Propyl gallate (PG), a long-standing synthetic antioxidant, is integral to the food, cosmetic and pharmaceutical industries for its established effectiveness in inhibiting lipid peroxidation. This review synthesizes the evolving scientific narrative of PG, reframing it from a simple preservative to a multifaceted bioactive compound and metabolic precursor. It details PG's physicochemical properties, chain-breaking antioxidant mechanism and applications in advanced active packaging. A central focus is its metabolic fate: PG is rapidly and extensively hydrolyzed to gallic acid (GA) upon ingestion. This transformation is critical, as the systemic biological activities and toxicological profile are largely attributable to its metabolites, positioning PG as a pro-drug. This metabolic context clarifies the historical discrepancy between in vitro genotoxicity, driven by reactive oxygen species (ROS) generation, and its general lack of in vivo genotoxicity. The review examines PG's dual bioactivity, where its pro-oxidant potential underlies promising anti-cancer effects via the induction of apoptosis in various cancer cell lines and restores antibiotic efficacy against resistant bacteria. By summarizing current toxicological data, including its role as a contact allergen, this work highlights the urgent need for future research designed to precisely differentiate the in vivo activities of PG from GA, enabling a more nuanced understanding of its complex and often paradoxical biological role.
{"title":"Beyond Preservation: Propyl Gallate's Evolving Story as a Metabolic Precursor and Bioactive Compound","authors":"Woo Hyun Park","doi":"10.1111/bcpt.70153","DOIUrl":"https://doi.org/10.1111/bcpt.70153","url":null,"abstract":"<p>Propyl gallate (PG), a long-standing synthetic antioxidant, is integral to the food, cosmetic and pharmaceutical industries for its established effectiveness in inhibiting lipid peroxidation. This review synthesizes the evolving scientific narrative of PG, reframing it from a simple preservative to a multifaceted bioactive compound and metabolic precursor. It details PG's physicochemical properties, chain-breaking antioxidant mechanism and applications in advanced active packaging. A central focus is its metabolic fate: PG is rapidly and extensively hydrolyzed to gallic acid (GA) upon ingestion. This transformation is critical, as the systemic biological activities and toxicological profile are largely attributable to its metabolites, positioning PG as a pro-drug. This metabolic context clarifies the historical discrepancy between in vitro genotoxicity, driven by reactive oxygen species (ROS) generation, and its general lack of in vivo genotoxicity. The review examines PG's dual bioactivity, where its pro-oxidant potential underlies promising anti-cancer effects via the induction of apoptosis in various cancer cell lines and restores antibiotic efficacy against resistant bacteria. By summarizing current toxicological data, including its role as a contact allergen, this work highlights the urgent need for future research designed to precisely differentiate the in vivo activities of PG from GA, enabling a more nuanced understanding of its complex and often paradoxical biological role.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70153","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626205","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Olav Spigset, Hege-Merete Krabseth, Magnus Strømmen, Arne Helland
Background
The impact of bariatric surgery on the pharmacokinetics of codeine, oxycodone or tramadol is largely unknown.
Methods
In patients treated with these opioids before and after bariatric surgery, serial drug concentrations were measured throughout a dose interval preoperatively and 1, 6 and 12 months postoperatively.
Results
Eight patients treated with codeine (n = 2), oxycodone (n = 2) or tramadol (n = 4) were included. In the patients using codeine, the area under the concentration–time curve during a dose interval (AUC) was moderately increased for the active metabolites morphine and morphine 6-glucuronide 6–12 months after bariatric surgery. For oxycodone, there were only negligible AUC changes. In the tramadol group, there were no discernible AUC changes considered to be caused by the surgical procedure. There were no apparent changes in maximum concentrations or times to achieve maximum concentrations after surgery for any of the drugs or their metabolites.
Conclusion
From a pharmacokinetic point of view, we found no evidence that particular follow-up procedures should be needed for codeine, oxycodone and tramadol in patients undergoing bariatric surgery and continuing drug treatment. However, as always, doses should be adjusted based on clinical effect and the occurrence of adverse drug reactions.
