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OBJECTIVE: To determine the pharmacokinetics (PK) of metoclopramide administered via intravenous continuous rate infusion (IV CRI) and subcutaneous (SC) bolus and evaluate for gastrointestinal motility and adverse side effects. STUDY DESIGN: Experimental study; randomized, crossover design. ANIMALS: Six healthy adult horses. METHODS: Each horse received metoclopramide via IV CRI (0.04 mg/kg/h for 24 h) and SC bolus (0.08 mg/kg once), with ≥1 week washout period between. Plasma was analyzed by UPLC-MS/MS. Compartmental modeling was used to determine PK parameters for each treatment; nonparametric superposition was used to simulate multiple SC bolus regimens. Gastrointestinal motility and evidence of adverse effects were monitored. RESULTS: Tmax (h) for SC bolus was 0.583 ± 0.204 versus 17.3 ± 6.41 for IV CRI, while Cmax (ng/mL) was 27.7 ± 6.38 versus 43.6 ± 9.97, respectively. AUC (h × ng/mL) was calculated as 902 ± 189 for 24 h IV CRI versus 244 ± 37.4 simulated for 0.08 mg/kg SC bolus every 8 h. Simulations revealed similar exposure between groups with administration of 0.96 mg/kg/day SC bolus, divided into three, four, or six doses. SC bolus bioavailability was estimated as 110 ± 11.5%. No clear trends in motility alteration were identified. No adverse effects were noted. CONCLUSION: Repeated SC boluses of metoclopramide at 0.08 mg/kg would result in lower total drug exposure and Tmax than IV CRI administration but would be highly bioavailable. CLINICAL SIGNIFICANCE: Higher and/or more frequent SC bolus doses are needed to achieve a similar AUC to IV CRI. No adverse effects were noted; however, evaluation of alternative dosing strategies is warranted.
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Antieméticos , Estudios Cruzados , Metoclopramida , Metoclopramida/farmacocinética , Metoclopramida/administración & dosificación , Animales , Caballos/sangre , Masculino , Infusiones Intravenosas/veterinaria , Femenino , Inyecciones Subcutáneas/veterinaria , Antieméticos/farmacocinética , Antieméticos/administración & dosificación , Antieméticos/sangre , Área Bajo la Curva , Motilidad Gastrointestinal/efectos de los fármacosRESUMEN
BACKGROUND: Antibiotic resistance genes (ARGs) transfer rapidly among bacterial species all over the world contributing to the aggravation of antibiotic resistance crisis. Antibiotics at sub-inhibitory concentration induce horizontal gene transfer (HRT) between bacteria, especially through conjugation. The role of common non-antibiotic pharmaceuticals in the market in disseminating antibiotic resistance is not well studied. OBJECTIVES: In this work, we indicated the effect of some commonly used non-antibiotic pharmaceuticals including antiemetic (metoclopramide HCl) and antispasmodics (hyoscine butyl bromide and tiemonium methyl sulfate) on the plasmid-mediated conjugal transfer of antibiotic resistance genes between pathogenic E. coli in the gastric intestinal tract (GIT). METHODS: Broth microdilution assay was used to test the antibacterial activity of the tested non-antibiotic pharmaceuticals. A conjugation mating system was applied in presence of the studied non-antibiotic pharmaceuticals to test their effect on conjugal transfer frequency. Plasmid extraction and PCR were performed to confirm the conjugation process. Transmission electron microscopy (TEM) was used for imaging the effect of non-antibiotic pharmaceuticals on bacterial cells. RESULTS: No antibacterial activity was reported for the used non-antibiotic pharmaceuticals. Plasmid-mediated conjugal transfer between isolates was induced by metoclopramide HCl but suppressed by hyoscine butyl bromide. Tiemonium methylsulfate slightly promoted conjugal transfer. Aggregation between cells and periplasmic bridges was clear in the case of metoclopramide HCl while in presence of hyoscine butyl bromide little affinity was observed. CONCLUSION: This study indicates the contribution of non-antibiotic pharmaceuticals to the dissemination and evolution of antibiotic resistance at the community level. Metoclopramide HCl showed an important role in the spread of antibiotic resistance.
