[Current challenges for therapy of comorbid patients: a new look at celecoxib. A review].

The use of non-steroidal anti-inflammatory drugs (NSAIDs) for a wide range of diseases is increasing, in part due to an increasing elderly population. Elderly patients are more vulnerable to adverse drug reactions, including side effects and adverse effects of drug-drug interactions, often occurring in this category of patients due to multimorbidity and polypharmacy. One of the most popular NSAIDs in the world is celecoxib. It is a selective cyclooxygenase (COX)-2 inhibitor with 375 times more COX-2 inhibitory activity than COX-1. As a result, celecoxib has a better gastrointestinal tract safety profile than non-selective NSAIDs. Gastrointestinal tolerance is an essential factor that physicians should consider when selecting NSAIDs for elderly patients. Celecoxib can be used in a wide range of diseases of the musculoskeletal system and rheumatological diseases, for the treatment of acute pain in women with primary dysmenorrhea, etc. It is also increasingly used as part of a multimodal perioperative analgesia regimen. There is strong evidence that COX-2 is actively involved in the pathogenesis of ischemic brain damage, as well as in the development and progression of neurodegenerative diseases, such as Alzheimer's disease. NSAIDs are first-line therapy in the treatment of acute migraine attacks. Celecoxib is well tolerated in patients with risk factors for NSAID-associated nephropathy. It does not decrease the glomerular filtration rate in elderly patients and patients with chronic renal failure. Many meta-analyses and epidemiological studies have not confirmed the increased risk of cardiovascular events reported in previous clinical studies and have not shown an increased risk of cardiovascular events with celecoxib, irrespective of dose. COX-2 activation is one of the key factors contributing to obesity-related inflammation. Specific inhibition of COX-2 by celecoxib increases insulin sensitivity in overweight or obese patients. Combination therapies may be a promising new area of treatment for obesity and diabetes.

[Problems of polypragmasia and drug interaction in the treatment of uncomplicated acute rhinosinusitis]. / Problemy polipragmazii i lekarstvennogo vzaimodeistviya v terapii neoslozhnennogo ostrogo rinosinusita.

This publication discusses polypragmasia and drug interactions in the treatment of uncomplicated acute rhinosinusitis in children and adults. Treatment of rhinosinusitis on an outpatient basis in multimorbid patients may be accompanied by multiple prescriptions, which increases the risk of drug interactions. The article reflects the most significant inappropriate combinations of both medicines and biologically active additives, herbal preparations. The advantages of using drugs with proven effectiveness, in particular intranasal glucocorticosteroids, are considered.

[The use of antidepressants for the treatment of chronic pain: a focus on elderly patients.]

A possible tool to improve the efficacy and safety of managing elderly and senile patients with chronic pain may be the use of adjuvant analgesics, in particular, antidepressants. Available clinical data indicate the possibility of using antidepressants as an alternative to opioid analgesics and non-steroidal anti-inflammatory drugs. The review includes the analysis of the comparative characteristics and peculiarities of prescribing tricyclic antidepressants, selective serotonin and norepinephrine reuptake inhibitors, and selective serotonin reuptake inhibitors as painkillers in elderly patients. Recommendations are given on the use of various representatives of the antidepressant group in elderly patients with various types of pain, aimed at minimizing possible adverse drug reactions and improving the quality of life of this category of patients.

Features of the choice and the use of antiepileptic drugs as analgesics in elderly.

High prevalence of chronic pain in elderly results in active search of new approaches for the effective and safe management of this category of patients. Antiepileptic drugs may provide analgesic affect in different types of chronic pain (mainly, in neuropathic pain). Variety of antiepileptics used as analgesics have variable efficacy and safety profile in elderly. «Old¼ antiepileptics (phenobarbital, clonazepam, ethosuximide, carbamazepine, phenytoin, valproate, etc.) and «new¼ (gabapentin, pregabalin, oxcarbazepine, lamotrigine, levetiracetam, topiramate, zonisamide, tiagabine) are considered in this review with insights on pharmacokinetic features of these drugs in elderly, profile of side effects, parameters of analgesic efficacy.

