[Study of allelic variants of the CYP2D6 and CYP3A genes on the effectiveness and safety of tamsulosin therapy in patients with BPH: results of a pilot study].

INTRODUCTION: Tamsulosin is a member of the group of selective 1-adrenoblockers. Tamsulosin monotherapy is the most common first-line option in patients with lower urinary tract symptoms (LUTS) associated with benign prostatic hyperplasia (BPH) and can be used regardless on severity of LUTS. The CYP2D6, CYP3A4, and CYP3A5 enzymes are involved in the metabolism of tamsulosin. Carriage of different allelic variants of CYP2D6, CYP3A4 and CYP3A5, involved in its metabolism, may potentially affect the variability of efficacy and safety of the drug. AIM: To evaluate the effect of carriage of allelic variants of cytochrome P450 superfamily enzyme genes (CYP2D6*3, CYP2D6*4, CYP2D6*9, CYP2D6*10, CYP2D6*41, CYP3A4*3, CYP3A4*22 and CYP3A5*3) on the efficiency and safety of tamsulosin in patients with LUTS associated with BPH. MATERIALS AND METHODS: All phases of the study were completed by 106 patients with LUTS/BPH (N40 according to ICD 10). All patients received monotherapy with tamsulosin 0.4 mg/day for a minimum of 8 weeks. Based on the severity of symptoms, they were divided into two groups using the International Prostate Symptom Score (IPSS). In Group 1, there were patients with moderate symptoms (IPSS score of 8-19) (n=57), while Group 2 consisted of those with severe symptoms (IPSS score >20) (n=49). Treatment outcomes were assessed using the IPSS score with determination of quality of life (QoL), transrectal ultrasound with evaluation of prostate volume and residual urine, and uroflowmetry. Follow-up visits were at 2, 4, and 8 weeks after the start of therapy. Genotyping of all patients was performed using polymerase chain reaction to determine the CYP2D6 (*3, *4, *9, *10, and *41), CYP3A4 (*3, *22), and CYP3A5*3 markers. RESULTS: In the group of patients with moderate symptoms, carriers of the CYP2D6*10 and CYP2D6*41 polymorphisms showed a significantly greater reduction in symptoms according to the overall IPSS score at 8 weeks (p=0.046) and in the micturition symptom subscale starting from 4 weeks of treatment (p<0.05). Carriers of the CYP2D6*10 polymorphism in both groups were associated with a decrease in residual urine volume at 8 weeks (p<0.05). The presence of the CYP3A5*3 variant in those with severe symptoms significantly improved quality of life during therapy. Allelic variants of the CYP2D6 and CYP3A genes did not affect the frequency of adverse events. CONCLUSION: The results obtained by calculating the prognostic significance of individual polymorphic markers pointed to the contribution of CYP2D6*10 and CYP2D6*41. Tamsulosin therapy is more effective in patients with LUTS who are carriers of these allele variants. The safety parameters of tamsulosin were not influenced by the studied polymorphic variants. It was found that CYP3A5*3 was associated with an increase in the subjective assessment of the patient's quality of life, but it is too early to draw final conclusions. The issue of the contribution of genetic factors to the efficiency and safety of treatment of LUTS in BPH requires further study with a larger sample size and analyzed parameters.

[Polypragmasia and interdrug interactions as risk factors of falling in elderly patients.]

This article presents the results of the analysis of data from patients over 75 years of age from a multidisciplinary hospital with cardiovascular disease and comorbid conditions. Pharmacotherapy of gerontological patients with multiple risk factors for falls was analysed in terms of the presence of polypragmasy and drug-drug interactions hazardous to the risk of falls. In the group of patients who experienced a fall in hospital compared to patients without a fall, the prescription lists audit showed a predominance of medicines (drugs) and drug combinations compromised by an increased risk of this serious adverse event. An audit of prescriptions of patients at increased risk of falls as a means of combating polypharmacy and identifying drugs that may cause falls can be conducted using the «Traffic light classification of FRIDs¼ and drug checkers to identify clinically relevant combinations. The use of these clinical and pharmacological tools can improve the quality and safety of medical care in a hospital setting.

