-
Medical Oncology (Northwood, London,... Jun 2024FOXM1, a proto-oncogenic transcription factor, plays a critical role in cancer development and treatment resistance in cancers, particularly in breast cancer. Thus, this...
FOXM1, a proto-oncogenic transcription factor, plays a critical role in cancer development and treatment resistance in cancers, particularly in breast cancer. Thus, this study aimed to identify potential FOXM1 inhibitors through computational screening of drug databases, followed by in vitro validation of their inhibitory activity against breast cancer cells. In silico studies involved pharmacophore modeling using the FOXM1 inhibitor, FDI-6, followed by virtual screening of DrugBank and Selleckchem databases. The selected drugs were prepared for molecular docking, and the crystal structure of FOXM1 was pre-processed for docking simulations. In vitro studies included MTT assays to assess cytotoxicity, and Western blot analysis to evaluate protein expression levels. Our study identified Pantoprazole and Rabeprazole as potential FOXM1 inhibitors through in silico screening and molecular docking. Molecular dynamics simulations confirmed stable interactions of these drugs with FOXM1. In vitro experiments showed both Pantoprazole and Rabeprazole exhibited strong FOXM1 inhibition at effective concentrations and that showed inhibition of cell proliferation. Rabeprazole showed the inhibitor activity at 10 µM in BT-20 and MCF-7 cell lines. Pantoprazole exhibited FOXM1 inhibition at 30 µM and in BT-20 cells and at 70 µM in MCF-7 cells, respectively. Our current study provides the first evidence that Rabeprazole and Pantoprazole can bind to FOXM1 and inhibit its activity and downstream signaling, including eEF2K and pEF2, in breast cancer cells. These findings indicate that rabeprazole and pantoprazole inhibit FOXM1 and breast cancer cell proliferation, and they can be used for FOXM1-targeted therapy in breast or other cancers driven by FOXM1.
Topics: Humans; Forkhead Box Protein M1; Drug Repositioning; Breast Neoplasms; Molecular Docking Simulation; Female; Rabeprazole; MCF-7 Cells; Cell Proliferation; Molecular Dynamics Simulation; Antineoplastic Agents; Pantoprazole; Cell Line, Tumor; Pyridines; Thiophenes
PubMed: 38918225
DOI: 10.1007/s12032-024-02427-0 -
JAMA Network Open Jun 2024Potentially inappropriate medication (PIM) exposes patients to an increased risk of adverse outcomes. Many lists of explicit criteria provide guidance on identifying PIM...
IMPORTANCE
Potentially inappropriate medication (PIM) exposes patients to an increased risk of adverse outcomes. Many lists of explicit criteria provide guidance on identifying PIM and recommend alternative prescribing, but the complexity of available lists limits their applicability and the amount of data available on PIM prescribing.
OBJECTIVE
To determine PIM prevalence and the most frequently prescribed PIMs according to 6 well-known PIM lists and to develop a best practice synthesis for clinicians.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional study used anonymized electronic health record data of Swiss primary care patients aged 65 years or older with drug prescriptions from January 1, 2020, to December 31, 2021, extracted from a large primary care database in Switzerland, the FIRE project. Data analyses took place from October 2022 to September 2023.
EXPOSURE
PIM prescription according to PIM criteria operationalized for use with FIRE data.
MAIN OUTCOMES AND MEASURES
The primary outcomes were PIM prevalence (percentage of patients with 1 or more PIMs) and PIM frequency (percentage of prescriptions identified as PIMs) according to the individual PIM lists and a combination of all 6 lists. The PIM lists used were the American 2019 Updated Beers criteria, the French list by Laroche et al, the Norwegian General Practice Norwegian (NORGEP) criteria, the German PRISCUS list, the Austrian list by Mann et al, and the EU(7) consensus list of 7 European countries.
