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1.
Health Technol Assess ; 25(63): 1-116, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34782054

RESUMO

BACKGROUND: Around one-third of pregnant women suffer from moderate to severe nausea and vomiting, causing physical and emotional distress and reducing their quality of life. There is no cure for nausea and vomiting in pregnancy. Management focuses on relieving symptoms and preventing morbidity, and often requires antiemetic therapy. National guidelines make recommendations about first-, second- and third-line antiemetic therapies, although care varies in different hospitals and women report feeling unsupported, dissatisfied and depressed. OBJECTIVES: To determine whether or not, in addition to intravenous rehydration, ondansetron compared with no ondansetron and metoclopramide compared with no metoclopramide reduced the rate of treatment failure up to 10 days after drug initiation; improved symptom severity at 2, 5 and 10 days after drug initiation; improved quality of life at 10 days after drug initiation; and had an acceptable side effect and safety profile. To estimate the incremental cost per treatment failure avoided and the net monetary benefits from the perspectives of the NHS and women. DESIGN: This was a multicentre, double-dummy, randomised, double-blinded, dummy-controlled 2 × 2 factorial trial (with an internal pilot phase), with qualitative and health economic evaluations. PARTICIPANTS: Thirty-three patients (who were < 17 weeks pregnant and who attended hospital with nausea and vomiting after little or no improvement with first-line antiemetic medication) who attended 12 secondary care NHS trusts in England, 22 health-care professionals and 21 women participated in the qualitative evaluation. INTERVENTIONS: Participants were randomly allocated to one of four treatment groups (1 : 1 : 1: 1 ratio): (1) metoclopramide and dummy ondansetron; (2) ondansetron and dummy metoclopramide; (3) metoclopramide and ondansetron; or (4) double dummy. Trial medication was initially given intravenously and then continued orally once women were able to tolerate oral fluids for a maximum of 10 days of treatment. MAIN OUTCOME MEASURES: The primary end point was the number of participants who experienced treatment failure, which was defined as the need for further treatment because symptoms had worsened between 12 hours and 10 days post treatment. The main economic outcomes were incremental cost per additional successful treatment and incremental net benefit. RESULTS: Of the 592 patients screened, 122 were considered eligible and 33 were recruited into the internal pilot (metoclopramide and dummy ondansetron, n = 8; ondansetron and dummy metoclopramide, n = 8; metoclopramide and ondansetron, n = 8; double dummy, n = 9). Owing to slow recruitment, the trial did not progress beyond the pilot. Fifteen out of 30 evaluable participants experienced treatment failure. No statistical analyses were performed. The main reason for ineligibility was prior treatment with trial drugs, reflecting an unpredicted change in prescribing practice at several points along the care pathway. The qualitative evaluation identified the requirements of the study protocol, in relation to guidelines on anti-sickness drugs, and the diversity of pathways to care as key hurdles to recruitment while the role of research staff was a key enabler. No important adverse events or side effects were reported. LIMITATIONS: The pilot trial failed to achieve the recruitment target owing to unforeseen changes in the provision of care. CONCLUSIONS: The trial was unable to provide evidence to support clinician decisions about the best choice of second-line antiemetic for nausea and vomiting in pregnancy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN16924692 and EudraCT 2017-001651-31. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 63. See the NIHR Journals Library website for further project information.