[Pages from the history of therapeutic schools of the Central Institute for Improvement of Doctors - Russian Medical Academy of Continuous Professional Education].

In the 1930s, therapeutic scientific and pedagogical schools were formed at the Central Institute for Advanced Training of Physicians: Cardiology School of prof. Dmitry D. Pletnev, School of Clinical Hematology and Emergency Care of prof. Alexander N. Kryukov, School of Dietetics and Gastroenterology of prof. Manuel I. Pevzner and School of Hematology of prof. Joseph A. Kassirsky. 2022 marks the 125th anniversary of the birth of an outstanding therapist, academician of the USSR Academy of Medical Sciences, Major General of the Medical Service, prof. Miron S. Vovsi. Along with the fact that M.S. Vovsi belongs to the scientific and pedagogical school of cardiology of prof. D.D. Pletnev, he managed to create his own. M.S. Vovsi is one of the creators of modern military field therapy, expanded the understanding of the pathogenesis of nephritis, pneumonia, coronary heart disease, hypertension, heart failure, he introduced new methods for diagnosing and treating these therapeutic pathologies that have not lost their relevance today.

[CYP2D6 gene polymorphic markers role in determining the optimal treatment tactics for portal hypertension in patients with liver cirrhosis].

AIM: To study the polymorphic markers CYP2D6*4 (G1846A, rs3892097), CYP2D6*6 (T1707del, rs5030655), CYP2D6*10 (C100T, rs1065852), CYP2D6*41 (G2988A, rs28371725) and CYP2D6*3 (A2549del, rs4986774) role in treatment optimization of portal hypertension with propranolol in patients with liver cirrhosis (LC). MATERIALS AND METHODS: The study included 60 patients with LC who received propranolol therapy at a daily dose of 30 mg for 14 days. The efficacy of treatment was assessed by ultrasonography measuring the linear blood flow velocity of portal vein. Genotyping of CYP2D6*4, CYP2D6*6, CYP2D6*10, CYP2D6*41 and CYP2D6*3 was carried out by real-time polymerase chain reaction. Evaluation of the CYP2D6 activity was carried out by determining the ratio of pinoline and its metabolite concentration in morning urine using high performance liquid chromatography with mass spectrometry. RESULTS: Positive hemodynamics in the form of any increase in the mean linear blood flow velocity of the portal vein compared to baseline was observed in 41 patients. Portal vein mean linear blood flow rate increased from 10.43.9 to 14.74.3 cm/s (p0.001). Of these, 29 patients showed an increase in this indicator by 20% from the initial one with a dynamic of 5.5 cm/s (p0.001). The regression analysis constructed by us revealed the presence of a statistically significant effect of the CYP2D6 gene polymorphic marker G1846A carriage on the propranolol therapeutic effect (p0.05). There was no statistically significant effect of polymorphic markers T1707del, C100T, G2988A, and A2549del of the CYP2D6 gene (p0.05). No convincing reliable dependence of CYP2D6 activity on the severity of LC was revealed (p0.05). CONCLUSION: An association was found between CYP2D6 gene polymorphic marker G1846A carriage and the hemodynamic effect of propranolol in patients with LC of the Russian population. There is a more significant positive dynamics of manifestations of portal hypertension on the background of propranolol therapy in carriers of the homozygous GG CYP2D6*4 genotype, in contrast to patients with the heterozygous GA genotype. Based on the results of the study, an algorithm has been developed for personalizing the treatment of patients with LC with nonselective b-adrenergic blockers using the method of CYP2D6 genotyping. Carriage of polymorphic markers T1707del, C100T, G2988A and A2549del gene CYP2D6 does not affect the effectiveness of propranolol therapy in patients with LC.

[Evaluation of the association of polymorphisms of the CYP2C8 gene with the efficacy and safety of ketorolac in patients with postoperative pain syndrome].