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Escherichia coli , Transferencia de Gen Horizontal , Plásmidos , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Plásmidos/genética , Metoclopramida/farmacología , Pruebas de Sensibilidad Microbiana , Antibacterianos/farmacología , Farmacorresistencia Bacteriana/genética , Farmacorresistencia Bacteriana/efectos de los fármacos , Conjugación Genética , Farmacorresistencia Microbiana/genética , Farmacorresistencia Microbiana/efectos de los fármacosRESUMEN
Green spectrophotometric and HPLC methods have been developed for the quantification of metoclopramide. In the spectrophotometric method, it was determined by direct absorbance measurement at 273 nm wavelength using ultrapure water as solvent. The Extend C18 column was used for the HPLC method. The mobile phase system consisted of a combination of ethanol and formic acid solution (pH 2.0; 30:70 v/v). Isocratic elution was applied and the flow rate was set at 1.0 mL min-1. Metoclopramide was detected at 273 nm. The methods performed were economical, rapid, environmentally friendly, and simple, providing metoclopramide analysis within 5 min. The methods have been successfully applied in pharmaceutical products without matrix interference. The results of the application of the developed methods to pharmaceutical products were statistically compared and no significant difference was observed between the methods. In addition, the greenness assessment of the developed methods was performed using AGREE software. Our developed methods, based on the use of solvents such as ethanol and water, are proposed as a more environmentally and analyst-friendly option for the quantification of metoclopramide in pharmaceutical products than other methods currently in use.
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Etanol , Metoclopramida , Cromatografía Líquida de Alta Presión/métodos , Metoclopramida/análisis , Agua , Preparaciones FarmacéuticasRESUMEN
The focus of the research was to overcome the limitations of metoclopramide (MTC) when administered intranasally. The aim was to improve its bioavailability, increase patient compliance, and prolong its residence time in the nasal cavity. MTC-loaded liposomes were prepared by applying the film hydration method. A study was conducted to determine how formulation variables affected encapsulation efficiency (EE %), mean particle size (MPS), and zeta potential (ZP). The MTC-liposomes were further loaded into the in situ gel (gellan gum) for longer residence times following intranasal administration. pH, gelling time, and in vitro release tests were conducted on the formulations produced. In vivo performance of the MTC-loaded in situ gels was appraised based on disparate parameters such as plasma peak concentration, plasma peak time, and elimination coefficient compared to intravenous administration. When the optimal liposome formulation contained 1.98% of SPC, 0.081% of cholesterol, 97.84% of chloroform, and 0.1% of MTC, the EE of MTC was 83.21%, PS was 107.3 nm. After 5 h, more than 80% of the drug was released from MTC-loaded liposome incorporated into gellan gum in situ gel formulation (Lip-GG), which exhibited improved absorption and higher bioavailability compared to MTC loaded into gellan gum in situ gel (MTC-GG). Acceptable cell viability was also achieved. It was found out that MTC-loaded liposomal in situ gel formulations administered through the nasal route could be a better choice than other options due to its ease of administration, accurate dosing, and higher bioavailability in comparison with MTC-GG.
