Group Of Drugs Research Articles

Contact dermatitis: etiopathogenetic aspects of the formation of the clinical picture and the rational choice of external therapy

Contact dermatitis is one of the most common skin diseases in many countries, especially among occupational dermatoses. This pathology is considered as an inflammatory skin disease caused by direct exposure to environmental factors. Obligate irritants have a direct damaging effect on the cells of the epidermis and, due to the activation of the predominantly innate immune system, lead to the development of dermatitis in any person. The action of facultative irritants is associated with a delayed type IV cell-mediated allergic reaction, which causes the development of the disease when exposed to substances with sensitizing properties in predisposed individuals. The severity and nature of the symptoms of contact dermatitis depend both on the type of irritant and on the individual characteristics of the organism. A necessary condition for the effectiveness of the treatment of contact dermatitis is the elimination of the allergen. To suppress the inflammatory response, topical glucocorticosteroids are the first-line drugs. The ease of use and the speed of relief of the symptoms of the disease can lead to the uncontrolled use of this group of drugs, in this regard, the article provides an analysis of the necessary conditions and rules for the use of topical glucocorticosteroids. Attention is focused on the risk of developing skin xerosis when they are prescribed. A modern method for the prevention of epidermal barrier dysfunction based on the use of preparations containing topical glucocorticosteroid in combination with ceramides is described. We present our own clinical observations of patients with contact dermatitis treated with this drug, while demonstrating a pronounced positive dynamics of the skin pathological process and regression of subjective symptoms without the development of side effects.

Honey Mushroom, Armillaria mellea (Agaricomycetes) and Its Fermentation Products Target Regulation of OAT1/OAT3 Proteins to Reduce Hyperuricemia in Mice.

Disorders of purine metabolism are the main cause of hyperuricemia. Current drugs for the treatment of hyperuricemia usually cause a degree of cardiovascular damage. This study aimed to investigate the therapeutic effects of Armillaria mellea fruiting body (AFB), Armillaria rhizomorph (AR) and Armillaria mellea fermentation product (after rhizomorphs removal) (AFP) on hyperuricemic mice. The hyperuricemia mouse model was established by oral administration of potassium oxonate 0.9 g⋅kg-1 and hypoxanthine 0.5 g⋅kg-1 for two weeks. Starting from the third week, the intragastric administration of the intervention drug group was as follows: Allopurinol 0.013 g⋅kg-1, AFB (3.9 and 7.8 g⋅kg-1), AR (3.9 and 7.8 g⋅kg-1), AFP (1.95 and 3.9 g⋅kg-1) once daily for 14 days. Results showed that AFB, AR, and AFP reduced the contents of serum uric acid, serum creatinine, and blood urea nitrogen in hyperuricemic mice and the mechanism of action might be through up-regulation of the expression levels of organic anion transporter 1/organic anion transporter 3 proteins in kidney tissue. AR and AFP both exhibited better uric acid-lowering effects than AFB, which may be due to the higher purine content of AFB. Armillaria mellea and its fermentation products can treat hyperuricemia by up-regulating OAT1 protein and OAT3 protein, reducing uric acid content in mice.

Effect of Carboprost Tromethamine Combined with Uterine Strap Suture in the Treatment of Patients with Postpartum Hemorrhage Caused by Uterine Atony

Objective: To explore and analyze the effect of carboprost tromethamine combined with uterine strap suturein the treatment of postpartum hemorrhage caused by uterine atony. Methods: A total of 90 patients with postpartum hemorrhage due to uterine atony who were admitted to the Obstetrics Department of Dazhou Women and Children’s Hospital from July 2020 to July 2023 were included in the study. They were grouped by odd and even numbers, and divided into the surgery group (n = 45) and the drug group (n = 45). The surgery group was treated with carboprost tromethamine and uterine strap suture, and the drug group was treated with carboprost tromethamine. The total effective rate, blood coagulation index, fibrinolytic function level, bleeding, and hemoglobin changes were compared between the two groups. Results: The total effective rate of the surgery group was significantly higher than that of the medication group (P < 0.05). Before treatment, the blood coagulation indicators were insignificant between the groups (P > 0.05); after treatment, the blood coagulation indicators in the surgery group were significantly better than those in the drug group (P < 0.05). Before treatment, the levels of fibrinolytic functions were insignificant between the groups (P > 0.05); aftertreatment, the levels of fibrinolytic functions in the surgery group were significantly better than those in the drug group (P < 0.05). The 2 h and 24 h blood loss and hemoglobin changes in the surgery group were significantly lower than those in the drug group (P < 0.05). Conclusion: Carboprost tromethamine combined with strap sutures can effectively control postpartum hemorrhage caused by uterine atony.

