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Nutrients Apr 2019Inadequate breast milk supply is a frequently reported reason for early discontinuation of breastfeeding and represents a critical opportunity for intervening to improve... (Review)
Review
Inadequate breast milk supply is a frequently reported reason for early discontinuation of breastfeeding and represents a critical opportunity for intervening to improve breastfeeding outcomes. For women who continue to experience insufficient milk supply despite the utilisation of non-pharmacological lactation support strategies, pharmacological intervention with medications used to augment lactation, commonly referred to as galactagogues, is common. Galactagogues exert their pharmacological effects through altering the complex hormonal milieu regulating lactation, particularly prolactin and oxytocin. This narrative review provides an appraisal of the existing evidence regarding the efficacy and safety of pharmaceutical treatments for lactation insufficiency to guide their use in clinical practice. The greatest body of evidence surrounds the use of domperidone, with studies demonstrating moderate short-term improvements in breast milk supply. Evidence regarding the efficacy and safety of metoclopramide is less robust, but given that it shares the same mechanism of action as domperidone it may represent a potential treatment alternative where domperidone is unsuitable. Data on remaining interventions such as oxytocin, prolactin and metformin is too limited to support their use in clinical practice. The review provides an overview of key evidence gaps and areas of future research, including the impacts of pharmaceutical galactagogues on breast milk composition and understanding factors contributing to individual treatment response to pharmaceutical galactagogues.
Topics: Domperidone; Dopamine Antagonists; Female; Galactogogues; Humans; Lactation
PubMed: 31035376
DOI: 10.3390/nu11050974 -
British Journal of Clinical Pharmacology Mar 2021The aim of this study was to evaluate the risk of trauma associated with the use of antidopaminergic antiemetics in a real-world setting.
AIMS
The aim of this study was to evaluate the risk of trauma associated with the use of antidopaminergic antiemetics in a real-world setting.
METHODS
A self-controlled case series analysis was performed using the EGB database, the representative sample of the French national healthcare insurance system database. All subjects aged 18 years and over who presented with at least 1 trauma-related hospitalization and 1 supply for domperidone, metoclopramide or metopimazine between 2009 and 2014 were included in the study. Associations were evaluated by incidence rate ratios.
RESULTS
Included exposed cases were 7610 for domperidone cohort, 2189 for metoclopramide and 3911 for metopimazine. Incidence rate ratio for trauma-related hospitalization during the first 7 days of exposure period compared to unexposed period was 1.53 (95% confidence interval 1.29-1.80) for domperidone, 2.00 (1.37-2.91) for metoclopramide and 2.30 (1.71-3.09) for metopimazine.
CONCLUSION
We found an increased risk of hospitalizations for traumatic injuries for the main marketed antidopaminergic antiemetics during the first days of use. The highest risk was observed for metopimazine, which could relate to its pharmacological profile and central effects.
Topics: Adolescent; Adult; Antiemetics; Databases, Factual; Domperidone; Hospitalization; Humans; Metoclopramide
PubMed: 32737898
DOI: 10.1111/bcp.14510 -
Wiener Medizinische Wochenschrift (1946) May 2017The prokinetic cisapride, an important therapeutic option in functional gastrointestinal (GI) disorders, was withdrawn from the market 15 years ago due to rare severe... (Comparative Study)
Comparative Study Review
Modulation of gastrointestinal motility beyond metoclopramide and domperidone : Pharmacological and clinical evidence for phytotherapy in functional gastrointestinal disorders.
The prokinetic cisapride, an important therapeutic option in functional gastrointestinal (GI) disorders, was withdrawn from the market 15 years ago due to rare severe side effects. Likewise in 2014, the use of metoclopramide (MCP) and domperidone in functional GI disorders (FGID) was restricted, consequently leaving a therapeutic gap in clinical practice. A systematic review revealed that the herbal medicinal product (HMP) STW 5 presents a therapeutic option equivalent to MCP and cisapride. STW 5 is the only HMP for which efficacy has been shown in randomized controlled clinical trials (RCTs) in functional dyspepsia and irritable bowel syndrome, based on its multitarget effect on numerous etiological factors. Due to an outstanding favorable safety profile, STW 5 allows an effective and safe use in FGID without a limitation of the duration of the treatment.