[Pharmacoeconomics analysis of using a fixed combination of budesonide/formoterol in patients with asthma in the health care system of the Russian Federation].

AIM: To evaluate the budgetary impact of using budesonide + formoterol (Symbicort Turbuhaler) as maintenance therapy in real clinical practice compared with standard therapy for asthma of varying severity: for mild asthma with on-demand salbutamol; for moderate and severe asthma with the drug salmeterol + fluticasone and salbutamol on demand. MATERIALS AND METHODS: A static mathematical model was built to assess the impact on the budget when introducing the drug budesonide + formoterol (Symbicort Turbuhaler) in the treatment of asthma into clinical practice from the point of view of the state. Demographic data was taken from the official data of the Federal State Statistics Service. Direct medical costs included the cost of medicines, the cost of hospitalization of patients associated with the development of asthma exacerbations, and the cost of scheduled outpatient visits. Indirect costs considered the loss of GDP due to hospitalization of patients against the background of asthma exacerbations. A one-way sensitivity analysis was performed to confirm the robustness of the study results. RESULTS: Assessment of direct costs in the treatment of mild, moderate and severe asthma showed that a gradual increase in the proportion of patients receiving the drug budesonide + formoterol (Symbicort Turbuhaler) over the years to 5.5, 7.7 and 9.7% accordingly, led to an increase in the cost of pharmacotherapy over 3 years by 1.7 billion rubles, while direct non-drug costs associated with the treatment of complications that developed during the treatment of asthma decreased by 8.3 billion rubles. Thus, the reduction in total direct costs amounted to RUB 6.7 billion. At the same time, indirect costs decreased by 6.0 billion rubles. The total reduction in all costs (direct and indirect) when switching patients to budesonide + formoterol (Symbicort Turbuhaler) amounted to 12.5 billion rubles. In addition, the use of the drug budesonide + formoterol (Symbicort Turbuhaler) resulted in a decrease in the number of exacerbations: in the first year by 3137, in the second by 4393 and in the third by 5534 cases. A total of 13 064 asthma exacerbations were prevented over 3 years. CONCLUSION: Increasing the proportion of patients with asthma of varying severity receiving therapy with budesonide + formoterol (Symbicort Turbuhaler) will reduce the financial burden on both the healthcare system and the budgetary system.

[Rational treatment of patients with functional dyspepsia].

Functional dyspepsia is one of the most common functional disorders of the gastrointestinal tract, which resulted from impaired motor skills, visceral hypersensitivity, increased mucosal permeability, disorders of the autonomic nervous system, etc. There is no specific therapy for this disease, which often leads to the irrational use of various groups of drugs. Drug therapy is recommended only during periods of symptoms. The main options of pharmacotherapy include the use of proton pump inhibitors, phytotherapeutic drugs, eradication therapy of Helicobacter pylori. Against the background of possible motor disorders, prokinetics are also one of the possible treatment options, but cisapride has long been withdrawn from sale due to cardiotoxicity, the use of domperidone and metoclopramide is limited due to side effects, especially with long-term therapy, so currently the only prokinetic that can be used in everyday clinical practice is itopride. In refractory cases, tricyclic antidepressants and psychotherapeutic approaches are another effective treatment option.

[Pharmacotherapy for acute respiratory infections caused by influenza viruses: current possibilities].

Routinely the influenza virus significantly contributes to the formation of the annual incidence of acute respiratory infections, with a peak in winter season. The high level of mutagenic potential of influenza viruses is a standard factor determining the complexity of the rational choice of pharmacotherapy. The upcoming epidemiological season 20202021 brings additional challenges for health care practitioners mediated by the widespread prevalence in the human population of a new infection caused by the SARS-CoV-2 virus affecting the respiratory system among many organs and systems. An adequate choice of pharmacotherapy tools should be based on high efficiency and safety of drugs, with a possible reduction in such negative factors as polypharmacy. This review includes comparative pharmacological characteristics of drugs with activity against RNA viruses, along with parameters of their clinical efficacy.

