dose of 15 and 30 mg on an empty stomach or after meals and multiple doses in a daily dose of 15 mg.Material and methods. JSC “Valenta Pharm” conducted an open-label, three-stage, randomized, two-periods, cross-over comparative clinical trial of Vespireit®. At stages 1 and 2, healthy volunteers were screened and randomized into two equal groups (Group 1 and Group 2), as well as the distribution of participants in Group 3. Then, at stage 1, healthy volunteers (n=24) took Vespireit® once at a dose of 15 mg on an empty stomach or after meals, at stage 2, volunteers (n=24) took Vespireit® once at a dose of 30 mg on an empty stomach or after meals. Stage 3 was conducted in 18 volunteers as a non-randomized, non-comparative study with Vespireit® 15 mg on an empty stomach once daily for 5 days. During the study, blood samples were collected from each subject to determine the concentration of test compounds in blood plasma and subsequently calculate their pharmacokinetic parameters. Quantitative determination of buspirone and its two metabolites, 6-hydroxybuspirone (6OH-bus) and 1-(2-pyrimidinyl)-piperazine (1-PP), was performed by a validated high-performance liquid chromatography method with tandem mass spectrometric detection. During the study, tolerability and safety were also evaluated: adverse events, vital signs, laboratory parameters and electrocardiogram parameters were recorded.Results. When the study drug Vespireit®, prolonged-release tablets, was administered once at a dose of 15 mg to healthy volunteers after a meal, an increase in the relative bioavailability and relative degree of absorption of buspirone was observed compared with the fasting state, which was accompanied by a 1.5- and 2.5-fold increase in the AUC0–t and Cmax of buspirone, respectively. In addition, the Cmax of 6-OH-bus increased 1.4-fold and the Cmax of 1-PP increased 1.2-fold. Meal had no effect on the AUC0–t of 6-OH-bus and 1-PP. When the study drug was administered once at a dose of 30 mg after a meal, an increase in the relative bioavailability and relative degree of absorption of buspirone was observed compared with fasting, which was accompanied by an increase in the AUC0–t and Cmax by 1.5- and 2.1-fold, respectively. A 1.2-fold increase in the Cmax of 6-OH-bus was also observed. Food had no effect on the AUC0–t of 6-OH-bus and on the AUC0–t and Cmax of 1-PP. No accumulation of buspirone and its metabolites was observed with repeated dosing.Conclusion. In the study, the values of pharmacokinetic parameters of the new drug Vespireit® in the prolonged-release tablets dosage form were determined both with single administration on an empty stomach and after meals and with multiple administration. The differences and advantages over buspirone preparations in the form of immediate-release tablets are shown: higher relative bioavailability of buspirone with a reduction in interindividual differences in bioavailability and Cmax, more stable plasma concentration of buspirone with reduced peak values of the active substance and metabolite 1-PP, a 1.2-fold increase in AUC0–∞, a 2-fold increase in T1/2, and a 2-fold increase in the degree of retardation (MRT) for buspirone, a 1.4-fold increase in Cmax and MRT of 6-OH-bus, a decrease in AUC0–∞, AUC0–t, and T1/2 of metabolite 1-PP, and a decrease in the ratio of the concentration of 1-PP to the concentration of buspirone and to 6-OH-bus. A favorable safety profile of Vespireit® was demonstrated.

An important role in the development and evolution of hypertension in females is applied to sex hormones. Estrogen deficiency and hyperandrogenism, characteristic of periand postmenopause, are links in the pathogenesis of hypertension in this period of a woman's life and are accompanied by an increase in sympathetic nervous system activity, renin-angiotensin-aldosterone system activation, salt sensitivity, abdominal obesity and metabolic syndrome, left ventricle hypertrophy, left atrial dilatation with a high risk of atrial fibrillation, stroke and heart failure development. The paper discusses antihypertensive therapy during periand postmenopause, effectiveness and tolerability of different drug classes. Special attention is paid to the mechanism of action of selective I1-imidazoline receptor agonist moxonidine, which in women during this period both effectively reduces high blood pressure and has a beneficial metabolic effect, what is documents in studies of monotherapy, combined antihypertensive therapy with major classes and in combination with menopausal hormone therapy. The paper presents the joint expert opinion concerning above mentioned issues.

Intracranial hemorrhage (ICH) is characterized by a high level of disability and mortality. One of the most important reasons that lead to an increased risk and an increase in the ICH prevalence are antithrombotic drugs: anticoagulant, antiplatelet and thrombolytic. The main risk factors for ICH are advanced age, arterial hypertension, and the use of antithrombotic drugs of different groups. Treatment of ICH while taking drugs affecting hemostasis, is an extremely difficult task and there is not enough sufficiently convincing recommendations and evidence. The decision to resume therapy with the drug, that led to the development of ICH, and the timing of this resumption, is also not a completely clear problem that requires a balance between ischemic and hemorrhagic complications. The most important aspect of prevention is strict adherence to current recommendations regarding combinations of antithrombotic drugs and protocols for thrombolytic therapy, which will minimize the risks of ICH.

Intracerebral hemorrhage (ICH), which is a form of hemorrhagic stroke, is an extremely serious disease. This pathology is characterized by very high levels of disability and mortality. Despite the improvement in the treatment of those diseases that can lead to ICH, its frequency is currently increasing, which is largely due to the use of drugs, in which case the term «drug-induced intracerebral hemorrhage» (DI ICH) is used. One of the main reasons for drug-induced ICH is an increase in the frequency of prescribing anticoagulant therapy for the prevention of ischemic stroke in atrial fibrillation, as well as dual antithrombotic therapy. In addition to anticoagulants, thrombolytic drugs can lead to the development of this pathology. According to the literature, an increase in the risk of developing ICH is also associated with therapy with antidepressants from the group of selective serotonin reuptake inhibitors, as well as high doses of statins. Risk factors for this adverse reaction are age, smoking, hypertension, and thrombocytopenia. Treatment of DI ICH is an extremely difficult task and includes the withdrawal of the culprit medication, antihypertensive therapy, correction of intracranial hypertension, and, in some cases, the administration of antidotes. The main method of prevention is the use of antiplatelet drugs and other drugs, the use of which is associated with an increased risk of developing DI ICH, in strict accordance with modern protocols and recommendations.

Мочевая кислота (МК) — это конечный продукт пуринового обмена, являющийся основной составляющей клеточных запасов энергии, таких как аденозинтрифосфат (АТФ), а также компонентом дезоксирибонуклеиновой (ДНК) и рибонуклеиновой (РНК) кислот. На сегодняшний день в Российской Федерации нормальным показателем МК в сыворотке крови считается 40 кг/м2 , по сравнению с пациентами с ИМТ

Atrial fibrillation (AF) is the main cause of cardioembolic ischemic stroke (IS), it occurs in 25–35% of patients with IS, and its presence increases the risk of recurrent stroke compared with patients with sinus rhythm. The main method of preventing recurrent IS in AF is the administration of oral anticoagulants (OACs); in non-valvular AF, direct OACs (DOACs) have an advantage. Meta-analysis of randomized clinical trials showed a 19% greater reduction of stroke and systemic embolism risk in the DOACs group compared to warfarin (p

Pulmonary arterial hypertension is a condition characterized by an increase in mean pressure in the pulmonary artery. This pathology is associated with high mortality, and specific therapy for pulmonary arterial hypertension does not affect the cause of the disease and is extremely expensive. In this regard, it is especially important to study the modifiable etiological factors of pulmonary arterial hypertension. One such factor is drugs. One of the leading groups of drugs-inductors is anorexigenic drugs. It was the representatives of this group, such as aminorex, who were the first inducers of pulmonary hypertension. Moreover, this adverse reaction was so significant that it led to the withdrawal of these drugs. Currently, the leading role in the context of drug-induced pulmonary hypertension is played by such drugs as anticancer, antiviral drugs, and interferons. These drugs lead to pulmonary hypertension through various pathophysiological mechanisms. The leading measures to prevent this pathology are to limit the use of culprit medications, reduce the spread of HIV infection, since several groups of drugs can be used to treat HIV-infected patients, leading to the development of pulmonary hypertension.

