-
Neurogastroenterology and Motility Mar 2020Despite increasing knowledge regarding gastroparesis (GP) in adults, little is known regarding the incidence, prevalence, and natural history of childhood GP.... (Review)
Review
BACKGROUND
Despite increasing knowledge regarding gastroparesis (GP) in adults, little is known regarding the incidence, prevalence, and natural history of childhood GP. Exacerbating the knowledge gap in pediatric GP is both the lack of normative data for gastric emptying scintigraphy in children and lack of GP-specific pediatric reported outcome measures.
PURPOSE
The aim of this article was to review the available literature on pediatric GP and identify similarities and differences with studies in adults. We performed a comprehensive search in MEDLINE and Google Scholar from inception to April 2019 for articles published in English using the following combination of keywords: gastroparesis, pediatric gastroparesis, outcomes, metoclopramide, erythromycin, domperidone, cisapride, and gastric neurostimulator. The limited available pediatric data, often retrospective, suggest marked differences between adult and pediatric GP in several aspects including etiology, concomitant co-morbidities (eg, psychiatric disorders), clinical symptom presentation, diagnostic evaluation, response to therapies, and clinical outcome. Further research in pediatric GP is needed and holds the promise to further elucidate the mechanisms of this disorder in children and lead to pediatric-focused therapies.
Topics: Child; Female; Gastroparesis; Humans; Male
PubMed: 31407456
DOI: 10.1111/nmo.13699 -
Journal of Animal Science Aug 2021The goal of this project was to determine the effects of domperidone given throughout lactation on hormonal and metabolic status, lactational performance, and gene...
The goal of this project was to determine the effects of domperidone given throughout lactation on hormonal and metabolic status, lactational performance, and gene expression in mammary epithelial cells of sows. Second parity sows were divided in two treatment groups: 1) daily intramuscular injections with canola oil (Control, CTL, n = 24), or 2) daily intramuscular injections with 0.5 mg/kg body weight (BW) of domperidone (DOMP, n = 23). Injections were given at 08h05 starting the day after farrowing until weaning. Over the first 4 d of treatment, DOMP sows also received 0.5 mg/kg BW of domperidone per os twice daily, whereas CTL sows were fed the vehicle. Litter size was standardized to 11 ± 1 within 24 h of birth and piglets were weighed at birth, 24 h postpartum, and on days 7, 22 (weaning on day 23), 35, and 56. Sow feed intake was recorded daily. Representative milk samples were obtained aseptically on day 21 of lactation from 15 sows per treatment for compositional analyses and milk fat globules were used to measure mRNA abundances of various genes. Jugular blood samples were obtained from all sows on days 2, 8, 16, and 23 of lactation to measure concentrations of prolactin, insulin-like growth factor-1 (IGF-1), leptin, adiponectin, insulin, glucose, urea, and free fatty acids (FFA). Concentrations of prolactin (P < 0.001) and FFA (P < 0.01) were increased in DOMP compared with CTL sows, whereas concentrations of insulin were decreased (P < 0.05). Urea concentrations were increased by treatment (P < 0.05) on days 16 and 23 of lactation, and those of IGF-1 were increased (P < 0.01) on day 16. Piglets from DOMP sows were heavier than those from CTL sows on day 22 (P < 0.01). Milk composition was unaffected by treatment. The mRNA abundance in milk fat globules for casein beta and whey acidic protein were lower (P ≤ 0.05) in DOMP than CTL sows. The long form of the prolactin receptor and the signal transducer and activator of transcription 5A mRNA abundances tended to be lower (P < 0.10) in DOMP than CTL sows. In conclusion, hyperprolactinemia induced by domperidone during lactation affected the endocrine and metabolite status of sows and stimulated growth of their suckling piglets.
Topics: Animals; Diet; Domperidone; Female; Lactation; Milk; Pregnancy; Swine; Weaning
PubMed: 34175933
DOI: 10.1093/jas/skab200 -
Australian Prescriber Feb 2018
Review
PubMed: 29507453
DOI: 10.18773/austprescr.2018.002 -
Maedica Jun 2015Galactorrhoea has varied causes including physiological as in pregnancy, lactation, stress, or it can be pathological or drug induced. Its evaluation comprises of a...