Prevalence and risk factors of potentially prescribing omissions in elderly and senile patients: clinical practice in Russian hospitals.

A retrospective pharmacoepidemiological study (included data from medical records of 401 patients ≥65 years of age who received treatment in hospitals) was aimed to measure prevalence of potentially prescribing omissions (PPOs) among older people using Screening Tool to Alert doctors to Right Treatment 2 (START-2) criteria (2015) and to investigate associated risk factors. Statistical analysis includes methods of parametric and nonparametric statistics. We compared patients who had PPOs with those had not PPOs. It was found that hypertension, diabetes mellitus and high levels of concomitant diseases were more characteristic for people with PPOs, and they received more medications. There were no significantly differences in terms of age and gender. Polypharmacy was observed in 36,7% of patients. Using the START-2 criteria, 633 episodes of PPOs were indicated (67,3% of patients). 94,7% PPOs were mainly associated with under-use of statins, aspirin, b-blockers and angiotensin-converting enzyme inhibitors. Multivariate analyses revealed strong association of PPOs prevalence with the number of prescribed medications and comorbidities, especially, ischaemic heart disease and hypertension. Cardiovascular medications were the most common among PPOs.

[Clinical and economic comparison of utilization of reslizumab, mepolizumab and benralizumab in the treatment of severe eosinophilic asthma].

During last few years, the approaches to the management of patients with severe asthma have been revised. Monoclonal antibodies (MABs), inhibitors of interleukin-5 (reslizumab, mepolizumab, benralizumab) have been recently introduced for the treatment of severe eosinophilic asthma. The mentioned drugs were approved in Russia and included into the list of Vitally Essential Drugs. AIM: The aim of this study was to compare the clinical and economic consequences of the use of biological agents that antagonize IL-5 in the treatment of severe eosinophilic asthma in adults. MATERIALS AND METHODS: Two methods of clinical and economic research were used: assessment of the cost-effectiveness ratio and analysis of the budget impact. The effectiveness of the drugs was assessed using indirect comparison; special attention was paid to comparability of the patient groups in the studies chosen for such an assessment. Two approaches were used for calculation of the cost of therapy for severe asthma: using DRGs (applicable to most regions of Russia), and without the use of DRGs, which is relevant only for few Russian regions. RESULTS: Basing on the data obtained from a budget impact study without the use of DRG, it was shown that reslizumab was dominating for patients with body mass of up to 70 kg, while for the patients with body mass of 70 to 110 kg, mepolizumab was dominating, while utilization of reslizumab appeared to be somewhat more expensive. In the group of patients with body mass over 110 kg, mepolizumab also was dominating. The calculation of the cost-effectiveness ratio (CER) showed that reslizumab appeared to be dominating over two other MABs, The results of the study using the DRG demonstrated that the cost of an annual course of benralizumab in most cases in Russia would exceed the amount that can be compensated by Territorial Funds for Mandatory Medical Insurance to a healthcare institution for therapy of bronchial asthma in one adult patient with genetically engineered drugs. Therefore, further comparisons were made for reslizumab and mepolizumab only. Analysis of the impact on the budget demonstrated that treatment with reslizumab and mepolizumab would represent a similar burden for the budget. When applying cost-effectiveness analysis, reslizumab was more cost-effective than mepolizumab (regardless of patient body mass). CONCLUSION: Thus, the results of the clinical and economic study suggested that, basing on the cost-effectiveness analysis, reslizumab appeared to be the dominant IL-5 antagonist (regardless of body mass if DRG approach was used and in patients with body mass up to 110 kg, if such an approach was not used). Basing on budget impact analysis, calculations without use of DRG approach showed superiority of reslizumab over mepolizumab and benralizumab for the patients with body mass up to 70 kg and the DRG-based approach showed equal burden for the budget for reslizumab and mepolizumab for the patients with any body mass.

[The concept of chronic obstructive pulmonary disease clinical control as a decision - making tool in real clinical practice for optimizing of basic pharmacotherapy].

