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Frontiers in Pharmacology 2021Prokinetic agents amplify and coordinate the gastrointestinal muscular contractions to facilitate the transit of intra-luminal content. Following the institution of... (Review)
Review
Prokinetic agents amplify and coordinate the gastrointestinal muscular contractions to facilitate the transit of intra-luminal content. Following the institution of dietary recommendations, prokinetics are the first medications whose goal is to improve gastric emptying and relieve symptoms of gastroparesis. The recommended use of metoclopramide, the only currently approved medication for gastroparesis in the United States, is for a duration of less than 3 months, due to the risk of reversible or irreversible extrapyramidal tremors. Domperidone, a dopamine D2 receptor antagonist, is available for prescription through the FDA's program for Expanded Access to Investigational Drugs. Macrolides are used off label and are associated with tachyphylaxis and variable duration of efficacy. Aprepitant relieves some symptoms of gastroparesis. There are newer agents in the pipeline targeting diverse gastric (fundic, antral and pyloric) motor functions, including novel serotonergic 5-HT agonists, dopaminergic D antagonists, neurokinin NK antagonists, and ghrelin agonist. Novel targets with potential to improve gastric motor functions include the pylorus, macrophage/inflammatory function, oxidative stress, and neurogenesis. In the current review, we discuss the use of pharmacological approaches with potential to enhance motor functions in the management of gastroparesis.
PubMed: 34504426
DOI: 10.3389/fphar.2021.711500 -
Journal of Pharmacy & Pharmaceutical... 2010Poor production of breast milk is the most frequent cause of breast lactation failure. Often, physician prescribe medications or other substances to solve this problem.... (Review)
Review
Poor production of breast milk is the most frequent cause of breast lactation failure. Often, physician prescribe medications or other substances to solve this problem. The use of galactogogues should be limited to those situations in which reduced milk production from treatable causes has been excluded. One of the most frequent indication for the use of galactogogues is the diminution of milk production in mothers using indirect lactation, particularly in the case of preterm birth. The objective of this review is to analyze to the literature relating to the principal drugs used as galactogogues (metoclopramide, domperidone, chlorpromazine, sulpiride, oxytocin, growth hormone, thyrotrophin releasing hormone, medroxyprogesterone). Have been also analyzed galactogogues based on herbs and other natural substances (fenugreek, galega and milk thistle). We have evaluated their mechanism of action, transfer to maternal milk, effectiveness and potential side effects for mother and infant, suggested doses for galactogogic effect, and recommendation for breastfeeding.
Topics: Animals; Breast Feeding; Female; Galactogogues; Humans; Infant; Infant, Newborn; Infant, Premature; Lactation; Plant Extracts; Premature Birth
PubMed: 20816003
DOI: 10.18433/j3ds3r -
Critical Care (London, England) Aug 2016Intolerance to enteral nutrition is common in critically ill adults, and may result in significant morbidity including ileus, abdominal distension, vomiting and... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Intolerance to enteral nutrition is common in critically ill adults, and may result in significant morbidity including ileus, abdominal distension, vomiting and potential aspiration events. Prokinetic agents are prescribed to improve gastric emptying. However, the efficacy and safety of these agents in critically ill patients is not well-defined. Therefore, we conducted a systematic review and meta-analysis to determine the efficacy and safety of prokinetic agents in critically ill patients.
METHODS
We searched MEDLINE, EMBASE, and Cochrane Library from inception up to January 2016. Eligible studies included randomized controlled trials (RCTs) of critically ill adults assigned to receive a prokinetic agent or placebo, and that reported relevant clinical outcomes. Two independent reviewers screened potentially eligible articles, selected eligible studies, and abstracted pertinent data. We calculated pooled relative risk (RR) for dichotomous outcomes and mean difference for continuous outcomes, with the corresponding 95 % confidence interval (CI). We assessed risk of bias using Cochrane risk of bias tool, and the quality of evidence using grading of recommendations assessment, development, and evaluation (GRADE) methodology.
