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Naunyn-Schmiedeberg's Archives of... Jun 2024Clozapine has been considered the "gold standard" in the treatment of schizophrenia for many years. Clozapine has a superior effect, particularly in the treatment of...
Clozapine has been considered the "gold standard" in the treatment of schizophrenia for many years. Clozapine has a superior effect, particularly in the treatment of negative symptoms and suicidal behaviour. However, due to its numerous adverse reactions, clozapine is mainly used for treatment-resistant schizophrenia. The aim of this paper is to analyze the results of clinical studies on clozapine from 2012-2022. PubMed was used as the database. Sixty-four studies were included and categorised by topic. The pharmacokinetic properties of clozapine tablets and a clozapine suspension solution did not differ markedly. Clozapine was superior to olanzapine and risperidone in reducing aggression and depression. A long-term study showed that metabolic parameters changed comparably with olanzapine and clozapine after 8 years. Risperidone and ziprasidone can be used as an alternative to clozapine. Scopolamine, atropine drops, and metoclopramide are effective in the treatment of clozapine-induced hypersalivation. Eight drugs, including liraglutide, exenatide, metformin, and orlistat, are potentially effective in the treatment of clozapine-induced weight gain. Ziprasidone, haloperidol, and aripiprazole showed a positive effect on symptoms when added to clozapine. No investigated drug was superior to clozapine for the treatment of schizophrenia. Ziprasidone and risperidone can also be used well for the treatment of schizophrenia. In the treatment of clozapine-induced hypersalivation and weight gain, some drugs proved to be effective.
PubMed: 38918233
DOI: 10.1007/s00210-024-03209-1 -
Biomedicine & Pharmacotherapy =... Sep 2023Acute myeloid leukemia (AML) is a prevalent form of leukemia in adults. As its survival rate is low, there is an urgent need for new therapeutic options. In AML,...
Acute myeloid leukemia (AML) is a prevalent form of leukemia in adults. As its survival rate is low, there is an urgent need for new therapeutic options. In AML, FMS-like tyrosine kinase 3 (FLT3) mutations are common and have negative outcomes. However, current FLT3-targeting agents, Midostaurin and Gilteritinib, face two significant issues, specifically the emergence of acquired resistance and drug-related adverse events leading to treatment failure. Rearranged during transfection (RET), meanwhile, is a proto-oncogene linked to various types of cancer, but its role in AML has been limited. A previous study showed that activation of RET kinase enhances FLT3 protein stability, leading to the promotion of AML cell proliferation. However, no drugs are currently available that target both FLT3 and RET. This study introduces PLM-101, a new therapeutic option derived from the traditional Chinese medicine indigo naturalis with potent in vitro and in vivo anti-leukemic activities. PLM-101 potently inhibits FLT3 kinase and induces its autophagic degradation via RET inhibition, providing a superior mechanism to that of FLT3 single-targeting agents. Single- and repeated-dose toxicity tests conducted in the present study showed no significant drug-related adverse effects. This study is the first to present a new FLT3/RET dual-targeting inhibitor, PLM-101, that shows potent anti-leukemic activity and fewer adverse effects. PLM-101, therefore, should be considered for use as a potential therapeutic agent for AML.
Topics: Adult; Humans; fms-Like Tyrosine Kinase 3; Leukemia, Myeloid, Acute; Protein Kinase Inhibitors; Mutation; Proto-Oncogene Proteins c-ret
PubMed: 37392657
DOI: 10.1016/j.biopha.2023.115066 -
Frontiers in Veterinary Science 2023The aim of the present study was to evaluate cardiac indices using M-mode echocardiography after the administration of metoclopramide and ondansetron in donkeys. For...