Assuntos
Antieméticos , Antieméticos/uso terapêutico , Análise Custo-Benefício , Feminino , Humanos , Metoclopramida/uso terapêutico , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Ondansetron/uso terapêutico , Gravidez , Qualidade de Vida , Vômito/induzido quimicamente , Vômito/tratamento farmacológico
2.
J Med Case Rep ; 15(1): 520, 2021 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-34688305

RESUMO

BACKGROUND: Acute dystonic reactions caused by drugs are uncommon in daily practice, whether in outpatient or in emergency settings. Such types of unfavorable reaction may cause the treating physician's working diagnosis to be misled at a certain point. CASE PRESENTATION: A 25-year-old Hindu female from Dharan with no previous medical history was being treated for acid peptic disease. Her local physician prescribed oral tablet metoclopramide 10 mg three times a day for 7 days and tablet pantoprazole 40 mg once daily for 7 days. After 24 hours of ingestion of 10 mg of tablet metoclopramide, she was admitted to our Koirala Institute of Health Sciences emergency department with sudden history of facial twitching, slurred speech, and abnormal tongue protrusion. Metoclopramide-induced acute dystonic reaction was diagnosed. After resuscitation, her symptoms reduced quickly, and she was successfully discharged home the same day. CONCLUSIONS: Early diagnosis would be aided by the use of clinical background along with focus on drug history usage, preventing life-threatening pitfalls. To decrease the acute dystonic reaction associated with metoclopramide use, higher frequency of prescription patterns should be taken into account.


Assuntos
Distonia , Doenças da Língua , Adulto , Distonia/induzido quimicamente , Serviço Hospitalar de Emergência , Feminino , Humanos , Metoclopramida/efeitos adversos
3.
Paediatr Drugs ; 23(6): 591-599, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34693501

RESUMO

BACKGROUND: Gastroesophageal reflux (GER) is more frequent in premature infants. Metoclopramide was introduced routinely in premature babies followed in ambulatory care by the Colombian Kangaroo Mother Care program (KMCP), based on a 2004 Cochrane review. AIM: Because of the recent controversy on the use of metoclopramide in children, this study was conducted to evaluate the effectiveness and safety of metoclopramide given as GER disease (GERD) prophylaxis. METHODS: A randomized clinical trial was conducted between April 2017 and January 2019 in 466 premature infants discharged home and followed at a KMCP. Double-blind allocation to metoclopramide versus placebo was performed, 0.2 mg/kg three times daily, administered 15 min before feeding, up to term. Exclusion criteria were oxygen dependency, any perinatal neurological problem or parent's participation refusal. The incidence of GERD symptoms and adverse events that could be associated with the use of metoclopramide were recorded by parents weekly (e.g., emesis, cyanosis or apnea, post-prandial crying episodes, extrapyramidal symptoms, tremor, and drowsiness). RESULTS: A total of 466 subjects were recruited, most of them late preterm. The groups' baseline characteristics were similar. Median duration of the intervention was approximately 3 weeks, at which time most patients were at term. In the longitudinal mixed effects analysis, we did not find clinically significant differences in GERD-related symptoms between groups, either in minor or severe side effects. CONCLUSION: Results show absence of effectiveness in the systematic use of metoclopramide as prophylaxis of GERD symptoms in premature infants. Additionally, no adverse effects attributable to the drug were found. ClinicalTrials.gov: NCT02907632; September 20, 2016. Retrospectively registered.


Assuntos
Refluxo Gastroesofágico , Doenças do Prematuro , Método Canguru , Criança , Refluxo Gastroesofágico/tratamento farmacológico , Refluxo Gastroesofágico/prevenção & controle , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Metoclopramida/efeitos adversos
4.
PLoS One ; 16(9): e0257584, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34543335

RESUMO

BACKGROUND: Nausea and vomiting of pregnancy affects up to 80% of pregnant women, it typically occurs during the first trimester which is the most sensitive time for environmental exposures given organogenesis. Metoclopramide is an antiemetic drug used widely during NVP, but the findings of studies evaluating its safety of use in pregnancy is inconsistent. Therefore, we conducted a systematic review and meta-analysis to assess whether metoclopramide use during first trimester of pregnancy is associated with the risk of major congenital malformations. METHODS: The systematic search using database included Pubmed, Embase, Web of science, and Cochrane library. Studies written in English, comprising with an exposed group and a control group, reporting major congenital malformation as an outcome were included. RESULTS: Six studies assessing a total number of 33374 metoclopramide-exposed and 373498 controls infants were included in this meta-analysis. No significant increase in the rate of major congenital malformation was detected following metoclopramide use during first trimester (OR, 1.14; 95% CI, 0.93-1.38). CONCLUSIONS: Metoclopramide use during first trimester of pregnancy was not associated with the risk of major congenital malformations.


