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he liver is one of the organs most often affected by medication (MP) intake. Drug-induced liver damage with cholestasis (LIPCH), on the one hand, rarely leads to death in comparison with the hepatocellular type, but, on the other hand, is more often characterized by a long, in some cases chronic course. This type of liver damage is characterized by an increase in the activity of alkaline phosphatase (ALP) > 2 upper limits of normal (ULN) or the ratio of alanine aminotransferase (ALT) / ALP < 2 in chronic course. Non-steroidal anti-inflammatory drugs (NSAIDs) are among the most readily available (including over-the-counter) and widely used drugs in clinical practice and are often the cause of LIPCH. This article summarizes the available data at the time of preparation of the article on the prevalence, mechanisms of development and features of LIPPH while taking NSAIDs. A separate section is highlighted on the features of the management of such patients. In particular, in accordance with both domestic and foreign clinical guidelines for the drug genesis of liver damage, it is recommended to stop taking the inducer drug and prescribe ursodeoxycholic acid (UDCA). The efficacy of UDCA in patients with LIPCH, including those associated with the use of NSAIDs, has been confirmed by the results of a large number of randomized placebo-controlled clinical trials. Among the UDCA preparations on the market of the Russian Federation, one cannot fail to pay attention to Exho® (CJSC «Canonpharma Production»), which is bioequivalent to the reference drug, is produced in compliance with GMP standards on a high-tech production base, which ensures its quality, and an affordable price and a large the choice of dosage forms makes it possible to successfully use this drug, including in special categories of patients, for example, elderly patients and/or those suffering from dysphagia.

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.

Arterial hypertension (AH) is one of the most important risk factors for development of myocardial infarction, chronic heart failure, stroke, cognitive disorders and dementia, and chronic kidney disease. Currently, special attention is paid to increased blood pressure variability (BPV) as a new risk factor for development of cardiovascular and cerebrovascular complications. The available evidence-based body of clinical studies demonstrates the importance of reducing not only the blood pressure itself but also the increased BPV to provide significant improvement of the prognosis and limits the risk of complications. This notion has been validated in consensus documents on the management of patients with AH. Among antihypertensive drugs, the fixed-dose combination (FC) amlodipine/perindopril has demonstrated a unique capability for reducing all types of BPV (visit-to-visit, day-to-day, during 24 h). According to current clinical guidelines, this combination belongs to first-line FCs indicated for most patients with AH. A distinctive feature of the FC amlodipine/perindopril is numerous data from real-life clinical practice, which support both its high antihypertensive efficacy and the ability to decrease high BPV. Therefore, the FC amlodipine/perindopril can be recommended for a broad range of AH patients to achieve BP control and to improve the prognosis.

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.

Introduction. Polypharmacy and the administration of potentially non-recommended drugs are the causes of adverse drug reactions. The absence of potentially recommended drugs leads to a decrease in the duration and quality of life, an increased risk of complications from various organs and systems.The purpose of the study. To analyze the structure of prescribed drugs in patients over 65 years of age with atrial fibrillation (AF) and chronic kidney disease (CKD) stages 3 and 4 for the presence of рolypharmacy and compliance of prescriptions with the criteria STOPP/START.Materials and methods. 125 case histories were analyzed in patients 65 years and older with AF and CKD. Patients were divided into two groups: group 1 – patients with AF and CKD 3a (n = 51; 84.3 % of women; mean age 86.1 ± 6.4 years; mean score on the CHA(2) DS(2)-VASc scale 6.2 ± 1.1 points; mean score on the HAS-BLED scale 3.00 ± 0.68 points); group 2 – patients with AF and CKD 3b and 4 stages (n = 39; 84.6 % of women; mean age 87.9 ± 4.7 years; mean score on the CHA(2) scale; DS(2)-VASc 6.1 ± 1.2 points; the average score on the HAS-BLED scale is 3.10 ± 0.71 points). All 100 % of patients in both groups had a high risk of stroke on the CHA(2) DS(2)-VASc scale (≥ 2 points for men; ≥ 3 points for women), 82.4 % of patients in group 1 and 79.5 % of patients in group 2 had a high risk of bleeding on the HAS-BLED scale (≥ 3 points). According to the prescribing sheets of medical histories, the frequency of polypharmacy was evaluated, as well as the structure of drug prescriptions according to the STOPP/START criteria.Results. The number of patients who were prescribed ≥5 drugs was 100 % in group 1 and 94.9 % in group 2. The number of patients receiving ≥10 drugs at the same time was 11.8 % and 20.5 % in group 1 and 2, respectively. In 64.7 % of patients from group 1 and in 53.8 % of patients from group 2, potentially non-recommended but prescribed drugs (STOPP) are present in the prescribing lists. At the same time, 96.1 % and 100 % of patients in groups 1 and 2, respectively, were not prescribed drugs that are recommended for elderly patients (START criteria).Conclusion. Patients with AF and CKD aged 65 years and older are often prescribed potentially non-recommended drugs that significantly reduce the quality of life and increase the risk of adverse drug reactions. These patients were also often not prescribed potentially recommended drugs that are necessary to improve the prognosis, reduce the risk of complications, and reduce the number of hospitalizations. The revealed facts dictate the need to optimize pharmacotherapy in elderly and senile patients with AF and CKD in a hospital setting.

