ПУТИ ПОВЫШЕНИЯ БЕЗОПАСНОСТИ КОМБИНАЦИИ ЛЕКАРСТВЕННЫХ СРЕДСТВ, ОКАЗЫВАЮЩИХ ВЛИЯНИЕ НА ИНТЕРВАЛ QT, В АМБУЛАТОРНО-ПОЛИКЛИНИЧЕСКОЙ ПРАКТИКЕ

Prolongation of QT interval is a predictor of fatal disorders of cardiac rhythm and sudden death. Side effects of medications is one of the main causes of prolonged QT interval. In the clinical practice, drugs with potential and conventional risks of QT interval prolongation are combined. Threats of such a combination can be amplified if there is a potential of the drugs' interaction on the metabolic level. Materials and methods. In order to detect cases of drug-induced QT interval prolongation, 935 medical files of patients registered at the municipal polyclinic were analyzed. The website of drugs.com was used to categorize clinical significance of interaction between drugs. Results. In a municipal polyclinic, pharmacotherapy of those with coronary disease is administered without consideration of predicted drug interaction, related to changes in the activity of isoenzymes of cytochrome P450. The prescription of clinically significant potentially dangerous combination of amiodarone + torasemide makes 13.3% out of a total number of drug combinations, causing prolongation of QT interval. The potential mechanism of interaction between amiodarone and torasemide, providing impact on QT interval prolongation on the metabolic level is a competition of substrates on the level of CYP 2C8 and the result of CYP 2C9 inhibiting by amiodarone. Conclusion: The potential to predict the prolongation of QT interval resulting from drug interaction and replacement of drugs in such combinations with some other will allow enhancing the safety of combined pharmacotherapy with drugs with potential and conventional risks of QT interval prolongation. Увеличение интервала QT является предиктором фатальных нарушений сердечного ритма и внезапной смерти. Влияние лекарственных средств (ЛС) – одна из основных причин развития синдрома удлиненного QT. В клинической практике ЛС с вероятным и условным риском удлинения интервала QT комбинируют. Опасность такой комбинации может быть усилена при наличии потенциальной возможности взаимодействия ЛС между собой на уровне метаболизма. Материал и методы. Для выявления случаев удлиненного интервала QT, обусловленного приемом ЛС, проведен анализ 935 амбулаторных медицинских карт больных, наблюдавшихся в городской поликлинике. Категоризацию клинической значимости взаимодействий ЛС проводили с использованием сайта drugs.com. Результаты. Фармакотерапия больных ишемической болезнью сердца в условиях городской поликлиники проводится без учета прогнозируемых взаимодействий ЛС, связанных с изменением активности изоферментов цитохрома Р450. Назначение клинически значимой потенциально опасной комбинации ЛС амиодарон + торасемид составляет 13,3% от общего количества комбинаций ЛС, удлиняющих интервал QT. Вероятным механизмом взаимодействия амиодарона и торасемида, влияющих на продолжительность интервала QT на уровне метаболизма, является конкуренция субстратов на уровне CYP 2С8 и ингибирование амиодароном CYP 2С9. Вывод. Возможность прогнозирования удлинения интервала QT в результате взаимодействия ЛС и замена в таких комбинациях ЛС другими позволит повысить безопасность комбинированной фармакотерапии при применении ЛС с вероятным и условным риском удлинения интервала QT.

ОЦЕНКА И ВЕДЕНИЕ ЖЕЛУДОЧНО-КИШЕЧНЫХ ТЯГОСТНЫХ СИМПТОМОВ У ВЗРОСЛЫХ ПАЦИЕНТОВ ПРИ ОКАЗАНИИ ПАЛЛИАТИВНОЙ МЕДИЦИНСКОЙ ПОМОЩИ

According to calculation methods recommended by World Health Organisation, in Russia, approximately 600,000 people (from 378,46 to 561,52 per 100,000 population) are need of palliative care. Palliative care includes various medical interventions aimed at pain relief and management of other severe manifestations of the disease, life quality improvement of incurably ill citizens and this care can be provided on the out-patient and in-patient basis by medical workers who had training in the provision of such care (pp. 36 of FZ-323). Due to the above, it is necessary to work out standard approaches to assessment and management of main severe symptoms in the patients in need of palliative care. The article discusses the opportunities for management of severe gastrointestinal symptoms in the adults patients in need of palliative care with life expectancy from several weeks to several years. Pharmacological and non-pharmacological methods, individual approach attentive to details are to be combined for the effective management of severe events. Согласно рекомендованным Всемирной организацией здравоохранения методам расчета, в РФ потребность в паллиативной медицинской помощи (ПМП) взрослому населению составляет около 600 тыс. человек (от 378,46 до 561,52 на 100 тыс. населения). ПМП является комплексом медицинских вмешательств, направленных на избавление от боли и облегчение других тяжелых проявлений заболевания, в целях улучшения качества жизни неизлечимо больных граждан и может оказываться в амбулаторных и стационарных условиях медицинскими работниками, прошедшими обучение по оказанию такой помощи (ст. 36 ФЗ № 323-ФЗ). В связи с этим возникла необходимость стандартизации подходов к оценке и купированию основных тягостных симптомов у пациентов, нуждающихся в оказании ПМП. В статье обсуждаются возможности купирования желудочно-кишечных тягостных симптомов у взрослых паллиативных пациентов с ожидаемой продолжительностью жизни от нескольких недель до нескольких лет. Для эффективного купирования тягостных проявлений необходимо использовать сочетание фармакологических и нефармакологических методов коррекции, индивидуальный подход с вниманием к деталям.