AIM: To evaluate the possible association of CYP2C8 gene polymorphisms with the clinical efficacy and safety of ketorolac in relation to postoperative pain. MATERIALS AND METHODS: The study included 107 patients after video laparoscopic cholecystectomy, who received ketorolac (30 mg 2.0 w/m 3 r/d) as postoperative pain relief. All patients were genotyped for CYP2C8. The pain syndrome was assessed using the visual analog scale, the McGill pain questionnaire. The profile of adverse reactions was assessed by the dynamics of red blood counts, as a possible trigger for the development of gastrointestinal bleeding according to the method of global assessment of triggers (Global Trigger Tool GTT). RESULTS: According to visual analog scale data: in carriers of the genotype CYP2C8*3 (rs10509681) and CYP2C8*3 (rs11572080) after 12, 24, 36, 48 hours the intensity of pain syndrome is lower than in carriers of the wild type (p0.05). According to the McGill pain questionnaire, there were no statistically significant differences in pain intensity between the two groups. CONCLUSION: In carriers of the genotype CYP2C8*3 (rs10509681) and CYP2C8*3 (rs11572080), the effectiveness of anesthesia with ketorolac is higher than in carriers of the wild type. Carriage of the genotype CYP2C8*3 (rs10509681) and CYP2C8*3 (rs10509681) does not affect the risk of developing adverse reactions after ketorolac anesthesia.

[Molecular genetic predictors of the efficacy and safety of tamsulosin therapy].

Individual differences in efficacy and safety of drugs between patients are a significant problem in modern pharmacotherapy. The bodys pharmacological response to the administration of a particular drug is determined by multiple factors, where up to 50% of the variability of the pharmacological response may be determined by the genetic variability of the body. The article presents an up-to-date review of the data on genetic polymorphisms influencing the efficacy and safety of tamsulosin therapy in patients with lower urinary tract symptoms associated with benign prostatic hyperplasia.

Effects of CYP2C19 genetic polymorphism on the steady-state concentration of citalopram in patients with major depressive disorder.

Citalopram is commonly prescribed to patients suffering from major depressive disorder. Some of them do not respond adequately to therapy with citalopram, while many of them experience type A adverse drug reactions. Current research revealed that CYP2C19 isoenzyme is involved in the biotransformation of citalopram. The objective of our study was to investigate the impact of 681G>A polymorphism of the CYP2C19 gene on the efficacy, safety and the concentration/dose indicator of citalopram. Our study enrolled 130 patients with major depressive disorder and comorbid alcohol use disorder (average age-38.7 ± 14.1 years). Therapy regimen included citalopram in an average daily dose of 31.1 ± 14.4 mg per week. Therapy efficacy and safety were evaluated using the international psychometric scales. For genotyping, we performed the real-time polymerase chain reaction. Our findings revealed the statistically significant results in terms of the treatment efficacy evaluation (HAMD scores at the end of the treatment course): (GG) 8.0 [8.0; 9.0] and (GA) 10.0 [9.0; 11.0], p < 0.001. In the safety profile (the UKU scores), the statistical significance was also obtained: (GG) 3.0 [3.0; 4.0] and (GA) 5.0 [4.0; 5.0], p < 0.001. We revealed a statistical significance for concentration/dose indicator of citalopram in patients with different genotypes: (GG) 2.543 [1.659; 4.239] and (GA) 4.196 [2.643; 5.753], p < 0.001). The effect of CYP2C19 genetic polymorphism on the efficacy and safety profiles of citalopram was demonstrated in a group of 130 patients with major depressive disorder.

[CYP2C8, PTGS-1, 2 gene polymorphisms prevalence associated with sensitivity to non-steroidal anti-inflammatory drugs among North Caucasus ethnic groups].