Galactorrhoea has varied causes including physiological as in pregnancy, lactation, stress, or it can be pathological or drug induced. Its evaluation comprises of a thorough history, physical examination, laboratory tests and imaging studies. We report herewith two interesting cases of galactorrhoea. The first case was a rare adverse effect of a commonly used drug (domperidone and rabeprazole) and the second case was of mild hypothyroidism leading to galactorrhoea. Prolactin levels were normal in both the cases, emphasizing that not every case of galactorrhoea is associated with high serum levels of prolactin. Secondly, galactorrhoea may be present in patients who are clinically euthyroid, in such cases dynamic tests of thyroid function can identify the cause of galactorrhoea.
PubMed: 28275406
DOI: No ID Found -
CMAJ Open 2021Trends in off-label postpartum use of domperidone and the impact of safety advisories on its use remain unknown. Our objectives were to describe postpartum use of... (Observational Study)
Observational Study
BACKGROUND
Trends in off-label postpartum use of domperidone and the impact of safety advisories on its use remain unknown. Our objectives were to describe postpartum use of domperidone in Canada, to evaluate the impact of Health Canada advisories on prescribing patterns, and to describe the association between domperidone use and a composite end point of sudden cardiac death or ventricular tachycardia (VT) among postpartum patients.
METHODS
We conducted a multidatabase cohort study involving pregnant patients with live births between 2004 and 2017 using administrative health databases from 5 Canadian provinces (British Columbia, Alberta, Saskatchewan, Manitoba and Ontario). We excluded patients with less than 1 year of prepregnancy database history and with approved indications for domperidone. We assessed domperidone use in the 6 months postpartum and the impact of the 2012 and 2015 Health Canada advisories on prescribing via interrupted time series analysis. We estimated crude rates of VT and sudden cardiac death.
RESULTS
We included 1 190 987 live births. Mean maternal age was 28.6 (standard error 0.6) years. Domperidone use increased over time, from 7% in 2003-2005 to 12% in 2009-2011, when it plateaued. The 2012 advisory was followed by a drop in use and a reduction in slope, and the 2015 advisory had a more modest impact. Crude analysis suggests that domperidone may be associated with increased VT or sudden cardiac death (0.74 v. 0.37 per 10 000 person-years; difference per 10 000 person-years: 0.37, 95% confidence interval -0.67 to 1.41).
INTERPRETATION
Postpartum domperidone use increased between 2004 and 2017, with prescribing attenuated after Health Canada advisories and a very low absolute rate of VT or sudden cardiac death. These findings suggest that Health Canada advisories affected prescribing; any potential increase in VT or sudden cardiac death with use of domperidone is small and could not be confirmed in this large study STUDY REGISTRATION: ClinicalTrials.gov, no. NCT04024865.