Chronic kidney disease is one of the most common diseases in general medical practice, due to their secondary damage to the kidneys in arterial hypertension, chronic heart failure, and diabetes mellitus. The coexistence of hypertension and diabetes increases the likelihood of developing chronic kidney failure tenfold. In turn, chronic kidney disease is an important independent risk factor for the development of cardiovascular complications, including fatal ones, due to the direct relationship of the pathogenetic mechanisms of cardiorenal relationships. Approaches to the treatment of chronic kidney disease should be aimed both at preventing the risks of developing renal dysfunction, and at treating existing pathology. The multifactorial nature of the disease and the complex etiopathogenetic relationships determine the need to optimize existing approaches to the treatment of chronic kidney disease in multimorbidity patients with concomitance cardiovascular diseases and diabetes mellitus. This is also due to the fact that, unlike other target organs, compensation for background disease does not always prevent further deterioration of kidney function. According to the recommendations of the main scientific communities, in such cases, it is advisable to start therapy with the most effective angiotensin-converting enzyme inhibitors that combine nephro-and cardioprotective effects and have a dual route of elimination from the body, which is especially important in multimorbidity, the aim to prevent polypharmacy, reduce the risk of drug interactions and, consequently, side effects. This article reviews the literature data indicating the high efficacy and safety of the angiotensin converting enzyme inhibitor fosinopril in patients with chronic kidney disease in combination with cardiovascular diseases and diabetes mellitus.

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.

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.

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.

Asthenia is a non-specific syndrome common in general practice and occurs in patients with acute and chronic somatic disorders, including infectious ones. The novel coronavirus infection (COVID-19) is one of the leading causes of severe and persistent asthenia. The hypothalamicpituitary- adrenal axis is essential for the development of asthenia since its dysfunction provoked by various factors (including infections) results in electrolyte metabolism impairment with hypokalemia and hypomagnesemia. This paper describes a hypothetical pathogenic mechanism of asthenia after the COVID-19, which implies over-activation of the renin-angiotensin-aldosterone system that, in particular, leads to hypokalemia. The role of pharmacotherapy prescribed for the COVID-19 is highlighted. Study results demonstrate a high rate of hypokalemia in patients with the COVID-19 and suggest a direct correlation between the severity of hypokalemia and the activity of viral infection. Furthermore, the detection of electrolyte abnormalities is essential in both acute infection and convalescence. Finally, the authors consider ways of relieving this pathological condition. KEYWORDS: novel coronavirus infection, COVID-19, post-infectious asthenia, angiotensin-converting enzyme, hypokalemia, hypomagnesemia. FOR CITATION: Ebzeeva E.Yu., Ostroumova O.D., Krotkova I.F. et al. Electrolyte deficiency after the novel coronavirus infection and post- COVID asthenia. Russian Medical Inquiry. 2021;5(5):245–251 (in Russ.). DOI: 10.32364/2587-6821-2021-5-5-245-251.

Among the causes of acute interstitial nephritis, drug-induced acute interstitial nephritis accounts for 50 to 78 % of all cases. Th e review summarizes the literature data on drugs that cause acute interstitial nephritis. Search in eLibrary databases.RU, PubMed®, MEDLINE, EMBASE, manuals and guidelines, materials of adverse drug reactions databases, instructions for the medical use of drugs. it was held until October 2020. Th e most probable mechanisms of its development are considered. Most attention is paid to non-steroidal anti-infl ammatory drugs, anticoagulants, antibiotics, antitumor drugs (immune checkpoint inhibitors), which are widely used in clinical practice. Th e symptoms of drug-induced acute interstitial nephritis are variable and oft en non-specific; therefore, a kidney biopsy is required for an accurate diagnosis. The main direction of treatment of drug-induced acute interstitial nephritis is the cancellation of nephrotoxic drugs, if this condition is not feasible and/or the duration of acute interstitial nephritis is less than 3 weeks, the biopsy has minimal interstitial fibrosis and there are no serious contraindications, then the possibility of using it should be considered.

