Prevention Of Adverse Reactions Research Articles

Analysis of the experience and procedural complications of trans-radial access versus trans-femoral access for hepatic arterial perfusion chemotherapy in patients with advanced hepatic malignancies:a retrospective study

Objective: To analyze the differences between trans-radial access (TRA) and trans-femoral access (TFA) in hepatic arterial perfusion chemotherapy (HAIC) in terms of patient experience, postoperative complications, and patient preferences; explore whether TRA in HAIC is associated with better patient experience and compliance; and determine whether it is safer than TFA. Methods: The study was a retrospective cohort study of patients with advanced hepatocellular carcinoma and liver metastases from colorectal cancer treated with HAIC. We enrolled a total of 91 patients with advanced liver malignancies treated with HAIC from November 2022 to May 2023 in the Department of Interventional Therapy and Hepatobiliary Medicine at Tianjin Medical University Cancer Hospital. The patients were divided into three groups: group TRA (n=20, receiving TRA HAIC only), group TFA (n=33, receiving TFA HAIC only), and crossover group [n=19, receiving TFA HAIC (Cross-TFA group) first, followed by TRA HAIC (Cross-TRA group)]. Meanwhile, to facilitate the expression of partial results, all patients receiving TRA HAIC were defined as the TRA-HAIC group (n=39, TRA+Cross-TRA group), and all patients receiving TFA HAIC were defined as the TFA-HAIC group (n=52, TFA+Cross-TFA group). The primary research index was the Quality of Life (QOL) visualization scale score. The secondary research index included approach-related and catheter-related adverse events, duration of surgery, and mean length of patient stay. We used various statistical methods such as Mann-Whitney U test, t-test, Chi-square test, Fisher's exact test, univariate logistic regression analysis, and multi-factor analysis. Results: TRA patients had significantly lower QOL scores than TFA patients (all P<0.001). The QOL scores of the Cross-TRA group were significantly lower than those of the Cross-TFA group (pain at the puncture site Z=-3.24, P=0.001, others P<0.001). The QOL scores of the Cross-TRA group were compared with those of the TRA group, which showed that the scores of the Cross-TRA group in overall discomfort (Z=-3.07,P=0.002), postoperative toilet difficulty (Z=-2.12, P=0.034), and walking difficulty (Z=-2.58, P=0.010) were significantly lower than those of the TRA group. Satisfaction scores were significantly higher in the Cross-TRA group than in the Cross-TFA group (Z=-3.78, P<0.001), and patients were more likely to receive TRA HAIC as the next procedure (χ2=30.42, P<0.001). In terms of mean length of stay, patients receiving TRA HAIC had a significantly lower mean length of stay than those receiving TFA HAIC (50.1±3.2 h vs. 58.4±6.4 h, t=7.98, P<0.001). The incidence of radial artery occlusion (RAO) as an approach-related adverse event was 15.4% (6/39) in the TRA-HAIC group, which was significantly higher than that in the TFA-HAIC group (15.4% vs. 0, χ2=8.56, P=0.005). Notably, multifactorial analysis of RAO-related factors showed that intraoperative enoxaparin use and patency of radial artery flow during pressure were significantly associated with a reduced risk of postoperative RAO (P=0.037 for enoxaparin use and P=0.049 for pressure). Conclusions: With respect to procedure approach, TRA was significantly better than TFA in terms of patient satisfaction and mean length of stay. Through further process optimization and prevention of adverse reactions, the incidence of adverse reactions can be maintained at a relatively low level, so that patients can benefit from TRA in future operations in terms of cost-effectiveness and medical efficiency.

Preferences for oral nutritional supplement therapy among postoperative patients with gastric cancer: a discrete choice experiment.