Assuntos
Antieméticos/efeitos adversos , Anormalidades Congênitas/etiologia , Metoclopramida/efeitos adversos , Antieméticos/uso terapêutico , Feminino , Humanos , Metoclopramida/uso terapêutico , Náusea/tratamento farmacológico , Razão de Chances , Gravidez , Primeiro Trimestre da Gravidez , Vômito/tratamento farmacológico
5.
J Pharm Biomed Anal ; 205: 114306, 2021 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-34385016

RESUMO

A comprehensive forced degradation study for bromopride was carried out in accordance with International Conference on Harmonization (ICH) recommendations followed by the identification and prospecting of the major degradation products. The analytical quality by design (AQbD) concepts were used to develop a stability-indicating method for bromopride and five organic impurities quantitation by ultra-high performance liquid chromatography with UV detection (UHPLC-UV). Two screenings and one optimization design were performed, including a Monte Carlo simulation to assess the Method Operable Design Region (MODR). The AQbD approach provided a high degree of method understanding in a very short period of time, less than two weeks, and the validated MODR provided information on robust analytical conditions contributing to the assignment of suitable control strategies.


Assuntos
Cromatografia Líquida de Alta Pressão , Limite de Detecção , Metoclopramida/análogos & derivados , Método de Monte Carlo , Reprodutibilidade dos Testes
6.
Biomed Res Int ; 2021: 5550653, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34447851

RESUMO

Introduction: The gastric residual volume (GRV) monitoring in patients with mechanical ventilation (MV) is a common and important challenge. The purpose of this study was to compare the effect of neostigmine and metoclopramide on GRV among MV patients in the intensive care unit (ICU). Methods: In a double-blind randomized clinical trial, a total of 200 mechanically ventilated ICU patients with GRV > 120 ml (6 hours after the last gavage) were randomly assigned into two groups (A and B) with 100 patients in each group. Patients in groups A and B received intravenous infusion of neostigmine at a dose of 2.5 mg/100 ml normal saline and metoclopramide at a dose of 10 mg/100 ml normal saline, within 30 minutes, respectively. GRV was evaluated 5 times for each patient, once before the intervention and 4 times (at 3, 6, 9, and 12 hours) after the intervention. In addition, demographic characteristics including age and gender, as well as severity illness based on the sequential organ failure assessment score (SOFA), were initially recorded for all patients. Results: After adjusting of demographic and clinical characteristics (age, gender, and SOFA score), the generalized estimating equation (GEE) model revealed that neostigmine treatment increased odds of GRV improvement compared to the metoclopramide group (OR = 2.45, 95% CI: 1.60-3.76, P < 0.001). However, there is a statistically significant time trend (within-subject differences or time effect) regardless of treatment groups (P < 0.001). Conclusion: According to the results, although neostigmine treatment significantly improved GRV in more patients in less time, within 12 hours of treatment, all patients in both groups had complete recovery. Considering that there was no significant difference between the two groups in terms of side effects, it seems that both drugs are effective in improving the GRV of ICU patients.


