Safety Of Drug Therapy Research Articles

A Comparison of Molecular Techniques for Improving the Methodology in the Laboratory of Pharmacogenetics.

One of the most critical goals in healthcare is safe and effective drug therapy, which is directly related to an individual's response to treatment. Precision medicine can improve drug safety in many scenarios, including polypharmacy, and it requires the development of new genetic characterization methods. In this report, we use real-time PCR, microarray techniques, and mass spectrometry (MALDI-TOF), which allows us to compare them and identify the potential benefits of technological improvements, leading to better quality medical care. These comparative studies, as part of our pharmacogenetic Five-Step Precision Medicine (5SPM) approach, reveal the superiority of mass spectrometry over the other methods analyzed and highlight the importance of updating the laboratory's pharmacogenetic methodology to identify new variants with clinical impact.

Evaluating the impact of loperamide on irinotecan-induced adverse events: a disproportionality analysis of data from the World Health Organization pharmacovigilance database (VigiBase).

SN-38, the active metabolite of irinotecan, may cause adverse events necessitating treatment discontinuation and management. Diarrhea, which is treated with loperamide, is one such event. However, loperamide may delay SN-38 elimination, causing more adverse events. Therefore, understanding the adverse events caused by symptomatic drugs is crucial for safe drug therapy. This study aimed to assess the association between loperamide and irinotecan-induced adverse events. We analyzed data up to December 2022 from VigiBase, the World Health Organization's adverse event database. The study used reporting odds ratios (RORs) to evaluate the associations between concomitant medications and irinotecan-induced adverse events. Fisher's exact probability test was used to analyze the adverse events. Logistic regression analysis was performed to identify associated adverse event signals. Of the 32,520,983 cases analyzed, 57,454 involved the use of irinotecan. Among these, 1589 (2.8%) patients were co-treated with loperamide. Signals for neutropenia (ROR 1.37, 95% confidence interval (CI) 1.20-1.57, p < 0.001), anemia (ROR 1.81, 95% CI 1.43-2.30, p < 0.001), and alopecia (ROR 1.89, 95% CI 1.30-2.74, p < 0.01) were detected with concomitant loperamide. Multivariate logistic regression analysis confirmed that concomitant loperamide use was associated with signals for neutropenia, anemia, and alopecia. Our results suggest that loperamide increases the risk of irinotecan-induced adverse events and enhances irinotecan toxicity. The study methodology may be useful for predicting adverse event risk when choosing symptomatic therapy drugs during irinotecan use.

Drug therapy safety during pregnancy and breastfeeding

The treatment of dermatological diseases during pregnancy and breastfeeding poses particular challenges for the therapist for medical and legal reasons. Maternal and fetal influencing factors must be taken into account and the special need for protection of the fetus, infant, and mother must be considered in the treatment decision, usually outside of the approval process. Due to the lack of or insufficient evidence for most therapies during pregnancy and breastfeeding, an individual risk-benefit assessment should always be carried out, which also takes into account the risk of nontreatment. In the case of difficult or potentially momentous decisions, information from relevant databases, intercollegiate consultation and, if possible, advice from aclinical ethics committee should be obtained. In any case, the parents, and in particular the mother, should be carefully informed and their consent should be obtained and documented. Recommendations can be made for common chronic inflammatory and infectious dermatoses, but these should be reviewed on acase-by-case basis. For other therapy situations, an individual analysis and decision-making process is necessary. Overall, however, it can be stated that digital data processing and availability, combined with careful analysis, empathetic consideration and information for those affected, enables asuccessful treatment decision to be made in the vast majority of cases.

A retrospective comparative case series of efficacy and safety of radiofrequency thermocoagulation versus drug therapy in patients with trigeminal neuralgia: A clinical case report.