PurposesPatients after gastrectomy have poor compliance with oral nutritional supplement (ONS) therapy. Incorporating patient preferences into treatment decisions allows possible product improvements or treatment focus adjustments. The purpose of this research was to investigate the preferences for ONS therapy among postoperative patients with gastric cancer, and to provide person-centered oral nutrition management strategies.MethodsA discrete choice experiment was designed and implemented within a Chinese cancer population. The survey was administered via paper-based questionnaires during face-to-face interviews with assistance from health professionals. A mixed logit model was used to estimate respondents’ preferences for different levels of nutrition therapy attributes.ResultsOne hundred ninety respondents valued “Adverse reactions-almost none” (β 3.43 [SE, 0.28]) the most, followed by “Flavor-good taste” (β 0.68 [SE, 0.13]) and “Follow-up frequency-once every 2 weeks” (β 0.52 [SE, 0.13]), and were willing to pay more for these attribute levels. Respondents would be 93.73% more likely to accept a nutrition therapy program if there were almost no adverse reactions compared to the frequent adverse reactions.ConclusionsHealth professionals should pay attention to the management and prevention of adverse reactions when prescribing nutritional products, and provide diversified ONS products when necessary to meet patient preferences. When formulating intervention strategies, health professionals should also consider the different characteristics of patients, acknowledge the importance of the role of nurse specialists in a novel model of multidisciplinary nutritional care, standardize ONS information, follow up regularly, and encourage patients’ families to participate in daily nutrition care.Supplementary informationThe online version contains supplementary material available at 10.1007/s00520-022-07154-8.

Clinical efficacy evaluation and prevention of adverse reactions in a randomized trial of a combination of three drugs in the treatment of cancerous pudendal neuralgia.

To explore the clinical efficacy, safety, and prevention of major adverse reactions of the non-steroidal anti-inflammatory drug celecoxib combined with OxyContin and Pregabalin in the treatment of cancerous pudendal neuralgia. A total of 51 patients presenting with pelvic malignancies with cancerous pudendal neuralgia were selected, and random number table method was used to allocate them to either the experimental group (n=27) or control group (n=24). The control group was treated with OxyContin combined with Pregabalin, and the experimental group was treated with Celecoxib on the basis of the control group. At 24 hours after treatment, the clinical effective rate of the experimental group was 92.6%, which was significantly higher than the 66.7% of the control group (P<0.05). The numerical rating scale (NRS) scores of the 2 groups of participants on the 7th and 14th days after treatment were lower than before treatment (P<0.05), and the NRS scores of the participants in the experimental group had decreased more significantly. At the same time, the average daily consumption of OxyContin on the 7th and 14th day of the experimental group was lower than that of the control group (P<0.05). Compared with the control group, the incidence of constipation and dysuria in the experimental group was significantly reduced (P<0.05). Co-occurring in both groups during treatment, 10 participants with urinary dysfunction were treated with tamsulosin hydrochloride sustained-release capsules, no urinary retention occurred, catheterization was avoided, tamsulosin hydrochloride sustained-release capsules could be stopped after 1 week, and urination was smooth (P<0.05). After treatment, the quality of life of the 2 groups of participants had improved compared to before treatment, and the improvement was more significant in the experimental group. When treating patients with cancerous pudendal neuralgia with OxyContin and Pregabalin, the addition of celecoxib has a significant effect, which can effectively improve the patient's pain, improve their quality of life to a certain extent, and reduce the consumption of OxyContin. Lowering the dose of OxyContin reduces the occurrence of adverse reactions related to the drug, especially the incidence of constipation and urinary retention. Tamsulosin hydrochloride sustained-release capsules can effectively relieve urinary disorders caused by OxyContin. Chinese Clinical Trial Registry ChiCTR2100046045.

Monitoring the manufacturing and quality of medicines: a fundamental task of pharmacovigilance.