Assuntos
Esvaziamento Gástrico/efeitos dos fármacos , Metoclopramida/uso terapêutico , Neostigmina/uso terapêutico , Respiração Artificial/métodos , Antieméticos/uso terapêutico , Estado Terminal/terapia , Método Duplo-Cego , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Parassimpatomiméticos/uso terapêutico , Respiração Artificial/efeitos adversos
7.
Support Care Cancer ; 29(12): 8097-8107, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34398289

RESUMO

BACKGROUND: Nausea and vomiting are a common clinical symptom in the advanced cancer patient. Pharmacologic management is important. Evidence for drug choices and guidelines are needed to help clinicians manage nausea and vomiting in this population METHODS: Evidence from a systematic review published in 2010, initial MASCC guidelines developed from a systematic review of literature to 2015, and a new systematic review of randomized trials published between 2015 and February 2, 2021, was combined to establish a new guideline. RESULTS: A search of the literature between 2015 and February 2, 2021, revealed 257 abstracts of which there was one systematic review and 4 randomized trials which were used to modify the guideline. The new guideline is as follows: First Line: Metoclopramide (II) multiple small RCTs including a placebo-controlled trial, haloperidol (II) multiple non-placebo-controlled RCTs, high consensus. Second line: Methotrimeprazine (II) 1 well-powered non-placebo-controlled RCT, olanzapine (II) 1 placebo-controlled pilot RCT, high consensus. Third line: Tropisetron (II) large unblinded lower quality non-placebo-controlled RCT, levosulpiride (II) 1 blinded non-placebo-controlled pilot RCT, high consensus. DISCUSSION: Haloperidol, metoclopramide, methotrimeprazine, olanzapine tropisetron, and levosulpiride have been antiemetics used in randomized trials with antiemetic activity demonstrated. There are only three placebo-controlled randomized trials we could find in our literature review. Placebo responses varied significantly between two randomized trials. More randomized placebo-controlled trials with either metoclopramide or haloperidol rescue are needed to clarify antiemetic choices in advanced cancer. CONCLUSION: First-line antiemetics for nausea and vomiting in advanced cancer are metoclopramide and haloperidol, and second-line medications are methotrimeprazine and olanzapine.


Assuntos
Antieméticos , Neoplasias , Antieméticos/uso terapêutico , Humanos , Metoclopramida/uso terapêutico , Náusea/induzido quimicamente , Náusea/tratamento farmacológico , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Vômito/tratamento farmacológico
8.
Nutrients ; 13(6)2021 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-34205461

RESUMO

Malnourishment is prevalent in patients suffering from head and neck cancer. The postoperative period is crucial in terms of nutritional support, especially after composite resection and reconstruction surgery. These patients present with a number of risk factors that aggravate feeding intolerance, including postoperative status, prolonged immobility, decreased head elevation, mechanical ventilation, and applied sedative agents. Routine management protocols for feeding intolerance include prokinetic drug use and post-pyloric tube insertion, which could be both limited and accompanied by detrimental adverse events. This single-blind clinical trial aimed to investigate the effects of acupuncture in postoperative feeding intolerance in critically ill oral and hypopharyngeal cancer patients. Twenty-eight patients were randomized into two groups: Intervention group and Control group. Interventions were administered daily over three consecutive postoperative days. The primary outcome revealed that the intervention group reached 70% and 80% of target energy expenditure (EE) significantly earlier than the control group (4.00 ± 1.22 versus 6.69 ± 3.50 days, p = 0.012), accompanied by higher total calorie intake within the first postoperative week (10263.62 ± 1086.11 kcals versus 8384.69 ± 2120.05 kcals, p = 0.004). Furthermore, the intervention group also needed less of the prokinetic drug (Metoclopramide, 20.77 ± 48.73 mg versus 68.46 ± 66.56 mg, p = 0.010). In conclusion, digestion-specific acupuncture facilitated reduced postoperative feeding intolerance in oral and hypopharyngeal cancer patients.