In real clinical practice, the problem of polymorbidity and, in particular, its cardiometabolic phenotype, is now widespread. One of the its variants is a combination of arterial hypertension with diabetes mellitus, overweight, cognitive impairment, and peripheral atherosclerotic arterial disease. The clinical significance of such polymorbidity portrait, on the one hand, lies in its frequent occurrence, and, on the other hand, in the cardiovascular risk amplification in the settings of simultaneous coexistence of diseases initially characterized by an extremely unfavorable prognosis for the patient. The article presents a clinical case of a patient with a such polymorbidity variant and considers the nicergoline potential in the complex correction of mutually associated comorbidities. The nicergoline ability to improve cognitive functioning, to have a beneficial effect on peripheral circulation, which is reflected in an increase in the distance of painless walking, and also to realize some antihypertensive effect has been demonstrated. No less important is the fact that the high therapeutic efficacy of nicergoline was combined with an optimal safety profile, which consists in good tolerability of therapy and the absence of adverse drug reactions.

More than 60 % of all depressive syndromes are reactive depression, which occurs in response to internal and external influences. One of the variants of reactive depression is drug-induced (drug-induced) or iatrogenic depression, which is a possible side effect of a number of medications. Depressogenic effect is described in both psychotropic and somatotropic drugs. Depressions that occur when using psychotropic drugs are most often associated with the duration of administration and large doses of the drug. Some antihypertensive, antiarrhythmic, hypolipidemic drugs, antibiotics, hormones, antiparkinsonian drugs and antineoplastic agents are most often mentioned in the series of somatotropic drugs that have a depressogenic effect. Drug-induced depression is one of the most controversial issues. this article presents a systematization of available literature data on depression associated with taking various drugs.

Chronic fatigue syndrome (CFS) is a state of constant, impairing quality of life, fatigue, lasting more than 6 months, inexplicable by any of coexisting patient’s pathological conditions. The prevalence of CFS in the world is approximately 2 % of the population (120–140 mln inhabitants of Earth). The etiology of CFS is unknown. Several theories of development of CFS have been proposed (immune, infectious, endocrine, metabolic, neurological, psychiatric), however, none of them fully explains the clinical manifestations of CFS. There is no specific treatment for this condition. This article presents the clinical case of a patient B 45 years old with CFS, who received treatment with regular physical exercises, diet (limiting consumption of coffee and caffeine-containing products, alcohol, salt intake to less than 5 g per day, an increase in the consumption of plant foods and products containing potassium, calcium, magnesium), as well as intake of Mildronat, a positive dynamics was observed, manifested by an increase in productivity at work, decrease in fatigue, a decrease in the daily variability of blood pressure and a decrease in heart rate at rest.

The clinical example in this article shows the successful experience of using the neuroprotective agent citicoline (Noocyl) in a comorbid patient after an ischemic stroke with motor and cognitive impairment in combination with antihypertensive, hypolipidemic, and antiplatelet therapy. High efficiency and good tolerance of this drug, the ability to improve cognitive and motor processes are shown.

Effective and safe treatment of patients with polymorbidity is an urgent task of modern healthcare. Of particular difficulty is the treatment of patients with cardiovascular comorbidity, which requires an integrated approach to the treatment and development of a special, so-called patient-oriented approach. Modern scientific evidence proposes the use of levocarnitine, as part of complex therapy to increase its effectiveness. So, it was shown that levocarnitine can have a beneficial effect on blood pressure in patients with hypertension, especially those who are overweight and obese. Levocarnitine is also effective in the treatment of heart failure, which has been studied in several clinical studies, which demonstrated its ability to increase the ejection fraction of the left ventricle, stroke volume of blood and other indicators. Optimization of the bioavailability of nitrogen oxide (NO) and a decrease in systemic oxidative stress while taking levocarnitine plays an important positive role in complex therapy in patients with coronary artery disease: exertional angina and post-infarction cardiosclerosis, reducing the number of anginal attacks. Since levocarnitine has powerful antioxidant effects, it also has the neuroprotective effect found in in vitro studies in animal experiments. In case of impaired renal function, due to accelerated elimination and impaired reabsorption, a deficiency of levocarnitine in the body tissues develops, and therefore the US Food and Drug Administration (US FDA) decided on the possibility of using levocarnitine in patients on hemodialysis. Thus, taking into account the positive effects of levocarnitine in a number of frequently combined diseases, it can be considered as the drug of choice in the treatment of patients with polymorbidity.