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Liposomas , Metoclopramida , Conejos , Humanos , Animales , Disponibilidad Biológica , Administración Intranasal , Náusea , Lípidos , Geles , Tamaño de la Partícula , Sistemas de Liberación de MedicamentosRESUMEN
OBJECTIVES: To assess the comparative effectiveness and safety of parenteral agents for pain reduction in patients with acute migraine. BACKGROUND: Parenteral agents have been shown to be effective in treating acute migraine pain; however, the comparative effectiveness of different approaches is unclear. METHODS: Nine electronic databases and gray literature sources were searched to identify randomized clinical trials assessing parenteral agents to treat acute migraine pain in emergency settings. Two independent reviewers completed study screening, data extraction, and Cochrane risk-of-bias assessment, with differences being resolved by adjudication. The protocol of the review was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42018100096). RESULTS: A total of 97 unique studies were included, with most studies reporting a high or unclear risk of bias. Monotherapy, as well as combination therapy, successfully reduced pain scores prior to discharge. They also increased the proportion of patients reporting pain relief and being pain free. Across the pain outcomes assessed, combination therapy was one of the higher ranked approaches and provided robust improvements in pain outcomes, including lowering pain scores (mean difference -3.36, 95% confidence interval [CI] -4.64 to -2.08) and increasing the proportion of patients reporting pain relief (risk ratio [RR] 2.83, 95% CI 1.74-4.61). Neuroleptics and metoclopramide also ranked high in terms of the proportion of patients reporting pain relief (neuroleptics RR 2.76, 95% CI 2.12-3.60; metoclopramide RR 2.58, 95% CI 1.90-3.49) and being pain free before emergency department discharge (neuroleptics RR 4.8, 95% CI 3.61-6.49; metoclopramide RR 4.1, 95% CI 3.02-5.44). Most parenteral agents were associated with increased adverse events, particularly combination therapy and neuroleptics. CONCLUSIONS: Various parenteral agents were found to provide effective pain relief. Considering the consistent improvements across various outcomes, combination therapy, as well as monotherapy of either metoclopramide or neuroleptics are recommended as first-line options for managing acute migraine pain. There are risks of adverse events, especially akathisia, following treatment with these agents. We recommend that a shared decision-making model be considered to effectively identify the best treatment option based on the patient's needs.
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Trastornos Migrañosos , Humanos , Analgésicos/administración & dosificación , Servicio de Urgencia en Hospital , Metoclopramida/administración & dosificación , Trastornos Migrañosos/tratamiento farmacológico , Metaanálisis en Red , Manejo del Dolor/métodos , Ensayos Clínicos Controlados Aleatorios como AsuntoRESUMEN
INTRODUCTION: Gastroparesis is a chronic disorder characterized by decreased gastric emptying and presents with nausea, vomiting, and abdominal pain which impacts patients' quality of life greatly. The treatment modalities available for gastroparesis have been expanding over the past 2 decades. Currently, there are multiple options available for gastroparesis, albeit with only one FDA-approved medication until June 2021. AREAS COVERED: We review the different treatments available for gastroparesis and discuss the recently FDA-approved intranasal formulation of metoclopramide. This nasal spray guarantees metoclopramide absorption within 15 min of application bypassing first pass metabolism in the liver and overcoming the limitations of the oral formulation not passing into the small intestine for absorption because of a gastroparetic stomach or a patient unable to take the oral metoclopramide because of nausea and vomiting. EXPERT OPINION: We now find ourselves in an oasis after spending many years in a 'desert' regarding pharmacologic therapies available for gastroparesis. The expansion of the research involving dopamine receptor antagonists and delving into alternative mechanisms of alleviating gastroparesis symptoms has been crucial in the landscape of gastroparesis. This is especially true as our knowledge of gastroparesis has proven that simply improving gastric emptying does not necessarily translate to clinical improvement.
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Vaciamiento Gástrico , Gastroparesia , Calidad de Vida , Humanos , Administración Intranasal , Antagonistas de Dopamina/uso terapéutico , Vaciamiento Gástrico/efectos de los fármacos , Fármacos Gastrointestinales/uso terapéutico , Fármacos Gastrointestinales/farmacología , Fármacos Gastrointestinales/administración & dosificación , Gastroparesia/tratamiento farmacológico , Gastroparesia/fisiopatología , Metoclopramida/uso terapéuticoRESUMEN
BACKGROUND: Vomiting is one of the most common adverse events of chemotherapy. The purpose of this study was to systematically review the clinical efficacy of acupoint injection of metoclopramide in the treatment of post-chemotherapy vomiting. METHODS: We searched 4 general English databases and 4 conventional Chinese databases, all with a time frame from database creation to December 2022. The retrieved clinical trials of acupoint injection of metoclopramide for post-chemotherapy vomiting were then subjected to meta-analysis and trial sequential analysis. RESULTS: A total of 12 studies were included, with a total sample size of 965 cases. Meta-analysis showed that acupoint injection of metoclopramide was effective in improving anti-vomiting effective rate [odds ratioâ =â 5.67, 95% confidence intervalâ =â (3.80,8.47), Pâ <â .00001] compared with intramuscular/intravenous injection, and trial sequential analysis showed that this benefit was conclusive. Subgroup analysis demonstrated that acupoint injection significantly improved the anti-vomiting effective rate at doses of 10 mg qd, 20 mg qd, and 30 mg qd, as well as at durations of 1 day and 5 days. Subgroup analysis also indicated that injection at the Zusanli acupoint significantly increased the anti-vomiting effective rate, while injection at the Neiguan acupoint had an anti-vomiting effective rate comparable to that of the control group. Harbord regression showed no significant publication bias (Pâ =â .730). CONCLUSION: Acupoint injection of metoclopramide for post-chemotherapy vomiting is more effective than intramuscular and intravenous injections and is not limited by dose or duration of treatment, which may be the preferred way of administration.