Assuntos
Terapia por Acupuntura , Estado Terminal/terapia , Digestão , Neoplasias Hipofaríngeas/terapia , Neoplasias Bucais/terapia , Cuidados Pós-Operatórios/métodos , Idoso , China , Ingestão de Energia , Metabolismo Energético , Humanos , Masculino , Desnutrição/etiologia , Desnutrição/terapia , Metoclopramida/uso terapêutico , Pessoa de Meia-Idade , Apoio Nutricional/métodos , Método Simples-Cego , Resultado do Tratamento
10.
Medicine (Baltimore) ; 100(26): e26465, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34190170

RESUMO

ABSTRACT: Acute dystonic reactions are a worrying reason for presentation to the pediatric emergency department and the pediatric neurology clinic in childhood. It must be diagnosed and treated quickly. The aim of this study was to examine the clinical presentations, etiological factors, and prognosis of patients presenting to our regional tertiary pediatric neurology clinic with a diagnosis of acute dystonic reactions in children.Nine pediatric patients who were treated for acute dystonic reactions between May, 2018 and May, 2020 and had adequate follow-up were included in the study. Medical record data were reviewed age, gender, etiology, features of family, treatment, and results.Three of the patients were female and 6 were male. Their average age was 11 years (4-17). All patients were evaluated as a drug-induced acute dystonic reaction. Of the 9 patients, 5 were due to metoclopramide, 3 were due to risperidone, and 1 was due to aripiprazole. It was learned that a similar situation against other drugs developed in the family history of 3 patients. As a treatment, all of them were intramuscularly applied biperiden suitable for their weight and 30 minutes dramatic improvement was observed. Additional dose had to be administered in only 1 case. All cases were discharged for 24 hours. No problem was observed in their follow-up.Drug-induced acute dystonic reaction can be diagnosed and has a clinical picture that completely resolves when effective treatment is applied. However, it should not be forgotten that it can reach life-threatening dimensions clinically.


Assuntos
Aripiprazol/efeitos adversos , Biperideno/administração & dosagem , Distonia , Metoclopramida/efeitos adversos , Risperidona/efeitos adversos , Idade de Início , Antipsicóticos/administração & dosagem , Antipsicóticos/efeitos adversos , Aripiprazol/administração & dosagem , Criança , Suscetibilidade a Doenças , Antagonistas dos Receptores de Dopamina D2/administração & dosagem , Antagonistas dos Receptores de Dopamina D2/efeitos adversos , Distonia/induzido quimicamente , Distonia/diagnóstico , Distonia/tratamento farmacológico , Distonia/epidemiologia , Feminino , Humanos , Injeções Intramusculares , Masculino , Anamnese , Metoclopramida/administração & dosagem , Parassimpatolíticos/administração & dosagem , Risperidona/administração & dosagem , Resultado do Tratamento , Turquia/epidemiologia
11.
Ugeskr Laeger ; 183(21)2021 05 24.
Artigo em Dinamarquês | MEDLINE | ID: mdl-34060465

RESUMO

This case report describes a 57-year-old male with symptoms of tardive akathisia after long-term metoclopramide treatment. As metoclopramide is a dopamine receptor antagonist, it has the potential to cause drug-induced movement disorders, including akathisia, which is characterised by an inner restlessness resulting in a need for constant movement. Tardive akathisia, in contrast to acute akathisia, evolves after prolonged exposure to the triggering medication and can be a permanent condition. Treatment duration of metoclopramide should be restricted, and awareness of neurological side effects is important.


Assuntos
Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Metoclopramida , Acatisia Induzida por Medicamentos/etiologia , Antagonistas de Dopamina/efeitos adversos , Humanos , Masculino , Metoclopramida/efeitos adversos , Pessoa de Meia-Idade , Agitação Psicomotora
14.
Blood Press ; 30(5): 322-326, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34176388