An increase in the life expectancy of the population and the number of polymorbid patients with a combination of two or more diseases in different age categories, including among young people, has led to a significant increase in the cost of medical care in the field of public health. The transition from original drugs to generic ones has become a common measure to contain these costs. While this is an important goal for healthcare systems around the world, the impact of this practice on patient outcomes needs to be carefully considered. In some cases, generics may represent a suitable alternative to branded products, but this is not always the case. In particular, studies have shown that changing the drug can negatively affect not only patients' adherence to treatment, but also clinical outcomes, and a subsequent increase in the total cost of treatment, therefore, the use of generics in clinical practice still causes caution and concerns on the part of both the doctor and the patient. Due to the high prevalence of dyslipidemia and hypercholesterolemia both worldwide and in Russia, in this review the problem of choosing an original drug or generic is described by the example of such a hypolipidemic agent as rosuvastatin. According to numerous studies, rosuvastatin is one of the most potent and widely prescribed statins. Considering that most of the clinically significant effects of this drug are demonstrated in relation to its original form, the review emphasizes the importance of prescribing the original drug rosuvastatin in routine clinical practice.

Drug-induced tremor (DIT) is a term used to describe tremors that develop or increase in severity due to various medications administration. As multiple drugs are associated with DIT it is quite common in clinical practice and medication dose is frequently associated with tremor severity. DIT is associated with commonly prescribed drugs such as amiodarone, antidepressants, β-agonists, cyclosporine, lithium, tacrolimus and valproic acid. DIT mechanisms include dopamine receptors block, gamma-aminobutyric acid depletion, cholinergic deficiency. DIT risk factors include older age, female sex, longer administration of drugs associated with tremor or/and their administration in higher doses, history of tremor in the patient and/or relatives, excessive caffeine intake. It is necessary to establish a causal relationship between the use of a potential inducer drug and the development/intensification of tremor to diagnose DIT. If DIT is detected, the inducer drug should be discontinued or its dose reduced. To decrease DIT risk, it is recommended to avoid prescribing drugs which are most commonly associated with DIT.

The use of medicines may in some cases be associated with the development of drug-induced diseases (DIDs) аnd other adverse drug reactions (ADRs), which leads to an increase in morbidity/mortality rates, and/or symptoms forcing a patient to seek medical attention or resulting in hospitalisation. ADRs may develop due to changes in a patient’s genotype, which entail an inadequate pharmacological response. The aim of the study was to analyse and summarise literature data on genetic risk factors that cause DIDs аnd other ADRs. It was shown that the polymorphism of genes encoding enzymes of drug metabolism (CYP, UGT, NAT, TPMT, EPHX, GST, etc.) or carriers (transporters) of drugs (P-gp, BCRP, MRP, OATP, OCT, etc.) can change the pharmacokinetics of drugs, affecting their activity. Polymorphism of RYR1, CACNA1S, MT-RNR1, VKORC1, and other genes encoding receptors targeted by drugs, and human leukocyte antigen (HLA) gene, may affect drug pharmacodynamics by modifying drug targets or changing the sensitivity of biological pathways to pharmacological effects of medicines. Changes in drug pharmacokinetics and pharmacodynamics may cause DIDs аnd other ADRs. The use of pharmacogenetic tests will allow a personalised approach to patients’ treatment and prevention or timely detection of potential ADRs during therapy. Before prescribing some medicines, clinicians should use recommendations on their dosing based on pharmacogenetic tests, which are posted on the official websites of Pharmacogenomics Research Network (PGRN), Pharmacogenomics Knowledgebase (PharmGKB), and Clinical Pharmacogenetics Implementation Consortium (CPIC). The results of ongoing clinical studies on the effect of gene polymorphism on drug safety will soon allow for higher personalisation of the choice of pharmacotherapy and prevention of many ADRs, including DIDs.

Drug administration, can be potentially associated with adverse drug reactions (ARDs), including serious ones, contributing to an increase in the risk of death or the development of conditions that potentially increase mortality and / or morbidity and / or become the cause of clinical manifestations, requiring the patient to seek medical attention or hospitalization - so called drug-induced diseases (DID). Some pathological conditions, like chronic heart failure (CHF), are potential risk factors for DID due to changes in the pharmacokinetics and pharmacodynamics of drugs. For example, after oral administration of fosinopril, the average T1/2 value in patients with CHF II - III NYHA functional class was 14.2 (±7.3) hours, and in healthy individuals of the control group - 11.0 (±5.2) hours. Values of AUC per os and Cmax were also slightly higher in patients with heart failure (HF) than in healthy individuals, and Cl per os, on the contrary, were lower. After intravenous administration of fosinopril, similar results were observed. Another example is the altered absorption of furosemide in patients with decompensated heart failure. Thus, in patients with heart failure, as the edema syndrome is corrected, the time to the onset of the maximum drug concentration in the blood serum (Tmax ) decreases by 27 % and Cmax increases by 29 %, which may indicate a decrease in the slowdown in the absorption rate (by 57 %). Since furosemide is mainly excreted in the urine unchanged, the observed changes in Cmax and Tmax could be associated with delayed gastric emptying, decreased intestinal motility, or edema of the intestinal wall. Individual selection of the dose and dosing regimen, taking into account the characteristics of the pharmacokinetics of drugs in patients with CHF, will help improve the quality of life and prevent potential ADR.

The use of many drugs is associated with the risk of adverse drug reactions (ADRs), including those that increase mortality and / or morbidity and / or seek medical help or hospitalization, so called «drug-induced diseases» (DID). There is a number of factors that increase the risk of DID (risk factors) including comorbid diseases (for example, chronic kidney disease, hepatic impairment, obesity etc.). These pathologic conditions induce changes in pharmacokinetics (PK) and pharmacodynamics of drugs, thereby increasing the risk of ADRs. One of these diseases is heart failure (HF). Most studies of PK changes were conducted among patients with LVEF from 40 to 45 %, and excluded patients with concomitant diseases that could affect the PK of drugs (for example, serious liver and / or kidney diseases), therefore in polymorbid patients, trial findings may not be applicable. HF may be associated with a decrease in bioavailability, a decrease in volume of distribution, a change in the activity of cytochrome P450 isoenzymes, etc. Individual dose and dosage regimen adjustment can significantly reduce risks, improve the quality of medical care and improve the prognosis in patients with heart failure.