Topics: Domperidone; Gastrointestinal Diseases; Gastrointestinal Motility; Humans; Irritable Bowel Syndrome; Metoclopramide; Phytotherapy; Plant Extracts; Randomized Controlled Trials as Topic
PubMed: 28424994
DOI: 10.1007/s10354-017-0557-3 -
Pharmaceuticals (Basel, Switzerland) May 2023Even before behavioral disturbances, neuroleptics, amphetamine, and domperidone application rapidly emerged severe occlusion/occlusion-like syndrome, shared innate...
Innate Vascular Failure by Application of Neuroleptics, Amphetamine, and Domperidone Rapidly Induced Severe Occlusion/Occlusion-like Syndromes in Rats and Stable Gastric Pentadecapeptide BPC 157 as Therapy.
Even before behavioral disturbances, neuroleptics, amphetamine, and domperidone application rapidly emerged severe occlusion/occlusion-like syndrome, shared innate vascular and multiorgan failure in rats, comparable to occlusion/occlusion-like syndrome described with vessel(s) occlusion or similar noxious procedures application. As therapy, i.e., activation of the collateral pathways, "bypassing key" (activated azygos vein pathway, direct blood flow delivery), the stable gastric pentadecapeptide BPC 157 is a novel solution. Recently, BPC 157 therapy particularly counteracted neuroleptic- or L-NAME-induced catalepsy, lithium intoxication, and schizophrenia positive and negative symptoms (amphetamine/methamphetamine/apomorphine/ketamine). In rats with complete calvariectomy, medication (BPC 157 10 µg/kg, 10 ng/kg ip or ig) was given 5 min after distinctive dopamine agents (mg/kg ip) (haloperidol (5), fluphenazine (5), clozapine (10), risperidone (5), olanzapine (10), quetiapine (10), or aripiprazole (10), domperidone (25), amphetamine (10), and combined amphetamine and haloperidol) and assessed at 15 min thereafter. All neuroleptic-, domperidone-, and amphetamine-induced comparable vascular and multiorgan failure severe syndrome was alleviated with BPC 157 therapy as before major vessel(s) occlusion or other similar noxious procedures. Specifically, all severe lesions in the brain (i.e., immediate swelling, hemorrhage), heart (i.e., congestion, arrhythmias), and lung (i.e., congestion, hemorrhage), as well as congestion in the liver, kidney, and gastrointestinal (stomach) tract, were resolved. Intracranial (superior sagittal sinus), portal, and caval hypertension and aortal hypotension were attenuated or eliminated. BPC 157 therapy almost annihilated arterial and venous thrombosis, peripherally and centrally. Thus, rapidly acting Virchow triad circumstances that occur as dopamine central/peripheral antagonists and agonist essential class-points, fully reversed by BPC 157 therapy, might be overwhelming for both neuroleptics and amphetamine.
PubMed: 37375736
DOI: 10.3390/ph16060788 -
Pediatrics and Neonatology Sep 2021Domperidone and erythromycin are commonly used as prokinetic agents for feeding intolerance in preterm neonates; however, no data from a previous study have compared...
BACKGROUND
Domperidone and erythromycin are commonly used as prokinetic agents for feeding intolerance in preterm neonates; however, no data from a previous study have compared their efficacy. This study aimed to compare the efficacy of orally administered domperidone and erythromycin for the treatment of feeding intolerance in preterm infants.
METHODS
This retrospective cohort study included preterm neonates with a birthweight of <1800 g and gestational age <37 weeks. Data were collected from medical records at Queen Sirikit National Institute of Child Health (QSNICH) from 2006 to 2014. The primary outcome was the time to establish full enteral feeding (150 ml/kg/day) after starting oral domperidone or erythromycin for the treatment of feeding intolerance in preterm neonates. The secondary outcome was adverse effects associated with domperidone and erythromycin therapy.