RESUMO

PURPOSE: Pheochromocytoma, a catecholamine-secreting tumour leading to neurological and cardiovascular life-threatening conditions through hypertension crisis, occurs in 0.1-0.5% of hypertensive patients, but it is extremely rare in pregnancy (0.0018-0.006%). Some classes of drugs, even commonly used in pregnancy, can trigger catecholamine secretion, precipitating the clinical situation. MATERIALS AND METHODS AND RESULTS: We report a 33-year-old woman, gravida 2 para 1, with previous mild hypertension, was admitted to the emergency room, at 28 2/7 weeks of gestation due to headache, tachycardia and severe arterial hypertension (220/120 mm Hg) triggered by the antiemetic metoclopramide used for a week because of nausea. In the emergency room, a paradoxical rise in blood pressure followed intravenous labetalol infusion was observed. Both metoclopramide and labetalol-triggered hypertensive crisis raised the suspicion of an undiagnosed pheochromocytoma. Diagnostic work-up showed elevated normetanephrine urinary excretion ​​and a right adrenal pheochromocytoma by abdominal magnetic resonance imaging. Oral alpha-1 and beta-1-adrenergic antagonist and calcium-channel blocker were started. At 33-weeks of gestation, she underwent a caesarean section giving birth to a female child. Seven weeks later she underwent a video-laparoscopic right adrenalectomy which normalised her blood pressure. CONCLUSIONS: Both metoclopramide, a selective dopamine type-2 receptor antagonist and partial agonist of 5-hydroxytryptamine 4 receptor, and labetalol, a non-selective ß-adrenoreceptor-blocker with weak α1-adrenergic antagonism, exacerbated an acute hypertensive crisis revealing an unrecognised pheochromocytoma in a pregnant patient. Careful attention to potential drug-triggered catecholamine crises and especially early recognition of pheochromocytomas, are mandatory in hypertensive pregnant women. A missed or delayed diagnosis could result in catastrophic results affecting foetal and maternal outcomes.


Assuntos
Neoplasias das Glândulas Suprarrenais , Hipertensão , Feocromocitoma , Neoplasias das Glândulas Suprarrenais/complicações , Neoplasias das Glândulas Suprarrenais/diagnóstico , Adrenalectomia , Adulto , Cesárea , Feminino , Humanos , Hipertensão/complicações , Hipertensão/tratamento farmacológico , Recém-Nascido , Metoclopramida/efeitos adversos , Feocromocitoma/complicações , Feocromocitoma/cirurgia , Gravidez
15.
Yakugaku Zasshi ; 141(4): 599-610, 2021.
Artigo em Japonês | MEDLINE | ID: mdl-33790125

RESUMO

Elneopa NF No. 1 and No. 2 infusions are total parenteral nutrition solutions packaged in four-chambered infusion bags. They have been used as home parenteral nutrition, with various drugs injected into the infusion bags, for treating patient symptoms. In this study, we investigated the stability of six drugs, including famotidine, scopolamine butylbromide, furosemide, bromhexine hydrochloride, betamethasone sodium phosphate, and metoclopramide hydrochloride in the infusion bags under dark conditions at 4℃ for 7 days. Additionally, we developed a high-performance liquid chromatography method to determine drug concentrations in the infusions. The concentrations of injected famotidine, scopolamine butylbromide, and betamethasone sodium phosphate remained unchanged when the four chambers of Elneopa NF No. 1 and No. 2 were opened and the infusions were mixed. Their respective concentrations in the upper and lower chambers also remained unchanged. The concentration of furosemide in the upper chamber of the No. 1 infusion bag decreased after 5 days, although no change was observed in the other chambers and the mixed infusions with the four chambers opened. The concentration of bromhexine hydrochloride slightly decreased in the upper chambers (approximately 3%) after the co-infusion but decreased significantly in the other chambers and the mixed infusions with the four chambers opened. The concentration of metoclopramide hydrochloride significantly decreased in the upper chambers after the co-infusion; however, no change in concentration was observed in the other chambers and the mixed infusion with the four chambers opened. The results of this study provide useful information on home-based parenteral nutrition.