Among drug-induced liver injuries (DILI), the cholestatic type is second in frequency (from 20 to 40%), the most common is the hepatocellular variant (up to 78%). For this reason, practitioners of various specialties, including neurologists and psychiatrists, do not monitor cholestasis parameters, and drug-induced liver injury with cholestasis (DILIС) remains unrecognized. The urgency of this problem is great, because the frequency of deaths in DILIС is only slightly lower than t in the hepatocellular type; in addition, it DILIС is much more likely to become persistent increasing the risk of chronic liver injury.Among the drugs used in neurology and psychiatry, the “leaders” in terms of the number of DILIС are antidepressants, both tricyclic (amitriptyline, imipramine) and selective serotonin reuptake inhibitors (SSRIs: paroxetine, sertraline, fluoxetine, citalopram, escitalopram), antidepressants), antipsychotics (chlorpromazine, fluphenazine), anticonvulsants (mainly carbamazepine).If the patient has a history of DILI caused by any of the forementioned medications, the agent should be switched to another drug from the same group with a minimal risk of DILI. If there is a history of DILI associated with antidepressants, it is recommended to choose SSRIs. It is necessary to monitor not only the activity of transaminases and bilirubin, but also the cholestasis parameters (alkaline phosphatase, γ-glutamyl transpeptidase) during treatment.

Any drug is potentially associated with the risk of adverse drug reactions (ADRs), the incidence of which in developed and developing countries is estimated at 6.3 (3.3—11.0) and 5.5 % (1.1—16.9), respectively. Many ADRs increase mortality and / or morbidity and / or cause clinical manifestations that require a patient to seek medical help or hospitalization; a special term has been introduced — drug-induced diseases. Food can interact with drugs and increase the risk of ADRs, including serious ones. The simultaneous intake of food and drugs can affect the bioavailability, pharmacokinetics, pharmacodynamics and therapeutic efficacy of drugs due to changes in drug absorption and metabolism. A striking example of the effect of food on the pharmacokinetic profile of drugs is the change in the bioavailability of the tyrosine kinase inhibitor lapatinib: compared with taking on an empty stomach, the bioavailability of lapatinib in a single dose of 1 500 mg after taking it together with high-calorie standard food increases by an average of 325 % — 4.25 times. In other words, the concentration of the drug in the blood serum after taking one tablet at the same time with food is comparable to taking 4 tablets on an empty stomach. Currently, there are no recommendations for choosing a dosage regimen for drugs depending on the qualitative and quantitative composition of food, as well as taking into account potential interactions with food components, although these recommendations are extremely necessary for patients and healthcare professionals. In this regard, this article summarizes the data available at the time of writing in open sources concerning the effect of food on the absorption and metabolism of drugs, and also describes the possible mechanisms of interaction.

Drug-induced parkinsonism (DIP) is the most common drug-induced movement disorder and is most commonly associated with antipsychotic drugs, monoamine reuptake inhibitors, and calcium channel blockers. DIP manifests as a typical movement disorder, which makes it practically indistinguishable from idiopathic Parkinson's disease (PD) and requires differential diagnosis. DIP symptoms develop fairly quickly (hours to weeks) after the antipsychotic is started or after the dose is increased. Therefore, DIP is predominantly a clinical diagnosis that must be kept in mind when a patient develops typical symptoms during treatment onset or increasing the dose of drugs that most often lead to such an adverse reaction (ADR). DIP evaluation includes using the Naranjo algorithm, which helps assess a causal relationship between drug intake and the development of parkinsonism symptoms. The primary DIP treatment is the reduction of the dose of the inducer drug, or its cancellation, or replacement with another drug. In patients with schizophrenia and antipsychotic-induced DIP, dose reduction, replacement with another medication, or prescription of a drug with anticholinergic activity may be possible. The awareness of the doctor and the patient about the possibility of developing this ADR is crucial in the prevention of DIP. Therefore, choosing a drug with the lowest risk of developing DIP is necessary for pharmacotherapy.

Drug-induced parkinsonism (DIP) is one of the most frequent extrapyramidal disorders that develops against the background of prescribing a large number of medications. Initially, DIP was described as an adverse drug reactions (ADRs) against the background of the use of antipsychotic drugs, but later recognized as ADRs of a number of other drugs, including prokinetics, antidepressants, calcium channel blockers and antiepileptic drugs. The relative risk of developing LIP on the background of taking typical antipsychotics increased by 2.92 times compared to patients who do not take these drugs. The risk of developing DIP in patients receiving flunarizine is increased by 2.75-4.07 times. The risk of DIP with the use of antidepressants is increased by 2.14 times, among the drugs of this group with an increased risk of DIP, the use of selective serotonin reuptake inhibitors is most often associated with DIP (relative risk 1.24). Among other antidepressants, there is evidence of the development of DIP against the background of the use of duloxetine, mirtazapine, amitriptyll clomipramine, venlafaxine, trazodone. Among anticonvulsants, DIP can rarely develop against the background of the appointment of valproic acid, gabapentin, pregabalin, carbamazepine, oxcarbazepine. The risk of DIP in patients receiving metoclopramide is extremely low (0.06%), but it is 2.16 times higher compared to people who do not take this drug. Among drugs from other groups, DIP can occur against the background of the use of lithium carbonate, tacrolimus, cyclosporine, amiodarone, captopril, amphotericin B. If DIP develops, it is necessary, if possible, to reduce the dose or cancel the inducer drug, or replace it with another drug with minimal risk of DIP. Symptoms of DIP most often regress within a few weeks or months after dose reduction or withdrawal of the drug inducer. If the symptoms persist longer, it is necessary to exclude the presence of Parkinson’s disease or dementia with with Lewy bodies.

Drug-induced nephrotoxicity is the third most common cause of acute kidney injury (AKI). The aim of the study was to analyse and summarise data on the factors and mechanisms responsible for increased risk of drug-induced AKI, to analyse potential methods of its prevention and treatment. At present, the following phenotypes of drug-induced AKI are distinguished: acute vascular disease, acute glomerular disease, acute tubular injury / necrosis, and acute interstitial nephritis. It was discovered that most often these complications occur following the use of antimicrobial drugs, renin-angiotensin-aldosterone system inhibitors, non-steroidal anti-inflammatory drugs, and anticancer drugs, including targeted therapy. Risk factors for drug-induced AKI include age >65, female gender, low body weight, pre-existing chronic kidney disease, hypovolemia, hypoalbuminemia, acute and chronic heart failure, diabetes, malignancies, liver cirrhosis, prolonged use of nephrotoxic drugs, and simultaneous use of two or more nephrotoxic drugs. Discontinuation of the drug which resulted in kidney failure is the first and foremost principle for managing not only drug-induced, but all AKI patients. The use of potentially nephrotoxic drugs should be avoided, especially in high-risk patients, in order to prevent drug-induced AKI. If a patient needs a drug that affects renal hemodynamics, the therapy should begin with a minimum effective dose, and combinations of two and more nephrotoxic drugs should be avoided. Close monitoring of kidney function is crucial for high-risk patients. They should also be informed about the importance of adequate water consumption schedule for prevention of hypovolemia.

The new coronavirus infection COVID-19 from the moment of the first message to the present has spread rapidly in more than two hundred countries around the world, posing a serious threat to the life and health of the population. Most patients who have recovered from COVID-19 continue to complain of shortness of breath, increased fatigue, chest pain, palpitations and other symptoms. Currently, the presence of symptoms 12 weeks after the acute phase of the new coronavirus infection COVID-19 is collectively referred to as post-covid syndrome. Studies have shown that this syndrome occurs frequently in recovered patients with COVID-19, regardless of their age and severity of the disease. This feature significantly distinguishes post-covid syndrome from other syndromes after an infection, and therefore the study of the mechanisms of its development, methods of diagnosis and treatment is an important public health problem. Particular attention is paid to patients with comorbidities, especially those with hypertension and cardiovascular diseases, since they have a more severe outcome after infection and higher case mortality rate. The current drug regimens for patients with post-covid syndrome and concomitant diseases are symptomatic. The most common manifestations of post-covid syndrome from the cardiovascular system are an increase in blood pressure and heart rate. In this regard, this review discusses the prospects for the use of a fixed combination of bisoprolol and amlodipine in the treatment of patients with post-covid syndrome, accompanied by an increase in blood pressure and heart rate.