AIM: Find the prevalence of CYP2C8*3 (rs10509681; rs11572080), PTGS-1 (rs10306135; rs12353214) and PTGS-2 (rs20417) alleles and genotypes in four ethnic groups among Laks, Avars, Dargins and Kumyks. MATERIALS AND METHODS: The study involved 400 volunteers from four ethnic groups living in Republic of Dagestan: 100 participants from each group. Carriage of polymorphic markers was determined by reverse transcription polymerase chain reaction. RESULTS: Minor allele frequency of the CYP2C8 (rs10509681) was 5.5% in Avars, 10% in Dargins, Laks and Kumyks 6.5% both; CYP2C8 (rs11572080) was 5.5% in Avars, 9.5% in Dargins, 6.5% in Laks, 8.5% in Kumyks; PTGS-1 (rs10306135) in Avars 10.5%, in Dargins 13.0%, in Laks 9.5% and Kumyks 7.5%; PTGS-1 (rs12353214) in Avars 9.0%, in Dargins 4.5%, in Laks 7.5%, in Kumyks 8.0%; PTGS-2 (rs20417) in Avars 1.0%, in Dargins 2.5%, in Laks 3.5%, in Kumyks 5.0%. There were no significant differences between groups. CONCLUSION: The study of CYP2C8 and PTGS-1 and 2 gene polymorphisms is promising for predicting the effectiveness and safety of non-steroidal anti-inflammatory drug therapy, due to the high prevalence of these polymorphisms in ethnic groups in the North Caucasus.

[Drug therapy of atrial fibrillation in elderly patients.]

Currently, studies of the causes of atrial fibrillation are actively conducted. However, molecular and cellular mechanisms of atrial fibrillation have not been precisely established so far. Great success in the treatment of atrial fibrillation was achieved thanks to the development of surgical methods. However, these approaches, unfortunately, are not always applicable to elderly and senile patients. Antiarrhythmic drugs used in atrial fibrillation, exhibit a large number of side effects. Much attention of researchers is now attracted by fundamentally new directions in the drug treatment of atrial fibrillation. These include predserdno-selective antifibrillatory funds. Drugs, the action of which is aimed at at atrial remodeling, inflammation and fibrosis, so is of interest. Effective suppression of atrial remodeling, inflammation and fibrosis prevents the formation of a permanent form of atrial fibrillation. A new approach to the treatment of atrial fibrillation, taking into account the vegetative status of the patient, will undoubtedly increase its effectiveness.

[Results of decision support system implementation for prescribing anticoagulants to patients with atrial fibrillation in hospital].

BACKGROUND: In 819% of patients with atrial fibrillation (AF) with anticoagulant therapy (ACT), hemorrhagic complications occur, including due to excess doses of AC. At the same time, ACT is necessary for patients with AF, since anticoagulants effectively reduces the risk of ischemic stroke. To make a decision on the appointment of ACT, it is necessary to correlate the risks of ischemic stroke and bleeding, this requires knowledge of current clinical using ACT recommendations and instructions. Among patients admitted to hospital, 30% receive ACT, so increasing adherence to clinical recommendations for prescribing AC to patients with AF by doctors of various profiles is an urgent task. AIM: To analyze the adherence of physicians to recommendations for prescribing ACT before and after the introduction of decision support system (DSS) in patients with AF in a multi-specialty hospital. MATERIALS AND METHODS: A single-center non-randomized study with historical control to assess adherence to recommendations based on the analysis of medical prescriptions and the structure of drug errors in patients with AF in a multi-specialty hospital in Moscow before and after the introduction of DSS. Compliance with the recommendations of physicians was evaluated in the sections indications /contraindications to AC and dosage regimen of AC. The presence of deviations from the clinical recommendations /instructions for medical use of AC was regarded as management of the patient with non-compliance with recommendations. Physicians adherence level to recommendations was calculated as the ratio of cases of compliance with recommendations to the total number of cases. RESULTS: In the control and experimental groups, there was a significant increase in the proportion of POAC at discharge in comparison with admission to hospital: from 54.5 to 76.8% (p=0.0005) and from 63 to 85.7% (p=0.0002), respectively. However, only in the experimental group it was possible to significantly reduce the number of patients without a prescribed ACT (if there are indications) from 7.6 to 1% (p=0.04) in comparison with admission. During the study, it was possible to significantly increase physicians adherence level to the recommendations for the AC dosage regimen in patients with AF from 59% (44 discrepancies for 107 prescriptions) to 84.6% (16 discrepancies for 104 prescriptions); p0.005. Before the introduction of the DSS, the analysis of drug prescriptions revealed 56 drug errors (0.5 errors per patient), after the introduction of the DSS, the number of drug errors significantly decreased to 21 (0.2 errors per patient); p0.05. After the introduction of DSS, the number of sub-therapeutic doses of AC was reduced from 31 (27.7%) to 8 (7.6%); p0.05. CONCLUSION: The level of adherence to the recommendations for prescribing ACT to patients with AF in the hospital is high. The use of DSS increases the level of adherence to the recommendations on the AC dosage regimen in patients with AF, as well as eliminates errors in calculating the risk of ischemic stroke and systemic thromboembolic complications, and contributes to reducing the frequency of prescribing sub-therapeutic doses of AC.