The trigeminal neuralgia (TN) is characterized by a unilateral, episodic, electric shock-like pain in the distribution of the trigeminal nerve. Both drug therapy and radiofrequency thermocoagulation (RT) are used to treat TN. To compare the efficacy and safety of RT and drug therapy in patients with TN. Between October 2020 and December 2022, 62 patients with TN were allocated to undergo TN treatment (group A) or drug therapy (group B). In group A, 30 patients received RT treatment, whereas 32 patients in group B receive drug treatment. Pain relief, clinical outcomes, and adverse events in both groups were evaluated. And significantly greater reduction in Visual Analogue Scale scores was noted in group A than in group B in the initial 2-week period (P < .05). The excellent rate was 93.3% (28/30) in group A, whereas it was 68.8% (22/32) in group B during the initial 2-week period (P < .05). A total of 62 patients were followed up at least 12 months, with a mean follow-up time of 14.5 months. But there were no statistically significant differences between the 2 groups at the final follow-up. A total of 24 patients had facial numbness in group A. In contrast, ten patients in group B complained of discomfort including sedation, dizziness, nausea, vomiting. During the follow-up period, 4 patients in group A and 6 patients in group B experienced recurrent pain. RT is a safety and effective treatment for patients with classic TN, providing more benefits of quicker pain relief and higher patient's satisfaction, compared with traditional drug therapy.

Antibody-based biological antiviral drugs for the prevention and treatment of acute respiratory viral infections in immunocompromised patients: focus on safety

The safety of drug therapy is of particular importance for immunocompromised patients. This aspect acquires high importance in the context of choosing tactics for the prevention and treatment of acute respiratory viral infections. The review presents data on the features of the antiviral immune response and common cold/influenza in patients with a burdened allergic history and a brief overview of the results of clinical studies on the effectiveness and safety of innovative biological antiviral drugs based on antibodies to biological targets – Ergoferon, Anaferon for children and Anaferon. The drugs have a targeted effect on the immune system in accordance with their pharmacological targets, have a significant evidence base, including a meta-analysis of clinical trials for each drug according to the indication "acute respiratory viral infections/influenza", as well as individual studies, including double-blind placebo-controlled randomized, with this pathology in immunocompromised patients. The article also includes the results of a generalized safety analysis of the use of the above drugs for the prevention and treatment of acute respiratory viral infections/influenza in patients with concomitant allergic and autoimmune pathology. The results of the conducted studies, meta-analyses and generalized statistical analysis of data on the use of the drugs Anaferon for children, Anaferon, Ergoferon for the prevention and treatment of acute respiratory viral infections/ influenza indicate proven efficacy and a favorable safety profile and allow us to recommend drugs for wide use with preventive and therapeutic purposes in accordance with indications, including patients with allergic and autoimmune pathology.

Subcutaneous Semaglutide during Breastfeeding: Infant Safety Regarding Drug Transfer into Human Milk.

Postpartum mothers and their healthcare providers often face the challenge of limited data regarding the safety of drug therapies during lactation. Pregnancy can lead to sustained weight gain, and obesity can negatively impact both physical and psychological well-being. The introduction of GLP-1 agonists to augment weight loss has become a topic of interest for many postpartum mothers. Our study aims to investigate the transmission of semaglutide into human milk in the first steps to ensure the safety and health of both lactating mothers and their breastfed infants. Semaglutide quantification was performed using high-resolution liquid chromatography-mass spectrometry. InfantRisk Center Human Milk biorepository released milk samples from eight women collected at 0, 12 and 24 h post-semaglutide administration. Semaglutide was extracted using protein precipitation in methanol, followed by chromatographic separation. Linear calibration curves for the method ranged between 2.5-30 ng/mL, with a limit of detection of 1.7 ng/mL and a limit of quantification of 5.7 ng/mL (LLOQ). Semaglutide was not detected in any of the collected human milk samples. A worst-case scenario of the relative infant dose (RID) was calculated using the LLOQ as the drug concentration in milk when considering semaglutide's bioavailability and long-acting dose profile. The maximum RID projected was 1.26%, far below the standard 10% safety threshold. While questions about long-term infant outcomes, the safety of maternal nutrient intake, and the nutrient content of breast milk remain, our findings suggest that semaglutide concentrations in human milk are unlikely to pose clinical concerns for breastfed infants. These results support healthcare providers in making informed decisions regarding postpartum therapeutic interventions.

Medication Reconciliation as Part of Admission Management-A Survey to Improve Drug Therapy Safety in a Urology Department.