{"title":"Effect of Bariatric Surgery on the Pharmacokinetics of Codeine, Oxycodone and Tramadol—A Case Series","authors":"Olav Spigset, Hege-Merete Krabseth, Magnus Strømmen, Arne Helland","doi":"10.1111/bcpt.70149","DOIUrl":"https://doi.org/10.1111/bcpt.70149","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>The impact of bariatric surgery on the pharmacokinetics of codeine, oxycodone or tramadol is largely unknown.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>In patients treated with these opioids before and after bariatric surgery, serial drug concentrations were measured throughout a dose interval preoperatively and 1, 6 and 12 months postoperatively.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Eight patients treated with codeine (<i>n</i> = 2), oxycodone (<i>n</i> = 2) or tramadol (<i>n</i> = 4) were included. In the patients using codeine, the area under the concentration–time curve during a dose interval (AUC) was moderately increased for the active metabolites morphine and morphine 6-glucuronide 6–12 months after bariatric surgery. For oxycodone, there were only negligible AUC changes. In the tramadol group, there were no discernible AUC changes considered to be caused by the surgical procedure. There were no apparent changes in maximum concentrations or times to achieve maximum concentrations after surgery for any of the drugs or their metabolites.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>From a pharmacokinetic point of view, we found no evidence that particular follow-up procedures should be needed for codeine, oxycodone and tramadol in patients undergoing bariatric surgery and continuing drug treatment. However, as always, doses should be adjusted based on clinical effect and the occurrence of adverse drug reactions.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-11-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70149","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145626207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Poisoning from organophosphorus compounds (OPCs) poses a significant health issue, especially in countries without proper testing facilities, including cholinesterase (ChE) levels. This study aimed to evaluate the effectiveness of a three-element score called PGI, incorporating pH, the Glasgow Coma Scale (GCS) and impaired systolic blood pressure, in predicting mortality and the need for mechanical ventilation (MV) in acute OPC poisoning. A retrospective cross-sectional study was conducted using medical records of 202 patients admitted for acute OPC poisoning over 3 years. The findings indicated an 11.4% mortality rate and a 25.7% underwent MV. A strong negative correlation was observed between the PGI score and serum ChE level (r = −0.6430, p < 0.0001). The PGI scores of 2 and above were a strong predictor for mortality and MV need. Among PGI components, blood pH < 7.23 was the best mortality predictor, while a GCS < 12 effectively predicted the need for MV (AUC = 0.920). Although the PGI score outperformed PSS in predicting adverse outcomes, it did not show a statistically significant difference compared to serum ChE. The PGI score is a reliable prognostic tool that could replace PSS and serum ChE in predicting the severity of OPC poisoning, as well as the risk of mortality and MV need.
有机磷化合物中毒是一个重大的健康问题，特别是在没有适当检测设施（包括胆碱酯酶水平）的国家。本研究旨在评估PGI三要素评分（包括pH值、格拉斯哥昏迷评分（GCS）和收缩压受损）在预测急性OPC中毒患者死亡率和机械通气需求（MV）方面的有效性。对202例急性OPC中毒患者3年来的医疗记录进行回顾性横断面研究。结果显示死亡率为11.4%，MV发生率为25.7%。PGI评分与血清ChE水平呈显著负相关(r = -0.6430, p
{"title":"PGI Score: A Promising Alternative to Serum Cholinesterase for Predicting Mortality and Adverse Outcomes in Acute Organophosphorus Poisoning: A Cross-Sectional Study","authors":"Ghada Attia Sagah, Fatma Gaber Sobeeh, Esraa Hamdy Nassar, Ahmed Fawzy Selim, Asmaa Fady Sharif","doi":"10.1111/bcpt.70145","DOIUrl":"10.1111/bcpt.70145","url":null,"abstract":"<div>\u0000 \u0000 <p>Poisoning from organophosphorus compounds (OPCs) poses a significant health issue, especially in countries without proper testing facilities, including cholinesterase (ChE) levels. This study aimed to evaluate the effectiveness of a three-element score called PGI, incorporating pH, the Glasgow Coma Scale (GCS) and impaired systolic blood pressure, in predicting mortality and the need for mechanical ventilation (MV) in acute OPC poisoning. A retrospective cross-sectional study was conducted using medical records of 202 patients admitted for acute OPC poisoning over 3 years. The findings indicated an 11.4% mortality rate and a 25.7% underwent MV. A strong negative correlation was observed between the PGI score and serum ChE level (<i>r</i> = −0.6430, <i>p</i> < 0.0001). The PGI scores of 2 and above were a strong predictor for mortality and MV need. Among PGI components, blood pH < 7.23 was the best mortality predictor, while a GCS < 12 effectively predicted the need for MV (AUC = 0.920). Although the PGI score outperformed PSS in predicting adverse outcomes, it did not show a statistically significant difference compared to serum ChE. The PGI score is a reliable prognostic tool that could replace PSS and serum ChE in predicting the severity of OPC poisoning, as well as the risk of mortality and MV need.