RESULTS
This study included 115 867 patients 65 years or older (mean [SD] age, 76.0 [7.9] years; 55.8% female) with 1 211 227 prescriptions. Among all patients, 86 715 (74.8%) were aged 70 years or older, and 60 670 (52.4%) were aged 75 years or older. PIM prevalence among patients 65 years or older was 31.5% (according to Beers 2019), 15.4% (Laroche), 16.1% (NORGEP), 12.7% (PRISCUS), 31.2% (Mann), 37.1% (EU[7]), and 52.3% (combined list). PIM prevalence increased with age according to every PIM list (eg, according to Beers 2019, from 31.5% at age 65 years or older to 37.4% for those 75 years or older, and when the lists were combined, PIM prevalence increased from 52.3% to 56.7% in those 2 age groups, respectively). PIM frequency was 10.3% (Beers 2019), 3.9% (Laroche), 4.3% (NORGEP), 2.4% (PRISCUS), 6.7% (Mann), 9.7% (EU[7]), and 19.3% (combined list). According to the combined list, the 5 most frequently prescribed PIMs were pantoprazole (9.3% of all PIMs prescribed), ibuprofen (6.9%), diclofenac (6.3%), zolpidem (4.5%), and lorazepam (3.7%). Almost two-thirds (63.5%) of all PIM prescriptions belonged to 5 drug classes: analgesics (26.9% of all PIMs prescribed), proton pump inhibitors (12.1%), benzodiazepines and benzodiazepine-like drugs (11.2%), antidepressants (7.0%), and neuroleptics (6.3%).
CONCLUSIONS AND RELEVANCE
In this cross-sectional study of adults aged 65 or older, PIM prevalence was high, varied considerably depending on the criteria applied, and increased consistently with age. However, only few drug classes accounted for the majority of all prescriptions that were PIM according to any of the 6 PIM lists, and by considering this manageable number of drug classes, clinicians could essentially comply with all 6 PIM lists. These results raise awareness of the most common PIMs and emphasize the need for careful consideration of their risks and benefits and targeted deprescribing.
Topics: Humans; Switzerland; Aged; Cross-Sectional Studies; Primary Health Care; Potentially Inappropriate Medication List; Female; Male; Inappropriate Prescribing; Aged, 80 and over; Prevalence; Practice Patterns, Physicians'
PubMed: 38904960
DOI: 10.1001/jamanetworkopen.2024.17988 -
Cureus May 2024Black hairy tongue is a benign condition that can be associated with several varying causes. Its etiology is often linked with fungal infection and adverse reactions to...
Black hairy tongue is a benign condition that can be associated with several varying causes. Its etiology is often linked with fungal infection and adverse reactions to various drugs. We present a case of an adult patient who developed a black hairy tongue while on ceftriaxone and pantoprazole for 10 days. The fungus on his tongue was not identified as the causative agent, and recovery was achieved by changing his medications. Ceftriaxone was replaced with trimethoprim/sulfamethoxazole 5 mg/kg intravenous, and pantoprazole was fully stopped. The black lesion on the tongue was observed to regress over several days. Clinicians should be aware of this particular side effect of certain antibiotics.
PubMed: 38899273
DOI: 10.7759/cureus.60685 -
Journal of Clinical Medicine May 2024: To define if the use of proton pump inhibitors (PPI) is associated with PDF prevalence and characteristics and with time of recovery after dialysis in patients on...
: To define if the use of proton pump inhibitors (PPI) is associated with PDF prevalence and characteristics and with time of recovery after dialysis in patients on maintenance hemodialysis. : Patients were defined as experiencing PDF if they spontaneously offered this complaint when asked the open-ended question: "Do you feel fatigued after dialysis?". Time of recovery after dialysis (TIRD) was also assessed for each patient. Each patient was invited to rate the intensity, duration and frequency of PDF from 1 to 5. We defined if patients used PPI (no PPI use or PPI use), the type of used PPI, the dose of used PPI, and the duration of the use of PPI (<1 year or ≥1 year). : A total of 346 patients were studied: 259 used PPI (55 used omeprazole, 63 esomeprazole, 54 pantoprazole, 87 lansoprazole, and 7 rabeprazole) and 87 did not. Two hundred and thirty-two patients declared PDF and 114 did not. The median [min-max] TIRD was 210 min [0-1440]. The prevalence of PDF in PPI users and PPI non-users was 67% and 68%, respectively ( = 0.878). The median [min-max] TIRD did not differ significantly between PPI users and PPI non-users (180 [0-1440] and 240 [0-1440], respectively; = 0.871). Median PDF intensity, duration, frequency, and severity did not differ significantly between PPI use and no use. The prevalence of PDF was similar among the different types of PPI use and did not differ with respect to PPI non-users. Duration of PPI exposure was <1 year in 40 patients and ≥1 year in 219 patients. The prevalence of PDF did not differ between the two exposures. The correlation matrix between PPI equivalent dose, PPI treatment duration and PDF frequency, PDF characteristics, and TIRD showed whether there was statistical significance. : The use of PPI is not associated with PDF and time of recovery after dialysis in patients on maintenance hemodialysis.