The aim of the present study was to evaluate cardiac indices using M-mode echocardiography after the administration of metoclopramide and ondansetron in donkeys. For this purpose, 10 apparently healthy Egyptian Baladi donkeys () were used in a crossover prospective study. Two trials were conducted with the administration of metoclopramide hydrochloride anhydrous at a dose of 0.25 mg Kg and ondansetron hydrochloride sodium at a dose of 0.15 mg Kg. The control group (placebo) received a total volume of 50 mL of isotonic saline at 0.9%. An echocardiographic examination was performed using a Digital Color Doppler Ultrasound System equipped with a 2-3.9 MHz phased array sector scanner transducer. In general, the fractional shortening (FS%) was significantly affected by the time for metoclopramide ( = 0.031) and ondansetron ( = 0.047) compared with those of placebo, with treatment with metoclopramide provoking significantly higher percentages of FS% at T60 ( = 0.009) and T90 ( = 0.028) compared with those for ondansetron and placebo. The interaction of time x treatment also showed a statistically significant alteration of FS% ( < 0.05), while the values returned to the basal line at T240. Metoclopramide induced a significant decrease in E-point to septal separation (EPSS) at T90 ( = 0.005), and T240 ( = 0.007) compared with ondansetron and placebo. The time x treatment interaction also showed a significant ( < 0.05) variation in EPSS, with values returning to the basal line at T300. Mitral valve opening velocity (DE SLP) values were significantly affected by time ( = 0.004) in the metoclopramide group compared with those of ondansetron and placebo. Administration of metoclopramide and ondansetron provoked significant alterations of DE SLP at T60 ( = 0.039), T120 ( = 0.036), and T300 ( = 0.005) compared with placebo. In conclusion, caution should be exercised when administering both treatments, especially to animals with suspected cardiac problems.
PubMed: 37680391
DOI: 10.3389/fvets.2023.1189710 -
Scientific Reports Mar 2024Acute upper gastrointestinal hemorrhage (UGIH) is the most common emergency condition that requires rapid endoscopic treatment. This study aimed to evaluate the effects... (Randomized Controlled Trial)
Randomized Controlled Trial
Intravenous metoclopramide for increasing endoscopic mucosal visualization in patients with acute upper gastrointestinal bleeding: a multicenter, randomized, double-blind, controlled trial.
Acute upper gastrointestinal hemorrhage (UGIH) is the most common emergency condition that requires rapid endoscopic treatment. This study aimed to evaluate the effects of pre-endoscopic intravenous metoclopramide on endoscopic mucosal visualization (EMV) in patients with acute UGIH. This was a multicenter, randomized, double-blind controlled trial of participants diagnosed with acute UGIH. All participants underwent esophagogastroduodenoscopy within 24 h. Participants were assigned to either the metoclopramide or placebo group. Modified Avgerinos scores were evaluated during endoscopy. In total, 284 out of 300 patients completed the per-protocol procedure. The mean age was 62.8 ± 14.3 years, and 67.6% were men. Metoclopramide group achieved a higher total EMV and gastric body EMV score than the other group (7.34 ± 1.1 vs 6.94 ± 1.6; P = 0.017 and 1.80 ± 0.4 vs 1.64 ± 0.6; P = 0.006, respectively). Success in identifying lesions was not different between the groups (96.5% in metoclopramide and 93.6% in placebo group; P = 0.26). In the metoclopramide group, those with active variceal bleeding compared with the control group demonstrated substantial improvements in gastric EMV (1.83 ± 0.4 vs 1.28 ± 0.8, P = 0.004), antral EMV (1.96 ± 0.2 vs 1.56 ± 0.6, P = 0.003), and total EMV score (7.48 ± 1.1 vs 6.2 ± 2.3, P = 0.02). Pre-endoscopic intravenous metoclopramide improved the quality of EMV in variceal etiologies of UGIH, which was especially prominent in those who had signs of active bleeding based on nasogastric tube assessment.Trial Registration: Trial was registered in Clinical Trials: TCTR 20210708004 (08/07/2021).
Topics: Male; Humans; Middle Aged; Aged; Female; Gastrointestinal Hemorrhage; Metoclopramide; Esophageal and Gastric Varices; Endoscopy, Gastrointestinal; Administration, Intravenous; Double-Blind Method
PubMed: 38556533
DOI: 10.1038/s41598-024-57913-2 -
Medicine Dec 2023This case report presents a unique acute dystonic reaction (ADR) induced by metoclopramide in a 6-year-old male patient with pertussis-associated vomiting. The rarity of...