Eco-friendly electrochemical sensor for determination of conscious sedating drug “midazolam’’ based on Au-NPs@Silica modified carbon paste electrode

Benzodiazepines (BZDs) are a group of drugs prescribed for their sedating effect. Their misuse and addictive properties stipulate different authorities for developing simple, fast and accurate analytical methods for instantaneous detection. Differential pulse voltammetric technique (DPV) was utilized for the selective assay of midazolam hydrochloride (MDZ) in the pure, parenteral dosage forms and plasma samples. A chemically modified carbon paste electrode (CPE) was implemented during the study. The method depended on the electroreduction of MDZ on the surface of the electrode over a potential range of 0.0 V to −1.6 V. The electrode was fabricated using silica nanoparticles (Si-NPs) which were incorporated into the composition of the CPE and used to enhance the electrode performance. Then, to enhance the sensitivity of the method, a chronoamperometric modification step was applied for depositing gold nanoparticles (Au-NPs) on the carbon paste electrode surface. Modification with Au-NPs showed a higher reduction current peak for MDZ with well-defined peaks. Various parameters such as pH of the media and measurements scan rate were investigated and optimized to enhance the sensor sensitivity. The sensor showed a dynamic linear response over a concentration range of 4.0 × 10−7 M to 2.9 × 10−4 M of MDZ with a LOD of 2.24 × 10−8 M using 0.1 M acetate buffer (pH 5.6). The sensor was validated in accordance with the ICH guidelines regarding accuracy, precision and specificity for the selective assay of MDZ in the presence of excipients. A greenness evaluation was performed using three different assessment tools, namely, the “Green Analytical Procedure Index” (GAPI), the “Analytical Greenness metric” (AGREE) and the “Whiteness Analytical Chemistry tool” (WAC) using the RGB12 model.

Modern hepatoprotection: a narrative review of existing approaches and prospects for the use of biotechnological drugs

The prevalence of acute and chronic liver diseases is increasing worldwide, which affects the quality of life and can lead to dangerous, life-threatening complications. Almost 50.0 % of all cases of acute liver failure are caused by drugs, and the overall mortality due to drug-induced liver injury reaches 5.0–11.9 %. In 2020, the hospital incidence of diseases of the digestive organs in Ukraine amounted to 430,593 cases among the adult population, of which 11,976 were fatal.
 The aim of the study: to characterize modern approaches to hepatoprotection and prospects of biological therapy based on data from open sources of information.
 Materials and methods. Publications were selected based on the PubMed, ClinicalKey Elsevier, Cochrane Library, eBook Business Collection, and Google Scholar databases, which covered information about modern approaches to the treatment of liver diseases.
 Results. Patients with chronic liver disease are at risk of extrahepatic complications related to liver cirrhosis and portal hypertension, as well as organ-specific complications of certain liver diseases. These complications can impair the quality of life and increase morbidity and mortality before and after liver transplantation. With chronic damage to the liver by toxic substances, the development of fatty dystrophy against the background of connective tissue changes in the form of nonspecific reactive hepatitis is more often observed. Hepatoprotectors are a pharmacotherapeutic group of heterogeneous drugs that prevent the destruction of cell membranes and stimulate the regeneration of hepatocytes. According to the Anatomical Therapeutic and Chemical classification of drugs (ATC classification), hepatoprotectors take their place in the group of drugs affecting the digestive system and metabolism (A), intended for the treatment of diseases of the liver and biliary tract (A05). One of the promising directions of biological therapy in patients with liver pathology is the use of means obtained from the fetoplacental complex.
 Conclusions. Cell therapy in clinically significant volumes is an actual area of modern hepatology. The most promising directions of biological therapy in clinical hepatology are the use of mesenchymal stem cells, agents obtained from the fetoplacental complex, and gene therapy.