PubMed: 38892950
DOI: 10.3390/jcm13113241 -
Cureus May 2024Introduction Cancer chemotherapy regimens include multiple classes of adjuvant drugs as supportive therapy. Because of the concurrent intake of other drugs (like...
Prevalence, Attributes, and Risk Factors of QT-Interval-Prolonging Drugs and Potential Drug-Drug Interactions in Cancer Patients: A Prospective Study in a Tertiary Care Hospital.
Introduction Cancer chemotherapy regimens include multiple classes of adjuvant drugs as supportive therapy. Because of the concurrent intake of other drugs (like antiemetics, antidepressants, analgesics, and antimicrobials), there is a heightened risk for possible QT interval prolongation. There is a dearth of evidence in the literature regarding the usage of QT-prolonging anticancer drugs and associated risk factors that have the propensity to prolong QT interval. The purpose was to explore the extent of the use of QT-interval-prolonging drugs and potential QT-prolonging drug-drug interactions (QT-DDIs) in cancer patients attending OPD in a tertiary-care hospital. Methods This was a hospital-based, cross-sectional, observational study. Risk stratification of QT-prolonging drugs for torsades de pointes (TdP) was done by the Arizona Center for Education and Research on Therapeutics (AzCERT)/CredibleMeds-lists, and potential QT-DDIs were determined with four online DDI-checker-software. Results In 1331 cancer patients, the overall prevalence of potential QT-prolonging drug utilization was 97.3%. Ondansetron, pantoprazole, domperidone, and olanzapine were the most frequent QT-prolonging drugs in cancer patients. The top six antineoplastics with potential QT-prolonging and torsadogenic actions were capecitabine, oxaliplatin, imatinib, bortezomib, 5-fluorouracil, and bendamustine. Evidence-based pragmatic QTc interval prolongation risk assessment tools are imperative for cancer patients. Conclusion This study revealed a high prevalence of QT-prolonging drugs and QT-DDIs among cancer patients who are treated with anticancer and non-anticancer drugs. As a result, it's critical to take precautions, stay vigilant, and avoid QT-prolonging in clinical situations. Evidence-based pragmatic QTc interval prolongation risk assessment tools are needed for cancer patients.
PubMed: 38882995
DOI: 10.7759/cureus.60492 -
The American Journal of Case Reports Jun 2024BACKGROUND Compression of the vagus nerve by a pharyngeal mass is a well-documented condition that can result in sinus node dysfunction (SND). However, there is scarce...
BACKGROUND Compression of the vagus nerve by a pharyngeal mass is a well-documented condition that can result in sinus node dysfunction (SND). However, there is scarce literature on extrinsic vagal nerve compression from a tonsillar abscess. CASE REPORT A 59-year-old woman with a history of asthma and chronic throat discomfort presented to the Emergency Department with bradycardia, palpitations, and voice changes. Following a shellfish allergy hospitalization, an otolaryngology evaluation revealed an enlarged right tonsil, recommending tonsillectomy, but scheduling challenges persisted. The patient reported mild throat pain, dysphagia, hoarseness, rhinorrhea, and exertional dyspnea and was admitted for the evaluation of peritonsillar mass. She was found to be bradycardic with a heart rate of 47, with an electrocardiogram revealing SND. Albuterol and ipratropium nebulizers, as well as dexamethasone and pantoprazole, were initiated. With this treatment, the patient symptomatically improved with a new heart rate of 68. She was discharged with outpatient appointments, but was unfortunately lost to follow-up. CONCLUSIONS This case reveals sinus node dysfunction resulting from extrinsic vagal nerve compression by a tonsillar abscess. Pressure on the vagus nerve can trigger bradycardia and low blood pressure, possibly due to compensatory overfiring of afferent vagal nerve signals from local mass effect. Early recognition and antibiotic treatment are essential to prevent cardiac complications. Clinicians must remain vigilant for such extrinsic causes, particularly in patients with chronic sore throat and cardiac symptoms. Further research and case reports are needed to deepen our understanding of this rare yet significant association.