Admission of certain medications (drugs) can cause the development of atrial fibrillation (AF) in patients having non-evident cardiovascular disease (CVD). Also, it can accelerate the onset of AF in patients with pre-existing CVD. It is important to realize medications as potential cause of AF, especially in elderly people, since aging is associated with comorbidity and use of many medications simultaneously, that can lead to higher incidence of druginduced AF (DI AF). The article provides literature review on medications used to treat CVD, the admission of which can lead to the development of DI AF. Its onset can be associated with the use of cardiotonic, antiarrhythmic and antianginal medications, calcium channel blockers, diuretics, antiplatelet agents and some others with different evidence levels. The frequency, mechanisms of DI AF development and methods for its correction are described.

Nowadays, there is an increasing necessity to use a lot of medical products (MP) in one patient. This can lead to potential nephrotoxic adverse reactions (ADRs) among drugs. One of drug-induced kidney damage manifestations is acute tubular necrosis (ATN), which causes the development of severe complications associated with the use of hemodialysis and a high risk of mortality. The purpose of this review is to analyze literature data concerning groups of drugs and individual drugs, the intake of which is associated with the development of drug-induced ATN, risk factors, prevention and treatment methods. Among drug-induced ATN development risk factors are both general, associated with the development of drug-induced acute kidney damage (for example, age, history of chronic kidney disease, etc.), and specific ones, typical for certain groups of drugs. Most often, drug-induced ATN develops while taking antibacterial, antiviral and anticancer drugs. The main method of treatment for drug-induced ATN is abolition of nephrotoxic drugs, but if it is impossible, then there are certain patient management schemes. To prevent and to diagnose drug-induced ATN at early stages, that is the key for favorable prognosis, it is necessary to aware of doctors of different specialties about such pharmacotherapy complications.

In the article questions of prevention of stroke, including repeated ones, are considered. The choice of anticoagulant therapy is discussed in patients with atrial fibrillation and a number of concomitant diseases - coronary artery disease, diabetes mellitus, chronic kidney disease, chronic heart failure. The data of subanalyses of a randomized clinical trial of ARISTOTLE are presented, indicating a high profile of efficacy and safety of the new oral anticoagulant apixaban in these categories of patients.

Bilateral pneumonia is the most common clinical manifestation of a new variant of coronavirus infection At the same time, COVID-19 has a wide range of cardiovascular complications including acute heart failure, arrhythmias, acute coronary syndrome and myocarditis Myocardial damage is relatively common in COVID-19 (7-23%) We report a 56-year-old patient with a confirmed coronavirus infection The peculiarity of this clinical case is systemic manifestations of COVID-19 (lesion of lung, heart, kidneys and skin) Despite the presence of viral pneumonia, the patient’s clinical status was determined by myocardial damage A feature of this case was also the presence of skin damage © 2021, Media Sphera Publishing Group All rights reserved

This article deals with the epidemiological datashowing higher frequency of arterial hypertension (AH) in patients with ischemic heart disease (IHD). We discussed the basic characteristics of modern domestic and foreign recommendations for treating patients with combination of AH and IHD. We showed the target of blood pressure (BP) in this category of patients. This article deals with the priority groups of antihypertensive drugs, which have the advantages in the combination usage in patients with association of these diseases. We fixed special attention to the problem of BP variability (BPV) as a new risk factor for the development of coronary complications in patients with AH. We showed the possibility of fixed combination of perindopril and amlodipine in reducing interand intervisit BPV in patients with AH and IHD in actual clinical practice.

1 , N.Yu.Galeeva 1 The article presents the definition, classification and pathogenetic mechanisms of cognitive impairment in patients with arterial hypertension (AH). Dis- cusses the literature on the relationship of hypertension with risk of dementia. The possibilities of antihypertensive therapy in the prevention of dementia. Discussed in detail the results of the study Syst-Eur (Systolic Hypertension in Europe), in which the calcium antagonist (CA) nitrendipine ± enalapril re- duced the risk of developing dementia, including Alzheimer's disease, new cases, 50%. Neuroprotective action mechanisms are considered as a whole