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145585892","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Lung adenocarcinoma often carries driver mutations, such as EGFR mutations, which are effectively targeted by EGFR tyrosine kinase inhibitors (EGFR-TKIs) like osimertinib, a third-generation EGFR-TKI approved for treating T790M and other EGFR-activating mutations. However, the development of adaptive drug resistance remains a major challenge and is associated with poor prognosis in cancer therapy. Ganoderma microsporum immunomodulatory protein (GMI) has demonstrated anticancer properties in various cancers and exhibits synergistic cytotoxic effects when combined with several anticancer drugs. This study investigated the cytotoxic mechanisms of GMI on the lung cancer cell line H1975, which harbors the EGFR L858R/T790M double mutation, as well as on H1975/TR cells with osimertinib resistance. GMI treatment triggered apoptosis in H1975 cells, as indicated by plasma membrane phospholipid translocation and loss of mitochondrial membrane potential. GMI-treated cells displayed increased LC3BII and the development of acidic vesicular organelles, both of which are hallmarks of autophagy induction. Autophagy inhibition by 3-methyladenine and ATG gene silencing effectively decreased the cytotoxic effect of GMI, suggesting that GMI induces autophagic cell death in H1975/TR cells. This study is the first to reveal the novel role of GMI in inducing cytotoxic effects in H1975 cells and H1975/TR cells with osimertinib resistance through two different forms of cell death: apoptosis and autophagy, respectively.
{"title":"GMI, a Fungal Immunomodulatory Protein From Ganoderma microsporum, Induces Different Cytotoxicity in Parental and Osimertinib-Resistant EGFR-Mutated Lung Cancer Cells via Apoptotic and Autophagic Cell Death","authors":"Yu-Ting Kang, I-Lun Hsin, Pin-Tzu Su, Ya-Chu Hsieh, Hui-Yi Chang, Jiunn-Liang Ko, Jen-Ning Tsai","doi":"10.1111/bcpt.70143","DOIUrl":"10.1111/bcpt.70143","url":null,"abstract":"<div>\u0000 \u0000 <p>Lung adenocarcinoma often carries driver mutations, such as EGFR mutations, which are effectively targeted by EGFR tyrosine kinase inhibitors (EGFR-TKIs) like osimertinib, a third-generation EGFR-TKI approved for treating T790M and other EGFR-activating mutations. However, the development of adaptive drug resistance remains a major challenge and is associated with poor prognosis in cancer therapy. <i>Ganoderma microsporum</i> immunomodulatory protein (GMI) has demonstrated anticancer properties in various cancers and exhibits synergistic cytotoxic effects when combined with several anticancer drugs. This study investigated the cytotoxic mechanisms of GMI on the lung cancer cell line H1975, which harbors the EGFR L858R/T790M double mutation, as well as on H1975/TR cells with osimertinib resistance. GMI treatment triggered apoptosis in H1975 cells, as indicated by plasma membrane phospholipid translocation and loss of mitochondrial membrane potential. GMI-treated cells displayed increased LC3BII and the development of acidic vesicular organelles, both of which are hallmarks of autophagy induction. Autophagy inhibition by 3-methyladenine and ATG gene silencing effectively decreased the cytotoxic effect of GMI, suggesting that GMI induces autophagic cell death in H1975/TR cells. This study is the first to reveal the novel role of GMI in inducing cytotoxic effects in H1975 cells and H1975/TR cells with osimertinib resistance through two different forms of cell death: apoptosis and autophagy, respectively.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145562423","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frida Asker, Saga Gimerus, Naldy Parodi López, Susanna M. Wallerstedt
Queries from healthcare professionals to drug information centres may represent drug-related aspects of importance in healthcare. In this study, queries and replies from all drug information centres in Sweden, published on svelic.se (January 2023 to May 2024) and specifically related to the discipline of pharmacy, were explored. Pharmaceutical queries were defined in an iterative process starting with seven definitions of ‘pharmacy’ and independent assessments by two assessors. Three categories emerged: galenic queries, lookup queries and pharmacy practice queries. Out of 767 studied queries, 60 (8%) were categorised as pharmaceutical (kappa: 0.84), distributed across galenic (n = 46), lookup (n = 12) and pharmacy practice queries (n = 2). Galenic queries primarily concerned crushing or splitting of medications (n = 13), alternative routes of administration (n = 12) or compatibility (n = 10). Out of 21 drugs asked about in crushing/splitting-related queries, six lacked information in the national Medication Crushing Database. Out of nine specific drug pairs asked about in compatibility queries, two were incompatible, and information regarding seven was not obtainable from the national Pharmaceutical Compatibility Database. In conclusion, almost one tenth of queries to drug information centres in Sweden, recorded on svelic.se, were specifically pharmaceutical. The requested information was often for crushing/splitting-related queries, and seldom for compatibility queries, accessible from the knowledge resources.