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Puntos de Acupuntura , Antieméticos , Antineoplásicos , Metoclopramida , Vómitos , Metoclopramida/administración & dosificación , Metoclopramida/uso terapéutico , Humanos , Vómitos/tratamiento farmacológico , Antineoplásicos/administración & dosificación , Antineoplásicos/efectos adversos , Antieméticos/administración & dosificación , Antieméticos/uso terapéutico , Resultado del TratamientoRESUMEN
Background: Lactation induction in transgender women is a clinical and research priority in the field of breastfeeding medicine. To date, there are four case reports detailing successful induced lactation in transgender patients who wished to breastfeed. The Academy of Breast Feeding Medicine does not formally recommend a specific medication regimen for transgender patients due to lack of high-quality research. Case Presentation: A 50-year-old transgender woman with a hypercoagulable disorder who was able to lactate and breastfeed with novel hormone regimen management at a gender care clinic. Her baseline hormone treatment was an estradiol 0.3 mg transdermal patch every 72 hours and micronized progesterone 200 mg daily. Results: Within four weeks of initiating a modified hormone regimen (estradiol 0.4 mg patch every 72 hours, progesterone 300 mg daily, metoclopramide 10 mg three times daily), the patient was lactating spontaneously. On multiple occasions, she breastfed and expressed up to 30 mL of milk through pumping. Conclusion: This report offers a new effective hormone regimen for transgender patients who wish to lactate and cannot access domperidone-the galactagogue used in previous case reports. It also provides a review of previously published case reports on this subject. Future research in this field should prioritize cohort studies of transgender patients who desire lactation to further assess patient attitudes, experiences, and outcomes.
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Lactancia Materna , Estradiol , Lactancia , Personas Transgénero , Humanos , Femenino , Personas Transgénero/psicología , Persona de Mediana Edad , Estradiol/administración & dosificación , Progesterona/administración & dosificación , Metoclopramida/administración & dosificación , Masculino , Galactogogos/administración & dosificaciónRESUMEN
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).
