Objectives One of the key components of ERAS is adequate pain control in the postoperative period. There are no rational schemes for postoperative pain relief. At the same time, adequate postoperative pain relief promotes early activation and early rehabilitation of patients and shortens the duration of the postoperative stay, and does not cause postoperative complications associated with analgesia (weakness, intestinal paresis, nausea and vomiting). The aims of the present study are to assess the possible association of CYP2D6 and CYP2C9 polymorphisms with the efficacy and safety of tramadol and ketorolac in postoperative pain. Methods A total of 107 patients were genotyped for CYP2D6 and CYP2C9 polymorphisms. All patients underwent laparoscopic cholecystectomy. Postoperative pain relief was carried out with ketorolac and tramadol. Postoperative pain syndrome was assessed using a visual analogue scale and McGill pain questionnaire. The profile of side effects 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. Results Pain was statistically significantly lower in CYP2C9*2 carriers, according to visual analogue scale (VAS): after 12 h – by 1.5 (p=0.002); after 24 h – by 1.1 (p=0.012); after 36 h – by 1.05 (p=0.004); after 48 h – by 0.7 (p=0.026). In CYP2C9*3 carriers the results were not statistically significant. In carriers of CYP2D6*4 pain syndromes were higher at all-time intervals, but statistically reliable results were obtained only after 2 h – by 1.01 (p=0.054) and after 24 h – by 0.8 (p=0.035). The profile of adverse reactions for NSAIDs was evaluated by the dynamics of hemoglobin and erythrocyte indices. A more pronounced decrease in the relative difference in hemoglobin levels was noted in CYP2C9*2 and CYP2C9*3 polymorphism carriers – by 1.7 (p=0.00268) and-by 2.2 (p=0.000143), respectively. Conclusions CYP2D6 and CYP2C9 can predict analgesic effectiveness of tramadol and ketorolac. CYP2C9 can predict the risk of gastrointestinal bleeding, including those hidden to ketorolac.

Objectives One of the key components of ERAS is adequate pain control in the postoperative period. There are no rational schemes for postoperative pain relief. At the same time, adequate postoperative pain relief promotes early activation and early rehabilitation of patients and shortens the duration of the postoperative stay, and does not cause postoperative complications associated with analgesia (weakness, intestinal paresis, nausea and vomiting). The aims of the present study are to assess the possible association of CYP2D6 and CYP2C9 polymorphisms with the efficacy and safety of tramadol and ketorolac in postoperative pain. Methods A total of 107 patients were genotyped for CYP2D6 and CYP2C9 polymorphisms. All patients underwent laparoscopic cholecystectomy. Postoperative pain relief was carried out with ketorolac and tramadol. Postoperative pain syndrome was assessed using a visual analogue scale and McGill pain questionnaire. The profile of side effects 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. Results Pain was statistically significantly lower in CYP2C9*2 carriers, according to visual analogue scale (VAS): after 12 h – by 1.5 (p=0.002); after 24 h – by 1.1 (p=0.012); after 36 h – by 1.05 (p=0.004); after 48 h – by 0.7 (p=0.026). In CYP2C9*3 carriers the results were not statistically significant. In carriers of CYP2D6*4 pain syndromes were higher at all-time intervals, but statistically reliable results were obtained only after 2 h – by 1.01 (p=0.054) and after 24 h – by 0.8 (p=0.035). The profile of adverse reactions for NSAIDs was evaluated by the dynamics of hemoglobin and erythrocyte indices. A more pronounced decrease in the relative difference in hemoglobin levels was noted in CYP2C9*2 and CYP2C9*3 polymorphism carriers – by 1.7 (p=0.00268) and-by 2.2 (p=0.000143), respectively. Conclusions CYP2D6 and CYP2C9 can predict analgesic effectiveness of tramadol and ketorolac. CYP2C9 can predict the risk of gastrointestinal bleeding, including those hidden to ketorolac.

Pain is a significant problem in medicine. The use of PGx markers to personalize postoperative analgesia can increase its effectiveness and avoid undesirable reactions. This article describes the mechanisms of nociception and antinociception and shows the pathophysiological mechanisms of pain in the human body. The main subject of this article is pharmacogenetic approach to the selection of anesthetics. Current review presents data for local and general anesthetics, opioids, and non-steroidal anti-inflammatory drugs. None of the anesthetics currently has clinical guidelines for pharmacogenetic testing. This literature review summarizes the results of original research available, to date, and draws attention to this area.

хирургическая гастроэнтерология surgical gastroenterologyРезюме Цель: Целью исследования было оценить возможную ассоциацию полиморфизмов гена PTGS1 (rs10306135, rs12353214) с клинической эффективностью и безопасностью кеторолака в отношении послеоперационной боли.Материалы и методы: В исследование было включено 107 пациентов после видеолапароскопической холецистэктомии, которым в качестве послеоперационного обезболивания применяли кеторолак 30 мг. 3 раза в день. Всех пациентов генотипировали по PTGS1 (rs10306135, rs12353214). Оценка болевого синдрома осуществлялась при помощи визуальноаналоговой шкалы (ВАШ), опросника боли Мак-Гилла. Профиль нежелательных реакций оценивался по динамике показателей красной крови, как возможного триггера развития желудочно-кишечных кровотечений по методике глобальной оценке тригерров (GTT) Мурадян Андраник Александрович, к. м. н., ассистент кафедры неотложной и общей хирургии Сычев Дмитрий Алексеевич, д. м. н., профессор, член корр. РАН, ректор Благовестнов Дмитрий Алексеевич, д. м. н., профессор, декан хирургического факультета Петров Демьян Игоревич, к. м. н. ассистент кафедры неотложной и общей хирургии Скукин Дмитрий Сергеевич, врач-хирург хирургического отделения Епифанова Ирина Павловна, старший лаборант кафедры неотложной и общей хирургии Созаева Жаннет Алимовна, младший научный сотрудник отдела молекулярной медицины НИИ молекулярной и персонализированной медицины Качанова Анастасия Алексеевна, младший научный сотрудник отдела молекулярной медицины НИИ молекулярной и персонализированной медицины Денисенко Наталья Павловна, к. м. н., заведующий отделом персонализированной медицины НИИ молекулярной и персонализированной медицины Абдуллаев Шерзод Пардабоевич, канд. биол. наук, заведующий отделом молекулярной медицины НИИ молекулярной и персонализированной медицины Гришина Елена Анатольевна, д-р биол. наук, доцент, директор НИИ молекулярной и персонализированной медицины

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.