INTRODUCTION
This case report presents a unique acute dystonic reaction (ADR) induced by metoclopramide in a 6-year-old male patient with pertussis-associated vomiting. The rarity of such a reaction in pediatric patients underscores the significance of this case in contributing to the scientific literature. This report highlights the need for heightened awareness of the potential adverse effects of medications commonly used in pediatrics and emphasizes the importance of tailored interventions for this population.
MAIN SYMPTOMS AND IMPORTANT CLINICAL FINDINGS
Following the administration of metoclopramide for vomiting associated with pertussis cough, the patient exhibited distressing symptoms, including torticollis, facial grimacing, and tongue protrusion. These involuntary movements were promptly recognized, leading to the suspicion of an ADR. The clinical findings underscore the importance of vigilant monitoring for extrapyramidal symptoms following medication administration, especially in children.
THE MAIN DIAGNOSES, THERAPEUTIC INTERVENTIONS, AND OUTCOMES
The primary diagnosis of ADR induced by metoclopramide was confirmed, prompting the cessation of the medication and the initiation of anticholinergic therapy with benztropine. This intervention rapidly resolved the patient's symptoms, highlighting the importance of tailored and swift therapeutic strategies. The outcome demonstrated the efficacy of timely intervention in managing ADR in pediatric patients.
CONCLUSION
The main takeaway lesson from this case lies in the critical need for healthcare practitioners to remain vigilant for potential adverse reactions in pediatric patients, even when prescribing commonly used medications. The successful management of this case underscores the importance of prompt recognition, appropriate interventions, and continuous monitoring. Ultimately, this case contributes to the scientific literature by highlighting the unique manifestation of ADR in a pediatric patient, reinforcing the significance of individualized patient care and medication safety.
Topics: Male; Humans; Child; Metoclopramide; Whooping Cough; Vomiting; Dyskinesias; Torticollis
PubMed: 38050314
DOI: 10.1097/MD.0000000000036140 -
The Turkish Journal of Gastroenterology... Nov 2023The aim of this study was to explore the risk factors for the incidence of gastroscopy-assisted capsule endoscopy and the small bowel transit time in pediatric patients...
BACKGROUND/AIMS
The aim of this study was to explore the risk factors for the incidence of gastroscopy-assisted capsule endoscopy and the small bowel transit time in pediatric patients who underwent capsule endoscopy examination.
MATERIALS AND METHODS
A retrospective analysis was performed to analyze the clinical data collected from pediatric patients who underwent capsule endoscopy examination.
RESULTS
A total of 239 pediatric patients were enrolled in this study. About 196 (82.0%) patients completed the entire small bowel capsule endoscopy examination, while 3 (1.3%) patients were subjected to capsule retention. Only age, not gender, height, body weight, body mass index, chief complaint, and intestinal preparation medications, has been identified as a risk factor for the incidence of gastroscopy-assisted capsule endoscopy (P < .05) by multivariate logistic regression. Further analysis showed that the small bowel transit time in the self-swallowed group was shorter than that in the gastroscopy-assisted group, while no significant difference was obtained in other factors, including intestinal preparation medications, metoclopramide, and lesions in the small intestine, which did not significantly affect small bowel transit time compared with the corresponding control group (P > .05).
CONCLUSION
A comprehensive assessment is required before performing capsule endoscopy, because age has been identified as a critical risk factor for the incidence of gastroscopy-assisted capsule endoscopy in pediatric patients.
PubMed: 37966265
DOI: 10.5152/tjg.2023.22428 -
The Lancet Regional Health. Europe Jan 2024Infections and fever after stroke are associated with poor functional outcome or death. We assessed whether prophylactic treatment with anti-emetic, antibiotic, or...
Prevention of infections and fever to improve outcome in older patients with acute stroke (PRECIOUS): a randomised, open, phase III, multifactorial, clinical trial with blinded outcome assessment.
BACKGROUND
Infections and fever after stroke are associated with poor functional outcome or death. We assessed whether prophylactic treatment with anti-emetic, antibiotic, or antipyretic medication would improve functional outcome in older patients with acute stroke.