Topics: Adult; Antiemetics; Canada; Death, Sudden, Cardiac; Domperidone; Drug Utilization; Female; Humans; Interrupted Time Series Analysis; Lactation; Lactation Disorders; Off-Label Use; Postpartum Period; Practice Patterns, Physicians'; Pregnancy; Retrospective Studies; Risk Factors; Tachycardia, Ventricular
PubMed: 33990364
DOI: 10.9778/cmajo.20200084 -
Neurotherapeutics : the Journal of the... Jan 2016Identifying effective therapies for the treatment of progressive forms of multiple sclerosis (MS) is a highly relevant priority and one of the greatest challenges for... (Review)
Review
Identifying effective therapies for the treatment of progressive forms of multiple sclerosis (MS) is a highly relevant priority and one of the greatest challenges for the global MS community. Better understanding of the mechanisms involved in progression of the disease, novel trial designs, drug repurposing strategies, and new models of collaboration may assist in identifying effective therapies. In this review, we discuss various therapies under study in phase II or III trials, including antioxidants (idebenone); tyrosine kinase inhibitors (masitinib); sphingosine receptor modulators (siponimod); monoclonal antibodies (anti-leucine-rich repeat and immunoglobulin-like domain containing neurite outgrowth inhibitor receptor-interacting protein-1, natalizumab, ocrelizumab, intrathecal rituximab); hematopoetic stem cell therapy; statins and other possible neuroprotective agents (amiloride, riluzole, fluoxetine, oxcarbazepine); lithium; phosphodiesterase inhibitors (ibudilast); hormone-based therapies (adrenocorticotrophic hormone and erythropoietin); T-cell receptor peptide vaccine (NeuroVax); autologous T-cell immunotherapy (Tcelna); MIS416 (a microparticulate immune response modifier); dopamine antagonists (domperidone); and nutritional supplements, including lipoic acid, biotin, and sunphenon epigallocatechin-3-gallate (green tea extract). Given ongoing and planned clinical trial initiatives, and the largest ever focus of the global research community on progressive MS, future prospects for developing targeted therapeutics aimed at reducing disability in progressive forms of MS appear promising.
Topics: Clinical Trials as Topic; Forecasting; Humans; Immunologic Factors; Multiple Sclerosis, Chronic Progressive; Treatment Outcome
PubMed: 26729332
DOI: 10.1007/s13311-015-0409-z -
Journal of Controlled Release :... Jul 2023The nose-to-brain (N2B) pathway has garnered attention because it transports drugs directly into the brain. Although recent studies have suggested the necessity of...
The nose-to-brain (N2B) pathway has garnered attention because it transports drugs directly into the brain. Although recent studies have suggested the necessity of selective drug administration to the olfactory region for effective N2B drug delivery, the importance of delivering the formulation to the olfactory region and the detailed pathway involved in drug uptake in primates brain remain unclear. Here, we developed a combination system for N2B drug delivery comprising a proprietary mucoadhesive powder formulation and a dedicated nasal device (N2B-system) and evaluated it for nasal drug delivery to the brain in cynomolgus monkeys. This N2B-system demonstrated a much greater formulation distribution ratio in the olfactory region in an in vitro experiment using a 3D-printed nasal cast and in vivo experiment using cynomolgus monkeys, as compared to that in other nasal drug delivery systems that comprise of a proprietary nasal powder device developed for nasal absorption and vaccination and a commercially available liquid spray. Additionally, Texas Red-labeled dextran (TR-DEX, 3 kDa) was administered using the N2B-system to estimate the drug transition pathway from the nasal cavity to the brain. TR-DEX preferentially localized to the olfactory epithelium and reached the olfactory bulb through the cribriform foramina. Moreover, domperidone, a model drug with poor blood-brain barrier permeability, was administered to assess the brain uptake of medicine after olfactory region-selective administration by using the N2B-system. Domperidone accumulation in the brain was evaluated using positron emission tomography with intravenously administered [F]fallypride based on competitive inhibition of the dopamine D2 receptor (D2R). Compared to other systems, the N2B-system significantly increased D2R occupancy and domperidone uptake in the D2R-expressing brain regions. The current study reveals that the olfactory region of the nasal cavity is a suitable target for efficient nasal drug delivery to the brain in cynomolgus monkeys. Thus, the N2B-system, which targets the olfactory region, provides an efficient approach for developing effective technology for nasal drug delivery to the brain in humans.
Topics: Humans; Animals; Administration, Intranasal; Powders; Domperidone; Macaca fascicularis; Brain; Drug Delivery Systems; Pharmaceutical Preparations
PubMed: 37315691
DOI: 10.1016/j.jconrel.2023.06.005 -
Biomolecules & Therapeutics Nov 2023The lack of molecular targets hampers the treatment of triple-negative breast cancer (TNBC). In this study, we determined the cytotoxicity of domperidone, a dopamine D2...