Complete medication reconciliation during hospital admission is the rationale for further treatment decisions. A consecutive, controlled intervention study was conducted to assess discrepancies in medication reconciliation performed by nurses of the Urology Department compared to the Best Possible Medication History (BPMH) established by pharmacists. This study included pre-intervention (control group, CG), nursing training as a pharmaceutical intervention, and post-intervention (intervention group, IG) groups. The discrepancies were classified as "Missing" (not recorded but taken), "Added" (additionally recorded) "Strength" (incorrect documented dosage), "Intake" (incorrect intake time/schedule), "Double" (double prescription), and "Others" (no clear assignment). Additionally, high-risk drug subgroup discrepancies were particularly prevalent and were evaluated. Training success was compared concerning discrepancies in the CG and IG. Generally, the percentage of discrepancies per patient found was lower in the IG than in the CG (78.1% vs. 87.5%, significantly). The category most identified was "Missing" (IG, 33.3% vs. CG, 35.2%). Overall, a discrepancy of 7.4% each (discrepancies: IG, 27 vs. CG, 38) was determined for high-risk drugs while "Missing" occurred (77.8% vs. 52.6%, out of 7.4%). Despite nursing training only partially reducing discrepancies, the implementation of medication reconciliation using BPMH by pharmacists could improve the process, especially for high-risk drugs.

Synthesis and Anti-Trypanosoma cruzi Activity of New Pyrazole-Thiadiazole Scaffolds.

Chagas disease, a silent but widespread disease that mainly affects a socioeconomically vulnerable population, lacks innovative safe drug therapy. The available drugs, benznidazole and nifurtimox, are more than fifty years old, have limited efficacy, and carry harmful side effects, highlighting the need for new therapeutics. This study presents two new series of pyrazole-thiadiazole compounds evaluated for trypanocidal activity using cellular models predictive of efficacy. Derivatives 1c (2,4-diCl) and 2k (4-NO2) were the most active against intracellular amastigotes. Derivative 1c also showed activity against trypomastigotes, with the detachment of the flagellum from the parasite body being a predominant effect at the ultrastructural level. Analogs have favorable physicochemical parameters and are predicted to be orally available. Drug efficacy was also evaluated in 3D cardiac microtissue, an important target tissue of Trypanosoma cruzi, with derivative 2k showing potent antiparasitic activity and a significant reduction in parasite load. Although 2k potentially reduced parasite load in the washout assay, it did not prevent parasite recrudescence. Drug combination analysis revealed an additive profile, which may lead to favorable clinical outcomes. Our data demonstrate the antiparasitic activity of pyrazole-thiadiazole derivatives and support the development of these compounds using new optimization strategies.

Drug monitoring of antiretroviral drugs in children with perinatal HIV infection

Therapeutic drug monitoring is the practice of measuring the concentration of a drug in patient’s biological fluids to assess the effectiveness and safety of drug therapy. The results of determining the drug level in biological fluids can also indicate noncompliance of therapy regimen and low adherence to therapy.The aim. To compare the concentrations of some antiretroviral drugs (lopinavir, ritonavir, lamivudine, abacavir, zidovudine) in children living with HIV infection of different age groups.Methods. We examined 184 children with perinatal HIV infection who underwent therapeutic drug monitoring of nucleoside reverse transcriptase inhibitors (lamivudine, abacavir, zidovudine) and protease inhibitors (lopinavir, ritonavir). Children were divided into four age groups. Group 1 included children 1–2 years old (n = 7); group 2 – children 3–5 years old (n = 14); group 3 – children 6–11 years old (n = 78); group 4 – children 12–17 years old (n = 85). The concentration of antiretroviral drugs in blood plasma was determined using high-performance liquid chromatography with mass selective detection.Results. The lowest lopinavir concentration was found in children 12–17 years old (3782 [2117–5046] ng/ml), which was statistically significantly different from the similar values in children 6–11 years old (5614 [3521–7264] ng/ml; p = 0.011). For other antiretroviral drugs, no statistically significant differences in blood plasma concentrations were found in children of different age groups.Conclusion. The lowest lopinavir concentrations are detected in children older than 11 years. For the other studied antiretroviral drugs, this pattern was not revealed

Factors Determining Quality of Drug Information by Hospital Pharmacies-Results from Five-Year Annual Quality Assessment.