METHODS
We conducted an international, 2∗2∗2-factorial, randomised, controlled, open-label trial with blinded outcome assessment in patients aged 66 years or older with acute ischaemic stroke or intracerebral haemorrhage and a score on the National Institutes of Health Stroke Scale ≥ 6. Patients were randomly allocated (1:1) to metoclopramide (oral, rectal, or intravenous; 10 mg thrice daily) vs. no metoclopramide, ceftriaxone (intravenous; 2000 mg once daily) vs. no ceftriaxone, and paracetamol (oral, rectal, or intravenous; 1000 mg four times daily) vs. no paracetamol, started within 24 h after symptom onset and continued for four days. All participants received standard of care. The target sample size was 3800 patients. The primary outcome was the score on the modified Rankin Scale (mRS) at 90 days analysed with ordinal logistic regression and reported as an adjusted common odds ratio (an acOR < 1 suggests benefit and an acOR > 1 harm). This trial is registered (ISRCTN82217627).
FINDINGS
From April 2016 through June 2022, 1493 patients from 67 European sites were randomised to metoclopramide (n = 704) or no metoclopramide (n = 709), ceftriaxone (n = 594) or no ceftriaxone (n = 482), and paracetamol (n = 706) or no paracetamol (n = 739), of whom 1471 were included in the intention-to-treat analysis. Prophylactic use of study medication did not significantly alter the primary outcome at 90 days: metoclopramide vs. no metoclopramide (adjusted common odds ratio [acOR], 1.01; 95% CI 0.81-1.25), ceftriaxone vs. no ceftriaxone (acOR 0.99; 95% CI 0.77-1.27), paracetamol vs. no paracetamol (acOR 1.19; 95% CI 0.96-1.47). The study drugs were safe and not associated with an increased incidence of serious adverse events.
INTERPRETATION
We observed no sign of benefit of prophylactic use of metoclopramide, ceftriaxone, or paracetamol during four days in older patients with a moderately severe to severe acute stroke.
FUNDING
This project has received funding from the European Union's Horizon 2020 research and innovation programme under grant agreement No: 634809.
PubMed: 38074444
DOI: 10.1016/j.lanepe.2023.100782 -
European Review For Medical and... Oct 2023Linezolid is commonly used in intensive care units (ICU) but has the potential to interact with other drugs. This study aimed to evaluate the prevalence of potential...
OBJECTIVE
Linezolid is commonly used in intensive care units (ICU) but has the potential to interact with other drugs. This study aimed to evaluate the prevalence of potential drug-drug interactions in ICU patients receiving linezolid.
PATIENTS AND METHODS
Data of ICU patients receiving linezolid were extracted and included in the Hospital Prescription Analysis Program of China, and the risk of potential drug-drug interactions between concomitant drugs and linezolid was evaluated using the Lexicomp database.
RESULTS
A total of 3,712 ICU patients from 59 hospitals were included in the analysis, and patients received an average of 17 concomitant drugs. A total of 67.9% of patients had potential drug-drug interactions. Patients receiving concomitant drugs with risk ratings of "X", "D", and "C" categories were 20.8%, 30.4%, and 35.1%, respectively. Opioids were the most frequently prescribed drug class with drug-drug interactions (DDIs) in the "X" category, whereas butorphanol, metoclopramide, and sufentanil were the most contraindicated concomitant drugs.
CONCLUSIONS
ICU patients receiving linezolid have a high prevalence of potential drug-drug interactions, and efforts should be made to better recognize and manage this risk.
Topics: Humans; Linezolid; Cross-Sectional Studies; Prevalence; Drug Interactions; Intensive Care Units
PubMed: 37843351
DOI: 10.26355/eurrev_202310_33967 -
Drug Delivery Dec 2023A PEGylated Tween 80-functionalized chitosan-lipidic (PEG-T-Chito-Lip) nano-vesicular hybrid was developed for intranasal administration as an alternative delivery route...