{"title":"Questions in Healthcare Specifically Related to the Discipline of Pharmacy: A Descriptive Analysis of Queries to Drug Information Centres in Sweden","authors":"Frida Asker, Saga Gimerus, Naldy Parodi López, Susanna M. Wallerstedt","doi":"10.1111/bcpt.70139","DOIUrl":"10.1111/bcpt.70139","url":null,"abstract":"<p>Queries from healthcare professionals to drug information centres may represent drug-related aspects of importance in healthcare. In this study, queries and replies from all drug information centres in Sweden, published on svelic.se (January 2023 to May 2024) and specifically related to the discipline of pharmacy, were explored. Pharmaceutical queries were defined in an iterative process starting with seven definitions of ‘pharmacy’ and independent assessments by two assessors. Three categories emerged: galenic queries, lookup queries and pharmacy practice queries. Out of 767 studied queries, 60 (8%) were categorised as pharmaceutical (kappa: 0.84), distributed across galenic (<i>n</i> = 46), lookup (<i>n</i> = 12) and pharmacy practice queries (<i>n</i> = 2). Galenic queries primarily concerned crushing or splitting of medications (<i>n</i> = 13), alternative routes of administration (<i>n</i> = 12) or compatibility (<i>n</i> = 10). Out of 21 drugs asked about in crushing/splitting-related queries, six lacked information in the national Medication Crushing Database. Out of nine specific drug pairs asked about in compatibility queries, two were incompatible, and information regarding seven was not obtainable from the national Pharmaceutical Compatibility Database. In conclusion, almost one tenth of queries to drug information centres in Sweden, recorded on svelic.se, were specifically pharmaceutical. The requested information was often for crushing/splitting-related queries, and seldom for compatibility queries, accessible from the knowledge resources.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-11-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12625799/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145538894","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Valproic acid (VPA), a classic antiepileptic drug with a narrow therapeutic window, is widely used in paediatric epilepsy treatment. As only the unbound fraction of the drug is a pharmacologically active component, we established a population pharmacokinetic (PopPK) model for both unbound and total VPA in epileptic children to provide a clinical optimisation strategy. A total of 450 epileptic children providing 620 samples were included for modelling development. In addition, trough unbound and total VPA concentrations were simulated for typical patients to propose the dose regimen. A one-compartment model with first-order absorption and elimination was well developed to describe the pharmacokinetic characteristics of unbound VPA, and the Langmuir equation was used to explore the protein binding parameters. The final model indicated that the CLu/F of unbound VPA was significantly influenced by body weight, age-based maturation and daily dose. Proposed dosing regimens for children aged 0 to 12 years, simulated using the Monte Carlo method, recommended 10–30 mg/kg/day, decreasing with age. This PopPK model of VPA could be helpful to propose recommended dosage regimens to achieve the target therapeutic concentration window in clinical practice.