Drug information (DI) provided by hospital pharmacies aims to promote rational and safe drug therapy. While quality assessment for this task is recommended, more knowledge on the factors determining the quality is needed. We aimed to evaluate the impacts of different factors on the quality of DI provided by hospital pharmacies to healthcare professionals. Retrospectively, answers on fictitious enquiries about annual DI tests for German hospital pharmacies over five years were evaluated for content-related and structural requirements. Multivariate analysis was performed for the impact of the enquiry complexity, DI organization (specialized DI center; pharmacist responsible per day; DI on top of other routine tasks), and quality measures (second look; experience of answering pharmacist in DI/on ward; use of documentation database). In 2017-2021, 45, 71, 79, 118, and 122 hospital pharmacies participated. The enquiry complexity had a statistically significant impact on the content-related quality, with poor results for a higher complexity (years 2018/2021, OR 0.25/0.04, p < 0.01). The DI centers achieved better results regarding content-related quality than for a pharmacist responsible per day (OR 0.76/p = 0.65) or DI on top of routine tasks (OR 0.35/p = 0.02). The DI centers scored better in structural quality. The second look showed an overall trend of a better content-related and structural quality. In conclusion, specialized DI centers and second looks are recommended as quality-improving measures. Training for answering complex enquiries should be intensified.

Influence of Light Irradiation on the Degradation of Dezocine in Injections.

Dezocine, which is well-known as an analgesic, had about 45% share of the Chinese opioid analgesic market. Since drug products containing impurities could bring serious health consequences, it was important to control the generation of impurities and degradation products in the dezocine product. In this study, two kinds of photodegradation products (i.e., degradation product 1 and degradation product 2) in the dezocine injection were isolated using high-performance liquid chromatography. The possible structures of the photodegradation products were identified using both high-resolution mass spectrometry and nuclear magnetic resonance spectroscopy. In addition, the possible generation mechanism showed that degradation product 1 was the oxidation product of dezocine, and degradation product 2 was the coupled dimer of dezocine. Finally, we found that the degradation rate of dezocine increased with the increase in light intensity. Moreover, the degradation of dezocine easily occurred under ultraviolet light in comparison with visible light. A deeper insight into the generation of the photodegradation products in the dezocine injection would directly contribute to the safety of drug therapy based on the dezocine injection by minimizing the degradant/impurity-related adverse effects of drug preparations.

The impact of ABCB1, CYP3A4 and CYP3A5 gene polymorphisms on apixaban trough concentration and bleeding risk in patients with atrial fibrillation.

Apixaban, a direct oral anticoagulant, is increasingly used worldwide for the treatment and prevention of venous thromboembolism and ischemic stroke in patients with nonvalvular atrial fibrillation (AF). Obviously, one of the ways to enhance effectiveness and safety of drug therapy is a personalized approach to therapy, which involves pharmacogenetic and pharmacokinetic tests. The study aims to investigate the effect of CYP3A4*22, CYP3A5*3 and ABCB1 polymorphisms on the pharmacokinetics of apixaban and the risk of bleeding. A total of 84 patients were enrolled in this prospective observational study. All patients received apixaban 5 or 2.5 mg twice daily. Real-time polymerase chain reaction was used to evaluate single-nucleotide polymorphisms of the ABCB1 gene (rs1045642 and rs4148738), CYP3A4*22 (rs35599367) C>T, CYP3A5*3 (rs776746) A>G. A plasma trough concentration/dose (C/D) ratio was used as a pharmacokinetic index. The C/D ratio was higher in patients aged >80 years (F(1)=11.209, p=0.00124) and was affected by serum creatinine (>133 μmol/L, F(1)=6.7, p=0.01124). ABCB1 (rs1045642 and rs4148738), CYP3A5 (rs776746) and CYP3A4 (rs35599367) polymorphisms did not show a correlation with C/D ratio of apixaban. Multivariate logistic regression analyses showed that none of the clinical or genetic factors predicted the fact of bleeding. We report no significant association between ABCB1 gene polymorphisms (rs1045642 and rs4148738), CYP3A4*22 (rs35599367) C>T, CYP3A5*3 (rs776746) A>G and bleeding events on apixaban treatment. Complementing the existing criteria with pharmacogenetic and pharmacokinetics information for the patients with AF will enable further individualization of apixaban.

Interaction problems of drugs and food in older patients. Short Review

The interaction between drugs and food in the body of older patients is an important therapeutic problem. As a result of this interaction, both the assimilation of food by the patient's body and the effectiveness and safety of drug therapy can change. Older patients may develop several complications and adverse reactions that change the underlying disease course against the background of age-related metabolic and functional disorders that change both the drugs' pharmacokinetics and pharmacodynamics and the metabolism of food substances. Considering the compatibility mechanisms of medicinal substances with certain food products, compliance with appropriate food regimes is a necessary condition for the effectiveness and drug therapy safety for older patients. __________________________________________________________________________________________ Keywords: older patients; drugs; food; therapeutic problem; pharmacokinetics; pharmacodynamics

Impact of a DSS-supported medication review on the safety of drug therapy and quality of life in patients with antithrombotic therapy.