Topics: Humans; Female; Middle Aged; Sick Sinus Syndrome; Peritonsillar Abscess; Nerve Compression Syndromes; Vagus Nerve
PubMed: 38879750
DOI: 10.12659/AJCR.943944 -
The New England Journal of Medicine Jun 2024Whether proton-pump inhibitors are beneficial or harmful for stress ulcer prophylaxis in critically ill patients undergoing invasive ventilation is unclear.
BACKGROUND
Whether proton-pump inhibitors are beneficial or harmful for stress ulcer prophylaxis in critically ill patients undergoing invasive ventilation is unclear.
METHODS
In this international, randomized trial, we assigned critically ill adults who were undergoing invasive ventilation to receive intravenous pantoprazole (at a dose of 40 mg daily) or matching placebo. The primary efficacy outcome was clinically important upper gastrointestinal bleeding in the intensive care unit (ICU) at 90 days, and the primary safety outcome was death from any cause at 90 days. Multiplicity-adjusted key secondary outcomes were ventilator-associated pneumonia, infection, and patient-important bleeding.
RESULTS
A total of 4821 patients underwent randomization in 68 ICUs. Clinically important upper gastrointestinal bleeding occurred in 25 of 2385 patients (1.0%) receiving pantoprazole and in 84 of 2377 patients (3.5%) receiving placebo (hazard ratio, 0.30; 95% confidence interval [CI], 0.19 to 0.47; P<0.001). At 90 days, death was reported in 696 of 2390 patients (29.1%) in the pantoprazole group and in 734 of 2379 patients (30.9%) in the placebo group (hazard ratio, 0.94; 95% CI, 0.85 to 1.04; P = 0.25). Patient-important bleeding was reduced with pantoprazole; all other key secondary outcomes were similar in the two groups.
CONCLUSIONS
Among patients undergoing invasive ventilation, pantoprazole resulted in a significantly lower risk of clinically important upper gastrointestinal bleeding than placebo, with no significant effect on mortality. (Funded by the Canadian Institutes of Health Research and others; REVISE ClinicalTrials.gov number, NCT03374800.).
PubMed: 38875111
DOI: 10.1056/NEJMoa2404245 -
Alternative Therapies in Health and... Jun 2024This study aims to investigate the use of proton pump inhibitors (PPIs) among inpatients in a hospital and analyze the rationality of their use.
OBJECTIVE
This study aims to investigate the use of proton pump inhibitors (PPIs) among inpatients in a hospital and analyze the rationality of their use.
METHODS
We analyzed the medication records of 1986 inpatients from January 2023 to June 2023, focusing on patients using PPIs under the "Internet + medical service" model. Additionally, we compared and analyzed the drug use patterns, including dosage form, dosage, medication frequency, average daily cost, and sales amount, between two groups: those treated before and after the implementation of the "Internet + medical service" model. The control group comprised 1962 inpatients treated with PPIs from July 2022 to December 2022. We also compared drug inventory time, account coincidence rate, error rate, and nursing satisfaction between the two periods.
RESULTS
Among the hospitalized patients using PPIs, 892 cases were male (44.91%) and 1094 cases were female (55.09%). Regarding age distribution, 456 cases were aged 18-45 (22.96%), 845 cases were aged 46-65 (42.55%), and 685 cases were over 65 years old (34.49%). The top 10 departments with the highest frequency of PPI use included gastroenterology (8.36%), oncology, hematology, trauma orthopedics (6.95% each), cardiovascular medicine, neurology (6.39% each), general surgery (6.29%), respiratory, critical care (5.84%), renal rheumatology, immunology (5.79%), and spine surgery (5.59%). Omeprazole enteric-coated capsules accounted for the highest proportion (25.08%), followed by rabeprazole enteric-coated tablets (22.96%) and pantoprazole sodium enteric-coated tablets (20.04%). After implementing the "Internet + medical service" model, there was a reduction in irrational PPI use, medication error rates, and inventory time. Moreover, the account coincidence rate and satisfaction rate increased significantly (P < .05).
CONCLUSION
The utilization of PPIs in hospitals is notably high. Implementing the "Internet + medical service" model can effectively improve the rationality of PPI use. Clinicians should adhere to relevant indications when prescribing PPIs and conduct drug interventions to prevent overuse.
PubMed: 38870506
DOI: No ID Found -
Acta Anaesthesiologica Scandinavica Jun 2024Enteral nutrition may affect risks of gastrointestinal bleeding, pneumonia and mortality in critically ill patients and may also modify the effects of pharmacological...