RESULTS
Among the 150 preterm neonates enrolled in this study, 66 received domperidone, and 84 received erythromycin. The baseline characteristics and comorbidities were not significantly different between the two groups; however, the gestational age at birth of neonates in the domperidone group was significantly lower than that of those in the erythromycin group. The time to establish full enteral feeding did not differ between the domperidone (11 days, "IQR," [6, 17]) and erythromycin (10 days, IQR [7, 14]) groups (p = 0.622). No major adverse effects were noted. There were only three preterm infants who had elevated liver enzymes in each group, but the difference between groups was not significant.
CONCLUSION
From this study, the efficacy of oral domperidone was promising equivalent to oral erythromycin and seems to be one of the treatment options for feeding intolerance in preterm neonates. However, large randomized, controlled trials are needed to confirm the efficacy and safety of domperidone in this population.
Topics: Child; Domperidone; Erythromycin; Gastrointestinal Agents; Gastrointestinal Diseases; Gastrointestinal Motility; Humans; Infant; Infant, Newborn; Infant, Premature; Retrospective Studies
PubMed: 34167901
DOI: 10.1016/j.pedneo.2021.05.018 -
Frontiers in Pharmacology 2022Treatment of functional dyspepsia (FD) in children is generally symptomatic and unsatisfactory. Traditional Chinese medicines, such as Shenqu Xiaoshi Oral Liquid...
Treatment of functional dyspepsia (FD) in children is generally symptomatic and unsatisfactory. Traditional Chinese medicines, such as Shenqu Xiaoshi Oral Liquid (SXOL), have been recommended to alleviate dyspeptic symptoms. However, evidence of their safety and efficacy remains limited to date. AIM: To assess whether 2 weeks of therapy with SXOL was non-inferior to domperidone syrup in children with FD. In this randomized, double-blind, double-simulated, non-inferiority, multi-center clinical trial, we recruited children (3-14 years) with FD according to the Rome IV criteria from 17 tertiary medical centers across China. Patients were randomly allocated (1:1) to receive SXOL or domperidone syrup for 2 weeks. We compared the participants' clinical scores from both groups based on the severity and frequency of dyspepsia symptoms according to Rome IV criteria (0, 1, 2, and 4 weeks after randomization). The primary endpoint was the total response rate, which was defined as the proportion of patients with a decrease of 30% or more in the FD symptoms clinical score from baseline, at the end of the 2-weeks treatment. A non-inferiority margin of -10% was set. Secondary endpoints and adverse events were assessed. This trial is registered with www.Chictr.org.cn, number ChiCTR1900022654. Between February 2019 and March 2021, a total of 373 patients were assessed for eligibility, and 356 patients were enrolled and randomized. The clinical response rate at week two was similar for SXOL [118 (83.10%) of 142] and domperidone [128 (81.01%) of 158]; difference 2.09; 95% CI -6.74 to 10.71, thereby establishing non-inferiority. The total FD symptom scores were significantly improved in the two groups at 1-, 2-, and 4-weeks follow-up periods ( < 0.005). The decrease in symptom score compared with the baseline were similar between these two groups. Over the total study period, 10 patients experienced at least one treatment-related adverse event [six (3.37%)] in the SXOL group, four [(2.25%) in the domperidone group], although no serious adverse event was noted. Treatment with SXOL effectively improves dyspeptic symptoms and is well tolerated. In addition, it is not inferior to domperidone syrup and leads to sustained improvement in Chinese children with FD.
PubMed: 35185585
DOI: 10.3389/fphar.2022.831912 -
Parasites & Vectors Oct 2021Immunotherapeutic drugs, such as domperidone, have been shown to be promising treatments against canine leishmaniosis (CanL), but limited data are available. The aim of...
BACKGROUND
Immunotherapeutic drugs, such as domperidone, have been shown to be promising treatments against canine leishmaniosis (CanL), but limited data are available. The aim of this pilot study (therapeutic, prospective and non-controlled) was to evaluate the effect of domperidone on serum antibody titers of Leishmania infantum, globulins, gamma globulins, acute-phase proteins (e.g. C-reactive protein [CRP]), big endothelin-1 (big ET-1), serum creatinine (SC) and proteinuria in dogs with leishmaniosis affected by chronic kidney disease (CKD).