Polypharmacy is common among patients with antithrombotic medication, giving rise to concerns about Drug-Related Problems (DRPs). Therefore, these patients would benefit from a Medication Review (MR) along with pharmacist counselling to reduce the risks accompanying polymedication. This prospective study presents a concept for MRs that are applicable in German community pharmacies and can efficiently support pharmacist counselling and improve the safety of drug therapy. As this is a major challenge in everyday pharmacy practice, we used a Decision Support System (DSS) to evaluate its ability to support the process of pharmacist-led MRs. The primary endpoint was the impact of a community pharmacist on the reduction of DRPs. We investigated the impact of the interventions resulting from MRs on patients taking at least one antithrombotic drug as part of their polymedication regimen. Secondary endpoints were the reduction in the number of patients with bleeding risks and the improvement of patients' Quality of Life (QoL) and therapy adherence. Furthermore, the DSS used in the study was controlled for correct data assessment and plausibility of data. We selected adult patients who were taking no less than three different medications for long-term treatment, at least one of which had to be an antithrombotic drug, and who were customers in one of eight selected pharmacies over a period of 6months. Data from 87 patients were analyzed with DSS-support. A total of 234 DRPs were identified by the pharmacist (2.7 DRPs per patient). MR reduced DRPs by 43.2% which, resulting to a reduction of 1.2 DRPs per patient. The intervention also led to a significant improvement in the patients' QoL (assessed via EQ-5D-5L questionnaire; p < 0.001) and enhanced therapy adherence (assessed via A14 questionnaire; p < 0.001). The control of correct data assessment (with 93.8% concordance) and plausibility of data (with 91.7% concordance) of the DSS software were conducted by an external auditor. No significant effect was found for overall bleeding risk. The results of this study indicate that DSS-supported and structured MR conducted by pharmacists can contribute to a reduction in DRPs and significantly improve patient's QoL and adherence to treatment.

Development and validation of a new drug-focused predictive risk score for postoperative delirium in orthopaedic and trauma surgery patients

BackgroundPostoperative delirium (POD) is the most common complication following surgery in elderly patients. During pharmacist-led medication reconciliation (PhMR), a predictive risk score considering delirium risk-increasing drugs and other available risk factors could help to identify risk patients.MethodsOrthopaedic and trauma surgery patients aged ≥ 18 years with PhMR were included in a retrospective observational single-centre study 03/2022-10/2022. The study cohort was randomly split into a development and a validation cohort (6:4 ratio). POD was assessed through the 4 A’s test (4AT), delirium diagnosis, and chart review. Potential risk factors available at PhMR were tested via univariable analysis. Significant variables were added to a multivariable logistic regression model. Based on the regression coefficients, a risk score for POD including delirium risk-increasing drugs (DRD score) was established.ResultsPOD occurred in 42/328 (12.8%) and 30/218 (13.8%) patients in the development and validation cohorts, respectively. Of the seven evaluated risk factors, four were ultimately tested in a multivariable logistic regression model. The final DRD score included age (66–75 years, 2 points; > 75 years, 3 points), renal impairment (eGFR < 60 ml/min/1.73m2, 1 point), anticholinergic burden (ACB-score ≥ 3, 1 point), and delirium risk-increasing drugs (n ≥ 2; 2 points). Patients with ≥ 4 points were classified as having a high risk for POD. The areas under the receiver operating characteristic curve of the risk score model were 0.89 and 0.81 for the development and the validation cohorts, respectively.ConclusionThe DRD score is a predictive risk score assessable during PhMR and can identify patients at risk for POD. Specific preventive measures concerning drug therapy safety and non-pharmacological actions should be implemented for identified risk patients.

Challenges in the treatment of pediatric Mycoplasma pneumoniae pneumonia.