Hypocalcemia (HCa) is one of the main water-electrolyte disturbances in clinical practice. An acute decrease in serum calcium levels can lead to seizures, ventricular arrhythmias, bronchospasm and laryngospasm. Chronic HCa can result in disorientation and confusion. To prevent these complications, the risk factors for low calcium levels must be carefully evaluated. One of these factors is drugs, in which case we are talking about drug-induced (DI) HCa. The list of drugs-inducers of DI HCa is quite extensive, but the leading role in this disorder is played by drugs for the treatment of osteoporosis, antineoplastic and antiepileptic drugs, as well as drugs for anti-tuberculosis therapy. When taking zoledronic acid, DI HCa is observed with a frequency of up to 39%. When taking imatinib, a targeted anticancer drug, a decrease in calcium levels was observed in 40% of cases. The pathophysiological mechanisms of DI HCa can be a decrease in bone resorption, a decrease in the concentration of vitamin D, inhibition of the action of parathyroid hormone and impaired calcium absorption. Risk factors in most cases of DI HCa are vitamin D deficiency and hypomagnesemia. An acute decrease in calcium levels leads to symptoms of neuromuscular excitability, abnormalities on the electrocardiogram (ECG) and electroencephalogram (EEG). The basis for the treatment of DI HCa is the drug withdrawal and the appointment of calcium. It is also necessary to prescribe vitamin D. The main methods of prevention of DI HCa are to determine the level of calcium and vitamin D before starting therapy with culprit medication, and to correct its level. It is also important to prescribe additional amounts of calcium and vitamin D during therapy with such drugs. Awareness of the attending physicians about the problem of DI HCa, a thorough assessment of its risk factors and the prophylactic administration of calcium and vitamin D preparations will help to effectively prevent those serious complications resulting from a decrease in calcium levels in clinical practice.

The article analyzes 49 publications on adverse drug reactions occurring during therapy with antitumor drugs. It presents data on pneumotoxicity and its clinical manifestations for such anticancer drugs as bleomycin, busulfan, cyclophosphamide, chlorambucil, methotrexate, nitrosourea derivatives, and taxanes, while the mechanisms of lung injury are not entirely clear and require further research. The prevention of drug-induced lung injury requires raising awareness among practicing physicians of different specialties, primarily general practitioners, rheumatologists, clinical immunologists, pulmonologists, phthisiologists, and oncologists due to non-specific manifestations of drug-induced lung injury and the use of antitumor drugs for other diseases apart from cancer.

Cardiovascular diseases (CVD) are the leading cause of death among adults worldwide, including in the Russian Federation. At the same time, the leading position in the structure of causes of death from CVD is occupied by coronary heart disease (CHD) (16% of the total number of deaths in the world per year). The new clinical guidelines of the Ministry of Health of the Russian Federation for the management of patients with stable coronary heart disease in 2020 identify two main goals of conservative therapy – the elimination of symptoms of the disease and the prevention of cardiovascular complications (CVD). In this connection, when choosing antianginal therapy in patients with stable angina, it is necessary to consider the possibility of using combinations of both first-line and second-line drugs in order to really improve the effectiveness of treatment and achieve the goals set. It is advisable and justified to use more widely 2-line drugs, in particular trimetazidine, at any stage of therapy to enhance the antianginal effectiveness of b-blockers, calcium antagonists and prolonged-acting nitrates, especially in patients with hemodynamic features (arterial hypotension, rhythm and conduction disorders), which is demonstrated in the given clinical example. The effective addition of tremetazidine to the arsenal of traditional antianginal drugs is legislated in practice and is reflected in the new clinical recommendations of the Ministry of Health of the Russian Federation in 2020. The accumulated experience of using trimetazidine allows a pathogenetically sound approach to the treatment of stable CHD, restoring the balance between the need and delivery of oxygen to the heart muscle, and the safety profile expands the possibilities of use in patients with comorbid pathology.

Stroke is an acute disturbance of the blood supply to the brain, characterized by the sudden onset of focal neurological symptoms, which persists for more than 24 hours or leads to the death of the patient in a shorter period of time due to cerebrovascular pathology. In the world and in Russia, stroke remains one of the leading causes of death and disability. At the same time, ischemic stroke (IS) is more common – about 80% of cases. Many classes of drugs, such as oral contraceptives, nonsteroidal anti-inflammatory drugs, and various psychoactive substances, can contribute to the development of drug-induced IS (DI IS). Data upon the frequency of DI IS is limited. In part, this reflects the problem of identifying and confirming the causal relationship between drug prescription and the development of IS. DI IS risk factors include: abuse of caffeine and alcohol, older age, smoking, drug addiction, high doses of drugs containing provoking agents, the simultaneous use of several drugs, the presence of comorbid diseases. Adverse drug reactions develop due to the following pathophysiological mechanisms: cerebral embolism, vasoconstriction of cerebral arteries, vasculitis of the central nervous system, orthostatic hypotension. The management of a patient with a DI IS does not differ significantly from the management of a patient with IS of a different etiology and includes thrombolysis or mechanical thromboextraction (in the absence of contraindications), as well as rational methods of secondary prevention. It is necessary to completely cancel or reduce the dose of the drug, the use of which led to the development of a stroke. DI IS prevention measures include the choice of drugs with the lowest risk of its occurrence and the use of modern scales for assessing the risk of this phenomenon.

Administration of a rational and safe drug therapy is one of the most challenging issues for healthcare professionals. The frequency of hospitalizations due to the adverse drug reactions in the years 2000 — 2015 was estimated at 6.3 (3.3—11.0 %) for developed countries and 5.5 % (1.1—16.9 %) for developing countries. It is known that alcohol intake is a risk factor for many socially significant diseases, including arterial hypertension, coronary heart disease, chronic heart failure, etc., however, many doctors pay insufficient attention to the fact that many drugs, for example, beta-blockers, antidepressants, bezodisepines, calcium antagonists, can interact with alcohol when consumed simultaneously and, thus, increase the risks of adverse drug reactions. There are 2 main types of interactions between alcohol and drugs: pharmacokinetic (at the stage of absorption, distribution, metabolism and elimination) and pharmacodynamic (at the stage of effects and receptors). For example: the simultaneous intake of alcohol and paracetamol leads to the formation of toxic metabolites due to the induction of cytochrome P450 isoenzymes by alcohol. Another example is decrease in presystemic elimination and stimulation of the metabolism of tricyclic antidepressants; an increase in the elimination of imipramine and desipramine in patients with chronic alcoholism after detoxification therapy, and so on. In this article, the authors analyzed and systematized data from open literature sources in order to inform health care professionals about the possible risks associated with the interaction of alcohol and drugs and various pharmacological groups.