METHODS
Dogs were recruited if "exposed" to or "infected" with L. infantum and affected by CKD (IRIS stage 1 [proteinuric] or IRIS stage 2-3a [SC < 3.5 mg/dl; proteinuric or non-proteinuric]). After inclusion, an oral suspension of domperidone was administered, and the dogs were followed up for 180 days, with checks at 30, 60, 90 and 180 days after initial treatment.
RESULTS
Of the 14 recruited dogs, nine showed a statistically significant reduction in SC (χ = 9.1, df = 3, P = 0.028), but not in the urine protein/creatinine ratio (χ = 6.43, df = 3, P = 0.092). All dogs showed a significant reduction in antibody titers for L. infantum (χ = 9.56, df = 2, P = 0.008), globulins (χ = 11.08, df = 3, P = 0.011) and gamma globulins (χ = 12.38, df = 3, P = 0.006) during the study period. There was also a statistically significant reduction in CRP (χ = 16.7, df = 3, P = 0.001), but not in big ET-1 (χ = 2.04, df = 3, P = 0.563).
CONCLUSIONS
This study provides preliminary results on the ability of domperidone to improve SC and reduce anti-L. infantum antibody titers, globulins, gamma globulins and CRP in dogs with leishmaniosis and CKD.
Topics: Acute-Phase Proteins; Animals; Antibodies, Protozoan; Biomarkers; Creatinine; Dog Diseases; Dogs; Domperidone; Female; Inflammation; Leishmania infantum; Leishmaniasis; Male; Pilot Projects; Prospective Studies; Renal Insufficiency, Chronic
PubMed: 34629081
DOI: 10.1186/s13071-021-05030-8 -
Journal of Orthopaedic Surgery and... Jan 2023Steroid-induced osteonecrosis of the femoral head (SONFH) was a refractory orthopedic hip joint disease in the young and middle-aged people, but the pathogenesis of...
IRF8 and its related molecules as potential diagnostic biomarkers or therapeutic candidates and immune cell infiltration characteristics in steroid-induced osteonecrosis of the femoral head.
PURPOSE
Steroid-induced osteonecrosis of the femoral head (SONFH) was a refractory orthopedic hip joint disease in the young and middle-aged people, but the pathogenesis of SONFH remained unclear. We aimed to identify the potential genes and screen potential therapeutic compounds for SONFH.
METHODS
The microarray was obtained for blood tissue from the GEO database, and then it identifies differentially expressed genes (DEGs). The DEGs were analyzed to obtain the differences in immune cell infiltration. The gene functional enrichment analysis of SONFH was analyzed. The PPI of DEGs was identified through the STRING database, and the cluster modules and hub genes were ascertained using MCODE and CytoHubba, and the ROC curve of hub genes was analyzed, and the tissues distribution of hub genes was understood by the HPA, Bgee and BioGPS databases. The hub genes and target miRNAs and corresponding upstream lncRNAs were predicted by TargetScan, miRDB and ENCORI database. Subsequently, we used CMap, DGIdb and L1000FWD databases to identify several potential therapeutic molecular compounds for SONFH. Finally, the AutoDockTools Vina, PyMOL and Discovery Studio were employed for molecular docking analyses between compounds and hub genes.
