[Drug-induced cognitive impairment and dementia]. / Lekarstvenno-indutsirovannye kognitivnye narusheniya i dementsiya.

One of the reasons for the development or worsening of cognitive impairment (CI) may be the use of a number of drugs: non-steroidal anti-inflammatory drugs, antiarrhythmics, antidepressants, glucocorticosteroids, antitumor drugs and a number of others. The negative effect of drugs on cognitive functions is realized due to many pathophysiological mechanisms: disruption of hormonal regulation, decreased neuronal excitability, increased activity of gamma-aminobutyric acid receptors, decreased cerebral circulation, atrophic changes in the brain; many mechanisms have not been fully established. Risk factors for the development of drug-induced CIs are: old age or childhood, brain damage, chronic diseases, genetic factors, the patient's initial CI, polypharmacy, dose and duration of drug use, acute infectious diseases, metabolic disorders, dehydration, acute urinary retention, etc. To diagnose and differentially diagnose drug-induced CI, it is necessary to establish a connection between the start of taking a suspected drug-inducer and a decrease in cognitive functions. The first step in the treatment of drug-induced CI is the abolition of an inducer drug or a reduction in its dose, in cases where it is impossible to discontinue the drug and there is no replacement, special slow-release dosage forms can be considered. The main measures to prevent drug-induced CI include the use of drugs with the lowest risk of their development, assessment of drug interactions, and the use of modern scales to assess the risk of developing this side-effect (anticholinergic burden scale, etc.).

[Drug-induced uveitis]. / Lekarstvenno-indutsirovannyi uveit.

In recent years, an increasing amount of attention has been paid to medicinal products as possible risk factors in the development of eye diseases. The frequency of diagnosed drug-induced uveitis is growing yearly, which can be attributed to the appearance of new drugs - biological agents (immune checkpoint inhibitors, BRAF and MEK inhibitors, vascular endothelial growth factor inhibitors, tumor necrosis factor-α inhibitors), as well as systemic bisphosphonates and some antiviral drugs. The time interval between the beginning of the drug use and the appearance of uveitis symptoms varies from several days to months. Common symptoms include eye pain, photophobia, the appearance of floating opacities, and reduced vision associated with active inflammatory changes in the retina and optic nerve and outcomes of those inflammations. Timely diagnosis, cancellation of the drug that caused uveitis and appointment of adequate anti-inflammatory therapy in most cases effectively stops the symptoms of the disease, which determines the relevance of attention to the prevalence, pathogenesis, diagnosis and treatment of drug-induced uveitis.

[Rhinitis medicamentosa]. / Lekarstvenno-indutsirovannyi rinit.

One type of non-allergic non-infectious rhinitis is represented by a heterogeneous group of rhinitis medicamentosa, which can be divided into several pathogenetic types. The most common rebound nasal congestion associated with the use of topical decongestants. Excessive use of intranasal decongestants leads to a decrease in the number of alpha-adrenoreceptors on the surface of cell membranes and uncoupling their connection with the G-protein and the development of tachyphylaxis. To prevent the development of rebound nasal congestion caused by topical decongestants, it is important to limit the frequency of their use. In most cases, the duration of the use of vasoconstrictor drugs should be limited to 5-7 days, according to Patient information leaflets for the drugs. However, in patients who have had a history of episodes of rebound nasal congestion, which develops including the previously indicated periods, the duration of decongestant therapy should be limited to 3 days. Rhinitis associated with local inflammation is caused by the intake of acetylsalicylic acid (ASA) or other non-steroidal anti-inflammatory drugs. Currently, the so-called "aspirin triad" is well known - a combination of bronchial asthma, rhinosinusitis (often polyposis) and intolerance to ASA. Neurogenic rhinitis develops due to the use of drugs that violate vascular tone, for example, antihypertensive drugs or type 5 phosphodiesterase inhibitors. Drug-induced rhinitis has a significant impact on the patient's quality of life: nasal congestion, rhinorrhea, secondary night apnea, insomnia as a result of nasal breathing disturbances, headaches, irritability, weakness after sleepless nights disturb patients to a large extent. Timely diagnosis and withdrawal of a provocative drug, the use of topical corticosteroids in case of severe rhinitis are the basis of the treatment of rhinitis medicamentosa. In severe cases, there is a need, including surgical treatment, such as, for example, submucosal laser destruction of the lower nasal concha.

[Drug-induced seizures: prevalence, risk factors, treatment and prevention]. / Lekarstvenno-indutsirovannye épilepticheskie pristupy: rasprostranennost', faktory riska, lechenie i profilaktika.