{"title":"Population Pharmacokinetics Model and Simulation of Unbound and Total Valproic Acid in Epileptic Children Using a Protein Binding Model","authors":"Tingting Yue, Limei Zhao, Ya'nan Chen, Shansen Xu","doi":"10.1111/bcpt.70142","DOIUrl":"10.1111/bcpt.70142","url":null,"abstract":"<div>\u0000 \u0000 <p>Valproic acid (VPA), a classic antiepileptic drug with a narrow therapeutic window, is widely used in paediatric epilepsy treatment. As only the unbound fraction of the drug is a pharmacologically active component, we established a population pharmacokinetic (PopPK) model for both unbound and total VPA in epileptic children to provide a clinical optimisation strategy. A total of 450 epileptic children providing 620 samples were included for modelling development. In addition, trough unbound and total VPA concentrations were simulated for typical patients to propose the dose regimen. A one-compartment model with first-order absorption and elimination was well developed to describe the pharmacokinetic characteristics of unbound VPA, and the Langmuir equation was used to explore the protein binding parameters. The final model indicated that the CL<sub>u</sub>/F of unbound VPA was significantly influenced by body weight, age-based maturation and daily dose. Proposed dosing regimens for children aged 0 to 12 years, simulated using the Monte Carlo method, recommended 10–30 mg/kg/day, decreasing with age. This PopPK model of VPA could be helpful to propose recommended dosage regimens to achieve the target therapeutic concentration window in clinical practice.</p>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-11-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145534387","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Amber Ruben, Jennie Herbin, Amy Lamb, Larry Leung, Jason Min, Inès Paschos, Wade Thompson, Emily G. McDonald, Cheryl A. Sadowski
{"title":"Supporting Medication Appropriateness Among Indigenous Peoples in Canada: Reflections on the Development and Implementation of a Network Action Plan","authors":"Amber Ruben, Jennie Herbin, Amy Lamb, Larry Leung, Jason Min, Inès Paschos, Wade Thompson, Emily G. McDonald, Cheryl A. Sadowski","doi":"10.1111/bcpt.70136","DOIUrl":"10.1111/bcpt.70136","url":null,"abstract":"","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145522930","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peter J. C. Stuijt, Stijn Crutzen, Mette Heringa, Jessica V. Hootsen, Barbara C. van Munster, Anita T. Wildeboer, Katja Taxis, Petra Denig
Background
Knowing whether patients' attitudes towards deprescribing differ by medication is important for implementing deprescribing in practice.
Objective
To assess whether there are within-patient differences in attitudes towards deprescribing the following cardiovascular and diabetes medications: statins, antihypertensives, sulfonylureas and insulins.
Methods
We administered the revised Patient Attitudes Towards Deprescribing questionnaire to Dutch primary care patients. The ‘appropriateness’ and ‘concerns’ factors were adapted to measure medication-specific attitudes. Pairwise comparisons of appropriateness and concerns factor scores were tested with Wilcoxon signed-rank tests and corrected to control the false discovery rate.
Results
Responses from 160 patients (median age: 79 years, 34% frail) were used for the comparisons. Appropriateness factor scores were higher for insulins compared to statins (n = 18, 3.9 versus 3.3, p < 0.031), antihypertensives (n = 21, 4.0 versus 3.6, p < 0.031) and sulfonylureas (n = 12, 3.8 versus 3.4, p < 0.031) and higher for sulfonylureas compared to antihypertensives (n = 26, 3.6 versus 3.4, p = 0.036) and statins (n = 27, 3.6 versus 3.2, p = 0.006). No statistical differences were found for the concerns factor scores.
Conclusion
Given the observed differences in appropriateness attitudes, patients may be more positive towards deprescribing statins and antihypertensives as compared to sulfonylureas and particularly insulins. Healthcare providers should be aware that patients can experience medication-specific barriers when discussing options for deprescribing.