[The pharmacogenetics of hypoglycemia and the glycemic variability at the patients ith type 2 diabetes mellitus].

AIM: To investigate the link between the hypoglycemia (registrated accurately by the professional Continuous Glucose Monitoring CGM; severe hypoglycemia at home) and the hetero-/homozygote carriage of single nucleotide polymorphisms (SNP) of cytochrome systems geneCYP2C9(rs1799853CYP2C9*2 иrs1057910CYP2C9*3) at the patients with Type 2 Diabetes Mellitus (T2DM) used sulphonylurea (SU). MATERIALS AND METHODS: In Study Case-Control 120 T2DM-SU-patients genotyped by SNPs of geneCYP2C9(using PCR-RT) had been done the professional CGM (System iPro2, Medtronic) recorded Time in Range of Hypoglycemia (TIR-HYPO), level of Minimal CGM-hypoglycemia (MinGl) and standard CGM-parameters of Glycemic Variability. Severe hypoglycemia at home was recorded from visit to visit. The odds ratio (OR) of metabolic disturbances had been assessed for carriage SNPs in comparison with wide alleles. RESULTS: The Study established that carriage of SNPsrs1799853andrs1057910geneCYP2C9at T2DM-SU-patients associated with rising of Glycemic Variability and frequency of CGM-hypoglycemia (MinGl decreasing, increasing of TIR-HYPO and number of Glycemia Excursion 4 mmol/L/h), as well as increasing severe hypoglycemia at home (p0.05). Thus, OR at the carriage ofrs1799853andrs1057910respectively equaled: for CGM-hypoglycemia 7.78 (3.0220.01) and 5.80 (0.23145.87); number of Glycemia Excursion 4 mmol/L/h 5.76 (2.2914.43) and 4.44 (1.4313.76); MinGl3.9 mmol/L 4.39 (1.7910.75) and 6.26 (1.8421.30); CV40% (vs30%) 3.63 (1.0412.62) and 15.22 (0.59393.94);p0.05. CONCLUSION: At the real clinical practice the assessment of carriage of SNPs of geneCYP2C9before inclusion of SU to glucose-lowering scheme of T2DM-therapy it necessary to carry out for the detecting patients with a higher risk of hypoglycemia and rising of Glycemic Variability.

[Analysis of carrying clinically significant allelic variants of TPMT and DPYD genes associated with the response to drug therapy in cancer practice among 9 ethnic groups of the Russian Federation].

AIM: To study the peculiarities of carrying clinically significant allelic variants of TPMT and DPYD genes associated with the response to drug therapy in cancer practice among 9 ethnic groups of the Russian Federation. MATERIALS AND METHODS: The study included 1446 conditionally healthy volunteers from 9 ethnic groups. Carriage of polymorphic TPMT and DPYD gene markers was detected by the Real-Time PCR (polymerase chain reaction) method. RESULTS: In all ethnic groups, the distribution of genotypes and alleles matched the equilibrium of Hardy-Weinberg. TPMT*3A (rs1800460) and TPMT*3C (rs1142345) were observed in heterozygous state in all investigated ethnic groups. In the Kabardinian group (n=204) the frequency of the TPMT*3A minor allele (MAF, %) was 2.94%; Balkars (n=200) 1.25%; Ossetians (n=239) 1.67%; Chuvashes (n=238) 1.89%: Mari (n=206) 1.21%; Tatars (n=141) 1.77%; Russians (n=134) 4.85%. The frequency of the TPMT*3C minor allele (MAF, %) in the Kabardinian group (n=204) MAF was 4.90%; Balkars (n=200) 1. 75%; Buryats (n=114) 0.44%; Ossetians (n=239) 1.88%; Chuvashes (n=238) 1.68%: Mari (n=206) 1.21%; Tatars (n=141) 1.42%; Russians (n=134) 4.48%. The results of the analysis of DPYD*2A polymorphism (rs3918290) demonstrated ethnic peculiarities of distribution. In the heterozygous state it was found only in the groups of Kabardins (n=204, MAF 1.22%), Balkars (n=200, MAF 2.00%), and Ossetians (n=239, MAF 0.63%). CONCLUSION: The results obtained in the study will be useful for developing personalized algorithms of antitumor therapy in cancer practice, including those aimed at increasing the safety of chemotherapy.