There is a growing interest to the problem of drug-induced epileptic seizures (ES) due to their relatively high prevalence, poor prognosis, a large number of different drugs associated with the development of drug-induced ES, and low awareness among general practitioners. Drug-induced ES are most often associated with the use of antidepressants, antipsychotics, antiepileptic drugs (overdose or as a result of discontinuation), antibiotics, immunosuppressants and immunomodulators, antitumor agents, analgesics, central nervous system stimulators, anesthetics etc. The prevalence of drug-induced ES varies with different drugs. It is estimated that about 6.1% of the first occurring ES are drug-induced. Risk factors for drug-induced ES include a history of epilepsy or ES, cancer, blood-brain barrier dysfunction, several concomitant neurological diseases, mental disorders, childhood, old and very old age, fever, impaired liver metabolism in patients with liver diseases, impaired drug excretion in patients with kidney diseases, polypharmacy, pharmacokinetic properties of the drugs themselves, allowing them to penetrate the blood-brain barrier in the central nervous system (lipophilicity, transport and communication with blood plasma proteins), drug concentration in blood serum, method and frequency of drug administration, single and daily doses of drugs. No clinical guidelines for the management of patients with drug-induced ES are available. It is recommended to identify patients at risk: elderly patients, patients with impaired liver and kidney function and patients receiving drugs that can cause ES and/or lower the seizure threshold. Benzodiazepines are the first-line treatment in drug-induced status epilepticus, barbiturates and propofol are the second-line treatment. The general principles for the prevention of drug-induced ES include careful selection of the optimal dose of drugs that can cause ES, especially in patients with impaired liver and/or kidney function, monitoring of several parameters in blood serum (for example, liver enzymes, electrolytes, glucose etc.), monitoring of the blood plasma concentration of certain drugs, avoiding the simultaneous administration of several drugs that stimulate the central nervous system, and a rapid discontinuation of such drugs.

[Drug-induced insomnia in old and very old patients]. / Lekarstvenno-indutsirovannaia insomniia u patsientov pozhilogo i starcheskogo vozrasta.

According to modern concepts, sleep disorders are considered as a common geriatric syndrome, which also emphasizes their polyfactorial genesis. One of the important factors inducing sleep disorders is the intake of various drugs, which becomes especially significant with the problems of polymorbidity and polypharmacy occurring in older age groups. The article provides a classification of drug-induced sleep disorders, which presents a wide range of conditions associated with a disturbance of the sleep-wake cycle. The authors present the frequency of insomnia associated with taking drugs from different pharmacological groups according to the literature, and consider mechanisms of insomnia development due to the effect on various receptors and neurotransmitter systems, as well as data on their effect on sleep structure. The article presents risk factors for drug-induced insomnia and discusses preventive measures and management of patients.

[Drug-induced hearing loss as a manifestation of drug-induced ototoxicity]. / Lekarstvenno-indutsirovannaia tugoukhost' kak proiavlenie lekarstvenno-indutsirovannoi ototoksichnosti.

The ability of drugs to have an ototoxic effect has been studied for a long time, however, the true prevalence of this undesirable phenomenon is unknown, which is due to the use of various audiological protocols, a wide range of reactions to drugs in different ethnic groups, and most importantly, the lack of caution with regard to otological symptoms due to their reversibility or lack of immediate threat to life. Drug-induced ototoxicity is a functional disorder of the inner ear (cochlea and/or vestibular apparatus) or eighth pair of cranial nerves. Pharmacotherapy, associated with the development of ototoxic drug reactions, may remain undervalued for a long time, often until irreversible hearing impairment is formed. The most frequently prescribed drugs that cause ototoxic phenomena include anticancer drugs, antibacterial drugs of the aminoglycoside group, loop diuretics, calcium channel blockers, non-steroidal anti-inflammatory drugs, antimalarial drugs, salicylates, etc. Monitoring the degree of hearing impairment before and during therapy is important in preventing the development of drug-induced ototoxicity and makes it possible to consider alternative treatment regimens in a timely manner. It is in this connection that the role of participation in the appointment of rational pharmacotherapy to patients with a potential risk of developing otological phenomena of a clinical pharmacologist and audiologist undoubtedly increases.

[Evidence database for deprescribing of antipsychotic drugs in elderly and senile patients]. / Dokazatel'naia baza snizheniia kolichestva i doz antipsikhotikov u patsientov pozhilogo i starcheskogo vozrasta.