The lack of molecular targets hampers the treatment of triple-negative breast cancer (TNBC). In this study, we determined the cytotoxicity of domperidone, a dopamine D2 receptor (DRD2) antagonist in human TNBC BT-549 and CAL-51 cells. Domperidone inhibited cell growth in a dose- and time-dependent manner. The annexin V/propidium iodide staining showed that domperidone induced apoptosis. The domperidone-induced apoptosis was accompanied by the generation of mitochondrial superoxide and the down-regulation of cyclins and CDKs. The apoptotic effect of domperidone on TNBC cells was prevented by pre-treatment with Mito-TEMPO, a mitochondria-specific antioxidant. The prevention of apoptosis with Mito-TEMPO even at concentrations as low as 100 nM, implies that the generation of mitochondrial ROS mediated the domperidone-induced apoptosis. Immunoblot analysis showed that domperidone-induced apoptosis occurred through the down-regulation of the phosphorylation of JAK2 and STAT3. Moreover, domperidone downregulated the levels of D2-like dopamine receptors including DRD2, regardless of their mRNA levels. Our results support further development of DRD2 antagonists as potential therapeutic strategy treating TNBC.
PubMed: 37899746
DOI: 10.4062/biomolther.2023.173 -
Cureus Aug 2022Acute gastroenteritis is one of the common diseases of childhood. Dehydration is the most frequent consequence of acute gastroenteritis, and vomiting is the most... (Review)
Review
Acute gastroenteritis is one of the common diseases of childhood. Dehydration is the most frequent consequence of acute gastroenteritis, and vomiting is the most distressing clinical manifestation. Various anti-emetic agents are used in practice to control vomiting. However, not all anti-emetic agents are safe and effective. This meta-analysis aims to compare the effectiveness of ondansetron and domperidone in the cessation of vomiting in children with acute gastroenteritis. The current meta-analysis was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A comprehensive search strategy was developed to identify prospective studies that compared the effectiveness of ondansetron and domperidone in the cessation of vomiting in children with acute gastroenteritis. The primary outcome was the number of children in whom there was a cessation of vomiting. The secondary outcomes included a number of children who required an additional dose of the assigned anti-emetic and the number of children who required intravenous rehydration therapy. Overall, seven randomized trials were included in the current meta-analysis. The pooled sample size of enrolled patients was 1,262, of which 639 patients were randomized to the ondansetron group and 623 were randomized to the domperidone group. In the ondansetron group, a higher number of children experienced cessation of vomiting (risk ratio [RR]: 1.22, 95% CI: 1.08-1.37, p-value=0.002), a lower proportion of children needed an additional dose of the assigned anti-emetic (RR=0.50, 95% CI: 0.33-0.77, p-value=0.002), and a lower number of children received intravenous rehydration (RR: 0.37, 95% CI: 0.16-0.83, p-value=0.02) as compared to domperidone group. Compared to domperidone, ondansetron was found to have better efficiency in aiming cessation of vomiting in children with gastroenteritis.
PubMed: 36072202
DOI: 10.7759/cureus.27636 -
The Cochrane Database of Systematic... Oct 2018Dyspepsia is a common condition associated with gastrointestinal (GI) disease. Prokinetics are the treatment of choice for functional dyspepsia (FD). However, the role... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Dyspepsia is a common condition associated with gastrointestinal (GI) disease. Prokinetics are the treatment of choice for functional dyspepsia (FD). However, the role of prokinetics in FD treatment is still controversial.
OBJECTIVES
We conducted a systematic review and meta-analysis of randomised control trials (RCTs) examining the efficacy of prokinetics in the treatment of FD. The primary outcome was overall absence of or improvement of symptoms and symptom scores at the end of treatment. We also evaluated quality of life (QoL) and adverse events as secondary outcomes.
SEARCH METHODS
We performed a systematic search of MEDLINE, Embase, the Cochrane Library, and CINAHL, from 1946 until September 2017. RevMan 5.3 was used to calculate pooled risk ratios (RR) of symptoms persisting or without improved QoL or adverse events, mean difference (MD) or standardised mean difference (SMD) of post-treatment symptoms scores, changes of symptom scores, and QoL, when appropriate with 95% confidence intervals (CI), using a random-effects model. Quality of evidence was evaluated using GRADE methodology.