Interstitial lesion is one of the causes of respiratory failure. Drugs are a modifiable etiological factor of lung damage. Medications most commonly associated with drug-induced interstitial lung disease include antineoplastic drugs, disease-modifying anti-rheumatic drugs and amiodarone. According to the latest literature data, the previously described link between anti-rheumatic drugs and interstitial lung diseases is very inconsistent. It may even be a protective effect of this group of drugs on the lung tissue. The relationship between statin use and interstitial lesions is also complex and not fully understood. It is necessary to carefully assess the appearance of respiratory tract complaints in patients taking statins as in other groups of patients. Prescription of additional diagnostic methods is necessary to close monitoring and prevention the toxic effect of these drugs. These actions, as well as the potential prescription of steroid therapy and change in the underlying disease treatment approaches, are an important factor in reducing the incidence of respiratory failure in the population.

The frequency of drug-induced pancreatitis (LIP) is from 2 to 5% of all cases of acute pancreatitis (OP), but it is much more common in risk groups – among children and HIV-infected patients. The use of a number of drugs (drugs) is associated with the development of lipids, among them a special place is occupied by antitumor drugs due to the great medical and social significance of oncological diseases and the appearance in recent years of a large number of new antitumor drugs. The purpose of this review was to review the literature data on antitumor drugs, the use of which is associated with the development of lipids. LI OP developed in 1.8% of patients treated with nivolumab or pembroluzumab. In total, in 14 phase 1-3 studies on the efficacy and safety of ipilimumab, the development of OP was reported in less than 1% of the subjects. Therapy with molecular-targeted targeted drugs, such as tyrosine kinase inhibitors (TKI) or other representatives of the kinase inhibitor class, is also associated with the development of OP. The HP database of the World Health Organization (WHO, World Health Organization Adverse Drug Reaction database) contains reports of individual clinical cases of OP development during treatment with proteosome inhibitors and antibody-drug conjugates. It is known that the following antitumor drugs are also associated with the development of pancreatitis: 6-mercaptopurine, L-asparaginase, tamoxifen, cisplatin, cytarabine, ifosfamide, paclitaxel, docetaxel, oxaliplatin, capecitabine, periwinkle alkaloids, cytosine, cisplatin, interferon alpha-2b, doxorubicin, tamoxifen, gefitinib, vinorelbine, levamizole, methotrexate, 5-fluorouracil, capecitabine, trans-retinoic acid.

Gender is an important factor affecting the risk of drug-induced adverse reactions in patients. According to scientific literature, the risk of drug-induced symptoms, syndromes, and diseases is 1.5–1.7 times higher in women than in men. The aim of the study was to analyse and systematise data on the factors responsible for increased risk of drug-induced diseases in women. It was demonstrated that the increased risk of complications in women following the use of certain pharmacological classes of drugs is associated with a combination of factors that affect pharmacokinetics and pharmacodynamics. These factors include anatomical and physiological characteristics, specificity of enzyme and transport protein activity/expression. Women, compared to men, have higher percentage of adipose tissue and lower percentage of water in the body, which affects the volume of distribution of lipophilic agents, such as opioids and benzodiazepines, resulting in their accumulation in the body. Women have a lower rate of renal excretion and elimination, as compared to men, which may lead to adverse reactions following the use of medicines with predominantly urinary excretion. Changes in the endocrine profile in women taking sex steroids as replacement therapy or a contraceptive measure, as well as fluctuations in endogenous sex steroids during the menstrual cycle, pregnancy, perimenopause, influence the volume of distribution, the activity of cytochrome P450 enzymes, and the glomerular filtration rate, and, thus, may affect the pharmacokinetics and pharmacodynamics of other medicinal products, which, in turn, affect the safety of pharmacotherapy. In order to increase the safety of pharmacotherapy in women, it is necessary to consider the revealed specific pharmacokinetic and pharmacodynamic parameters of the medicine in a given group of patients when selecting the treatment regimen, including the dosage regimen and routes of administration.

Daytime somnolence may be a symptom of different somatic, neurological and psychiatric diseases and develop due to abuse and/or discontinuation of various medications. Drug- induced hypersomnia (DIH) is defined as hypersomnolence caused by the intake of multiple drugs. DIH is one of the most frequently reported effects and/or side effects of drugs. DIH prevalence varies widely and can be as high as 75% in patients receiving specific medications. DIH risk factors include elderly and senile age, impaired drug metabolism, serum drug concentration, method and frequency of drug administration, single and daily doses of drugs, etc., as in many other drug- induced diseases and syndromes. DIH can occur both due to sedative agents administration and withdrawal of psychostimulants and other activating psychotropic medications. Most often, the development of DIH is associated with the use of levodopa-carbidopa, antipsychotics, antidepressants. The pathogenesis of DIH is complex and multifactorial and is associated with the mechanism of action of individual drugs and the presence of concomitant diseases. The article discusses the risk assessment of DIH development due to various medications, diagnosis and management tactics of patients with DIH.

One of the depression causes is the use of certain drugs, and in this case, the term drug-induced depression (DID), medication-induced or iatrogenic depression is used. Symptoms of DID are similar to those observed in patients with other types of depression. DID is also associated with morbidity and mortality. Its development leads to a decrease in treatment adherence, and in some cases, to discontinuation of drugs that have predictive value. The main point in the management of patients with DID is the rapid detection and correction of symptoms and the application of prompt measures to prevent their development when prescribing certain drugs. The features of the course of DID, pathogenetic mechanisms and risk factors for its development, possible approaches to the treatment and prevention are discussed.

According to the theory of inflammaging, aging of the body and the development of age-related diseases are a consequence of a chronic progressive generalized inflammatory process that develops and persists throughout life under the influence of negative factors of an infectious and non-infectious nature. Inflammaging has a number of features that distinguish it from acute inflammation: a chronic nature of inflammation, a low level of inflammation, blurry clinical state (in the early stages of clinical manifestations there may not be any at all). The key pathogenetic role in inflammation plays age-associated changes in the innate immune system, which are referred to in the English literature as “immunosenescence” and oxidative stress. The main source of reactive oxygen species and free radicals in the cells are mitochondria. With age, the concentration of intracellular glutathione, one of the main factors of the antioxidant protection of the cell, decreases and a pathological condition arises in which the rate of production of free radicals and reactive oxygen species significantly exceeds the antioxidant capabilities, which leads to the formation of oxidative stress and disruption of the structure and function of cells. Oxidative stress, inflammation and neuroinflammation are closely related to cognitive impairment, pathological state that is often observed in a group of elderly and senile patients. Further study of the pathogenesis of Inflammaging and the role of oxidative stress in it will potentially lead to development of methods to slow down aging and treat age-related cognitive impairments.

Optimizing diuretic therapy in patients with chronic heart failure is a complicated problem with many unresolved questions. Diuretics take an important place in the treatment of heart failure, which are used in almost 80% of cases. Currently, there are not enough clinical studies, which comparative effectiveness of loop diuretics, as well as studies aimed at personalizing diuretic therapy. Torasemide has several advantages over other loop diuretics; high bioavailability, longer half-life and duration of action provide predictable diuresis. The presence of favorable neurohormonal effects, consisting in a decrease of sympathetic activity and inhibition of the renin-angiotensin-aldosterone system, leads to the fact that hypokalemia rarely occurs. In addition, torasemide slows development of myocardial fibrosis and fosters reverse ventricular remodelling. The use of personalization methods is one of the ways to increase the efficiency and safety of pharmacotherapy with diuretics. The polymorphism of genes encoding systems of biotransformation and transporters of drug is an important factor that determines the individual characteristics of a patient. Pharmacogenetics of torasemide may be of significant importance for pharmacokinetics and pharmacodynamics, influencing the intensity of the diuretic effect and side effects. The clearance of torasemide after oral administration may vary by 47% due to genetic characteristics: the participation of the OATP1B1 polymorphism is approximately 15.5%, the CYP2C9 polymorphism is 20%, and the OAT1 and OAT4 polymorphisms are 10%. Due to the significant differences in the pharmacokinetics of torasemide, further study of the pharmacodynamic characteristics of torasemide in patients with genetic polymorphism is necessary.