The review deals with the problem of polypragmasia and associated adverse drug reactions, which is very relevant for the elderly and senile age. Based on the frequent unjustified prescription of antipsychotic drugs in clinical practice and the serious consequences associated with it, especially in elderly people with cognitive impairment, the aim of this review was to analyze the current literature and an evidence base for antipsychotic therapy optimization in elderly. One of the most effective way to decrease drug-associated harm is deprescribing, the planned process of decreasing dose, discontinuation of drug or switching to another one aimed to improve quality of life of the patient. The article describes different types of deprescribing, presents the results of the analysis of literature on deprescribing of antipsychotics in long-term use in elderly patients with dementia. Central to this is the analysis of a systematic review of Cochrane E. Van Leeuwen and co-authors (2018), the leading research in the evidence base of deprescribing. Based on the available literature, the authors make the conclusion about the safety of deprescribing of antipsychotic drugs. The effect of abrupt discontinuation of treatment with antipsychotic drugs was evaluated in available literature. Most of the evidence relates only to residents of nursing homes or to patients in long-term psychogeriatric or geriatric wards (in-patient treatment). However, the evidence base of deprescribing of antipsychotic drugs is small, many studies have methodological limitations, the initial characteristics of the patients included in the study are extremely heterogeneous, methodologies for diagnosing and determining the severity of dementia, types and dosages of antipsychotic drugs, duration of observation periods differed greatly. Attention is drawn to the short duration of observation periods. All of the above dictates the need for specially planned randomized clinical trials, the results of which will develop detailed algorithms for deprescribing antipsychotics.

[The Prediction Model of Cardiovascular Events Among the Russian Population: Methodological Aspects].

Modeling is the common approach for predicting not only the population health, but also the social and economic burden of disease, which is an important argument while making decisions in health care and prevention. AIM: To develop the model for predicting cardiovascular risk, applicable for the assessment of clinical and socio-economic effects of preventive and therapeutic actions at the level of the whole population or part (region, city, group of patients). MATERIAL AND METHODS: An analytical model for making decision was performed by using a Markov model consisting of Markov states and probabilities of transition from one state to another within a certain time interval. The model included risk factors and cardiovascular diseases (blood pressure, cholesterol, smoking) and probabilities of transition between them. Data was standardized by age for both males and females. Multivariate sensitivity analysis was performed. The literature search conducted using eLIBRARY.RU (http://elibrary.ru) and CyberLeninka (http://cyberleninka.ru). Consultations with experts in the field of coronary heart disease, stroke, heart failure were carried out. RESULTS: The model, allowing to compare the outcomes of two scenarios (absence/presence of intervention). The model included risk factors: arterial hypertension, smoking, hypercholesterolemia, and important CVD: coronary artery disease, myocardial infarction, unstable angina, heart failure, chronic heart failure after myocardial infarction, transient ischemic attack, stroke, atrial fibrillation. There was absorbent state - death. At the output from the model the patient state was defined as the sum of the Markov states characteristics during the model time horizon. Each result had the cost and outcome, which values could be calculated by simulation modeling ("cohort simulation"). The data analysis from prospective study had shown that mortality increases with age, as expected, but in different age groups impact of cardiovascular causes was different and declined with age. In the case of the blood pressure there was the expected increase of the death risk with the growth of pressure levels, both for males and females, except for males 60-64 years old who had a minimal risk of death at the blood pressure 140-149/90-99 mmHg, and among males with normal blood pressure the risk was higher. Smoking was associated with an expected increase of the death risk among all age groups in both sexes. In males, aged 40-64 years, the death risk was higher at the normal levels of cholesterol (2-5 mmol/l), than at the cholesterol levels equal 5-7 mmol/l. There were no data sources to assess probability of occurrence of the risk factors (hypertension, smoking, hypercholesterolemia) in patients who did not have these factors previously in our studies, and available literature. This requires the prospective studies on at least two slices of surveys (not just with the endpoint analysis). Analysis of the literature on search of prospective Russian studies that would evaluate the probability of transition from one state to another, and consultations with experts have identified that currently conducted studies do not provide all the necessary probability of transition on the basis of national data. In the absence of local data for the model is acceptable to use the results of meta-analyzes of international studies. CONCLUSION: Markov model will allow for prediction the effectiveness of different interventions, including their socio-economic consequences. The created model will allow in the future to make changes with the appearance of the results of new studies or new data in order to improve modeling accuracy.

[Studies on the function of external respiration in adults and children with anomalous position of the heart chordae]. / Dannye issledovaniia funktsii vneshnego dykhaniia u vzroslykh i detei s anomal'no raspolozhennymi khordami serdtsa.

AIM: To compare respiratory function in adults and children whose heart chordae were in anomalous position (AC) with reference to severity of heart connective tissue dysplasia syndrome. MATERIALS AND METHODS: The study included ninety one 6-14-year-olds and 125 adults with AC. The patients were divided into groups by the degree of atrioventricular valvular prolapse (AVVP). External respiration function was examined, and the loop flow-volume was registered by the pulmonological computer system. Inhalation bronchospasmolytic test with berotec was performed. RESULTS: Tracheobronchial dyskinesia related in degree to AVVP severity was found in 76 and 35% of the adults and children with AC and AVVP, respectively. The berotec test allowed more precise evaluation of tracheobronchial dyskinesia. CONCLUSION: Functional insufficiency of the connective tissue in patients with cardiac connective tissue dysplasia syndrome progresses with age.