The collection and assessment of individual case safety reports (ICSRs) is important to detect unknown adverse drug reactions particularly in the first decade after approval of new chemical entities. However, regulations require that these activities are routinely undertaken for all medicinal products, including older medicines such as generic medicinal products with a well-established safety profile. For the latter, the risk management plans no longer contain important risks, considered important safety concerns, on the basis that routine pharmacovigilance activity would not allow their further characterisation. Society assumes that unexpected adverse reactions causally related to pharmacological activity are very unlikely to be detected for such well-established medicines, but important risks can still occur. For these products, a change in the safety profile which is brand or source specific and usually local in nature, associated with failures with the adequate control of quality of manufacturing or distribution are important safety issues. These may be the consequence of manufacturing and pharmacovigilance quality systems that are not fully integrated over the product life cycle (e.g. inadequate control of quality defects affecting one or multiple batches; inadequate impact assessment of change/variation of manufacturing, quality control testing, storage and distribution processes; inadequate control over the distribution channels including the introduction of counterfeit or falsified products into the supply chain). Drug safety hazards caused by the above-mentioned issues have been identified with different products and formulations, from small molecules to complex molecules such as biological products extracted from animal sources, biosimilars and advanced therapy medicinal products. The various phases of the drug manufacturing and distribution of pharmaceutical products require inputs from pharmacovigilance to assess any effects of quality-related issues and to identify proportionate risk minimisation measures that often have design implications for a medicine which requires a close link between proactive vigilance and good manufacturing practice. To illustrate our argument for closer organisational integration, some examples of drug safety hazards originating from quality, manufacturing and distribution issues are discussed.Plain language summary Monitoring the manufacturing and quality of medicines: the fundamental task of pharmacovigilance Pharmacovigilance is the science relating to the collection, detection, assessment, monitoring, and prevention of adverse reactions with pharmaceutical products. The collection and assessment of adverse reactions are particularly important in the first decade after marketing authorisation of a drug as the information gathered in this period could help, for example, to identify complications from its use which were unknown before its commercialization. However, when it comes to medicines that have been on the market for a long time there is general acceptance that their safety profile is already well-established and unknown adverse reactions unlikely to occur. Nevertheless, even older medicines, such as generic drugs, can generate new risks. For these drugs a change in the safety profile could be the result of inadequate control of their quality, manufacturing and distribution systems. To overcome such an obstacle, it is necessary to fully integrate manufacturing and pharmacovigilance quality systems in the medicine life-cycle. This could help detect safety hazards and prevent the development of new complications which may arise due to the poor quality of a drug. Pharmacovigilance activities should indeed be included in all phases of the drugs’ manufacturing and distribution process, regardless of their chemical complexity to detect quality-related matters in good time and reduce the risk of safety concerns to a minimum.

Hemovigilance

Background and Objectives: Hemovigilance is defined as a set of surveillance procedures covering the whole transfusion chain that is intended to collect and assess information on unexpected or undesirable effects resulting from the therapeutic use of labile blood products and to prevent future occurrence and recurrence. The primary goal of the study was to reduce the incidence of adverse events among blood donors and to make blood donation a pleasant experience. Prevention of adverse reactions at the time of blood donation is an important aspect of blood donor motivation and blood donor retention for future blood donations. Methods: This is a one and half year's prospective study which was conducted by the department of Transfusion Medicine. The study assessed untoward blood donor reactions, as a measure to further maximize the elimination of untoward reactions encountered during or after blood donation to secure a healthy donation-transfusion chain. We analysed the causative factors that can lead to complications in blood donors at different phases of blood donation like pre-donation, during donation and post donation phases. Results: Out of 8180 whole blood collections, 252 blood donor complications were observed during the study period. Out of this, 8.73% (n=22) adverse reactions were observed during donation at blood centre, while 91.27% (n=230) reactions occurred in blood donation camps. Among the camp donations, 61.30% (n=141) were at outdoor camps and 38.70% (n=89) were inside Blood Mobile. We had 83.23% (n=6808) of male blood donors and 16.77% (n=1372) of female donors. Out of the 66 females who developed complications, majority were belonging to the age group of 18-25 years. We had 37.90% (n=3100) first time donors and 62.10% (n=5080) repeat donors. Among the repeat donors, 34.59% (n=1757) were regular repeat donors and 65.41% (n=3323) were irregular repeat donors. Out of 130 first time donors who developed complications, 91.5% (n=119) were systemic reactions. 57.1% (n=12) of regular repeat donors and 80.2% (n=81) of irregular repeat donors developed systemic complications. Conclusion: Hemovigilance reporting has reinforced our blood donor safety as well as transfusion safety. Regular reporting of the adverse donor complications helped us to improve proper documentation of all aspects of a complete blood donation sequence not only by the medical officers but also by the blood centre staff members.