The main goals of COPD therapy are to achieve clinical stability with minimal clinical manifestations and low risk of relapse. The proposed COPD control concept by analogy with asthma has not been quite well characterized yet. COPD control is defined as "the long - term maintenance of a clinical situation with a low impact of symptoms on the patient's life and absence of exacerbations." The situation of clinical control in COPD is considered desirable and potentially achievable for most patients with COPD. Pharmacotherapeutic options for COPD are constantly expanding. The control concept may be useful when the decision on treatment of COPD is made for dynamic adjustment of the therapy volume.

[Modern pharmacotherapy of uncomplicated infections of the lower urinary tract: the position of antibacterial and herbal preparations].

Lower urinary tract infections (UTIs) are one of the most common types of infections in women. The existing high risk of recurrent forms, including relapses and reinfection, suggests the paramount importance of the pharmacotherapy strategy chosen by the doctor for the primary episode of lower urinary tract infection, especially acute cystitis, determining the degree of rehabilitation. Current data on the resistance of the main pathogens of UTI to many broad-spectrum antibacterial drugs, on the one hand, and the risk of subsequent resistance formation with the use of reserve antibiotics, such as fluoroquinolones, cephalosporins of 3-4 generation, on the other hand, make the search for optimal antibiotic therapy an urgent task for clinical pharmacologists, urologists and therapists. The article presents an analysis of current data on the prevalence and resistance of major pathogens and provides an review of international and Russian clinical recommendations for the management of patients with lower UTIs, especially acute cystitis, including an analysis of the positions of antibacterial and herbal drugs.

[Symptomatic slow-acting drugs in the treatment of osteoarthritis: focus on glucosamine preparations]. / Simptomaticheskie lekarstvennye sredstva zamedlennogo deistviya pri lechenii osteoartrita: fokus na preparaty glyukozamina.

The article discusses the place of symptomatic slow-acting drugs in current guidelines for the treatment of osteoarthritis. Special emphasis is put ot glucosamine preparations, the attitude towards which, until recently, was ambiguous. The results of experimental and clinical studies demonstrating the advantages of crystalline glucosamine sulfate over preparations/food additives of glucosamine hydrochloride are presented. The differences in the pharmacodynamics and pharmacokinetics of glucosamine sulfate and glucosamine hydrochloride, which may be the reason for the ineffectiveness of the latter in clinical trials, are discussed.

[Gerontology Issues in Cardiology Practice].

Increase in life expectancy during the second part of the 20th century is accompanied by increase in proportion of elderly and senile age population. However, despite the increase in life expectancy, the prevalence of most chronic diseases and functional impairments rises with age. Elderly and senile age is associated with the risk of cardiovascular diseases (CVD), therefore the problem of managing elderly patients with CVD becomes especially urgent.

[Muramyldipeptide - based compounds in current medicine: focus on glucosaminylmuramyl dipeptide].

The role of immune mechanisms in the pathogenesis of almost all human diseases shown in recent decades, increase in antibiotic resistance and secondary immunodeficiency, aging of the population and widespread use of immunosuppressive drugs and procedures suggest a wider use of immunomodulators in current clinical practice, but the use of most of them limits the lack of knowledge. The most promising compounds for the development as immunomodulating agents and adjuvants for a wide range of vaccines are low molecular weight fragments of peptidoglycan - muramylpeptides. The article describes the mechanisms of action of muramylpeptides, their biological effects and properties of medicines developed on their basis. Special emphasis is placed to glucosaminylmuramyl dipeptide registered in the Russian Federation under the trade name Likopid, which is currently the best - studied drug in its group. The results of Likopid studies when used as a prophylactic and therapeutic agent for infections of various localization in adults and children, for oncological diseases and complications of chemotherapy and radiation therapy, psoriasis, atopic and other diseases are presented. It is emphasized that in diseases associated with human papillomavirus and plaque psoriasis, according to current criteria of evidence - based medicine, Likopid should be classified as drug with level A efficacy (high efficiency in 80-100% of patients). High safety of Likopid in adults and children, including newborns, is noted.