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Várices Esofágicas y Gástricas , Hemorragia Gastrointestinal , Masculino , Humanos , Persona de Mediana Edad , Anciano , Femenino , Hemorragia Gastrointestinal/etiología , Metoclopramida/uso terapéutico , Várices Esofágicas y Gástricas/complicaciones , Endoscopía Gastrointestinal/efectos adversos , Administración Intravenosa , Método Doble CiegoRESUMEN
An objective and validated index of nausea and vomiting such as the Pregnancy-Unique Quantification of Emesis (PUQE) and HyperEmesis Level Prediction (HELP) tools can be used to classify the severity of NVP and HG. [Grade C] Ketonuria is not an indicator of dehydration and should not be used to assess severity. [Grade A] There are safety and efficacy data for first line antiemetics such as anti (H1) histamines, phenothiazines and doxylamine/pyridoxine (Xonvea®) and they should be prescribed initially when required for NVP and HG (Appendix III). [Grade A] There is evidence that ondansetron is safe and effective. Its use as a second line antiemetic should not be discouraged if first line antiemetics are ineffective. Women can be reassured regarding a very small increase in the absolute risk of orofacial clefting with ondansetron use in the first trimester, which should be balanced with the risks of poorly managed HG. [Grade B] Metoclopramide is safe and effective and can be used alone or in combination with other antiemetics. [Grade B] Because of the risk of extrapyramidal effects metoclopramide should be used as second-line therapy. Intravenous doses should be administered by slow bolus injection over at least 3 minutes to help minimise these. [Grade C] Women should be asked about previous adverse reactions to antiemetic therapies. If adverse reactions occur, there should be prompt cessation of the medications. [GPP] Normal saline (0.9% NaCl) with additional potassium chloride in each bag, with administration guided by daily monitoring of electrolytes, is the most appropriate intravenous hydration. [Grade C] Combinations of different drugs should be used in women who do not respond to a single antiemetic. Suggested antiemetics for UK use are given in Appendix III. [GPP] Thiamine supplementation (either oral 100 mg tds or intravenous as part of vitamin B complex (Pabrinex®)) should be given to all women admitted with vomiting, or severely reduced dietary intake, especially before administration of dextrose or parenteral nutrition. [Grade D] All therapeutic measures should have been tried before considering termination of pregnancy. [Grade C].
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Antieméticos , Hiperemesis Gravídica , Ondansetrón , Humanos , Femenino , Embarazo , Hiperemesis Gravídica/terapia , Hiperemesis Gravídica/diagnóstico , Antieméticos/uso terapéutico , Antieméticos/administración & dosificación , Ondansetrón/uso terapéutico , Ondansetrón/administración & dosificación , Náuseas Matinales/terapia , Náusea/etiología , Náusea/terapia , Piridoxina/uso terapéutico , Piridoxina/administración & dosificación , Metoclopramida/uso terapéutico , Metoclopramida/administración & dosificación , Índice de Severidad de la Enfermedad , Complicaciones del Embarazo/tratamiento farmacológico , Complicaciones del Embarazo/terapiaRESUMEN
P-glycoprotein (P-gp, encoded in humans by the ABCB1 gene and in rodents by the Abcb1a/b genes) is a membrane transporter that can restrict the intestinal absorption and tissue distribution of many drugs and may also contribute to renal and hepatobiliary drug excretion. The aim of this study was to compare the performance and sensitivity of currently available radiolabeled P-gp substrates for positron emission tomography (PET) with the single-photon emission computed tomography (SPECT) radiotracer [99mTc]Tc-sestamibi for measuring the P-gp function in the kidneys and liver. Wild-type, heterozygous (Abcb1a/b(+/-)), and homozygous (Abcb1a/b(-/-)) Abcb1a/b knockout mice were used as models of different P-gp abundance in excretory organs. Animals underwent either dynamic PET scans after intravenous injection of [11C]N-desmethyl-loperamide, (R)-[11C]verapamil, or [11C]metoclopramide or consecutive static SPECT scans after intravenous injection of [99mTc]Tc-sestamibi. P-gp in the kidneys and liver of the mouse models was analyzed with immunofluorescence labeling and Western blotting. In the kidneys, Abcb1a/b() mice had intermediate P-gp abundance compared with wild-type and Abcb1a/b(-/-) mice. Among the four tested radiotracers, renal clearance of radioactivity (CLurine,kidney) was significantly reduced (-83%) in Abcb1a/b(-/-) mice only for [99mTc]Tc-sestamibi. Biliary clearance of radioactivity (CLbile,liver) was significantly reduced in Abcb1a/b(-/-) mice for [11C]N-desmethyl-loperamide (-47%), [11C]metoclopramide (-25%), and [99mTc]Tc-sestamibi (-79%). However, in Abcb1a/b(+/-) mice, CLbile,liver was significantly reduced (-47%) only for [99mTc]Tc-sestamibi. Among the tested radiotracers, [99mTc]Tc-sestamibi performed best in measuring the P-gp function in the kidneys and liver. Owing to its widespread clinical availability, [99mTc]Tc-sestamibi represents a promising probe substrate to assess systemic P-gp-mediated drug-drug interactions and to measure renal and hepatic P-gp function under different (patho-)physiological conditions.