COMPARISON OF PHARMACISTS PROFESSIONAL ACTIVITY OF UKRAINIAN PHARMACY ON PROVISION OF INFORMATION ON ADVERSE REACTIONS OF PHARMACEUTICAL PRODUCTS

The aim of the research is the comparison of professional activity of pharmacists of pharmaceutical institution in Ukraine with different education level in relation to their responsibilities in detection and prevention of adverse reactions (AR) or lack of efficacy of pharmaceutical products (PP), set out in the regulatory documentation on this matter. Materials and methods. The questionnaire was developed and used for pharmacists of pharmaceutical institution, taken training on cycles of postgraduate education during 2016–2018. 70 higher education pharmacists (HEPs) and 80 specialized secondary education pharmacists (SSEP) were inquired. The integrity was evaluated by Fisher's ratio test (F). For convenience of calculation the corresponding functions of MS Excel were used. Results. The majority of SSEPs and HEPs of Ukrainian pharmaceutical institutions are aware of their duty to provide information on AR or lack of efficacy of pharmaceutical products to the Department of Post-authorization Supervision of the State Expert Center of the Ministry of Health of Ukraine and are aware of the regulatory legal documentation on this issue, however they are not active enough to take necessary action filling in the “Adverse drug reaction reporting form” and sending it to the national department. One of the reasons for the underactivity of pharmacy workers, irrespective of their level of education, is the low organization of this process in pharmacy institutions, in particular the absence of the “Adverse drug reaction reporting forms”. Conclusion. Higher education pharmacist are more self-acting in completing “Adverse drug reaction reporting forms” and are less likely to shift their responsibilities to the pharmacy manager. It is critical to resolve the issue on enhancement of efficiency of detecting AR and/or lack of efficacy of PP in pharmacy institutions of Ukraine is to improve the quality of organizational work of pharmacy managers.

Impacto de un plan de mejora de calidad en la validación de la prescripción de fármacos sobre la seguridad de los pacientes hospitalizados

Background and objectivesMedication errors are the most common adverse events in healthcare. Pharmaceutical validation (PV) seeks to reduce them. The aims of this study were to assess the impact of the introduction of an automated tool for the validation (VPAT) of the high clinical relevance drugs prescription (HCRD) over time of pharmaceutical intervention (PI), and to quantify the number of medication errors detected before and after its implementation. Material and methodsA two phase retrospective-observational single centre study was designed. A pre-intervention phase (Pre-P): PV of beds with Unit Dose Dispensing (October 2015 - February 2016), was followed by a post-intervention phase (Post-P): PV using a VPAT of HCRD in hospital patients (October 2016 - February 2017).HCRD were selected from the list of high-risk drugs of Institute for Safe Medication Practices. The data was obtained from the PI record (Access®) and the computerised prescription. The variables collected were: age and gender of the patients included, data of drugs prescription, and time to PI. ResultsA total of 477 PI were analysed in 404 patients, with a mean age of 65.9±19.5 years (53.22% women). The mean time up to PI was 25.6±24.72h in the Pre-P, and 18.87±20.44h in the Post-P (P=0.01). In Pre-P, 106 PI were performed (35.85% prevention of adverse reactions) compared to 371 PI (39.62% medication reconciliation) in Post-P. ConclusionsThe VPAT enabled a greater number of medication errors to be detected and intervened in hospitalised patients, with a significantly reduced time to PI.