A PEGylated Tween 80-functionalized chitosan-lipidic (PEG-T-Chito-Lip) nano-vesicular hybrid was developed for intranasal administration as an alternative delivery route to help improve the poor oral bioavailability of BCS class-III model/antiemetic (metoclopramide hydrochloride; MTC). The influence of varying levels of chitosan, cholesterol, PEG 600, and Tween 80 on the stability/release parameters of the formulated nanovesicles was optimized using Draper-Lin Design. Two optimized formulations (Opti-Max and Opti-Min) with both maximized and minimized MTC-release goals, were predicted, characterized, and proved their vesicular outline light/electron microscopy, along with the mutual prompt/extended release patterns. The dual-optimized MTC-loaded PEG-T-Chito-Lip nanovesicles were loaded in intranasal gel (ISG) and further underwent pharmacokinetics/nose-to-brain delivery valuation on Sprague-Dawley rats. The absorption profiles in plasma (plasma-AUC) of the intranasal dual-optimized MTC-loaded nano-vesicular ISG formulation in pretreated rats were 2.95-fold and 1.64-fold more than rats pretreated with orally administered MTC and intranasally administered raw MTC-loaded ISG formulation, respectively. Interestingly, the brain-AUC of the intranasal dual-optimized MTC-loaded ISG was 10 and 3 times more than brain-AUC of the MTC-oral tablet and the intranasal raw MTC-loaded ISG, respectively. It was also revealed that the intranasal dual-optimized ISG significantly had the lowest liver-AUC (862.19 ng.g.h) versus the MTC-oral tablet (5732.17 ng.g.h) and the intranasal raw MTC-loaded ISG (1799.69 ng.g.h). The brain/blood ratio profile for the intranasal dual-optimized ISG was significantly enhanced over all other MTC formulations (P < 0.05). Moreover, the 198.55% drug targeting efficiency, 75.26% nose-to-brain direct transport percentage, and 4.06 drug targeting index of the dual-optimized formulation were significantly higher than those of the raw MTC-loaded ISG formulation. The performance of the dual-optimized PEG-T-Chito-Lip nano-vesicular hybrids for intranasal administration evidenced MTC-improved bioavailability, circumvented hepatic metabolism, and enhanced brain targetability, with increased potentiality in heightening the convenience and compliance for patients.
Topics: Rats; Animals; Metoclopramide; Polysorbates; Chitosan; Biological Availability; Rats, Sprague-Dawley; Drug Delivery Systems; Administration, Intranasal; Brain; Lipids; Drug Carriers
PubMed: 36916128
DOI: 10.1080/10717544.2023.2189112 -
Chemosphere Oct 2023An analytical method for quantification of seventeen pharmaceuticals and one metabolite was validated and applied in the analysis of hospital effluent samples. Two...
An analytical method for quantification of seventeen pharmaceuticals and one metabolite was validated and applied in the analysis of hospital effluent samples. Two different sampling strategies were used: seasonal sampling, with 7 samples collected bimonthly; and hourly sampling, with 12 samples collected during 12 h. Thus, the variability was both seasonal and within the same day. High variability was observed in the measured concentrations of the pharmaceuticals and the metabolite. The quantification method, performed using weighted linear regression model, demonstrated results of average concentrations in seasonal samples ranged between 0.19 μgL (carbamazepine) and higher than 61.56 μgL (acetaminophen), while the hourly samples showed average concentrations between 0.07 μgL (diazepam) and higher than 54.91 μgL (acetaminophen). It is described as higher because the maximum concentration of the calibration curve took into account the dilution factor provided by DLLME. The diurnal results showed a trend towards higher concentrations in the first and last hours of sampling. The risk quotient (RQ) was calculated using organisms from three different trophic levels, for all the analytes quantified in the samples. Additionally, in order to understand the level of importance of each RQ, an expert panel was established, with contributions from 23 specialists in the area. The results were analyzed using a hybrid decision-making approach based on a Fuzzy Analytic Hierarchy Process (FAHP) and the Technique for Order Preference by Similarity to Ideal Solution (TOPSIS) method, in order to rank the compounds by environmental risk priority. The compounds of greatest concern were losartan, acetaminophen, 4-aminoantipyrine, sulfamethoxazole, and metoclopramide. Comparison of the environmental risk priority ranking with the potential human health risk was performed by applying the same multicriteria approach, with the prediction of endpoints using in silico (Q)SAR models. The results obtained suggested that sulfamethoxazole and acetaminophen were the most important analytes to be considered for monitoring.
Topics: Humans; Acetaminophen; Hospitals; Sulfamethoxazole; Pharmaceutical Preparations
PubMed: 37406941
DOI: 10.1016/j.chemosphere.2023.139368