SELECTION CRITERIA
We included studies that were parallel group RCTs comparing one prokinetic with either placebo or another prokinetic of the same or different class for the treatment of FD. Studies involved adults who presented with dyspepsia symptoms and who had negative or insignificant findings on endoscopy as well as no other organic and metabolic disorders. Studies only including participants with primarily reflux or heartburn symptoms were excluded.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed study eligibility, study quality and performed data extraction.
MAIN RESULTS
From an initial 1388 citations, we identified 43 studies in 40 papers. Of those, 29 studies with 10,044 participants compared six prokinetics with placebo for the outcome of absence of symptoms or symptom improvement. There was a statistically significant effect of prokinetic treatment in reducing global symptoms of FD (RR of remaining dyspeptic = 0.81, 95% CI 0.74 to 0.89; number needed to treat for an additional beneficial outcome (NNTB) =7, very low-quality evidence) with considerable heterogeneity; I = 91% (P < 0.00001). After removing cisapride from the analysis, the effect of prokinetics in global symptom improvement still persisted, compared to placebo (RR 0.87, 95% CI 0.80 to 0.94), but was still based on very low-quality evidence. The result showed persistence of significant improvement in subgroups of studies at unclear or at low risk of bias (RR 0.86, 95% CI 0.80-0.92), and in subgroups by molecules of cisapride (RR 0.71, 95% CI 0.54 to 0.93; NNTB = 4), acotiamide (RR 0.94, 95% CI 0.91 to 0.98; NNTB = 20) and tegaserod(RR 0.89, 95% CI 0.82 to 0.96; NNTB = 14).Ten studies compared different types of prokinetics with each other and the most commonly used comparator was domperidone, 10 mg three times a day (eight of the 10 studies). There was a significantly better post-treatment symptom score in other prokinetics, compared to domperidone (SMD -0.19, 95% CI -0.35 to -0.03, very low-quality evidence), but no difference in reducing global symptom (RR 0.94, 95% CI 0.83 to 1.07), and mean difference symptom scores (SMD -0.13, 95% CI -0.31 to 0.05). We found five studies that assessed quality of life, but there was no benefit in improving quality of life with prokinetic treatment (SMD 0.11, 95% CI -0.10 to 0.33; participants = 1774). The adverse events in individual prokinetics was not different from placebo (RR 1.09, 95% CI 0.95 to 1.25; participants = 3811; studies = 17). However, when we looked at the adverse effects by each prokinetic, there were overall greater adverse effects in the active treatment group with cisapride (RR 1.31, 95% CI 1.03 to 1.65; P = 0.03). The most common side effects were diarrhoea, abdominal discomfort and nausea. The funnel plot was asymmetric (Egger's test, P = 0.02) implying reporting bias or other small-study effects may be, in part, driving the benefit of prokinetics compared to placebo in this meta-analysis. The GRADE assessment of the quality of the evidence in each outcome are mostly low or very low due to concerns around risk of bias in study design, unexplained heterogeneity and possible publication bias.
AUTHORS' CONCLUSIONS
Due to low, or very low, quality of evidence, we are unable to say whether prokinetics are effective for the treatment of functional dyspepsia . We are uncertain which of the individual prokinetic drugs is the most effective as well as whether prokinetics can improve quality of life. Apart from cisapride, prokinetics are well-tolerated. Good quality RCTs are needed to verify the efficacy of prokinetics.
Topics: Benzamides; Benzyl Compounds; Cisapride; Domperidone; Dyspepsia; Erythromycin; Gastrointestinal Agents; Humans; Indoles; Morpholines; Numbers Needed To Treat; Quality of Life; Randomized Controlled Trials as Topic; Thiazoles
PubMed: 30335201
DOI: 10.1002/14651858.CD009431.pub3