Adverse events when treating XDR tuberculosis

The article presents the results of a clinical study on the frequency and spectrum of adverse events (AEs) that occur during treatment with an anti-tuberculosis drug (thioureidoiminomethylpyridinium perchlorate, Tpp). The purpose of the study was to determine the frequen-cy and nature of adverse events when TPP is included in the treatment regimen and to develop an algorithm for the prevention of adverse reactions. Materials and methods: 125 (N=125) patients with MDR and XDR tu-berculosis were examined. 70.4% (88) patients developed adverse events. Results and discussion: At the same time, adverse reactions occurred in 58.3% (35) of the main group, and in 69.2% (45) of the control group. There were no significant differences in the frequency of adverse events between the main and control groups (2=1.608, 95% CI 0.298-1.298, p&gt;0.05). In the control group, diges-tive and hepatobiliary AEs were more frequent (up by 8.6% and 3.5%, respectively). On the other hand, derma-tological reactions prevailed in the main group (up by 3.8%). Tpp was not shown to be the main cause of drug induced hypothyroidism, it can jointly reinforce thyrotox-ic effect when used in combination with protionamide and/or PASA (para-aminosalicylic acid). Statistic analy-sis showed no significant differences in any class of AEs between the groups (p&gt;0.05 for all AE categories). Up to 68% of adverse reactions were mild (1 and 2 grade). Con-clusion. Thioureidoiminomethylpyridinium perchlorate is not the main cause of drug induced hypothyroidism, it can jointly reinforce thyrotoxic effect when used in combina-tion with protionamide and/or PASA.

Применение природных средств в комплексной профилактике и лечении респираторных инфекций у детей

In pediatric practice, much attention is paid to natural components used for the prevention and treatment of respiratory infections. Nasal drops Tamba Tuya (Adonis LLC, Russia) contain extracts of peloid from lake Tambukan, thuja, essential oils of fir, lavender, vitamin E, dexpanthenol, dihydroquercetin, glycerol, olive oil, and peach oil. These components are effective for the prevention and treatment of rhinitis, adenoiditis, bacterial complications, as well as for prevention of adverse reactions from decongestants. We have developed a method of its application that has not only local, but also systemic effects in children. Step 1: nasal rinsing with saline solutions; step 2: instilling Tamba Tuya drops (1–2 drops in each nostril) three times a day; step 3: infriction of the drops into the skin on the temples for 2–3 minutes as aromatherapy, which ensures penetration of the drug components through the skin into the blood with a systemic effect. Minimum course duration: 2 weeks. The use of the drops from the first days of respiratory infections in 30 children aged 4 to 7 years in the experimental group (30 children were in the control group) ensured milder (76.3% compared to 60% in the control group) and shorter disease (by 2 days). The majority of participants (83.3%) from the experimental group demonstrated rapid resolution of rhinitis symptoms and lower need for decongestants. A total of 86.6% of children in the experimental group and 53.3% of controls showed an improvement in emotional and behavioral responses, including activity, adaptability, intensity, mood, and distraction. Key words: children, prevention, treatment, respiratory infections

Topical Issues of Drug Safety, Possibilities of Improving of Pharmacovigilance

Since 2010, Russia has been developing new drug legislation, internal quality control and safety of medical organizations, and has developed algorithms for submitting Individual Case Safety Reports (ICSR) using an automated information system. On April 1, 2019, Russia launched an updated national database of ICSR, which uses the international ICH E2B data standard, which may increase the amount of reporting to the Uppsala monitoring center. This publication covers the key aspects of pharmacovigilance system development in the Russian Federation. The analysis of pharmacovigilance structure in the Russian Federation is carried out, its main problems are designated. Presents methods to identify causal relationships between adverse reaction and drug, evaluation of its degree of validity (questionnaires, algorithms, and scale), as already recommended by the WHO, and the new modifi ed versions. The expediency of using a scale for determining the degree of reliability of a causal relationship «an undesirable reaction — drug interaction» when analyzing spontaneous reports of undesirable reactions that may be caused by drug interactions is noted. An effective method of detection and prevention of adverse reactions is presented — the Global Trigger Tool (GTT). The question of the need for motivation and training of medical personnel in the correct design of spontaneous messages, as well as methods of identifying the causal relationship between adverse reactions of drugs. The directions of optimization of pharmacovigilance system are proposed, including methods of more effective active surveillance in the identifi cation and prevention of adverse reactions.