Arterial hypertension (AH) remains one of the main causes of disability and death worldwide, including in Russia. At the same time, the risks of coronary and cerebrovascular events increase in the presence of additional risk factors. The most common modifiable risk factors are metabolic disorders, including pre-diabetes, dyslipidemia, peripheral arterial atherosclerosis, and obesity, which also imposes certain features on the choice of optimal pharmacotherapy. Currently, the terminology of comorbid conditions continues to be discussed depending on their pathogenesis and the presence or absence of dominance of one disease over others, i.e. polymorbidity, comorbidity and multimorbidity. At the same time, “associative polymorbidity” is distinguished with a certain set of diseases that often occur in conjunction with each other with individual susceptibility of the body. One of the most common phenotypes of polymorbidity occurring in all age groups in both sexes is cardiometabolic, which is based on the formation of insulin resistance, sympathetic overactivity and chronic inflammation. This article provides a clinical example of the use of a fixed combination of angiotensin II receptor blocker telmisartan and calcium channel blocker amlodipine with the addition of an I1-imidazoline receptor agonist moxonidine in real clinical practice in a polymorbid cardiometabolic patient with target organ damage (left ventricular hypertrophy and microalbuminuria). High antihypertensive (favorable effect on 24-hour blood pressure, especially in the early morning) and organoprotective effectiveness of this combination, its possibilities in correcting additional risk factors (reduced heart rate, body weight and a positive effect on metabolic parameters), due to a synergistic effect on the central pathogenetic mechanisms of hypertension and obesity – insulin resistance and sympathetic overactivity.

Some patients are more likely to have drug-induced diseases due to a number of risk factors, such as older age. The aim of the study was to analyse the effect of older age on pharmacokinetics and pharmacodynamics of medicines and the risk of developing drug-induced diseases. The analysis of scientific literature demonstrated that changes in the functions of body organs and systems caused by natural aging processes may potentially affect pharmacokinetics and pharmacodynamics of medicines and increase the risk of adverse drug reactions. For instance, older people have a decreased cardiac output both at rest and during exercise, weight loss, loss of elasticity of elastic vessels, a reduced number of functioning nephrons, poorer renal filtration capacity, decreased liver volume, a reduced number of functioning hepatocytes, decreased hepatic blood flow. These changes directly affect absorption, metabolism, distribution, and excretion of medicines, which in turn can affect their safety profiles. Consideration of age-related changes in the functions of body organs and systems, regular monitoring of the efficacy and safety of the prescribed medicine, changing the dosage regimen, and revision of the treatment sheet by healthcare professionals will help optimize pharmacotherapy and reduce the risk of adverse reactions and drug-induced diseases in older patients.

Clinical guidelines have long been one of the working tools of the modern doctor, helping him quickly navigate the most effective proven methods of treatment and prevention of various diseases, and also to adapt these methods to the specific tasks of their patients and to achieve maximum personalization of treatment. Clinical practice guidelines are drawn up by professional non-profit associations and are approved by the Scientific Council of the Ministry of Health of the Russian Federation, while often one recommendation is prepared by two or even three associations. The peculiarity of the recommendations offered to your attention is that not only endocrinologists, but also therapists, cardiologists, gynecologists, gastroenterologists, and experts of many other specialties are involved in the prevention and treatment of obesity. The Multidisciplinary Working Group presents this a project in a multidisciplinary journal to bring together the efforts of several professional associations that associated with the need to pay attention not only to obesity itself but also to comorbid conditions. We are looking forward to constructive criticism and a comprehensive discussion of the problem on the pages of our journal.

The outbreak of the coronavirus disease 2019 (COVID-19) pandemic is an ongoing public health emergency that has caused unprecedented morbidity and mortality. COVID-19 is a disease caused by severe acute respiratory syndromerelated coronavirus 2 (SARS-CoV-2), which affects not only the lungs but also the cardiovascular system. A strong theoretical justification for the multisystem effect of COVID-19 is the close relationship between it and endothelial dysfunction, which, according to expert consensus, is crucial for the pathogenesis and severity of the disease. Endothelial dysfunction is considered as the main pathophysiological process in the severe and/or prolonged course of COVID-19, and is probably the common denominator of many clinical aspects of severe COVID-19. This review presents scientific data on the effect of perindopril and amlodipine in patients with hypertension and/or coronary heart disease and COVID-19 on endothelial function.

Atrial fibrillation is a serious adverse reaction associated with the use of anticancer drugs. The aim of the study was to analyse scientific literature on the prevalence, pathophysiological mechanisms, and risk factors of anticancer drug-induced atrial fibrillation, ways of its prevention and treatment. The results of the study showed that the incidence of drug-induced atrial fibrillation varies depending on a specific anticancer drug and ranges from 1 to 86%. It is associated with the use of herbal anticancer agents, alkylating agents, protein kinase inhibitors, monoclonal antibodies, immunosuppressants, antitumor antibiotics, antimetabolites, hormonal anticancer agents, hormone antagonists, etc. Most often, atrial fibrillation develops following the use of such drugs as gemcitabine (in combination with vinorelbine), cisplatin, melphalan, ibrutinib, cetuximab, trastuzumab, alemtuzumab, and doxorubicin. It was demonstrated that the pathophysiological mechanisms underlying the development of atrial fibrillation induced by anticancer drugs include electrophysiological abnormalities, myocardial injury, inflammation, immune response, apoptosis, and oxidative stress. Risk factors for the development of anticancer drug-induced atrial fibrillation are not clearly defined yet and continue to be the subject of research. Prevention of drug-induced atrial fibrillation in cancer patients requires a multidisciplinary approach involving participation of an oncohematologist and a cardiologist. The doctors in charge should also be vigilant regarding potential development of this adverse reaction.

Drug-induced dystonia (DID) is a rarely diagnosed adverse reaction to a sufficiently large number of drugs. Acute DID (ADID) occurs soon after starting to take a drug or raising its dose, and switching from one antipsychotic medication to another, especially to its injectable dosage form. Tardive DID (TDID) develops a few months or years after starting drug intake or 3 months after stopping therapy. The diagnosis of TDID is based on the persistence of dystonic hyperkinesis for more than 1 month, the use of a dopamine receptor blocking agent, and the absence of other causes of its development. The risk factors for DID are male sex; young age (less than 30 years of age); a history of dystonic reactions; hypocalcemia, alcohol use while taking the drug. DID is most commonly related to therapy with antipsychotics, metoclopramide, antidepressants, and antiepileptic drugs. The short-term use of anticholinergic drugs (benzotropin, diphenhydramine) is effective in treating ADID. Anticholinergic drugs and atypical antipsychotics (clozapine, quetiapine), benzodiazepines, muscle relaxants (baclofen), and dopamine reuptake inhibitors (tetrabenazine) are used to treat TDID. To prevent DID, it is very important that a physician should be aware of that this unwanted adverse reaction may occur and that a drug with the lowest risk for DID should be chosen.