Assuntos
Betametasona/análogos & derivados , Bromoexina , Brometo de Butilescopolamônio , Embalagem de Medicamentos , Famotidina , Furosemida , Metoclopramida , Soluções de Nutrição Parenteral/análise , Nutrição Parenteral Total no Domicílio , Betametasona/análise , Bromoexina/análise , Brometo de Butilescopolamônio/análise , Estabilidade de Medicamentos , Famotidina/análise , Furosemida/análise , Metoclopramida/análise
18.
Eur J Pharmacol ; 901: 174074, 2021 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-33811834

RESUMO

It is unclear whether metoclopramide and domperidone act on human cardiac serotonin 5-HT4-receptors. Therefore, we studied transgenic mice that only express the human 5-HT4 receptor in cardiomyocytes in the atrium and in the ventricle (5-HT4-TG), their wild type-littermates (WT) and isolated human atrial preparations. We found that only metoclopramide but not domperidone enhanced the force of contraction in left atrial preparations (pEC50 = 6.0 ± 0.1; n = 7) from 5-HT4-TG, isolated spontaneously beating right atrial preparations (pEC50 = 6.1 ± 0.1; n = 7) from 5-HT4-TG, Langendorff perfused hearts from 5-HT4-TG, living 5-HT4-TG and human right atrial muscle preparations obtained during bypass surgery of patients suffering from coronary heart disease. The maximum inotropic effect of metoclopramide was smaller (81 ± 2%) than that of 5-HT on the left atria from 5-HT4-TG. The maximum increase in the beating rate due to metoclopramide was 93 ± 2% of effect of 5-HT on right atrial preparations from 5-HT4-TG. Metoclopramide and domperidone were inactive in WT. We found that metoclopramide but not domperidone increased the phosphorylation state of phospholamban in the isolated perfused hearts or muscle strips of 5-HT4-TG, but not in WT. Metoclopramide, but not domperidone, shifted the positive inotropic or chronotropic effects of 5-HT in isolated left atrial and right atrial preparations from 5-HT4-TG dextrally, resp., to higher concentrations: the pEC50 of 5-HT for increase in force was in the absence of metoclopramide 8.6 ± 0.1 (n = 5) versus 8.0 ± 0.3 in the presence of 1 µM metoclopramide (n = 5; P < 0.05); and the beating rate was 7.8 ± 0.2 (n = 7) in the absence of metoclopramide versus 7.2 ± 0.1 in the presence of 1 µM metoclopramide (n = 6; P < 0.05). These results suggested that metoclopramide had an antagonistic effect on human cardiac 5-HT4 receptors. In summary, we showed that metoclopramide, but not domperidone, was a partial agonist at human cardiac 5-HT4-receptors.


Assuntos
Fármacos Cardiovasculares/farmacologia , Domperidona/farmacologia , Antagonistas de Dopamina/farmacologia , Metoclopramida/farmacologia , Receptores 5-HT4 de Serotonina/efeitos dos fármacos , Idoso , Animais , Proteínas de Ligação ao Cálcio/metabolismo , Coração/efeitos dos fármacos , Humanos , Técnicas In Vitro , Masculino , Camundongos Transgênicos , Pessoa de Meia-Idade , Contração Miocárdica/efeitos dos fármacos , Miócitos Cardíacos/efeitos dos fármacos , Miócitos Cardíacos/metabolismo , Fosforilação , Receptores 5-HT4 de Serotonina/genética , Agonistas do Receptor 5-HT4 de Serotonina/farmacologia , Antagonistas do Receptor 5-HT4 de Serotonina/farmacologia
19.
Fish Physiol Biochem ; 47(4): 951-960, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-33895896