New isoniazid derivatives with improved pharmaco-toxicological profile: Obtaining, characterization and biological evaluation

Tuberculostatic drugs are the most common drug groups with global hepatotoxicity. Awareness of potentially severe hepatotoxic reactions is vital, as hepatic impairment can be a devastating and often fatal condition. The treatment problems that may arise, within this class of medicines, are mainly of two types: adverse reactions (collateral, toxic or hypersensitive reactions) and the initial or acquired resistance of Mycobacterium tuberculosis to one or more antituberculosis drugs. Prevention of adverse reactions, increase treatment adherence and success rates, providing better control of tuberculosis (TB). In this regard, obtaining new drugs with low toxicity and high tuberculostatic potential is essential. Thus, in this work, we have designed or synthesized new derivatives of isoniazid (INH), such as new Isonicotinoylhydrazone (INH-a, INH-b and INH-c). These derivatives demonstrated good biocompatibility, antimicrobial property similar to that of parent isoniazid and last but not least, a significantly improved Pharmacotoxicological profile compared to that of isoniazid.

Genetic diversity of cytochrome P450 3A with different metabolic activity in domestic cats.

Knowledge on genetic polymorphisms of metabolising enzymes including cytochrome P450 (CYP) is very limited in cats. We investigated polymorphisms in CYP3A131, one of the major CYP isoforms in the feline liver and small intestine. Eight non-synonymous variants and one synonymous variant of feline CYP3A131 were identified in 29 cats. A major non-synonymous type was not observed. Metabolic parameters (Km and Vmax) of dibenzylfluorescein hydroxylation were ranged within about 2 times for the identified non-synonymous variants by using a heterologous coexpression system of CYP3A131 and feline cytochrome P450 reductase in Escherichia coli. The results confirmed the polymorphic nature of CYP3A131 as a basis for effective application of medicines and prevention of adverse reactions in the treatment of domestic cats.

Genetic diversity of cytochrome P450 1A2 with different metabolic activities in domestic cats.

Knowledge of genetic polymorphisms of metabolizing enzymes of medical drugs and xenobiotics including cytochrome P450 (CYP) is very limited in cats. We investigated polymorphisms in CYP1A2, one of the major CYP isoforms in the feline liver. Wild-type and three non-synonymous polymorphic variants, but no synonymous variant, were identified in feline CYP1A2 in 50 alleles of domestic cats in Japan. Metabolic parameters, Km and Vmax, of ethoxyresorufin hydroxylation by CYP1A2 were shown to range within two times for identified non-synonymous variants by using a heterologous coexpression system. The results confirmed the polymorphic nature of CYP1A2 as a basis for effective application of medicines and prevention of adverse reactions in the treatment of domestic cats as well as for hereditary disorders.

Prevention of adverse reactions: Journey from blood safety to transfusion safety

.

Genetic diversity of cytochrome P450 2A with different metabolic activities in domestic cats.

Knowledge of genetic polymorphisms of cytochrome P450 (CYP), the most important xenobiotic metabolizing enzyme, is very limited in cats. Preliminarily, we investigated genetic polymorphisms in CYP2A13, one of the major CYP isoforms in the liver and lung. Four synonymous and three non-synonymous polymorphic variants were identified in feline CYP2A13 in domestic cats in Japan, without an obvious major type. Metabolic parameters, Km and Vmax, of coumarin hydroxylation of CYP2A13 were shown to range within two times for the identified non-synonymous polymorphic variants by using heterologous coexpression system in Escherichia coli. The results confirmed the polymorphic nature of CYP2A13 as a basis for effective application of medicines and prevention of adverse reactions in treatment of domestic cats.