Methods of Pharmacological Treatment of Chronic Thromboembolic Pulmonary Hypertension Current Approaches to the Patients Management.

In this paper we have discussed epidemiology, pathogenesis, and approaches to treatment of chronic thromboembolic pulmonary hypertension (CTEPH). CTEPH is a unique potentially curable form of pulmonary hypertension. The gold standard of CTEPH treatment is pulmonary thromboendarterectomy. However, about 40% of patients with CTEPH are inoperable due to distal surgically inaccessible lesions of the pulmonary vasculature, severe hemodynamic impairments, or other contraindications. In addition, nearly half of patients have persistent or recurrent pulmonary hypertension following surgery. Current guidelines support the use of pharmacotherapy in these patients. In the article we have presented results of main clinical studies of targeted drugs therapy (endothelin receptor antagonists, prostanoids, phosphodiesterase type 5 inhibitors, soluble guanylate cyclase stimulators) of patients with CTEPH. The only drug that has demonstrated robust clinical efficacy in terms of improvment hemodynamic parameters, exercise capacity and patients' quality of life is the stimulator of the soluble guanylate cyclase riociguat. The efficacy and safety of riociguat have been investigated in short-term and long-term studies with follow-up up to 6 years. Results of these studies have constituted the basis forits approval by the regulatory authorities of more than 50 countries for the treatment of inoperable CTEPH and persistent or recurrent CTEPH after pulmonary thromboendarterectomy. In the European Union, USA and many other countries, riociguat is the only pharmacological agent approved for these indications.

[Vascular endothelial growth factor inhibitors in the treatment of neovascular age-related macular degeneration]. / Primenenie blokatorov éndotelial'nogo faktora rosta sosudov pri lechenii vozrastnoĭ neovaskuliarnoĭ makuliarnoĭ degeneratsii.

Neovascular age-related macular degeneration (AMD) is the leading cause of vision loss in older patients. An important role in angiogenesis is played by regulatory mechanisms (an increase in the number of proliferating endothelial and stromal cells and morphological alterations in the vascular network) induced by factors from the vascular endothelial growth factor (VEGF) family. Since 2006, the key treatment of neovascular AMD includes agents that inhibit the activity of VEGF. This review covers the effectiveness and safety of the use of anti-VEGF agents in neovascular AMD patients. A comparison is drawn between monoclonal antibody-based therapy and a new drug from the VEGF-Trap group.

[Enoxaparin is a low-molecular-weight heparin with a complex chemical structure and various non-anticoagulant properties]. / Énoksaparin - nizkomolekuliarnyi geparin so slozhnoi khimicheskoi strukturoi i raznoobraznymi neantikoaguliantnymi svoistvami.

The paper discusses the non-anticoagulant properties of unfractionated heparin and enoxaparin and their relation to their chemical structures. It is emphasized that enoxaparin has multiple, often interrelated, non-anticoagulant effects that can complement its antithrombotic activity and enhance the efficiency of therapy in patients receiving the drug for various indications. The realization of these effects requires the complex structure with the standard distribution of molecular weight (Mw) (average Mw, about 4500 Da, as well as Mw of less than 2000 Da (<20%), 2000 to 8000 Da (>68%), and more than 8000 Da (<18%), and with the standard content of 1.6-anhidro rings (15-25%), which is determined by the source of raw materials and by the production technology of the original drug and cannot be fully reproduced when designing its bioanalogues.

[Budget impact analysis of antiplatelet therapy with ticagrelor and clopidogrel in patients with acute coronary syndrome after coronary artery bypass surgery]. / Analiz «vliyaniya na byudzhet¼ primeneniya antitrombotsitarnoi terapii tikagrelorom i klopidogrelom u patsientov s ostrym koronarnym sindromom, perenesshikh operatsiyu koronarnogo shuntirovaniya.

