Indian Journal of Pharmacology最新文献

Background: Consumers are key stakeholders in drug safety, yet, till recently, their potential has remained untapped in terms of contributing to the drug safety data. The Medicines Side Effect Reporting Form for Consumer (MSERC), launched by the Pharmacovigilance Programme of India, is an important tool for the consumer to report adverse drug reactions (ADRs).

Objective: Our objective was to evaluate the awareness and acceptability of the MSERC among the general population and the quality of data entered by the consumers.

Methods: This was a cross-sectional study carried out at a tertiary healthcare center in Madhya Pradesh (Central India).

Results: The study included 203 participants, with 115 self-reports and 88 reports of ADRs experienced by a relative. All mandatory fields were filled by 149 (73.4%) participants. More than half of the reporters (113, 55.57%) took <5 min to fill the form and found it easy to fill it (123, 60.59%). Most of the participants expressed a willingness (186, 91.63%) to fill the MSERC. The time taken to complete the form and the difficulty in filling the form were significantly greater in the elderly (age >60 years). Significantly more women were aware about the MSERC (P = 0.026), as compared to men. Participants with graduate, postgraduate, or professional degrees took significantly less time to fill the form (P < 0.001) and found it easier to fill it (P = 0.019).

Conclusion: Awareness about the form was found in only 6.4% of the responders, highlighting a need to generate more awareness among the consumers about the MSERC form to improve the ADR reporting.

This network meta-analysis evaluated the efficacy and safety of the dextromethorphan-bupropion combination (AXS-05) in treating major depressive disorder (MDD). Data were retrieved from multiple databases, including PubMed, Embase, Scopus, Google Scholar, and ClinicalKey, yielding 60 records. After removing duplicates and excluding irrelevant studies, such as reviews, case reports, posters, and studies focusing on unrelated populations (e.g., Alzheimer's dementia), two randomized controlled trials (RCTs) - Tabuteau et al. (2022) and Iosifescu et al. (2022) - were selected for final analysis. The inclusion criteria focused on RCTs published between 2014 and 2024, involving adult participants (18-65 years) diagnosed with MDD, and reporting on the efficacy and safety of the dextromethorphan-bupropion combination. Studies that did not focus on MDD, were not in English, or lacked control groups were excluded. The findings indicate superior efficacy of the dextromethorphan-bupropion combination, with remission rates of 46.5% and 39.5%, compared to 16.2% for Bupropion alone and 17.3% for placebo. Despite a higher incidence of mild to moderate adverse events (72.9% vs. 64.6% for Bupropion), the combination's safety profile remained comparable, with no significant increase in treatment discontinuation. These results suggest that AXS-05 is a promising treatment for MDD, warranting further investigation in larger, diverse populations to confirm its long-term efficacy and safety.

Objectives: Nonalcoholic steatohepatitis (NASH) is a strong risk factor for end-stage liver disease. Trigonelline (TG) is a plant alkaloid with anti-oxidant, anti-dyslipidemic, and anti-insulin resistance activities. Everolimus (EV), a conventional drug and an mTOR inhibitor, has been demonstrated to improve metabolic outcomes. The synergistic effect of the co-treatment of TG and EV against NASH conditions remains unknown.

Materials and methods: We have developed a fast food (FF)-diet and thioacetamide-induced chronic steatohepatitis in a C57BL/6J mice model of 24 weeks duration. We have evaluated the synergistic protective effect of TG and EV at reduced doses to avoid any undesired toxic manifestations of the FF and thioacetamide. The study was demonstrated by comparative analysis across different groups after 24 weeks.

Results: Co-exposure to FF diet and thioacetamide resulted in chronic steatohepatitis, evident by focal necrosis, bridging fibrosis, loss of liver architecture, and excessive collagen deposition. Protein and gene analysis revealed enhanced de novo lipogenesis (SREBP-1, PPAR-Ƴ, CD36), inflammation (interleukin-6, tumor necrosis factor, CYP2E1), fibrosis (transforming growth factor beta, alpha-smooth muscle actin, tissue inhibitors of metalloproteinases-1), and extracellular matrix deposition (MMP-1, Col1A1). TG + EV at reduced doses showed marked synergistic effects in preventing inflammation, fibrosis, and lipogenesis markers.

Conclusion: This study provides a novel 24-week FF diet and thioacetamide-induced murine NASH model for possible preclinical drug discovery studies. Furthermore, our treatment regimen discovered the synergistic effect of TG and EV at reduced doses in preventing chronic steatohepatitis.

Heparin, a commonly used anticoagulant, has been associated with several cutaneous adverse effects, including skin necrosis, bruising/ecchymosis, urticaria, angioedema, red plaques, nodular lesions, and allergic contact dermatitis. Bullous hemorrhagic dermatosis (BHD) caused by heparin is a rare skin-related side effect. A 34-year-old woman diagnosed with anti-phospholipid syndrome was recently observed to develop hemorrhagic bullous dermatosis distant from the site of intravenous unfractionated heparin. Heparin therapy was continued for 5 days, followed by daily oral warfarin 2 mg, along with aspirin 75 mg, with monitoring of lesions. Two weeks later, skin lesions resolved spontaneously. BHD is nonthreatening and typically resolves on its own without the need for extensive treatment. Clinicians should be aware of the presentations of this self-limiting illness to avoid unnecessary workups.