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Miembro 1 de la Subfamilia B de Casetes de Unión a ATP , Metoclopramida , Humanos , Ratones , Animales , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Tomografía Computarizada por Rayos X , Subfamilia B de Transportador de Casetes de Unión a ATP/genética , Tomografía de Emisión de Positrones/métodos , Radiofármacos , Hígado/diagnóstico por imagen , Tomografía Computarizada de Emisión de Fotón Único , Riñón/diagnóstico por imagen , Nitrilos , Compuestos de Organotecnecio , Ratones NoqueadosRESUMEN
Moxifloxacin is a broad-spectrum antimicrobial agent that is commonly used in clinical practice. Here we report an unusual case of a patient with persistent hiccups caused by moxifloxacin. A man aged in his 40s was treated with moxifloxacin for tuberculous pleurisy. Hiccups occurred 2 hours after intravenous injection of moxifloxacin and lasted into evening. On the second day after injection, hiccups occurred again and made it difficult for him to fall asleep. The clinician ruled out gastrointestinal disease, nervous system disease, electrolyte disturbance and other factors. On assessing causality of the adverse drug reaction, the Naranjo scale for moxifloxacin was six, indicating a probable relationship of hiccups with moxifloxacin. Hiccups stopped 2 min after intramuscular injection of metoclopramide. To our knowledge, this is the first case report about moxifloxacin-induced persistent hiccups. Clinicians should be aware of the rare adverse reaction.
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Hipo , Humanos , Masculino , Hipo/inducido químicamente , Hipo/tratamiento farmacológico , Metoclopramida/uso terapéutico , Moxifloxacino/efectos adversosRESUMEN
CONTEXT: Malignant bowel obstruction (MBO) is a common complication of intra-abdominal cancer, frequently seen in advanced gastrointestinal and gynecologic cancer. Management of MBO can be challenging, particularly if the patient is not a surgical candidate. No consensus exists on how best to manage these patients medically. Retrospective studies suggest that the combination of dexamethasone, octreotide and metoclopramide may lead to relief of obstruction and improvement in symptoms associated with the obstruction. OBJECTIVES: This study seeks to prospectively evaluate the combination of drug "triple therapy" dexamethasone 4 mg BID, metoclopramide 10 mg Q6 and octreotide 300 mcg TID to assess tolerability, safety, and effect on symptoms and deobstruction. METHODS: Adults admitted at Roswell Park Comprehensive Cancer Center with malignant bowel obstruction were eligible. Eligible patients who constented to the study were started on the triple therapy with close monitoring of symptoms and for adverse effects. RESULTS: A total of 15 patients enrolled in the study. Two patients experienced bradycardia as adverse effect and there was no incidence of bowel perforation. All patients who completed the study had complete resolution of their nausea, and improvement in other symptoms including pain, constipation, tolerance of oral intake and resumption of bowel movements. Only two of the 15 patients were alive to complete the six-month post study follow up. CONCLUSION: "Triple therapy" with dexamethasone, metoclopramide, and octreotide for management of nonsurgical MBO in this small sample size appears safe and well tolerated however a diagnosis of inoperable MBO remains associated with poor prognosis and death within months.