{"title":"Patients' Attitudes Towards Deprescribing Differ Across Specific Cardiovascular and Diabetes Medication: A Survey Study Assessing Within-Patient Differences","authors":"Peter J. C. Stuijt, Stijn Crutzen, Mette Heringa, Jessica V. Hootsen, Barbara C. van Munster, Anita T. Wildeboer, Katja Taxis, Petra Denig","doi":"10.1111/bcpt.70140","DOIUrl":"10.1111/bcpt.70140","url":null,"abstract":"<div>\u0000 \u0000 \u0000 <section>\u0000 \u0000 <h3> Background</h3>\u0000 \u0000 <p>Knowing whether patients' attitudes towards deprescribing differ by medication is important for implementing deprescribing in practice.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Objective</h3>\u0000 \u0000 <p>To assess whether there are within-patient differences in attitudes towards deprescribing the following cardiovascular and diabetes medications: statins, antihypertensives, sulfonylureas and insulins.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Methods</h3>\u0000 \u0000 <p>We administered the revised Patient Attitudes Towards Deprescribing questionnaire to Dutch primary care patients. The ‘appropriateness’ and ‘concerns’ factors were adapted to measure medication-specific attitudes. Pairwise comparisons of appropriateness and concerns factor scores were tested with Wilcoxon signed-rank tests and corrected to control the false discovery rate.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Results</h3>\u0000 \u0000 <p>Responses from 160 patients (median age: 79 years, 34% frail) were used for the comparisons. Appropriateness factor scores were higher for insulins compared to statins (<i>n</i> = 18, 3.9 versus 3.3, <i>p</i> < 0.031), antihypertensives (<i>n</i> = 21, 4.0 versus 3.6, <i>p</i> < 0.031) and sulfonylureas (<i>n</i> = 12, 3.8 versus 3.4, <i>p</i> < 0.031) and higher for sulfonylureas compared to antihypertensives (<i>n</i> = 26, 3.6 versus 3.4, <i>p</i> = 0.036) and statins (<i>n</i> = 27, 3.6 versus 3.2, <i>p</i> = 0.006). No statistical differences were found for the concerns factor scores.</p>\u0000 </section>\u0000 \u0000 <section>\u0000 \u0000 <h3> Conclusion</h3>\u0000 \u0000 <p>Given the observed differences in appropriateness attitudes, patients may be more positive towards deprescribing statins and antihypertensives as compared to sulfonylureas and particularly insulins. Healthcare providers should be aware that patients can experience medication-specific barriers when discussing options for deprescribing.</p>\u0000 </section>\u0000 </div>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-11-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70140","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145511492","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
The three-finger neurotoxins interfere with cholinergic transmission at various postsynaptic sites in the peripheral and central nervous systems. Based on receptor selectivity, the neurotoxins can be broadly classified as α-neurotoxins, k-neurotoxins and muscarinic toxins. The three-finger neurotoxins are nonenzymatic and possess a conserved structural feature consisting of loops of β-stranded loops protruding from a globular hydrophobic core held together by conserved disulfide bonds. The snake venom neurotoxins were first reported approximately 60 years ago, and their discovery has since expanded our knowledge of membrane receptors and ion channels. The interactions of these neurotoxins with receptors are of special interest for their potential use in the treatment of neurodegenerative diseases, pain and cancer. This review focuses on the snake venom neurotoxins and neurotoxin-like proteins and their subtypes, structural aspects of their mechanisms of action and specificity for receptors or ligand-binding interfaces. Further, a detailed discussion is added on the pharmacological potential of these toxins for use as probes or potential targets in drug discovery.
{"title":"Snake Venom Three-Finger Neurotoxins and Neurotoxin-Like Proteins: Insights Into Their Structural and Functional Aspects Along With Their Pharmacological Potential","authors":"Manisha Choudhury, Manas Das","doi":"10.1111/bcpt.70144","DOIUrl":"10.1111/bcpt.70144","url":null,"abstract":"<p>The three-finger neurotoxins interfere with cholinergic transmission at various postsynaptic sites in the peripheral and central nervous systems. Based on receptor selectivity, the neurotoxins can be broadly classified as α-neurotoxins, k-neurotoxins and muscarinic toxins. The three-finger neurotoxins are nonenzymatic and possess a conserved structural feature consisting of loops of β-stranded loops protruding from a globular hydrophobic core held together by conserved disulfide bonds. The snake venom neurotoxins were first reported approximately 60 years ago, and their discovery has since expanded our knowledge of membrane receptors and ion channels. The interactions of these neurotoxins with receptors are of special interest for their potential use in the treatment of neurodegenerative diseases, pain and cancer. This review focuses on the snake venom neurotoxins and neurotoxin-like proteins and their subtypes, structural aspects of their mechanisms of action and specificity for receptors or ligand-binding interfaces. Further, a detailed discussion is added on the pharmacological potential of these toxins for use as probes or potential targets in drug discovery.</p>","PeriodicalId":8733,"journal":{"name":"Basic & Clinical Pharmacology & Toxicology","volume":"137 6","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1111/bcpt.70144","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145501904","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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