RESUMO

The use of recombinant gonadotropin-releasing hormone (rGnRH) has very rarely been tested in fish to promote spawning. This study evaluated the impact of recombinant chicken gonadotropin-releasing hormone (rcGnRH) with metoclopramide on the release of sex steroids and final maturation induction in goldfish (Carassius auratus) broodstock. For this purpose, goldfish broodstock was divided into four groups and treated with 0.9% NaCl with 20 mg/kg metoclopramide (Met) (C); 10 µg/kg body weight (BW) rcGnRH with 20 mg/kg metoclopramide (rcGn10); 15 µg/kg BW rcGnRH with 20 mg/kg metoclopramide (rcGn15); and 20 µg/kg BW rcGnRH with 20 mg/kg metoclopramide (rcGn20). The capability of the rcGnRH for eliciting biological response was tested in vivo by evaluating the changes of 17ß estradiol (E2), testosterone (T), and 17α, 20ß-dihydroxy-4-pregnen-3-one (DHP) and the induced spawning. Blood samples were obtained at 0 h, 12 h, and 24 h after injection. The rcGn10, rcGn15, and rcGn20 treatments induced lower E2 concentration, especially 24 h post-injection. T levels were significantly higher in rcGn10, rcGn15, and rcGn20 treatments 12 h post-injection than at 0 h and then decreased at 24 h post-injection. Furthermore, the rcGnRH tested significantly enhanced DHP secretion in rcGn10, rcGn15, and rcGn20 treatments 12 h post-injection before a decline at 24 h post-injection. No significant difference between the sampling times was found in the C treatment for the 3 sex steroids tested. The results also displayed that rcGnRH at 10-20 µg/kg of body weight can trigger spawning with the highest speed and efficiency of spawning at 20 µg/kg. The obtained results represent a possible strategy for enhancing the artificial reproduction and ovulation of broodstock fish by rGnRH and further support the use of recombinant hormones to promote reproduction in aquaculture.


Assuntos
Aquicultura/métodos , Hormônio Liberador de Gonadotropina/farmacologia , Reprodução/efeitos dos fármacos , Animais , Estradiol/sangue , Feminino , Carpa Dourada , Metoclopramida/farmacologia , Testosterona/sangue
20.
PLoS One ; 16(4): e0249645, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33819293

RESUMO

BACKGROUND: Some studies have indicated that the use of prokinetic agents may reduce pneumonia risk in some populations. Nasogastric tube insertion is known to increase the risk of pneumonia because it disrupts lower esophageal sphincter function. The aim of this study was to evaluate whether prokinetic agents could protect long-term nasogastric tube-dependent patients in Taiwan from being hospitalized for pneumonia. METHODS: A case-crossover study design was applied in this study. Long-term nasogastric tube-dependent patients who had a first-time admission to a hospital due to pneumonia from 1996 to 2013 that was recorded in the Taiwan National Health Insurance Research Database were included. The case period was set to be 30 days before admission, and two control periods were selected for analysis. Prokinetic agent use during those three periods was then assessed for the included patients. Conditional logistic regression was used to calculate the odds ratio (OR) for pneumonia admission with the use of prokinetic agents. RESULTS: A total of 639 first-time hospitalizations for pneumonia among patients with long-term nasogastric tube dependence were included. After adjusting the confounding factors for pneumonia, no negative association between prokinetic agent use and pneumonia hospitalization was found, and the adjusted OR was 1.342 (95% CI 0.967-1.86). In subgroup analysis, the adjusted ORs were 1.401 (0.982-1.997), 1.256 (0.87-1.814), 0.937 (0.607-1.447) and 2.222 (1.196-4.129) for elderly, stroke, diabetic and parkinsonism patients, respectively. CONCLUSION: Prokinetic agent use had no negative association with pneumonia admission among long-term nasogastric tube-dependent patients in Taiwan.


Assuntos
Intubação Gastrointestinal/efeitos adversos , Pneumonia/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Benzamidas/uso terapêutico , Estudos Cross-Over , Bases de Dados Factuais , Domperidona/uso terapêutico , Feminino , Humanos , Modelos Logísticos , Masculino , Metoclopramida/uso terapêutico , Pessoa de Meia-Idade , Morfolinas/uso terapêutico , Razão de Chances , Fatores de Risco , Taiwan
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