[Influence of CYP3A4, CYP3A5, and NR3C1 genes polymorphism on the effectiveness of glucocorticoid therapy in patients with endocrine ophthalmopathy]. / Vliyanie polimorfizma genov CYP3A4, CYP3A5 i NR3C1 na effektivnost' glyukokortikoidnoi terapii u bol'nykh endokrinnoi oftal'mopatiei.

For more than 60 years, glucocorticoid therapy has been practically the only method for treating patients with endocrine ophthalmopathy - non-specific autoimmune inflammation of the soft tissues of the orbit. Steroid-resistant forms of this disease are known to exist. The reasons for the formation of glucocorticoid resistance are not fully understood yet. PURPOSE: To study the possibilities of pharmacogenetic testing for the polymorphism of the glucocorticoid receptor gene NR3C1 and cytochrome P450 in predicting the effectiveness of glucocorticoid therapy in patients with edematous exophthalmos - one of the clinical forms of endocrine ophthalmopathy. MATERIAL AND METHODS: The results of glucocorticoid therapy were analyzed in 75 patients with different clinical forms of endocrine ophthalmopathy aged 27 to 84 years. All patients underwent standard ophthalmological examination, external examination of the eye with assessment of the state of periorbital tissues, determination of the shape and size of the palpebral fissure (vertical size), position of the eye in orbit, Hertel exophthalmometry, ultrasound scanning and computed tomography of the orbits. Genetic analysis of the polymorphism of the studied genes was carried out using real-time polymerase chain reaction (real-time PCR). RESULTS: The study did not find patterns in the distribution of homo- and heterozygous genotypes of A6986G polymorphic markers of the CYP3A5 gene, 6 C>T intron of the CYP3A4 gene and rs6190 of the NR3C1 gene in patients with endocrine ophthalmopathy and their effect on the glucocorticoid response (p>0.05). CONCLUSION: Results of pharmacogenetic testing of the gene for the glucocorticoid receptor NR3C1 and cytochrome P450 do not provide a reliable confirmation of the influence of the polymorphism of the studied genes on the effectiveness of glucocorticoid therapy in patients with endocrine ophthalmopathy.

Genotyping and phenotyping CYP3A4\CYP3A5: no association with antiplatelet effect of clopidogrel.

The objective of this study was to determine the impact of polymorphism of CYP3A subfamily isoenzymes (allelic variants of CYP3A4*22 and CYP3A5*3) on the efficacy clopidogrel in patients with an acute coronary syndrome (ACS), who have undergone percutaneous coronary intervention (PCI). Platelet activity was determined on a VerifyNow P2Y12 test system in 81 patients with ACS aged 37-91 who had PCI. The activity of CYP3A4/5 was expressed as the ratio of the concentrations of cortisol and 6ß-hydroxycortisol was performed by using high performance liquid chromatography. Genotyping was performed by using real-time polymerase real-time chain reaction. The frequencies for the CYP3A5 gene, rs 776746, were identified as follows: 77 (95.1%)-CC, 4 (4.9%)-CT; the allele frequencies by loci for the CYP3A4, rs rs35599367, were as follows: 78 (96.3%)-GG, 3 (3.7%)-AG. There was no statistically significant genotype-dependent difference between the presence of a minor T and G alleles and the presence of clopidogrel resistance (OR 3.53; 95% CI 0.46-26.94; p = 0.233 and p = 0.443, respectively). The average level of the metabolic relationship (6ß-hydroxycortisol/cortisol) between the clopidogrel-resistant group and the normal platelet reactivity group was not statistically significantly different: 3.3 ± 2.8 versus 3.2 ± 3.2; p = 0.947. So, the activity of CYP3A4/5 was not related to platelet aggregation rates in this model. Genotyping and phenotyping CYP3A4\CYP3A5 does not predict the antiplatelet effect of clopidogrel. More extensive research is required to establish their clinical relevance.