Pharmacotherapeutic approaches targeting stable angina: simple solutions to complex problems

Cardiovascular diseases, especially coronary heart disease (CHD), are the leading cause of disability; various registry data show that the annual mortality rate of such patients is 2–3%. This explains the interest of practitioners in the pharmacotherapy of stable forms of coronary artery disease using current progress in the understanding of the pathogenesis of this disease and treatment compliance. Features of the pathogenesis of CHD in the form of increased myocardial oxygen demand, increased pre- and afterload on the performance of the heart necessitate the prescription of rhythm-reducing drugs such as beta-blockers, calcium channel blockers, ivabradine or their combinations, as well as nitric-containing drugs; trimetazidine, ranolazine for the purpose of myocardial cytoprotection. However, the use of hemodynamic drugs (beta-blockers, calcium channel blockers) does not always effectively relieve the symptoms of angina pectoris, even when used in combination with other drugs. This dictates the need to improve the drug effect on the ischemic myocardium with due account for the hypoxia-induced metabolic dysfunction of cardiac myocytes. In this regard, the use of trimetazidine at the initial stages of ischemia  – at the level of  metabolic dysfunction does not allow for the development of delayed complications: contractile disfunction of cardiac myocytes and myocardium in general. A wealth of clinical experience has been gained in the use of trimetazidine to treat stable angina pectoris in elderly patients, left ventricular dysfunction and symptoms of chronic heart failure. Drugs with a patient-friendly dosage regimen have been created to improve treatment compliance in patients with coronary artery disease. One of these drugs is once-daily modified release matrix tablets of myocardial cytoprotector Deprenorm OD, 70 mg. The creation of drugs with a patient-friendly dosage regimen will help boost patient compliance to medication and, as a result, reduce the frequency of angina attacks and improve the quality of life in this category of patients

INTERCHANGEABILITY OF MYOCARDIAL CYTOPROTECTORS IN PATIENTS WITH ISCHEMIC HEART DISEASE. DIFFICULT QUESTIONS –SIMPLE SOLUTIONS

Indications for myocardial cytoprotector, trimetazidine, in patients with ischemic heart disease are analyzed and justified according to evidence based medicine. Results of a multicenter randomized comparative KARDIOKANON study are discussed in terms of efficacy and tolerability of two variants of the complex 12-week treatment in patients with angina II-III functional class, based on the original and generic drugs. The study showed clinical equivalence of the generic DeprenormR (Canonpharma Production) to the original trimetazidine.</p

UBIQUINONE IN THE TREATMENT OF ARTERIAL HYPERTENSION

The paper analyses the results of published studies on co-enzyme Q10 effectiveness in patients with arterial hypertension (AH). Co-enzyme Q10 plays an important role in cell energy metabolism, as a co-enzyme and antioxidant. Blood pressure reduction could be explained not only by oxidative stress prevention, but also by improved insulin response to blood glucose elevation. Considering antihypertensive effectiveness and good tolerability of co-enzyme Q10, this medication could be recommended for AH treatment as an alternative agent, or in combination with other antihypertensive drugs. However, to obtain more evidence on the mechanisms of its antihypertensive effect, further studies of co-enzyme Q10 are warranted

Comparative study of pharmacological correction strategies for moderate cognitive impairment in hypertensive patients

Objective: to investigate the prevalence of cognitive impairment (CI) and possibilities of its pharmacological correction in hypertensive patients, by comparatively evaluating the efficiency of different treatment options: antihypertensive therapy and its combinations with vasoactive drugs and the dopamine receptor agonist piribedil.Patients and methods. At the first stage of the investigation, the prevalence of CI was assessed in a continuous sample of hypertensive patients (n=350). The second stage included a naturalistic comparative study of the efficiency of various therapeutic strategies for moderate CI (MCI) in patients with Stage 1–2 hypertension (n=91). This investigation lasted 48 weeks and consisted of a 24-week treatment period and a 24-weeks follow-up period.Results and discussion. CI was diagnosed in 83.4% of patients in the continuous sample, while it reached the level of dementia in 16.9%. Therapy aimed at achieving and maintaining blood pressure (BP) targets did not lead to the regression of MCI. However, BP correction in combination with a 24-week piribedil therapy cycle was optimal in patients with CI. By the end of treatment, the Montreal Cognitive Assessment (MoCa) scores increased from 24.5Ѓ}0.8 to 27.5Ѓ}0.6 (p&lt;0.05) and from 24.9Ѓ}0.7 to 27.1Ѓ}0.8 (p&lt;0.05) in the groups of patients randomized to supplemental piribedil alone or in combination with nootropic and/or vascular drugs, respectively. There were no intergroup differences in the groups of patients randomized to supplemental piribedil. The time course of cognitive changes in the further follow-up period showed a longterm positive effect of piribedil on cognitive function.Conclusion. It is necessary to regularly screen for cognitive dysfunction in hypertensive patients. The most effective treatment in combination with a long-term piribedil therapy cycle for hypertension-associated MCI was to promote the achievement and retention of blood pressure targets