AIM: Clinical and economic examinations were made to study whether it is appropriate to use antiplatelet therapy (APT) with ticagrelor in combination with acetylsalicylic acid (ASA) versus a combination of clopidogrel and ASA in patients with acute coronary syndrome (ACS) following coronary artery bypass surgery (CABS). MATERIAL AND METHODS: A budget impact analysis was used. Data on the efficiency and safety of APT were taken from a relevant analysis in the subgroups of the randomized controlled trial PLATO. Direct medical cost due to APT and expenses on therapy for acute myocardial infarction, stroke, and massive bleeding, and those on medical care for patients dying from cardiovascular events and other causes, as well as indirect cost - gross domestic product (GDP) losses due to untimely death, were taken into account. The findings were assessed from the perspectives of society. RESULTS: The analysis indicated that direct medical costs per patient following CABS, both in case of calculation based on the recorded price for ticagrelor and on the median registered prices for clopidogrel generics, and based on the auction prices for comparison agents proved to be lower when clopidogrel was administered because of the higher cost of ticagrelor-based APT. At the same time GDP losses due to untimely death, as calculated per patient with ACS during post-CABS therapy with clopidogrel + ASA, were more than twice above average losses per patient taking ticagrelor in combination with ACA (107,122 and 221,645 rubles, respectively). From the registered price for ticagrelor and the median registered prices for clopidogrel generics, the total costs per patient with ACS following CABS were lower if Brilinta was used in combination with ASA versus therapy with clopidogrel in combination with ASA (210,092 and 273,257 rubles per year, respectively; the cost savings were 63,165 rubles per patient per year when ticagrelor was administered). On the basis of the auction prices for comparison drugs, the total costs per patient with ACS after CABS proved to be lower if Brilinta was used in combination with ASA versus therapy with brand name clopidogrel in combination with ASA (201,018 and 293,982 rubles per patients year, respectively; the cost savings were 92,963 rubles per patient per year when ticagrelor was used). CONCLUSION: The use of ticagrelor in combination with ASA ensures resource savings to treat ACS patients undergoing CABS as compared with a regiment including a combination of clopidogrel and ASA.

Successful Tigecycline Use in Combined Therapy of Ventilator-Associated Hospital-Acquired Pneumonia: a Clinical Case.

In patients under artificial lung ventilation (ALV) there is often observed development of severe ventilator-associated pneumonia (VAP) due to polyresistant hospital pathogens. It should be noted that in the patient described here with the initial diagnosis of community-acquired pneumonia rapidly subjected to prolonged ALV the previous antibacterial therapy by broad spectrum drugs significantly increased the risk of contamination just by multiresistant nosocomial strains, which hampered the starting therapy of nosocomial pneumonia either when there were not available or sometimes there were available microbial cultures. When the treatment of severe pneumonias caused by multiresistant hospital flora resistant to carbapenems is actual, in the alternative therapy it could be used tigecycline, a tetracycline from the group of glycylcyclines. A case of successful treatment of nosocomial VAP by tigecycline based on the results of the bronchoalveolar lavage (BAL) culture is described. The case is of interest because tigecycline was used as off label.

[The use of intranasal glucocorticosteroids in the treatment of rhinosinusitis: Focus on mometasone furoate]. / Intranazal'nye glyukokortikosteroidy v terapii rinosinusita: fokus na mometazona furoat.

The authors discuss the mechanism of action, effectiveness, and safety of intranasal glucocorticosteroids (inGCS) used to treat acute, recurrent and chronic rhinosinusitis (RS). The last version of the European guidelines concerning the application of inGCS assigns the highest level of evidence-Ia and the highest strength of recommendations-A to these medications when applied for the treatment of acute and polypoid rhinosinusitis. Moreover, they acquire the status of the agents of choice for the therapy of chronic RS without polyps. Mometasone furoate is one of the best explored preparations of this group of medicines. It is possessed of favourable pharmacodynamic and pharmacokinetic properties when prescribed for local application. The new mometasone furoate preparation in the form of an intranasal spray Dezrinit produced by "Teva" Ltd. was registered in the Russian Federation. In a comparative randomized clinical trial (RCT), the preparation was shown to be an equivalent to the Nasonex spray.