Effects of CYP2D6 activity on the efficacy and safety of mirtazapine in patients with depressive disorders and comorbid alcohol use disorder.

The objective of the study was to investigate the effects of CYP2D6 activity on the efficacy and safety of mirtazapine in patients with depressive disorders and comorbid alcohol use disorder who received mirtazapine. The study included 109 Russian patients who received mirtazapine at a dose of 30.0 [15.0; 45.0] mg per day. Genotyping of CYP2D6*4 (1846G > A, rs3892097) was performed using real-time polymerase chain reaction with allele-specific hybridization. The activity of CYP2D6 was evaluated by determining the concentration of endogenous substrate of the enzyme and its urinary metabolite - pinoline to 6-hydroxy-1,2,3,4-tetrahydro-beta-carboline ratio, using high-performance liquid chromatography - mass spectrometry. The statistically significant differences between the scores on the Hamilton Depression Rating Scale (HAMD) in patients with different genotypes were revealed by day 16: (GG) 5.0 [3.0; 6.0], (GA) 1.5 [1.0; 3.2] (p < 0.001), and for the The UKU Side Effects Rating Scale (UKU): (GG) 6.0 [6.0; 7.0], (GA) 8.5 [8.0; 10.0] (p < 0.001). The calculation of correlation coefficients between the differences in scale scores and metabolic rate showed the presence of statistically significant weak inverse correlation with the efficacy indicator evaluated by HAMD (r = -0.278, p < 0.05), but not by UKU (r = 0.274, p > 0.05). This study demonstrated that an increased CYP2D6 activity reduces the efficacy of treatment with mirtazapine.

[Influence of amiodarone on the spectral analysis of heart rate variability in patients with atrial fibrillation elderly and senile age.]

Atrial fibrillation is more common among elderly patients. Number of comorbidities, such as heart failure, coronary heart disease, disorders of the conduction system of the heart increases with age. Atrial fibrillation is a health problem. In developed countries, there is a high prevalence of the disease. The disease affects more than 33 million people worldwide. Spectral analysis of heart rate variability can be successfully used to evaluate the effectiveness of therapy. The use of this method gives an idea of the role of the autonomic nervous system in the regulation of chronotropic function of the heart. These data help to define conditions of manifestation of efficiency of antiarrhythmic drugs. In this study, spectral analysis were studied in patients with different forms of atrial fibrillation. The effect of amiodarone class III antiarrhythmic drug were studied this study. It is shown that the structure of spectrum of heart rate variability in patients with newly diagnosed atrial fibrillation differs significantly from that in patients with disease duration from 6 months to several years on the background of amiodarone.

[Initiation of pharmacotherapy as a risk factor for older patients.]

The article presents the literature and original data on the problems of falls in elderly patients. The connection of the fact of falling with initiation of therapy by a number of drugs known to have a negative impact on the risk of falling is considered. The article presents data on the frequency and structure of falls on the example of patients with cardiovascular diseases older than 75 years, treated in a multidisciplinary hospital. The analysis of the data showed a tendency of prevalence of the fact of falling in 1/3 patients (33,8%) in the first 5 days of hospital stay, which may be associated with high drug burden and the appointment of «new¼ drugs for the patient. The study noted that it was on the first day that the selection of therapy took place and additional drugs were often prescribed, leading to a state of polypragmasia. Analysis of individual groups of drugs was able to reliably confirm the relationship between the appointment of drugs that increase.