Possibilities of coenzyme q10 as a part of complex therapy of patients with chronic heart failure and its influence on indicators of quality of life

The research objective consisted in studying of influence of coenzyme Q10 as a part of complex therapy of patients with the chronic heart failure (CHF) on indicators of quality of life in comparison with traditional therapy without coenzyme Q10 addition. The research included 75 patients with CHF 1-3 of FC, the coronary heart disease (CHD) which complicated a current with a myocardial infarction in the anamnesis In comparative aspect were analyzed dynamics of physical and psychological components of quality of life of patients with CHF 1-3 of FC under the influence of traditional therapy and traditional therapy with coenzyme Q10 addition. The indicators of quality of life defined on the basis of questionnaires of EQ-5D-DL and SF-36, supplementing a disease picture, are multiple-factor criterion for evaluation of a condition of patients with CHF 1-3 of FC. Improvement of indicators of quality of life is more expressed under the influence of traditional therapy with coenzyme Q10 addition

A patient with atrial fibrillation and comorbidities in clinical practice

This article focuses on the etiology and pathogenesis of nonvalvular atrial fibrillation in patients with comorbidities such as coronary artery disease, heart failure, type 2 diabetes, and chronic kidney disease. The authors discuss the interconnection of atrial fibrillation and these diseases, and also note the need for protection of such patients (prevention of cardioembolic stroke and other systemic embolism, reduction of coronary risk, improvement of prognosis, slowing the progression of renal dysfunction, increasing medical adherence, etc.) by adequate antithrombotic therapy that does not lose effectiveness and/or safety in presence of multiple diseases and polypharmacy

Possibilities of nicorandil for coronary insufficiency correction in patients with ischemic heart disease and diabetes mellitus type 2

Cardiovascular complications of type 2 diabetes mellitus (T2DM) are now a global health problem, due to their main cause of mortality of these patients. Ischemic heart disease (IHD) among all cardiovascular diseases occupies a leading position. The purpose of the study was comparative assessment of possibilities of coronary reserve correction in patients with stable angina and T2DM by nitrates and activator of potassium channels by nicorandil. The study included 54 patients with stable angina of 2-3 functional classes (FC) and T2DM. The dynamics of frequency of angina attacks, mean FC of angina pectoris, exercise tolerance, vasoregulatory function of endothelium under the influence of therapy with nicorandil, isosorbide dinitrate (ISDN) and isosorbide-5-Mononitrate (I5MN) were analyzed. In patients with IHD and T2DM drug of choice for long-term treatment is nicorandil with greater antianginal and anti-ischemic efficacy compared with traditional nitrates. Nicorandil effectively corrects endothelial dysfunction, without causing the development of tolerance and without reducing its effectiveness while taking hypoglycemic therapy

THE WAYS TO ENHANCE SAFETY OF COMBINATIONS OF DRUGS PROLONGING QT INTERVAL IN THE OUT-PATIENT AND POLYCLINIC PRACTICE

Prolongation of QT interval is a predictor of fatal disorders of cardiac rhythm and sudden death. Side effects of medications is one of the main causes of prolonged QT interval. In the clinical practice, drugs with potential and conventional risks of QT interval prolongation are combined. Threats of such a combination can be amplified if there is a potential of the drugs' interaction on the metabolic level. Materials and methods. In order to detect cases of drug-induced QT interval prolongation, 935 medical files of patients registered at the municipal polyclinic were analyzed. The website of drugs.com was used to categorize clinical significance of interaction between drugs. Results. In a municipal polyclinic, pharmacotherapy of those with coronary disease is administered without consideration of predicted drug interaction, related to changes in the activity of isoenzymes of cytochrome P450. The prescription of clinically significant potentially dangerous combination of amiodarone + torasemide makes 13.3% out of a total number of drug combinations, causing prolongation of QT interval. The potential mechanism of interaction between amiodarone and torasemide, providing impact on QT interval prolongation on the metabolic level is a competition of substrates on the level of CYP 2C8 and the result of CYP 2C9 inhibiting by amiodarone. Conclusion: The potential to predict the prolongation of QT interval resulting from drug interaction and replacement of drugs in such combinations with some other will allow enhancing the safety of combined pharmacotherapy with drugs with potential and conventional risks of QT interval prolongation