The liver is the main organ responsible for the biotransformation and elimination of drugs, and therefore its function is often impaired by different medications. In this article, the authors inform practical health care professionals about the possible liver damage with cholestasis caused by drugs (DILI). Most often, DILI is caused some antibacterial drugs, steroids, barbiturates and some other drugs. DILI has no pathognomonic clinical manifestations. tte scientific literature describes both an asymptomatic increase of “liver” enzymes and the development of acute liver failure. Important diagnostic methods are the collection of anamnesis (especially the medicinal one), analysis of blood biochemical tests, and data from visual diagnostic methods. If the patient has DILI, it is necessary, whenever possible, to stop intake of a drug. ttere are no specific drugs recommended for pharmacotherapy of DILI but there is some the positive effect of ademetionine and ursodeoxycholic acid. ttere are no specific preventive measures for DILI. Healthcare practitioners are recommended not to use drugs off-label, optimize pharmacotherapy and fight with polypharmacy, monitore biochemical tests regularly etc.

Abstract VICTORY II study objective. Evaluation of Vamloset and Co-Vamloset safety and effectiveness in reaching target blood pressure (BP) level in patients with stages 23 arterial hypertension (AH). Materials and methods. Russian multicenter prospective clinical study conducted in 8 clinical centers in 6 cities in Russian Federation included 103 patients over 18 years of age with diagnosed essential hypertension of stages 23 (in accordance with 2013 European guidelines) who previously did not receive treatment (with office systolic BP sBP160 mm Hg and/or office diastolic BP dBP100 mmHg) or did not achieve target BP levels after receiving mono- or dual therapy. Office BP target levels comprised 139 mmHg for sBP and 89 mm Hg for dBP for patients without diabetes mellitus (DM), and 139 mm Hg for sBP and 84 mm Hg for dBP for patients with DM. All patients with stage 2 AH (group 1) were prescribed Vamloset (amlodipine/valsartan, 5/80 mg), patients with stage 3 AH Vamloset (amlodipine/valsartan, 5/160 mg). Therapy correction Vamloset (amlodipine/valsartan) in doses 5/160 mg, 10/160 mg and Co-Vamloset (amlodipine/valsartan/hydrochlorothiazide) in doses 10/160/12,5 mg, 10/160/25 mg (КРКА-RUS) was performed every 4 weeks according to provided schemes. At follow-up every 4 weeks the decision on necessity of antihypertensive treatment (AHT) correction were made by medical researcher in accordance with analysis of patients complaints, general condition and physical examination, results of office BP measurement, diary of BP self-control. In 40 patients in subgroup with additional assessment 24-hour BP monitoring, pulse wave velocity measurement, central BP evaluation, augmentation index calculation, and endothelium damage markers determination were performed. Results. Active phase of the study included 100 patients aged 59.510.9 years (59% female) suffering from AH for 83.48.4 months. The patients received treatment with study medication (safety population). The protocol population (sampling Per Protocol) included 80 patients who completed the study without severe protocol violation. At the moment of study entrance 83% of patients received AHT. In all patients treatment duration comprised 15.9 weeks. In Per Protocol population target office BP level was achieved by 90.0% (95% confidence interval 81.295.6%) of the patients. Overall clinical effectiveness (extremely high, very high, high, and sufficient) was achieved in 98.8% [95% confidence interval 93.2100%] of the patients. In group of patients with stage 2 AH target office BP level was achieved by 93.8% of patients, in group with stage 3 AH by 84.4% of patients. Mean BP change in study group was -32.2 mm Hg for SBP and -16.0 mm Hg for DBP. Among patients with stage 2 AH target office BP level was achieved by 93.8% of patients, with mean BP change -30,7 mm Hg for SBP and -15.5 mm Hg for DBP. In patients with stage 3 AH target BP levels were achieved in 84.4% of patients with mean BP change -34,6 mm Hg for SBP and -16.7 mm Hg for DBP. After 16 weeks of treatment in Full Analysis Set population with recovery of missed measures using Last Observation Carried Forward 40.2% of patients reached target BP levels according to BP self-control results. Considering the limitations of results evaluation this practice requires further assessment, standardization, and improvement. According to 24-hour BP monitoring reaults after 16 weeks of treatment 26.5% of patients achieved target BP daily profile (for patients from subgroup with additional assessment in Full Analysis Set population with recovery of missed measures using Last Observation Carried Forward), that indicates additional influence of studied AHT on the prognosis of patients with stages 23 AH. Conclusion. In clinical study VICTORY II Vamloset and Co-Vamloset optimal effectiveness and safety in patients with stage 2 and 3 arterial hypertension were shown.

VIII Eurasian Congress of Cardiology. Overview of symposiums. New opportunities for reducing cardiovascular risk in the Russian Federation. Systemic Hypertension

Heart failure (HF) is a growing public health problem with an estimated prevalence of 38 million patients worldwide. Congestion and formation of edema – are typical symptoms of heart failure. Diuretics are the mainstay of therapy in heart failure and are used to relieve congestion and improve exercise tolerance. Also, the administration of diuretics should be considered to reduce the risk of HF hospitalization. Loop diuretics are used by nearly 80% of all chronic HF patients and remain the drugs of choice. Although diuretics are one of the most prescribed classes of drugs, recommendations for their titration scheme for long-term use have not yet been finalized, nor have there been major prospective randomized controlled studies on the effect of diuretics on morbidity and mortality. A Cochrane meta-analysis has shown that in patients with chronic HF, loop and thiazide diuretics might reduce the risk of death and worsening of HF in comparison to placebo and could lead to improved exercise capacity. Guideline recommends the use lowest possible dose of diuretics due to probable electrolyte disturbances, further neurohormonal activation, accelerated kidney function decline, and symptomatic hypotension. Diuretic resistance is associated with an unfavorable prognosis and an increased risk of readmission. There are significant pharmacokinetic differences between the loop diuretics. Compared with furosemide, torasemide has a high bioavailability irrespective of food intake, and carries a longer half‐life and duration of effect; also, the benefits of torasemide are its additional anti-fibrotic and neurohormonal effects. Optimization of diuretic therapy in patients with HF remains a challenge and requires further research, as well as an individual approach to patients, since there is no convincing evidence base.

In patients with arterial hypertension (AH), an extremely important measure of the effectiveness of antihypertensive drugs (AHD) is not only a direct decrease in blood pressure (BP), but also its stable control throughout the 24 hours, preventing excessive morning surge and increased BP variability, which in turn are recognized cardiovascular risk factors. Currently, in the vast majority of hypertensive patients, the main antihypertensive therapy approach is using single-pill combinations (SPC) of AHD. Among the first-line combinations for a wide range of patients with AH and no special clinical conditions is amlodipine/telmisartan SPC. Distinctive features of these drugs, on the one hand, are unique pharmacological properties, consisting in an ultra-long antihypertensive effects, superior to other AHD in their classes; and on the other hand, there is an large body of evidence from numerous clinical trials confirming their high antihypertensive and target-organ protective potential as well as excellent capabilities in cardiovascular risk reduction. To assess the AHD effectiveness extent, several parameters have been proposed, of which the most rational and useful is the smoothness index, calculated using the ambulatory blood pressure monitoring data. Smoothness index describes both the degree of BP reduction and its distribution during the monitoring period. This index inversely associates with the changes in BP variability, and has predictive value in relation to the hypertension-mediated organ damage regression during different antihypertensive regimens. Amlodipine/telmisartan SPC has also been studied in many trials, including comparative ones with other AHD. In these works its direct powerful antihypertensive effect and a pronounced beneficial impact on the smoothness index have been proved, demonstrating stable BP control throughout the 24 hours (especially in the most dangerous morning hours), and also a decrease in BP variability. Therefore, amlodipine/telmisartan SPC can effectively reduce cardiovascular risk and improve prognosis in patients with AH.