Prevalence of Atrial Fibrillation and use of Oral Antithrombotic Therapy in Patients with Acute Coronary Syndrome.

PURPOSE: To assess the prevalence of atrial fibrillation (AF) and use of antithrombotic agents in adult patients with acute coronary syndrome (ACS). MATERIALS AND METHODS: We consecutively enrolled all ACS patients (n=1155) who were hospitalized in two Moscowbased percutaneous coronary intervention centers (each center performs over 500 PCIs a year) between October 2017 and February 2018. AF was diagnosed in 204 patients (17.7%). The risk of thromboembolic complications was assessed using the CHA2DS2-VASc Score. The risk of hemorrhagic complications was assessed using the HAS-BLED Score. The data were processed using StatSoft Statistica 10.0 and IBM SPSS Statistics v.23 software. RESULTS: The prevalence of diagnosed AF was 13.6%, while the prevalence of undiagnosed AF was 4.1%. Of the 179 discharged patients with AF, only 2 had a low risk of ischemic stroke (IS). One hundred and fifty patients (83.8%) eligible for oral anticoagulant therapy received oral anticoagulants. Patients with diagnosed AF were administered oral anticoagulants (OACs) significantly more often than patients with undiagnosed AF [125 (91.9%) vs. 25 (58.1%), р<0.001]. Novel oral anticoagulants (NOACs) were administered four times more often than vitamin K antagonists [120 (80.0%) vs. 29 (19.3%), р<0.001]. Rivaroxaban was used in 51.3% of cases. Of the 29 patients treated with warfarin, only 3 (10.3%) achieved the target international normalized ratio (INR) at discharge. Of the 107 patients who underwent percutaneous coronary intervention (PCI), 77 patients (80%) received an OAC and two antiplatelet agents (with 74% receiving this three-agent therapy for one month), 11 patients (10.3%) received an OAC and an antiplatelet agent, and 18 patients (16.8%) received two antiplatelet agents. The only antiplatelet agent used as part of the three-agent therapy was clopidogrel. The three-agent therapy without PCI was administered in 43.1% of cases. CONCLUSION: We found that the prevalence of AF in patients with ACS was high. The fact that doctors administered NOACs suggests that they are aware of the need to use these agents to prevent thromboembolic complications in AF patients.

[Comparative clinical and economic evaluation of pharmacogenetic testing application for dabigatran in patients with atrial fibrillation].

AIM: To evaluate the clinical and economic feasibility of pharmacogenetic testing (PGT) for dabigataran etexilate administration in the treatment of atrial fibrillation (AF) without valve in comparison with tactics without pharmacogenetic testing. MATERIALS AND METHODS: The pharmacoeconomic model was done using generalized data from published clinical, epidemiological and clinical - economic studies. RESULTS AND DISCUSSION: Application of PGT on the carrier of allelic variant rs2244613 of CES1 gene for adjustment of dabigatrane etexilate dosage in patients with non - valve AF may be more cost - effective strategy for prevention of thromboembolic complications in patients with non - valve AF. Thus, due to the decrease in the number of undesirable drug reactions in the form of minor and major bleedings, the difference in treatment costs in the group with PGT compared to the group with standard pharmacotherapy tactics per 100 patients was 11 827.65 rubles. The expected cost per patient per year for standard treatment was 36 051.35 rubles, while in the group with PGT it was 35 933.07 rubles. The difference was 1182.76 rubles in favor of the pharmacogenetic approach Conclusion. A PGT approach to correct dabigatrane dosage can reduce the cost of pharmacotherapy by reducing the risk of adverse reactions of minor and major bleeding.

[Micro-RNA as a new biomarker of activity of the cytochrome system P-450: significance for predicting the antiplatelet action of P2Y12 receptor inhibitors].

MicroRNAs are short non - coding RNAs that correlate with the levels of platelet activation which can be utilized as a biomarker when guiding P2Y12 inhibitors therapy. In this literature review, the perspectives of microRNA as a novel biomarker are discussed when guiding P2Y12 inhibitors therapy among the patients with coronary artery disease.