This report summarizes the clinical significance of macrolide-resistant and refractory MP pneumonia and discusses the efficacy and safety of alternative drugs, with a stepwise approach to the management of MP pneumonia recommended from the viewpoint of clinical practice. • Although MP pneumonia is usually a benign self-limited infection with response macrolides as first line therapy, severe life-threatening cases may develop if additional treatment strategies are not effectively implemented. • Macrolide-resistant and refractory MP pneumonia are two conditions that may complicate the clinical course of MP pneumonia, increasing the risk for exacerbation and even death. • This report summarizes the clinical relevance of macrolide-resistant and refractory MP pneumonia and discusses the efficacy and safety of alternative drug therapies. • A practical stepwise approach to the management of MP pneumonia is developed based on a comprehensive analysis of existing evidence and expert opinion.

Syringic acid attenuates acute lung injury by modulating macrophage polarization in LPS-induced mice

BackgroundAcute lung injury (ALI) is a continuum of lung changes caused by multiple lung injuries, characterized by a syndrome of uncontrolled systemic inflammation that often leads to significant morbidity and death. Anti-inflammatory is one of its treatment methods, but there is no safe and available drug therapy. Syringic acid (SA) is a natural organic compound commonly found in a variety of plants, especially in certain woody plants and fruits. In modern pharmacological studies, SA has anti-inflammatory effects and therefore may be a potentially safe and available compound for the treatment of acute lung injury. PurposeThis study attempts to reveal the protective mechanism of SA against ALI by affecting the polarization of macrophages and the activation of NF-κB signaling pathway. Trying to find a safer and more effective drug therapy for clinical use. MethodsWe constructed the ALI model using C57BL/6 mice by intratracheal instillation of LPS (10 mg/kg). Histological analysis was performed with hematoxylin and eosin (H&E). The wet-dry ratio of the whole lung was measured to evaluate pulmonary edema. The effect of SA on macrophage M1-type was detected by flow cytometry. BCA protein quantification method was used to determine the total protein concentration in bronchoalveolar lavage fluid (BALF). The levels of Interleukin (IL)-6, IL-1β, and tumor necrosis factor (TNF)-α in BALF were determined by the ELISA kits, and RT-qPCR was used to detect the expression levels of IL-6, IL-1β and TNF-α mRNA of lung tissue. Western blot was used to detect the expression levels of iNOS and COX-2 and the phosphorylation of p65 and IκBα in the NF-κB pathway in lung tissue. In vitro experiments were conducted with RAW267.4 cell inflammation model induced by 100 ng/ml LPS and A549 cell inflammation model induced by 10 μg/ml LPS. The effects of SA on M1-type and M2-type macrophages of RAW267.4 macrophages induced by LPS were detected by flow cytometry. The toxicity of compound SA to A549 cells was detected by MTT method which to determine the safe dose of SA. The expressions of COX-2 and the phosphorylation of p65 and IκBα protein in NF-κB pathway were detected by Western blot. ResultsWe found that the pre-treatment of SA significantly reduced the degree of lung injury, and the infiltration of neutrophils in the lung interstitium and alveolar space of the lung. The formation of transparent membrane in lung tissue and thickening of alveolar septum were significantly reduced compared with the model group, and the wet-dry ratio of the lung was also reduced. ELISA and RT-qPCR results showed that SA could significantly inhibit the production of IL-6, IL-1β, TNF-α. At the same time, SA could significantly inhibit the expression of iNOS and COX-2 proteins, and could inhibit the phosphorylation of p65 and IκBα proteins. in a dose-dependent manner. In vitro experiments, we found that flow cytometry showed that SA could significantly inhibit the polarization of macrophages from M0 type macrophages to M1-type macrophages, while SA could promote the polarization of M1-type macrophages to M2-type macrophages. The results of MTT assay showed that SA had no obvious cytotoxicity to A549 cells when the concentration was not higher than 80 μM, while LPS could promote the proliferation of A549 cells. In the study of anti-inflammatory effect, SA can significantly inhibit the expression of COX-2 and the phosphorylation of p65 and IκBα proteins in LPS-induced A549 cells. ConclusionSA has possessed a crucial anti-ALI role in LPS-induced mice. The mechanism was elucidated, suggesting that the inhibition of macrophage polarization to M1-type and the promotion of macrophage polarization to M2-type, as well as the inhibition of NF-κB pathway by SA may be the reasons for its anti-ALI. This finding provides important molecular evidence for the further application of SA in the clinical treatment of ALI.