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Obstrucción Intestinal , Neoplasias , Adulto , Humanos , Femenino , Metoclopramida/uso terapéutico , Octreótido/uso terapéutico , Fármacos Gastrointestinales/uso terapéutico , Estudios Retrospectivos , Estudios Prospectivos , Obstrucción Intestinal/terapia , Obstrucción Intestinal/complicaciones , Dexametasona/uso terapéutico , Cuidados Paliativos , Neoplasias/complicacionesRESUMEN
The dopaminergic system is implicated in the pathophysiology of migraine. However, the underlying mechanisms remain unclear. We explored the effects and mechanisms of dopaminergic system modulation in the in vivo and in vitro rat models of migraine. Dopaminergic agonist apomorphine, D2 receptor antagonists metoclopramide and haloperidol and 5-HT3 receptor antagonist ondansetron alone and together were tested in nitroglycerin-induced migraine model, in vivo. Likewise, the combinations of drugs were also tested on basal calcitonin gene-related peptide (CGRP) release in vitro hemiskull preparations. Mechanical allodynia was tested by von Frey filaments. CGRP concentrations in trigeminovascular structures and in vitro superfusates and c-Fos levels in the brainstem were determined by enzyme-linked immunosorbent assay. Meningeal mast cells were evaluated with toluidine blue staining. Apomorphine further enhanced nitroglycerin-induced mechanical allodynia, brainstem c-fos expression, trigeminal ganglion and brainstem CGRP concentrations and meningeal mast cell degranulation, in vivo. Haloperidol completely antagonised all apomorphine-induced effects and also alleviated changes induced by nitroglycerin without apomorphine. Metoclopramide and ondansetron partially attenuated apomorphine- or nitroglycerin-induced effects. A combination of haloperidol and ondansetron decreased basal CGRP release, in vitro, whereas the other administrations were ineffective. Apomorphine-mediated dopaminergic activation exacerbated nitroglycerin-stimulated nociceptive reactions by further enhancing c-fos expression, CGRP release and mast cell degranulation in strategical structures associated with migraine pain. Metoclopramide partially attenuated the effects of apomorphine, most likely because it is also a 5-HT3 receptor antagonist. Haloperidol with pure D2 receptor antagonism feature appears to be more effective than metoclopramide in reducing migraine-related parameters in dopaminergic activation- and/or NTG-induced migraine-like conditions.
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Hiperalgesia , Trastornos Migrañosos , Ratas , Animales , Hiperalgesia/inducido químicamente , Hiperalgesia/tratamiento farmacológico , Hiperalgesia/complicaciones , Péptido Relacionado con Gen de Calcitonina/metabolismo , Nitroglicerina/efectos adversos , Apomorfina/efectos adversos , Ondansetrón/efectos adversos , Haloperidol/efectos adversos , Metoclopramida/efectos adversos , Receptores de Serotonina 5-HT3 , Trastornos Migrañosos/inducido químicamente , Trastornos Migrañosos/tratamiento farmacológico , Trastornos Migrañosos/complicaciones , Modelos Teóricos , Receptores Dopaminérgicos/metabolismo , Modelos Animales de EnfermedadRESUMEN
BACKGROUND: Functional dyspepsia (FD) is felt as a discomfort or pain on the center line or upper abdomen. In this study, we aimed to compare the effects of Govarcin herbal capsule and Metoclopramide for alleviating gastrointestinal symptoms in patients with FD. METHODS: Totally, 106 patients enrolled in a double-blind, clinical trial study. The participants had FD and were divided into two groups receiving Govarcin and Metoclopramide by block randomization. The patients were treated for four weeks, taking one Govarcin capsule or Metoclopramide tablet after each meal. The rate of improvement in patients was assessed by mitigation of clinical symptoms, including epigastric pain, fullness, discomfort, nausea, vomiting and heartburn. Also, before and after intervention, we used Nepin questionnaire and ROME III. SPSS statistics 25 software was used for data analyzing. RESULTS: Clinical symptom score changes between Govarcin and Metoclopramide patients' groups showed that there was no significant difference in any of the clinical symptom scores (except for heartburn, p-value=0.012) between the study groups. Nepean score in Govarcin group before and after treatment were 19.3±4.8 and 8.9±2.8, respectively (p-value<0.001). For Metoclopramide group, these values were 19.8±3.5 and 9.4±2.1 respectively (p-value<0.001). No significant difference was found in terms of Nepean score between the Govarcin and Metoclopramide groups (p-value=0.995). CONCLUSION: Govarcin herbal capsule can be used to remedy symptoms in patients with FD. It seems that Govarcin is as effective as Metoclopramide in fighting symptoms of FD as no significant difference in efficacy has been demonstrated between them.