Uncovering forensic evidence of drug-facilitated sexual assault: Toxicological findings from Eastern Denmark from 2015–2022

In drug-facilitated sexual assault (DFSA), the victim is unable to provide consent or resists sexual activity due to substance intoxication by voluntary or covert consumption. Obtaining forensic evidence of the assault is challenged by rapid drug metabolism and late sample collection. The objective of this study was to present toxicological findings and associated demographics from police reported sexual assault cases in Eastern Denmark from 2015 to 2022. A total of 369 sexual assault cases were submitted for analysis and a subgroup of 268 cases were categorized as suspected DFSA cases. The majority of the total sexual assault victims were women at the age 15–25 and the perpetrators were often unknown or an acquaintance. Time from assault to sample collection was slightly longer for suspected DFSA cases (12–24 h) compared to non-DFSA (<12 h). Positive toxicology was observed in 86 % of cases and the most common drug groups included alcohol (45 %), drugs of abuse (38 %), antidepressants (14 %), antihistamines (12 %), and benzodiazepines (11 %). Hypnotics were detected to a smaller extent (7 %). A total of 77 drugs were detected and the most commonly observed were cocaine, tetrahydrocannabinol (THC), cetirizine, amphetamine, diazepam and sertraline. The high level of observed alcohol and drugs of abuse indicated that most DFSA cases in Eastern Denmark were of an opportunistic approach rather than proactive.

Tripterygium glycosides sensitizes cisplatin chemotherapeutic potency by modulating gut microbiota in epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is a fatal gynecological malignancy with limited therapeutic options. Previous research has demonstrated that Tripterygium glycosides (GTW) can enhance effectiveness of cisplatin (DDP) chemotherapy against EOC. However, the underlying mechanism of GTW alleviating EOC still remains unclear. In this article, an ID8 cell-derived xenograft mouse model was established to evaluate the anti-tumor efficacy of GTW combined with DDP. Consistent with previous findings, the results suggested that GTW combined with DDP can exhibit a stronger tumor suppressive effect than DDP alone. Additionally, GTW was found can further exert gastrointestinal protection against DDP by reducing pathological damage on colon tissue. Secondly, to verify whether gut microbiota play an instrumental role in GTW's anticancer effect, we treated mice models with antibiotic to eliminate gut microbiota. And our experimental results indicated that all drug groups showed a weaker tumor suppressive effect and more severe gastrointestinal damage post antibiotic supplement. At genus level, the relative abundance of Lactobacillus was dramatically diminished by the antibiotic treatment, while combined treatment of GTW and DDP can significantly restore the level. Moreover, we performed Lactobacillus acidophilus transplantation and healthy mice fecal microbiota transplantation experiments to further investigate the link between the anticancer effect of GTW and gut microbiota. Our results suggested that both cisplatin-sensitizing and intestinal barrier-protecting effects of GTW can be recovered to a different extent. In conclusion, our results indicated that GTW is a promising chemosensitization and intestinal barrier repair drug for EOC, and the potential mechanism may corelate with the restoration of the compromised intestinal microbial balance.

Liver resection for metastatic GIST tumor improves survival in the era of tyrosine kinase inhibitors: a systematic review and meta-analysis.

Survival for gastrointestinal stromal tumor (GIST) has been increasing over the years after the introduction of tyrosine kinase inhibitors. However, the role of metastasectomy for GIST is still controversial. Patients are currently treated with imatinib or sunitinib in case of imatinib failures as optimal medical therapy for metastatic GIST. The Pubmed, EMBASE, and Cochrane Library were systematically searched. Overall survival following liver resection ± tyrosine kinase inhibitor treatment for metastatic GIST was compared to treatment with tyrosine kinase inhibitors alone. Eleven studies including both randomized control trials and retrospective cohort studies were included in the final analysis with a total of 988 patients. Seven studies encompassed data on 556 patients with isolated liver metastases (219 surgery ± drug groups and 337 drug-only groups) were included. Overall survival was significantly improved in patients undergoing liver resection ± drug therapy in comparison to drug therapy alone. [HR (95%CI) = 2.10 (1.58, 2.79); p<0.00001]. Subgroup analysis showed that patients also had improved progression free survival based on 4 studies. [HR (95%CI) = 1.92 (1.43, 2.56); p<0.00001]. In case of concurrent liver and peritoneal metastases, patients showed improved overall survival with aggressive surgical approaches based on 10 studies. [HR (95%CI) = 1.90 (1.56, 2.31); p<0.00001]. This meta-analysis found that liver resection for patients with metastatic GIST regardless of peritoneal metastases improved progression free and overall survival in conjunction with tyrosine kinase inhibitors as compared with medical therapy alone. Furthermore, liver resections did not have any immediate detrimental impact on survival in the group of patients selected.

