А с т р а х а н с к а я г о с у д а р с т в е н н а я м е д и ц и н с к а я а к а д е м и я » , г. А с т р а х а н ь :Н П И к р а е в о й и н ф е к ц и о н н о й п а т о л о г и и А Г М А. г. А с т р а х а н ь И зу ч ен а ч асто та встр ечаем ости н еж елательн ы х побочны х р е ак ц и й н а п р о ти во ту б ер к у л езн ы е п р еп араты у вп ер вы е вы явл ен н ы х больн ы х ту б ер к у лезо м л егк и х п о д а н н ы м Г Б У З « О б л аст н о й кл и н и ч ески й п р оти вотуб еркул езн ы й д и сп ан сер» г А страхан и в 2 0 1 2-2 0 1 3 гг И сследо ван и е о тр аж ает ви ды н х ар ак те р н еж елательны х побочны х р еак ц и й на сп ец и ф и ч еск и е х н м н о п р еп а р агы У становлено, ч т о н а к о м б и н ац и ю п р о ти в о ту б ер к у л езн ы х п реп аратов н еж ел ател ь н ы е п обоч н ы е р еак ц и и встречаю тся чащ е, чем н а один п р о ти во ту б ер к у л езн ы й п р еп ар ат П о к азан а г ф ф е к т н в н о с т ь сп ец и ф и ч еск о й т ерап и и п ри н еж елательн ы х побочны х эф ф ек тах К лю ч евы е слова ту б е р к у л е з л е гк и х , п р о т и в о т у б е р к у л е зн ы е п реп араты , э ф ф е к т и в н о с т ь сп ец и ф и ч е с к о г о л е ч е н и я , п обоч н ы е эф ф е к т ы , м и к о б ак тер и я ту б е р к у л е за, хн м н о п р еп ар агы UNFAVORABLE SIDE EFFECTS ТО FIRST LINE ANTI-TUBERCULOSIS DRUGS
Введение Эффективной защитой от различных эндои экзотоксинов служит система биотрансформации, в частности, семейство ферментов глутатион-S-трансферазы (GST) [1]. Конъюгации с глутатионом подвергаются ксенобиотики с различной химической структурой, такие как эпоксиды, ареноксиды, гидроксиламины и т. д. В организме человека в основном экспрессируются GST классов µ (GSTМ), θ (GSTТ), π (GSTР). Среди них наибольшее значение в метаболизме ксенобиотиков играют GST класса µ. На данный момент выделено 5 изоферментов GSTМ (1-5). Ген GSTМ локализован в первой хромосоме локусе 1р 13.3. GSTМ1 экспрессируется в печени, почках, надпочечниках, желудке [2, 3]. Анализ данных литературы свидетельствует о наличии гендерных и этнических различий в формиро
Aim. To study the prevalence of С734A polymorphic marker of CYP1А2 genotype in population of children of different ethnical groups, and to estimate the phenotypic activity of CYP3A4 izoenzyme by age and gender for further increasing the theophylline treatment safety in children with bronchial asthma. Methods. 250 healthy children aged from 1 to 10 years from different ethnical groups (Russians, Kalmyks, Ingush, Chechens, Tatars). Each ethnical group consisted of 50 children. CYP1А2 izoenzyme genotype (by С734A polymorphic marker) was detected by polymerase chain reaction. CYP3A4 izoenzyme of liver cytochrome P 450 activity was measured by calculating urine 6-β-hydrocortisone level to urine cortisol level ratio. Urine 6-β-hydrocortisone and cortisol levels were measured by high precision Liquid chromatography-mass spectrometry. Results. It is the first time when high prevalence of CYP1А2 genotype was reported in children of 5 different nationalities living in Astrakhan region, associated both with slow and rapid CYP1А2 substrate drug metabolism, showing the importance of further individual studies on CYP1А2 genotype polymorphism. Age and gender-related features of CYP3A4 izoenzyme phenotype activity, that should be taken into account while choosing the most effective and safe methylxanthines dosing, were revealed. Conclusion. Before the long-term drug therapy of bronchial asthma using theophylline it is rational to investigate CYP1А2 gene polymorphism and CYP3A4 izoenzyme phenotype activity to increase treatment safety.
BACKGROUND: There is currently no widespread implementation of pharmacogenetic testing (PGx) methods in the practice of phthisiology service. OBJECTIVE: The aim of this study is to determine how informed and prepared phthisiologists, residents, and postgraduate students of the Russian Medical Academy of Continuing Professional Education (RMACPE, Moscow) use PGx techniques in their work to improve treatment safety, predict the occurrence of adverse reactions (ADRs), and personalize therapy. METHODS: A survey was conducted among phthisiologists (n = 314) living in different regions of the Russian Federation and studying at RMACPE, such as residents and post-graduate students (n = 185). The survey was developed on the Testograf.ru web platform and had 25 questions for physicians and 22 for residents and post-graduate students. RESULTS: More than 50% of respondents are ready to use PGx in clinical practice and thus are aware of the method’s possibilities. At the same time only a small part of participants were aware of the pharmgkb.org resource. The absence of PGx in clinical guidelines and treatment standards, according to 50.95% of phthisiologists and 55.13% of students of RMACPE, the absence of large-scale randomized clinical trials, according to 37.26% of phthisiologists and 43.33% of students, and the lack of physician knowledge on PGx, according to 41.08% of phthisiologists and 57.83% of students, are all factors that prevent the implementation of PGx in Russia. CONCLUSION: According to the survey, the overwhelming majority of participants recognize the importance of PGx and are willing to use the method in practice. However, there is a low level of awareness among all respondents about the possibilities of PGx and the pharmgkb.org resource. The implementation of this service could significantly increase patient compliance, lower ADRs, and enhance anti-tuberculosis (TB) therapy quality.
Relevance. The problem of antiplatelet therapy resistance is not fully solved, whereas its manifestations in the form of stent thrombosis cause a negative contribution in treatment and can lead to significant economic damage to the healthcare system. Pharmacogenetic testing as a personalization tool can potentially reduce the cost of treatment, which requires pharmacoeconomic research of pharmacogenetic methods. The aim of this study was a pharmacoeconomic evaluation of the pharmacogenetic testing implementation before the antiplatelet therapy in patients with acute coronary syndrome after percutaneous coronary intervention. Methods. In our study, a decision tree model was built with a time horizon of 1 year and a cost-effectiveness analysis was performed for six compared treatment strategies in patients with acute coronary syndrome after stent implantation with and without genotyping for the drugs clopidogrel, ticagrelor and prasugrel. Results. A treatment strategy with pharmacogenetic testing and the choosing of prasugrel for slow and intermediate metabolizers was the most preferred with CER 35 577.40 rubles per 1 unit of effectiveness. The most expensive strategy was the “blind” use of ticagrelor for all patients. Conclusion. Based on the modeling results, it can be concluded that the implementation of pharmacogenetic testing before prescribing antiplatelet drugs in patients with acute coronary syndrome undergoing stenting can potentially reduce the incidence of adverse events such as stent thrombosis and reduce the overall cost of treatment.
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