RESULTS
The microarray dataset GSE123568 was obtained related to SONFH. There were 372 DEGs including 197 upregulated genes and 175 downregulated genes by adjusted P value < 0.01 and |logFC|> 1. Several significant GSEA enrichment analysis and biological processes and KEGG pathway associated with SONFH were identified, which were significantly related to cytoskeleton organization, nucleobase-containing compound catabolic process, NOD-like receptor signaling pathway, MAPK signaling pathway, FoxO signaling pathway, neutrophil-mediated immunity, neutrophil degranulation and neutrophil activation involved in immune response. Activated T cells CD4 memory, B cells naïve, B cells memory, T cells CD8 and T cells gamma delta might be involved in the occurrence and development of SONFH. Three cluster modules were identified in the PPI network, and eleven hub genes including FPR2, LILRB2, MNDA, CCR1, IRF8, TYROBP, TLR1, HCK, TLR8, TLR2 and CCR2 were identified by Cytohubba, which were differed in bone marrow, adipose tissue and blood, and which had good diagnostic performance in SONFH. We identified IRF8 and 10 target miRNAs that was utilized including Targetsan, miRDB and ENCORI databases and 8 corresponding upstream lncRNAs that was revealed by ENCORI database. IRF8 was detected with consistent expression by qRT-PCR. Based on the CMap, DGIdb and L1000FWD databases, the 11 small molecular compounds that were most strongly therapeutic correlated with SONFH were estradiol, genistein, domperidone, lovastatin, myricetin, fenbufen, rosiglitazone, sirolimus, phenformin, vorinostat and vinblastine. All of 11 small molecules had good binding affinity with the IRF8 in molecular docking.
CONCLUSION
The occurrence of SONFH was associated with a "multi-target" and "multi-pathway" pattern, especially related to immunity, and IRF8 and its noncoding RNA were closely related to the development of SONFH. The CMap, DGIdb and L1000FWD databases could be effectively used in a systematic manner to predict potential drugs for the prevention and treatment of SONFH. However, additional clinical and experimental research is warranted.
Topics: Humans; Biomarkers; Femur Head; Gene Expression Profiling; Interferon Regulatory Factors; MicroRNAs; Molecular Docking Simulation; Osteonecrosis; RNA, Long Noncoding; Steroids
PubMed: 36627660
DOI: 10.1186/s13018-022-03381-1 -
Pharmaceutics Aug 2022Domperidone and metoclopramide are widely prescribed antiemetic drugs with distinct neurological side effects. The impact of P-glycoprotein (P-gp)-mediated efflux at the...
Comparison of the Blood-Brain Barrier Transport and Vulnerability to P-Glycoprotein-Mediated Drug-Drug Interaction of Domperidone versus Metoclopramide Assessed Using In Vitro Assay and PET Imaging.
Domperidone and metoclopramide are widely prescribed antiemetic drugs with distinct neurological side effects. The impact of P-glycoprotein (P-gp)-mediated efflux at the blood−brain barrier (BBB) on brain exposure and BBB permeation was compared in vitro and in vivo using positron emission tomography (PET) imaging in rats with the radiolabeled analogs [11C]domperidone and [11C]metoclopramide. In P-gp-overexpressing cells, the IC50 of tariquidar, a potent P-gp inhibitor, was drastically different using [11C]domperidone (221 nM [198−248 nM]) or [11C]metoclopramide (4 nM [2−8 nM]) as the substrate. Complete P-gp inhibition led to a 1.8-fold higher increase in the cellular uptake of [11C]domperidone compared with [11C]metoclopramide (p < 0.0001). Brain PET imaging revealed that the baseline brain exposure (AUCbrain) of [11C]metoclopramide was 2.4-fold higher compared with [11C]domperidone (p < 0.001), consistent with a 1.8-fold higher BBB penetration (AUCbrain/AUCplasma). The maximal increase in the brain exposure (2.9-fold, p < 0.0001) and BBB penetration (2.9-fold, p < 0.0001) of [11C]metoclopramide was achieved using 8 mg/kg of tariquidar. In comparison, neither 8 nor 15 mg/kg of tariquidar increased the brain exposure of [11C]domperidone (p > 0.05). Domperidone is an avid P-gp substrate that was in vitro compared with metoclopramide. Domperidone benefits from a lower brain exposure and a limited risk for P-gp-mediated drug−drug interaction involving P-gp inhibition at the BBB.
PubMed: 36015284
DOI: 10.3390/pharmaceutics14081658 -
Indian Journal of Pharmacology 2022
Topics: Female; Pregnancy; Humans; Domperidone; Galactorrhea; Amenorrhea
PubMed: 36537410
DOI: 10.4103/ijp.ijp_351_22