BACKGROUND
Enteral nutrition may affect risks of gastrointestinal bleeding, pneumonia and mortality in critically ill patients and may also modify the effects of pharmacological stress ulcer prophylaxis. We undertook post hoc analyses of the stress ulcer prophylaxis in the intensive care unit trial to assess for any associations and interactions between enteral nutrition and pantoprazole.
METHODS
Extended Cox models with time-varying co-variates and competing events were used to assess potential associations, adjusted for baseline severity of illness. Potential interactions between daily enteral nutrition and allocation to pantoprazole on outcomes were similarly assessed.
RESULTS
Enteral nutrition was associated with lower risk of clinically important gastrointestinal bleeding (cause-specific hazard ratio [HR]: 0.29, 95% confidence interval: [CI] 0.19-0.44, p < .001), higher risk of pneumonia (HR: 1.44, 95% CI: 1.14-1.82, p = .003), and lower risk of all-cause mortality (HR: 0.22, 95% CI: 0.18-0.27, p < .001). Enteral nutrition with allocation to pantoprazole was associated with a lower risk of mortality (HR: 0.27, 95% CI: 0.21-0.35, p < .001), similar to enteral nutrition with allocation to placebo (HR: 0.17, 95% CI: 0.13-0.23, p < .001). Allocation to pantoprazole with no enteral nutrition had little effect on mortality (HR: 0.83, 95% CI: 0.63-1.09, p = .179), whilst allocation to pantoprazole and receipt of enteral nutrition was mostly compatible with increased all-cause mortality (HR: 1.27, 95% CI: 0.99-1.64, p = .061). The test of interaction between enteral nutrition and pantoprazole treatment allocation for all-cause mortality was statistically significant (p = .024).
CONCLUSIONS
Enteral nutrition was associated with an increased risk of pneumonia and a reduced risk of gastrointestinal bleeding. The interaction between pantoprazole and enteral nutrition suggesting an increased risk of mortality requires further study.
PubMed: 38867404
DOI: 10.1111/aas.14471 -
PloS One 2024Abomasal ulcers are recognized in sheep of all ages, but research regarding therapeutic interventions is limited. Proton Pump Inhibitors (PPIs) such as pantoprazole, are...
Abomasal ulcers are recognized in sheep of all ages, but research regarding therapeutic interventions is limited. Proton Pump Inhibitors (PPIs) such as pantoprazole, are clinically used with a paucity of evidence regarding efficacy in mature sheep. Intravenous and subcutaneously administered pantoprazole dosed at 1.0 mg/kg in adult sheep will increase the pH of abomasal fluid compared to pre-administration baseline. The objectives were to assess the effect of pantoprazole, after single and multiple administration, on abomasal fluid pH in adult sheep. A third objective was to describe the pharmacokinetic parameters of IV and SC pantoprazole. Four clinically healthy adult Southdown ewes previously fitted with a gastrostomy tube in the abomasum were utilized in this randomized, 2-way cross-over trial. Ewes received pantoprazole (1.0 mg/kg) as a single and 3-dose regimen (every 24 hours). After a 10 day washout period the reverse treatment was applied. Blood for analysis of pantoprazole concentration was collected intermittently for 24 hours, and abomasal fluid pH was measured at intervals for a 96-hour period. The pH of the abomasal fluid was higher in pantoprazole treatments for up to 24 hours after dosing. Following intravenous administration of pantoprazole to study ewes, elimination half-life, volume of distribution, and clearance of pantoprazole was estimated as 3.29 hours, 0.35 L/kg, and 65.26 mL/hr/kg respectively. After subcutaneous dosing, maximum concentration, time to maximum concentration, half-life of elimination, and volume of distribution, were estimated as 2604 ng/mL, 0.55 hours, 2.48 hours, and 0.37 L/kg. Additionally, the bioavailability was estimated as 83.33%. Pantoprazole administered IV or SC may be useful for treatment or prevention of abomasal ulcers in adult sheep.
Topics: Animals; Pantoprazole; Sheep; Female; Injections, Subcutaneous; Hydrogen-Ion Concentration; Proton Pump Inhibitors; Abomasum; Administration, Intravenous; Cross-Over Studies; Injections, Intravenous
PubMed: 38865425
DOI: 10.1371/journal.pone.0304533