Протиепілептичні препарати: взаємодія, особливості застосування

При проведении фармацевтической опеки конкретного пациента (например больного эпилепсией) врач и провизор должны учитывать возможный факт взаимодействия противосудорожных препаратов между собой (при политерапии) или с препаратами других фармакотерапевтических групп (при лечении сопутствующих заболеваний, профилактике побочных реакций и т. д.). Кроме взаимодействия, важным фактором при отпуске противоэпилептических препаратов являются особенности применения препаратов этой фармакотерапевтической группы. Целью исследования было создание базы данных возможных взаимодействий противоэпилептических препаратов между собой и с лекарственными средствами других фармакотерапевтических групп. Обратить внимание на важнейшие особенности применения препаратов противосудорожного действия. Объектами исследования была информация о препаратах для лечения эпилепсии из государственных формуляров Украины и Великобритании, приказов МОЗ Украины, Государственного реестра лекарственных средств Украины, инструкций к противоэпилептическим препаратам и тому подобное. В исследовании были использованы методы библиографического и системного анализов. В результате проведенных исследований «Унифицированного клинического протокола медицинской помощи "Эпилепсии у взрослых"», Фармацевтической энциклопедии, рекомендаций Международной Лиги по борьбе с эпилепсией можно сделать предварительный обобщающий вывод, что препаратами первой линии выбора и такими, которые пользуются наибольшим спросом, являются вальпроевая кислота и ее соли, карбамазепин. Нами проведен сбор информации о возможных взаимодействиях противоэпилептических препаратов как между собой, так и с препаратами других фармакотерапевтических групп. Установлено, что наибольшее количество взаимодействий противоэпилептических препаратов происходит с такими группами препаратов: средства, действующие на нервную систему (и соответственно взаимодействие противоэпилептических препаратов между собой) – 237 фактов; противомикробные для системного применения – 78 фактов; средства, действующие на сердечно-сосудистую систему – 65 фактов и т. д. Чаще всего взаимодействия противоэпилептических препаратов как между собой, так и с препаратами других фармакотерапевтических групп происходят для препаратов 1 (базового) поколения – фенобарбитал, фенитоин, карбамазепин и др. Полученные данные можно использовать для информационного наполнения системы электронных рецептов. Информация может быть использована как на этапе выписки рецептов врачами, так и на этапе отпуска лекарственных средств из аптеки. Сравнение инструкций отечественных (генерических) и импортных (оригинальных) препаратов показало, что существенных различий в разделах «взаимодействие лекарственных средств», «особенности применения» для карбамазепина нет. Однако при назначении препаратов вальпроевой кислоты врач должен учитывать биофармацевтических аспекты, указанные в инструкциях к обоим препаратам.

The adverse reaction of dexmedetomidine combined with dezocine in gynecological laparoscopic surgery after general anesthesia

Objective To observe the adverse reaction of dexmedetomidine(Dex) combined with dezocine in gynecological laparoscopic surgery after general anesthesia. Methods 120 cases of gynecologic laparoscopic surgery, ASA Ⅰ-Ⅱ, according to random number table method were divided into three groups, 40 cases in each group.A group was intravenously injected Dex 1μg/kg 10min before induction, intravenously injected dezocine 5mg+ ondansetron 4mg 30min before the end of the operation.B group was intravenously injected dezocine 5mg+ ondansetron 4mg 30min before the end of surgery.C group was intravenously injected saline 1mL+ ondansetron 4mg.Before induction (T0), 5min before extubation (T1), extubation (T2), 10min after extubation (T3), the MAP, HR, SpO2 of three groups were recorded.The postoperative recovery time, degree of agitation, extubation and Ramsay sedation score, VRS analgesia 24h score, postoperative adverse reaction were compared among three groups. Results There was no difference in the recovery time among the three groups (t=0.94, 0.97, 1.02, all P>0.05). Compared with T0, the MAP of the three groups at the time of T2 increased, but the MAP of B group and C group was significantly higher (t=4.65, 5.201, all P 0.05). Conclusion General anesthesia in gynecological laparoscopic surgery using Dex combined with dezocine can make patients more stable circulation, improve patients' recovery quatity, it is a safe and effective method for prevention of adverse reaction after general anesthesia. Key words: Laparoscopes; Dexmedetomidine; Dezosin; Anesthesia, general

Assessment of different loading doses of dexmedetomidine hydrochloride in preventing adverse reaction after combined spinal-epidural anesthesia.