COST – EFFECTIVENESS ANALYSIS OF USING ANTIDIABETIC IN OUTPATIENT WITH TYPE 2 DIABETES MELLITUS

Type 2 diabetes Mellitus is a chronic disease that requires lifelong treatment. In the course of the disease, if blood sugar levels are not controlled, it can lead to complications of other diseases. The variety of antidiabetic drugs used in therapy can lead to differences in the cost effectiveness of therapy. The aims of this study is to analyze the cost-effectiveness of antidiabetic therapy in outpatients at Dr. Moewardi Hospital. Data collection in this study was carried out retrospectively using medical records of outpatients with type 2 diabetes mellitus and billing data from the hospital The data obtained were then presented descriptively and the ACER value was calculated for the 2 most widely used drug groups. The results of this study showed that 30 patients received a combination of Insulin Analog (Basal) + Insulin Analog (Prandial/Premixed) and and 11 patients received Insulin Analog (Basal/ Prandial/ Premixed). The percentage effectiveness of combination therapy Insulin Analog (Basal) + Insulin Analog (Prandial/ Premixed) was higher than Insulin Analog (Basal/ Prandial/ Premixed) (83.33 vs 72.72). The ACER value of Insulin Analog (Basal) + Insulin Analog (Prandial/ Premixed) (IDR 13.802,42) is lower than Insulin Analog (Basal/ Prandial/ Premixed) (IDR 18.356). Based on the cost effectiveness table, the combination of Insulin Analog (Basal) + Insulin Analog (Prandial / Premixed) is more effective so that the combination of Insulin Analog (Basal) + Insulin Analog (Prandial / Premixed) is more cost effective than Insulin Analog (Basal / Prandial / Premixed).

Implementation of Pharmacogenetics in First-Line Care: Evaluation of Its Use by General Practitioners.

Pharmacogenetics (PGx) can explain/predict drug therapy outcomes. There is, however, unclarity about the use and usefulness of PGx in primary care. In this study, we investigated PGx tests ordered by general practitioners (GPs) in 2021 at Dept. Clinical Chemistry, Erasmus MC, and analyzed the gene tests ordered, drugs/drug groups, reasons for testing and single-gene versus panel testing. Additionally, a survey was sent to 90 GPs asking about their experiences and barriers to implementing PGx. In total, 1206 patients and 6300 PGx tests were requested by GPs. CYP2C19 was requested most frequently (17%), and clopidogrel was the most commonly indicated drug (23%). Regarding drug groups, antidepressants (51%) were the main driver for requesting PGx, followed by antihypertensives (26%). Side effects (79%) and non-response (27%) were the main indicators. Panel testing was preferred over single-gene testing. The survey revealed knowledge on when and how to use PGx as one of the main barriers. In conclusion, PGx is currently used by GPs in clinical practice in the Netherlands. Side effects are the main reason for testing, which mostly involves antidepressants. Lack of knowledge is indicated as a major barrier, indicating the need for more education on PGx for GPs.

Indices of cellular and humoral immunity in a patient with a history of central precocious puberty in anamnesis

The etiology of precocious puberty includes organic anomalies, genetic mutations, but the primary cause remains unclear in the vast majority of cases. Gonadotropin-releasing hormone (GRH) agonists are used as a treatment of gonadotropin-dependent precocious puberty. Blocking the secretion of gonadotropin-releasing hormone, these drugs stop the premature development of sexual features, prevent premature closure of ossification zones, thereby increasing the child’s expected adult height. The interest in the effects of this group of drugs beyond the hypothalamic-pituitary-gonadal axis has been recently increased. A series of clinical cases have been reported on the development of autoimmune diseases, e.g., autoimmune thyroiditis, Graves disease and type 1 diabetes. The article presents a clinical observation of a patient with central form of premature development who exhibited satisfactory response to treatment with a GRH agonist drug. Further follow-up did not show any reproductive dysfunction. Upon immunological examination, a disturbance was revealed only in the cellular component of immunity. An increased metabolic activity of neutrophils was found, thus, probably, indicating a nonspecific inflammatory process. The levels of immunoglobulins A, M, G matched the reference values. Thus, the therapy with a drug from the group of GRH agonists was effective and safe in terms of influencing the patient’s immune system. The role of hormonal disorders and effects of GRH agonists on the development of immunopathological conditions require further research.