Renoprotective effect of diacetylrhein on diclofenac-induced acute kidney injury in rats via modulating Nrf2/NF-κB/NLRP3/GSDMD signaling pathways

Diclofenac (DF)-induced acute kidney injury (AKI) is characterized by glomerular dysfunction and acute tubular necrosis. Due to limited treatment approaches, effective and safe drug therapy to protect against such AKI is still needed. Diacetylrhein (DAR), an anthraquinone derivative, has different antioxidant and anti-inflammatory properties. Therefore, the aim of the current study was to investigate the renoprotective effect of DAR on DF-induced AKI while elucidating the potential underlying mechanism. Our results showed that DAR (50 and 100 mg/kg) markedly abrogated DF-induced kidney dysfunction decreasing SCr, BUN, serum NGAL, and serum KIM1 levels. Moreover, DAR treatment remarkably maintained renal redox balance and reduced the levels of pro-inflammatory biomarkers in the kidney. Mechanistically, DAR boosted Nrf2/HO-1 antioxidant and anti-inflammatory response in the kidney while suppressing renal TLR4/NF-κB and NLRP3/caspase-1 inflammatory signaling pathways. In addition, DAR markedly inhibited renal pyroptosis via targeting of GSDMD activation. Collectively, this study confirmed that the interplay between Nrf2/HO-1 and TLR4/NF-κB/NLRP3/Caspase-1 signaling pathways and pyroptotic cell death mediates DF-induced AKI and reported that DAR has a dose-dependent renoprotective effect on DF-induced AKI in rats. This effect is due to powerful antioxidant, anti-inflammatory, and anti-pyroptotic activities that could provide a promising treatment approach to protect against DF-induced AKI.

Потенциально неприемлемые назначения лекарственных препаратов у детей в критических состояниях: POPI-критерии в России

The POPI criteria (Pediatrics: Omission of Prescriptions and Inappropriate prescriptions) for assessment of treatment of comorbidities, complications and underlying conditions in children that are accepted as the only existing instrument for detection of potentially inappropriate prescriptions, make it possible to evaluate prescriptions in children at the inpatient and outpatients stages of care provision, similar to the Beers criteria for adults. The study was aimed to assess the structure and rate of potentially inappropriate prescribing in the pediatric anesthesiology and resuscitation department of the multidisciplinary children's hospital based on the adapted version of POPI criteria for non-antibiotic concomitant therapy of nosocomial infections. We analyzed 305 cases of non-antibiotic medication prescription per 100 patients included. The rate of potentially inappropriate prescribing was 31 cases (10.5%), among which potentially inappropriate medication was prescribed in 29 cases (9.5%), and potentially missed medication took place in three cases (1%). The highest rate of potentially inappropriate prescribing was reported for respiratory diseases. Assessment of concomitant therapy in the critically ill children with infections revealed no significant effects on the rate of adverse reactions to antibiotics in children. In the context of implementing medical information systems (MIS) and prescription sheets, integration of the adapted POPI criteria is topical in terms of maintaining the quality and safety of drug therapy for treatment of concomitant diseases, conditions, and complications in children.

Recent Approaches of Impurity Profiling in Pharmaceutical Analysis: A Concise Review

Purity profiling is the process of gathering and analyzing information to determine the biological safety of a specific impurity, hence highlighting its importance and range in pharmaceutical research. In the field of pharmaceuticals, impurity has no precise meaning. Identification, structural elucidation, and quantitative determination of impurities and degradation products in bulk medicinal materials and pharmaceutical formulations are all included in impurity profiling. Since unrecognized, possibly poisonous impurities are dangerous to health and should be found and determined by selective procedures in order to increase the safety of drug therapy, impurity profiling has become more significant in contemporary pharmaceutical analysis. Impurities are typically described using words like residual solvents, byproducts, transformation products, degradation products, interaction products, and related products. Impurity identification is carried out using different chromatographic methods in addition to passing the CGMP, QC, QA, and water activity tests, a pharmaceutical ingredient also needs to satisfy the requirements for a new impurity. It is important to separate and characterize impurities in order to collect and evaluate data that determines biological safety, which emphasizes the need for and promise of drug impurity profiling in pharmaceutical research. To separate and measure the pollutants, a range of instrumental analytical techniques have been consistently used. The detection and regulatory evaluation of organic impurities is a very challenging task because to the numerous sources of organic impurities, including microbiological contamination, API breakdown products, and traces of intermediates.