Background: Dipeptidyl peptidase 4 (DPP-4) inhibitors are primarily excreted renally. Linagliptin is an exception with excretion primarily through enterohepatic system and is expected to have a better renal profile, though real-world data are scarce. Comparative studies on the renal safety and glycaemic control with linagliptin versus popular DPP-4 inhibitors such as vildagliptin are crucial, especially in the background of COVID-19 pandemic that hugely impacted glycemic control in India's large type 2 diabetes mellitus (T2DM) population.

Materials and methods: Adult T2DM patients not controlled with metformin alone, added linagliptin (5 mg once daily) or vildagliptin (50 mg twice daily) in the tertiary care outpatient department setting were included in the study. Parameters such as glycosylated hemoglobin, fasting blood glucose, postprandial blood glucose, blood urea nitrogen, serum creatinine, estimated glomerular filtration rate (eGFR), change in renal function, glycemic control, and clinical parameters were compared at baseline, 2 months, and 6 months of treatment. All adverse events were analyzed using the WHO-UMC scale.

Results: Both groups achieved similar glycemic control, however, accompanied with impairment of renal parameters after 6 months. Compared to linagliptin, almost 300% rise in creatinine and 140% fall in eGFR were noted in the vildagliptin recipients. However, the difference in serum creatinine or eGFR could not attain statistical significance in the study.

Conclusion: Both linagliptin and vildagliptin can help to achieve glycemic control despite possible influence of the COVID-19 pandemic and are generally well tolerated. However, renal functions are better preserved with linagliptin. Further studies involving a larger sample size and longer follow-up are recommended before generalization of the findings of the present study.

The study aimed to examine the impact of the researcher-centered Basic Fit Translational Model and Delivery Design framework on outcomes such as visualization, progression, and self-reflection. We collected data through questionnaires, with thirty researchers participating in individual training sessions. The Wilcoxon signed-rank test's statistically significant results (3.0-7.0) demonstrated the ease of model adaptability and the need for researcher-centered model building. The basic fit model helps researchers identify their research type, visualize shortcomings, and collaborate in an extended network, leading to successful completion. The delivery design framework helps parallel-process multiple workflows, reducing translational lag time for patients and the pharma industry.

Objective: This study evaluated the anticancer activity (in silico and in vitro) of compounds derived from the Agelas nakamurai collected from Indonesian waters against the triple-negative breast cancer cancer cell line MDA-MB-231.

Background: The marine sponge genus Agelas is known to biosynthesize a variety of secondary metabolites with anticancer properties.

Materials and methods: The compounds were separated using open column and preparative high-performance liquid chromatography. The liquid chromatography-mass spectrometry/mass spectrometry and nuclear magnetic resonance data were used to characterize compounds. Antiproliferation test of isolated compounds was conducted against the MDA-MB-231 cell line. Meanwhile p53 MDM2 protein [PDB]: 4OQ3, and Estimated Glomerular Filtration Rate (EGFR) protein (PDB: 1T46) were utilized for molecular docking and dynamic (MD) analysis.

Results: LC-MS data of fraction F7 indicated the presence of agelasine D, ageloxime D, agelanin B, and midpacamide. Further purification of fraction F7 led to the agelasin D and ageloxime D. Both compounds inhibited the MDA-MB-231 cell line with IC50 values of 7.09 and 171.07 µM, respectively. The docking results showed that the binding affinity of agelasine D and ageloxime D to 4OQ3 and 1T46 were close, with scores ranging from -7.3 to -9.0 kcal/mol. MD simulation within 100 ns indicated agelasin D and ageloxime-D make stable binding to the targeted proteins with root-mean-square deviation <2Å.

Conclusions: The isolated compounds from A. nakamurai showed potent against the MDA-MB-231 cell line, based on in vitro and in silico analysis. The MD data supported that the compounds effectively inhibit cancer growth through the MDM2 or EGFR pathways. Thus, this study suggested further in vitro mechanism of action analysis.

Objectives: This study was conducted to find out the appropriateness of antimicrobial therapy in Medical wards of a tertiary care referral hospital in South India. Other objectives were to study the association between appropriateness of antimicrobial therapy and antibiotic consumption and in-hospital patient outcomes.

Methodology: A series of 32 clinical audits were done in the medical wards from January 2018 to June 2019 and a total of 220 patients were included in the study. All patients in whom an antimicrobial agent was initiated were assessed for the appropriateness of their use. Antibiotic consumption was studied using days of therapy. Appropriateness of antibiotic therapy and its impact on patient outcomes were also studied.

Results: Appropriate antimicrobial usage was seen in only 47% patients. Collection of all appropriate cultures before initiation of therapy, timely de-escalation, and intravenous (IV) to per oral step down contributed to lower rates of appropriateness. Patients who received appropriate antimicrobial therapy had significantly lower duration of therapy and nonsignificant lower deaths as compared to those who received inappropriate antimicrobial therapy.

Conclusions: Inappropriate antimicrobial usage is very high in medical wards of a tertiary care referral hospital and lead to higher antibiotic consumption higher in-hospital mortality. The collection of all appropriate cultures before initiation of antimicrobial agents, timely de-escalation, and IV to per oral step down can improve appropriateness.