Terapias que han demostrado eficacia en el COVID-19: una revisión narrativa

Background: The new coronavirus disease has accelerated the development of therapeutic guidelines for patients depending on their degree of severity. To date, many drugs have been studied. However, as time passed, only some of these therapeutic groups have been effective and have produced a reduction in patient mortality and morbidity. Methods: A search and identification of articles published in the following electronic data-bases was carried out: PubMed, Clinical Key, Web of Science, and Scopus; for their analysis and selection in English and Spanish. The literature research emphasizes the search for current guidelines on the treatment of COVID-19, including all degrees of severity, seeking the effectiveness of the medication. Results: For each listed drug, its pharmacodynamics, pharmacokinetics, and general re-commendations for use in adult patients with COVID-19, are described. Conclusions: Du-ring the COVID-19 pandemic, numerous groups of drugs have been studied, however, only a select group have shown to have a role in the treatment of the disease. The literature and guidelines support the use of these treatments.

Genetic determinants of antibiotic resistance in enterobacteria isolated during microbiological monitoring in the perinatal center

Relevance. Currently, studies of the prevalence of antibiotic resistance and its genetic characteristics are focused primarily on the adult population, although infection with multiple drug infection has been registered as etiological agents of a general infection in obstetric and gynecological and pediatric institutions. The study of the prevalence of genetic determinants of antibiotic resistance is an important area of scientific research.Aim. To analyze the results of the studies carried out to identify the genetic determinants of antibiotic resistance of enterobacteria isolated during microbiological monitoring in the perinatal center.Materials and methods. The genetic profile of antibiotic resistance was studied in ESBL-producing strains isolated from 45 women and 35 children examined at the departments of the Federal State Budgetary Institution «NII OMM» of the Ministry of Health of Russia. To determine the determinants of antibiotic resistance, 80 non-duplicate strains of 7 species of the Enterobacteriaceae family were studied. DNA of bacterial cells was isolated from a daily culture of microorganisms using the PROBA-NK kit, detection of the tem, ctx-M-1, shv genes; oxa-40-like, oxa-48-like, oxa-23-like, oxa-51-like, imp, kpc, ges, ndm, vim were carried out using the diagnostic kit «BacResista GLA» on the detecting amplifier DT-48 (DNA -technology, Russia). To assess the statistical significance of differences in the frequency of occurrence of genes, Pearson's c2 test with Yates' correction was used.Results and discussion. When analyzing the results of studies on the molecular genetic detection of antibiotic resistance determinants, which we conducted in 2022, it was found that 8 genovariants were found in bacterial strains isolated from patients of the departments of the Research Institute of OMM in Yekaterinburg, providing resistance to beta-lactam antibiotics. The dominant genome, as in 2021, remains blaCTX-M-1, found in 29 cases. The blaTEM gene was identified both in association with other genes and as a single variant in Escherichiae coli and Klebsiella pneumoniae strains. Of the eight strains of K. pneumoniae, 4 were found to have three antibiotic resistance genes blaCTX-M, blaTEM, blaSHV, strains with a genetic profile of blaCTX-M, blaTEM, blaSHV, blaNDM were isolated once; and blaTEM, blaSHV, blaKPC. In one strain of K. pneumoniae, phenotypically showing resistance to AB, no genetic determinants of AB resistance were found. In addition to resistance to beta-lactam antibiotics, the strains demonstrate resistance to such groups of antibacterial drugs as fluoroquinolones, phosphonic acid derivatives (fosfomycin), and aminoglycosides. The data obtained indicate that the intestines of newborns during their stay at the stationary stage of nursing in some cases are colonized by strains of enterobacteria with multidrug resistance. Consequently, children are a reservoir of resistant microorganisms and can be sources of pathogens of infectious diseases in families and children's organized groups.