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Dispepsia , Metoclopramida , Humanos , Metoclopramida/uso terapéutico , Método Doble Ciego , Dispepsia/tratamiento farmacológico , Masculino , Femenino , Adulto , Persona de Mediana Edad , Resultado del Tratamiento , Cápsulas , Medicamentos Herbarios Chinos/uso terapéuticoRESUMEN
BACKGROUND: The enhanced recovery after surgery (ERAS) method is designed for the patient to recover quickly, have less pain and have a more comfortable period after the surgery; that includes preoperative, intra and postoperative processes. ERAS has been started to be applied in cesarean section surgeries as the patients need to recover quickly. In the literature, there is no study about the results of ERAS in cesarean section about pain scores and complications. OBJECTIVES: It is aimed to compare the results of cesarean section patients using the ERAS method completely in patients who have had cesarean section without meeting some of the postoperative conditions of the ERAS criteria. STUDY DESIGN: It is a prospective study designed as postoperative metoclopramide, enema and routine opioids in group 1, enema and metoclopramide in group 2, metoclopramide only in group 3 and nothing in group 4. Postoperative pain scoring was done by using visual analog scale (VAS). Analysis of variance tests and t tests were used for results. RESULTS: There was no difference between groups according to age, parity, and birth weight. As a result, although there was no difference between the groups in terms of discharge time and complications, the VAS score used in pain scoring was found to be significantly lower in group 3 compared to the other groups (p: 0.000). Only metoclopramide group (group 3) had lowest VAS score. CONCLUSION: It has been revealed that the ERAS procedure does not need to be so detailed in the postoperative period, and the addition of metoclopramide may be sufficient. Since pain can be a subjective factor, other randomized studies are needed in terms of other criteria.
Asunto(s)
Cesárea , Recuperación Mejorada Después de la Cirugía , Embarazo , Humanos , Femenino , Metoclopramida/uso terapéutico , Estudios Prospectivos , Dolor Postoperatorio/tratamiento farmacológicoRESUMEN
The efflux transporter P-glycoprotein (P-gp) at the blood-brain barrier limits the cerebral uptake of various xenobiotics. To assess the sensitivity of [11C]metoclopramide to measure decreased cerebral P-gp function, we performed [11C]metoclopramide PET scans without (baseline) and with partial P-gp inhibition by tariquidar in wild-type, heterozygous Abcb1a/b(+/-) and homozygous Abcb1a/b(-/-) mice as models with controlled levels of cerebral P-gp expression. Brains were collected to quantify P-gp expression with immunohistochemistry. Brain uptake of [11C]metoclopramide was expressed as the area under the brain time-activity curve (AUCbrain) and compared with data previously obtained with (R)-[11C]verapamil and [11C]N-desmethyl-loperamide. Abcb1a/b(+/-) mice had intermediate P-gp expression compared to wild-type and Abcb1a/b(-/-) mice. In baseline scans, all three radiotracers were able to discriminate Abcb1a/b(-/-) from wild-type mice (2.5- to 4.6-fold increased AUCbrain, p ≤ 0.0001). However, only [11C]metoclopramide could discriminate Abcb1a/b(+/-) from wild-type mice (1.46-fold increased AUCbrain, p ≤ 0.001). After partial P-gp inhibition, differences in [11C]metoclopramide AUCbrain between Abcb1a/b(+/-) and wild-type mice (1.39-fold, p ≤ 0.001) remained comparable to baseline. There was a negative correlation between baseline [11C]metoclopramide AUCbrain and ex-vivo-measured P-gp immunofluorescence (r = -0.9875, p ≤ 0.0001). Our data suggest that [11C]metoclopramide is a sensitive radiotracer to measure moderate, but (patho-)physiologically relevant decreases in cerebral P-gp function without the need to co-administer a P-gp inhibitor.
Asunto(s)
Miembro 1 de la Subfamilia B de Casetes de Unión a ATP , Barrera Hematoencefálica , Ratones , Animales , Barrera Hematoencefálica/metabolismo , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/genética , Miembro 1 de la Subfamilia B de Casetes de Unión a ATP/metabolismo , Metoclopramida/metabolismo , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Subfamilia B de Transportador de Casetes de Unión a ATP/metabolismo , Tomografía de Emisión de PositronesRESUMEN
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.