Cardiovascular diseases are the leading cause of death both in the world and in the Russian Federation. The most significant contributors to the increase in mortality are arterial hypertension (AH) and ischemic heart disease (IHD). Dihydropyridine calcium channel blockers (CCBs) are the first line of treatment for these conditions. This is noted in the clinical guidelines for the diagnosis and treatment of AH and in the guidelines for the management of patients with chronic coronary syndromes. CCBs are a heterogeneous group of drugs that have both general and individual pharmacokinetic and pharmacodynamic properties. They are used in patients with AH and/or IHD, including those with concomitant diseases (diabetes mellitus, chronic kidney disease, bronchial asthma, chronic obstructive pulmonary disease, peripheral arterial disease). Felodipine is one of the CCBs. It has a combination of clinical effects, allowing the drug to be prescribed as a first-line therapy for AH, IHD and a combination of these diseases. This is noted in the registered indications for its use. This CCB has a sufficient evidence base of clinical trials demonstrating not only good antihypertensive and antianginal potential of the drug, but also the nephroprotection and cerebroprotection properties. The nephroprotective effect of felodipine is associated with a slowdown in the progression of chronic kidney disease, and the cerebroprotective effect is associated with a decrease in the risk of stroke and an improvement in cognitive functioning. The safety profile of felodipine is favorable: peripheral edema develops much less frequently. This is confirmed by the results of comparative studies. Felodipine is recommended for a wide range of patients with AH, IHD and their combination due to such clinical and pharmacological properties.

Drug-induced neutropenia and agranulocytosis are serious and potentially life-threatening complications of pharmacotherapy. The aim of the review was to systematise and analyse scientific literature on the prevalence, risk factors, pathogenesis, clinical picture, methods of prevention and treatment of drug-induced neutropenia and agranulocytosis, and medicinal products that most often lead to their development. The analysis revealed that one of the major reasons of drug-induced neutropenia and agranulocytosis is the use of cytotoxic drugs (alkylating agents, antimetabolites, taxanes), non-steroidal anti-inflammatory drugs, antibiotics, antiplatelet, antithyroid, antirheumatic, antiarrhythmic, and antipsychotic drugs. The incidence of drug-induced neutropenia and agranulocytosis is generally low—from 3 to 16 cases per 1 million patients annually. The main risk factors for the development of these conditions include old age, female sex, history of chemotherapy or radiation therapy, malnutrition, and comorbidities. The symptoms in patients with neutropenia and agranulocytosis regardless of etiology can include fever, chills, apathy, myalgia, weakness, pharyngitis, gingivitis, sinusitis, stomatitis, bronchitis, and sepsis. There are no practical methods for early diagnosis or prevention of drug-induced neutropenia and agranulocytosis. Successful management of these conditions relies on timely identification and immediate withdrawal of the potential causative drug. Prevention of chemotherapy-associated neutropenia may consist in reducing the dose of the chemotherapeutic agent. Practicing physicians should be aware of the risk of drug-induced neutropenia and agranulocytosis. It is important to raise awareness among healthcare professionals of the methods of diagnosis and prevention of these conditions, as well as specific aspects of managing patients with these conditions.

Atrial fibrillation (AF) and cognitive impairment (CI) are among the most important problems of the modern health care system, which are characterized by an extremely high prevalence with the increasing trend of the latter; they lead to lower quality of life, shorter duration, and a larger number of disabled people. The specific feature of AF and CI is the presence of common risk factors. To date, the data of an increasing number of studies allow cerebral microbleeds (CMBs) to be considered as a new risk factor for CI, inter alia in patients with AF. In recent years, special attention has been paid to the role of oral anticoagulants (OACs) in the prevention of CI in AF, which is reflected in a number of studies and meta-analyses. In terms of the effect of OACs on the risk of CMBs, there is reason to believe that the latter increases with the use of warfarin, the effects of direct OACs (DOAC) in this regard require further investigation. At the same time, among the DOACs, apixaban is the only drug that has been proven to have no negative effect on the risk of CMBs in a randomized controlled clinical trial. In general, the available data indicate the positive effect of OACs in reducing the risk of CI and dementia in AF; moreover, DOACs have an advantage in this respect. Among the DOACs, apixaban is promising due to its optimal efficacy and safety profile.

Older age is associated with changes in bone metabolism, a loss in its mineral density and volume, and the development of osteoporosis. The high prevalence of atrial fibrillation and osteoporosis in older age groups causes their frequent combination in this category of patients. It is known that some diseases and/or drugs used to treat them, exacerbating the natural violation of bone metabolism, contribute to the progression of osteoporosis and its complications, which in turn can negatively affect the prognosis and quality of life of the patient. Anticoagulants, widely used in the treatment of thromboembolic complications and in the prevention of stroke, can have an adverse effect on bone metabolism. The purpose of this review was to generalize and systematize the available literature data regarding the features of the influence of various representatives of the anticoagulants group on bone tissue. The article analyzes the effects of unfractionated heparin, low molecular weight heparins, vitamin K antagonists, oral anticoagulants on bone metabolism, bone mineral density, and fractures. This review provides data from articles and reviews published through February 2020, inclusive, accumulated in the English-language database of medical and biological publications “PubMed”. The literature data confirm the negative effect of unfractionated heparin on bone tissue, with a violation of bone metabolism, a decreased bone mineral density and the development of fractures. Compared with unfractionated heparin, low molecular weight heparins appear to be safer, and vitamin K antagonists, having a significant effect on bone metabolism, contribute to a decreased bone mineral density, mainly in people who are on long-term (more than 1 year) therapy. Oral anticoagulants, having the mildest effect on bone metabolism, is associated with a lower (compared to other anticoagulants) risk of decreased bone mineral density and the development of fractures, and are recognized as the safest against bone tissue.

Stroke remains one of the leading causes of death and disability both worldwide and in Russia. Acute cerebrovascular events have many risk factors, among them the most important is arterial hypertension (AH), which predisposes to the stroke development through the direct effect of increased hydrostatic blood pressure on the brain vascular system, followed by arterial remodeling and an increase in their stiffness. In addition, excessive blood pressure variability, activation of the tissue renin-angiotensin-aldosterone system, as well as target-organ damage - primarily the heart in the form of left ventricular hypertrophy, kidneys in the form of microalbuminuria and decrease in glomerular filtration rates. An additional risk factor for stroke is hyperuricemia, which is included in the current European and Russian guidelines for the management of AH as one of the new risk factors in patients with this disease. The state-of-the-art approach to antihypertensive therapy is the using of antihypertensive single-pill combinations, one of the frontline combinations in the absence of special clinical conditions is a combination of an angiotensin converting enzyme inhibitor and a calcium channel blocker. The reference drugs in both classes due to large body of evidence are ramipril and amlodipine, respectively. These drugs provide a high level of brain protection, not only due to the ultra-long and powerful antihypertensive action, but also through a unique potential in target-organ protection via left ventricular hypertrophy regression, antiatherosclerotic effects and improved endothelial function, renal protection, as well as the ability to decrease uric acid in the blood.