Preparation and anti-triple-negative breast cancer cell effect of a nanoparticle for the codelivery of paclitaxel and gemcitabine

Amphiphilic polymers (HA-ANI) were prepared by grafting hyaluronic acid (HA) and 6-(2-nitroimidazole)hexylamine (ANI) and then self-assemble in water to form nanoparticles (NPs) that could be loaded with paclitaxel (PTX) and gemcitabine (GEM) by dialysis. Infrared spectroscopy and 1H-NMR indicated the successful synthesis of HA-ANI. Three different ratios of NPs were prepared by adjusting the ratios of hydrophilic and hydrophobic materials, and the particle size decreased as the ratio of hydrophilic materials increased. When HA:ANI = 2.0:1, the nanoparticles had the smallest size distribution, good stability and near spherical shape and had high drug loading and encapsulation rates. In vitro release experiments revealed that NADPH could accelerate the drug release from NPs. Cellular uptake rate reached 86.50% at 6 h. The toxic effect of dual drug-loaded nanoparticles (P/G NPs) on MDA-MB-231 cells at 48 h was stronger than that of the free drug. The AO/EB double-staining assay revealed that a large number of late apoptotic cells appeared in the P/G NPs group, and the degree of cell damage was significantly stronger than that of the free drug group. In the cell migration assay, the 24 h-cell migration rate of the P/G NPs group was 5.99%, which was much lower than that of the free group (13.87% and 17.00%). In conclusion, MDA-MB-231 cells could effectively take up P/G NPs, while the introduction of the nano-codelivery system could significantly enhance the toxicity of the drug to MDA-MB-231 cells as well as the migration inhibition effect.

Подовження інтервалу QT як значуще кардіоваскулярне ускладнення під час системного лікування хворих на рак

Стрімке впровадження нових протипухлинних засобів та технологій лікування сприяло підвищенню виживання хворих на рак. Однак, розвиток серцево-судинних ускладнень на тлі протипухлинного лікування нерідко призводить до зниження якості та тривалості життя онкологічних хворих.Одним з проявів серцево-судинних ускладнень при застосуванні протипухлинних лікарських засобів є подовження інтервалу QT з різними порушеннями серцевого ритму.Стаття базується на аналізі рандомізованих клінічних досліджень і метааналізів та рекомендаціях Європейського товариства кардіологів з кардіо-онкології. Наведено опис факторів ризику і класифікація подовження інтервалу QT, спричиненого протипухлинною терапією. Проаналізовані основні групи протипухлинних лікарських засобів, які індукують зміни інтервалу QT. Розглянуті етапи і кратність огляду онкологічних хворих при різних патологічних станах та порушеннях гемостазу, що можуть призводити до подовження інтервалу QT під час лікування та в різні періоди після його проведення.Огляд присвячений аналізу змін інтервалу QT та клінічному застосуванню алгоритмів прийняття рішень щодо мінімізації кардіотоксичності з метою підвищення ефективності протипухлинного лікування онкологічних хворих.

Stigmasterol and gastrodin, two major components of banxia-baizhu-tianma decoction, alleviated the excessive phlegm-dampness hypertension by reducing lipid accumulation