We conducted the present study to investigate the effects of the different loading doses of dexmedetomidine hydrochloride in the prevention of adverse reactions after combined spinal-epidural anesthesia. A total of 200 patients that were admitted to the Department of Obstetrics at the Second Affiliated Hospital of Xi'an Jiaotong University hospital and treated with cesarean section through the use of combined spinal-epidural anesthesia from December, 2014 to June, 2016, were randomly divided into 4 groups. The therapeutic regimens of patients were shown as follows: group A was administered an intravenous pump of 10 ml/l physiological saline in surgery until the end of the delivery. group B was administered 0.2 µg/kg dexmedetomidine. group C was administered 0.4 µg/kg dexmedetomidine. group D was administered 0.6 µg/kg dexmedetomidine. The anesthesia plane was adjusted to the level below the T10 plane. After the onset of anesthesia, participants of each group were treated with an intravenous pump of dexmedetomidine at loading dose. After intravenous pumping for 10 min in each group during the surgery, patients were administered with an intraoperative maintenance dose of 0.2 µg/kg/h until the end of the delivery. The heart rate (HR), mean arterial pressure (MAP), Narcotrend index (NI), Ramsay sedation score and the incidence of adverse reactions at each time-point of the start of drug administration (T0), 10 min (T2), 30 min (T3), 60 min (T4), 90 min (T5) and the end of surgery (T6) were recorded. Within 24 h post-delivery, the degree of amnesia from using dexmedetomidine until the end of the delivery were followed up. Compared to group A and T0, the HRs of participants at T3-6 in groups B and C were decreased. The MAP at T1 in group D was increased. In groups B and C, the NIs were significantly decreased at T2-6, the Ramsay scores were increased at T3-6, and the differences were statistically significant (P<0.05). The follow-up within 24 h after delivery showed that the degree of anterograde amnesia from groups B to D was significantly higher than group A, with statistically significant difference (P<0.05). A combined spinal-epidural anesthesia with 0.6 µg/kg loading dose of dexmedetomidine, by intravenous pumping within 10 min before cesarean section, can achieve a satisfied sedative effect at 30 min after administration. It maintains the characteristics of intraoperative hemodynamic stability and less adverse reactions. Therefore, it is of great significance to improve the quality of cesarean section delivery.

The genetic profiles of CYP1A1, CYP1A2 and CYP2E1 enzymes as susceptibility factor in xenobiotic toxicity in Turkish population

Evaluation and sequencing of heritable alterations in the human genome and the large-scale identification of gene polymorphism for understanding the genetic background of individuals in response to potential toxicants are provided by toxicogenetics. Cytochrome P450 (CYP) enzymes play role not only phase I-dependent metabolism of xenobiotics but also metabolism of endogenous compounds. CYP1A1, CYP1A2 and CYP2E1 enzymes, which are in phase I enzymes, are responsible for metabolic activation and detoxification of several chemical compounds. In the present study, it was determined the genotype and allele frequency of CYP1A1∗2A, CYP1A2∗1C, CYP1A2∗1F, CYP2E1 and CYP2E1∗6, very common and functional single-nucleotide polymorphisms (SNPs), in Turkish healthy volunteers. It is believed that the determination of polymorphisms in the enzymes may be beneficial to prevent and reduce and adverse effects and death in response to drugs. The allele frequencies of these genes were 24%, 9%, 33%, 42%, and 12%, respectively. In the present study, the genotype profile of Turkish population was determined about critical enzymes for xenobiotic metabolism. It is suggested that the obtained results might be beneficial in order to dose adjustment of drugs and prevention of adverse reactions, and further investigation about mentioned enzymes and their polymorphisms.

SNP genetic polymorphisms of MDR-1, CYP1A2 and CYPB11 genes in four canine breeds upon toxicological evaluation.

The fields of pharmacogenetics and pharmacogenomics have become increasingly promising regarding the clinical application of genetic data to aid in prevention of adverse reactions. Specific screening tests can predict which animals express modified proteins or genetic sequences responsible for adverse effects associated with a drug. Among the genetic variations that have been investigated in dogs, the multidrug resistance gene (MDR) is the best studied. However, other genes such as CYP1A2 and CYP2B11 control the protein syntheses involved in the metabolism of many drugs. In the present study, the MDR-1, CYP1A2 and CYP2B11 genes were examined to identify SNP polymorphisms associated with these genes in the following four canine breeds: Uruguayan Cimarron, Border Collie, Labrador Retriever and German Shepherd. The results revealed that several SNPs of the CYP1A2 and CYP2B11 genes are potential targets for drug sensitivity investigations.