Ethnopharmacological relevanceBanxia baizhu tianma decoction (BBTD) originated from the Qing Dynasty Chinese medicine book “Medical Xinwu”, which has a clinical application history of more than 300 years. It's a classic prescription for expelling phlegm, extinguishing wind, strengthening the spleen (traditional Chinese medicine, ie, TCM, refers to the spleen channel) and dissipating excessive fluid based on TCM theory. BBTD is particularly effective in the treatment of excessive phlegm-dampness hypertension. However, the precise pharmacological effect of each herb of BBTD on hypertension treatment is not yet fully understood. Aim of the studyTo investigate the pharmacological effects of each herb in BBTD on hypertension treatment and to explore the mechanisms behind them. Materials and methodsA high-fat-diet fed animal model was developed to evaluate the efficacy of different groups of drugs in BBTD for the treatment of hypertension. Untargeted metabolism was used to detect the metabolic changes after modeling and drug intervention. Then, Stigmasterol (STI) and gastrodin (GAS), major components of Pinellia Ternate Makino and Gastrodia elata Blume, were selected for treatment on HepG2 cell steatosis model. Real-time quantitative polymerase chain reaction and Western blotting were used to detect changes of corresponding gene and protein after drug intervention to explore the exam anti-hyperlipidemia mechanism of STI and GAS combination. ResultsThe weight gain, elevated blood pressure and increased blood lipids induced by high-fat-diet were significantly decreased (p < 0.05) after each prescription medicine intervention in a dose-dependent manner. In addition, 28 differential metabolites (DMs) were detected after modeling and were regulated to normal at varying degrees after each drug group treatment. In addition, eight of the 28 DMs were significantly different from the model group after the full prescription drug intervention, primarily related to four metabolic pathways, while only two metabolites were significantly different from the model group after the unprincipled drug intervention, related to one metabolic pathway. In HepG2 hyperlipidemia cell model, STI, GAS and their combination significantly decreased TC, TG levels and lipid accumulation (p < 0.05), and decreased sterol regulatory element-binding protein 1c (SREBP-1c), fatty acid synthase (FAS), stearoyl-CoA desaturase-1 (SCD1) and their protein expressions (p < 0.05), increased adenosine monophosphate-activated protein kinase (AMPK) and it's protein expression (p < 0.05). The two drugs work better in combination than alone. ConclusionBBTD has been shown to be effective in reducing lipid accumulation in a high-fat rat model, as well as in restoring the model-induced abnormal metabolites to normal levels in a dose-dependent manner. Pinellia ternata Makino and Gastrodia elata Blume, the main components of BBTD, may regulate lipid metabolism through fatty acid biosynthesis, arginine and proline metabolism. Their main active agents, STI and GAS, effectively reduce lipid accumulation and lipid content in cells and regulate the expression levels of genes and proteins associated with lipid metabolism. These results suggest that BBTD may regulate lipid metabolism via AMPK/SREBP-1c pathway.

Adverse Effects of Antipsychotic Drugs - A Review

Antipsychotic drugs which are also known as Neuroleptics are group of psychotropic drugs or psychopharmacological agents1 that are primarily used to manage psychoses including delusions, hallucinations, paranoia, or disordered thought. Besides their antipsychotic action, they had been reported to have some adverse effects which can be seen in Cardiovascular system, Metabolic system, Skeletal and Muscular system, Cognitive and Emotional side effects, and Sexual dysfunction. These adverse effects were mainly observed when they used for longer duration or taken in larger doses or with sudden change in their dose. Keywords: Antipsychotic drugs, Adverse events, Side effects, Extrapyramidal symptoms

Neonatal ICU therapy: a literature review on pharmacotherapies

INTRODUCTION: The neonatal period is an age group of vulnerability, which is subject to adverse effects related to conventional drug treatments and therapies, many drugs are empirically applied in the neonatal ICU (NICU), in off-label or non-licensed ways, currently the scientific basis on pediatric pharmacological assistance is scarce, constituting an unpredictable scenario of adverse and severe drug reactions. OBJECTIVE: To analyze the main pharmacological practices in the neonatal ICU, observing the possible effects on the newborn patient. METHODOLOGY: literature review that used the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) methodology. The search for articles was carried out in PubMed, SciELO and LILACS databases, applying descriptors from Descritores em Ciências da Saúde (DeCS) and Medical Subject Headings (MeSH). RESULTS: 415 articles were found and 26 were included in the study. It was noted that there is a high prevalence of overdoses and unnecessary prolongation of antibiotic therapy, adverse effects linked to bacterial resistance and alteration of the newborn’s (NB) microbiota may occur, generally these drugs were used in the scenario of neonatal sepsis and in an off-label way, vancomycin stood out as the most widely used antibiotic among the studies. The NB’s respiratory problems were pharmacologically treated with exogenous surfactant, propofol, hydrocortisone and milrinone, the clinical situations of use include Respiratory Distress Syndrome in Neonates and sedation for intubation. Painful procedures are common in the NICU, requiring pharmacological measures such as the use of analgesics and sedatives, including fentanyl, morphine, dipyrone, non-steroidal anti-inflammatory drugs and benzodiazepines, the safe application is also difficulty with these medications. Local anesthetics, such as lidocaine, are the most used for surgical pain, epidural anesthesia helps to reduce surgical stress, and topical anesthetics are useful for pain caused by skin barrier rupture. The group of drugs most used in an off-label way, according to the Anatomic Therapeutic Chemical (ATC) classification, were the group of anti-infectives for systemic use and drugs that act on the nervous system. CONCLUSION: the need for more scientific depth in the context of pharmacology at the NICU became extremely explicit during the study’s development, the lack of consensus for appropriate medical prescriptions leads to the need for greater care when prescribing for neonates, considering the inherent characteristics of the organism of these patients that alter the pharmacokinetics and pharmacodynamics of medications.

Perfil de seguridad de nirmatrelvir-ritonavir: evidencia de eventos adversos por interacciones farmacológicas

ObjectiveThe aim of the study was to evaluate the safety profile of nirmatrelvir-ritonavir (NMV-r) in real clinical practice and to analyze the clinical relevance of drug-drug interactions in the development of adverse events. MethodsObservational, retrospective study in which safety data of patients treated with NMV-r between April and July 2022 in an outpatient setting were evaluated. The duration of follow-up was 28 days and the number of adverse reactions reported, as well as whether they were managed on an outpatient basis or required health care, and the presence of renal and hepatic function impairment were assessed. Concomitant treatment was reviewed, identifying theoretical drug-drug interactions (TDDIs) whose severity was defined using the Lexi-interact classification. ResultsThe study included 146 patients, 82 (56,16%) were women, whose median age was 65 years (22-95). The number of TDDIs detected and maintained during treatment with NMV-r was 164, with the percentage of patients with at least one interaction being 62,33%. The median number of TDDIs per patient was 1 (0-5). At least 1 adverse event (AE) was reported in 18 patients (11,84%). Eleven AEs were potentially related to any TDDI. Seven patients required contact with hospital assistance for AE management. Eight patients had impaired renal function and 2 had impaired liver function at 28 days. The main groups of drugs implicated in the occurrence of an AE were oral anticoagulants and calcium antagonists. ConclusionsOur results show a high number of TDDIs detected were detected between NMV-r and other drugs. This study provides greater knowledge of the drugs involved in such interactions and their potential relationship with the occurrence of adverse events.

Pharmacoepidemiological analysis of therapy for chronic heart failure

The aim of the study was to examine the schemes proposed in the clinical guidelines and to compare them with inpatient treatment methods.Materials and method, the case histories of 40 patients of cardiology department of Saratov medical preventive institution were analyzed. Men and women, aged from 50 to 80 years, with functional class (FC) II to IV, with reduced left ventricular ejection fraction (&lt; 40 %) and with such diseases in anamnesis as arterial hypertension, coronary heart disease, atherosclerosis, diabetes mellitus were in the inclusion group. The exclusion group included patients with noncardiac diseases, pediatric patients, patients under 50 and over 80 years old, patients with I class, preserved and intermediate LV ejection fraction (&gt; 40 %). The results of immunochromatographic analysis of NT-proBNP marker were studied, the identity of prescribed drugs to a certain group and their frequency of use, as well as the similarity of prescribed regimen to clinical guidelines were determined.Results. NT-proBNP level over 125 pg/ml was revealed in 21 out of 40 patients, arterial hypertension, atherosclerosis, ischemic heart disease were in the anamnesis testifying to high probability of CHF. Perindopril (80 %) and fosinopril (20 %) were the main angiotensin-converting enzyme inhibitors (ACEIs). Spironolactone (a К + -saving diuretic), thorasemide, furosemide (a loop diuretic) and indapamide (a thiazide-like diuretic) were used as diuretics. Among blockers, metoprolol (20 %), nebivolol (30 %), bisoprolol (50 %) were prescribed. Patients suffering from CHF and with a history of atherosclerosis were prescribed statins (rosuvastatin, atorvastatin) in addition to the main groups of drugs in all cases. Warfarin (9.5 %) and rivaroxaban (23.8 %) were present in 7 of 21 cases (33 %). In addition, 17 patients (81 %) were prescribed acetylsalicylic acid as an antiaggregant. Those with a history of diabetes mellitus (19 %) received metformin for glycaemic control, as an adjunctive therapy to the main combinations of drugs.Conclusions. The inpatient regimen used to treat patients with CHF is more in line with the clinical guidelines.