RESULTS
Thirteen RCTs (enrolling 1341 patients) met our inclusion criteria. Prokinetic agents significantly reduced feeding intolerance (RR 0.73, 95 % CI 0.55, 0.97; P = 0.03; moderate certainty), which translated to 17.3 % (95 % CI 5, 26.8 %) absolute reduction in feeding intolerance. Prokinetics also reduced the risk of developing high gastric residual volumes (RR 0.69; 95 % CI 0.52, 0.91; P = 0.009; moderate quality) and increased the success of post-pyloric feeding tube placement (RR 1.60, 95 % CI 1.17, 2.21; P = 0.004; moderate quality). There was no significant improvement in the risk of vomiting, diarrhea, intensive care unit (ICU) length of stay or mortality. Prokinetic agents also did not significantly increase the rate of diarrhea.
CONCLUSION
There is moderate-quality evidence that prokinetic agents reduce feeding intolerance in critically ill patients compared to placebo or no intervention. However, the impact on other clinical outcomes such as pneumonia, mortality, and ICU length of stay is unclear.
Topics: Chi-Square Distribution; Critical Illness; Diarrhea; Domperidone; Dopamine Antagonists; Enteral Nutrition; Erythromycin; Gastric Emptying; Humans; Intensive Care Units; Length of Stay; Metoclopramide; Residual Volume; Vomiting
PubMed: 27527069
DOI: 10.1186/s13054-016-1441-z -
The Cochrane Database of Systematic... May 2020Many women express concern about their ability to produce enough milk, and insufficient milk is frequently cited as the reason for supplementation and early termination... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many women express concern about their ability to produce enough milk, and insufficient milk is frequently cited as the reason for supplementation and early termination of breastfeeding. When addressing this concern, it is important first to consider the influence of maternal and neonatal health, infant suck, proper latch, and feeding frequency on milk production, and that steps be taken to correct or compensate for any contributing issues. Oral galactagogues are substances that stimulate milk production. They may be pharmacological or non-pharmacological (natural). Natural galactagogues are usually botanical or other food agents. The choice between pharmacological or natural galactagogues is often influenced by familiarity and local customs. Evidence for the possible benefits and harms of galactagogues is important for making an informed decision on their use.
OBJECTIVES
To assess the effect of oral galactagogues for increasing milk production in non-hospitalised breastfeeding mother-term infant pairs.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register, ClinicalTrials.gov, the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP), Health Research and Development Network - Phillippines (HERDIN), Natural Products Alert (Napralert), the personal reference collection of author LM, and reference lists of retrieved studies (4 November 2019).
SELECTION CRITERIA
We included randomised controlled trials (RCTs) and quasi-RCTs (including published abstracts) comparing oral galactagogues with placebo, no treatment, or another oral galactagogue in mothers breastfeeding healthy term infants. We also included cluster-randomised trials but excluded cross-over trials.
DATA COLLECTION AND ANALYSIS
We used standard Cochrane Pregnancy and Childbirth methods for data collection and analysis. Two to four review authors independently selected the studies, assessed the risk of bias, extracted data for analysis and checked accuracy. Where necessary, we contacted the study authors for clarification.
MAIN RESULTS
Forty-one RCTs involving 3005 mothers and 3006 infants from at least 17 countries met the inclusion criteria. Studies were conducted either in hospitals immediately postpartum or in the community. There was considerable variation in mothers, particularly in parity and whether or not they had lactation insufficiency. Infants' ages at commencement of the studies ranged from newborn to 6 months. The overall certainty of evidence was low to very low because of high risk of biases (mainly due to lack of blinding), substantial clinical and statistical heterogeneity, and imprecision of measurements. Pharmacological galactagogues Nine studies compared a pharmacological galactagogue (domperidone, metoclopramide, sulpiride, thyrotropin-releasing hormone) with placebo or no treatment. The primary outcome of proportion of mothers who continued breastfeeding at 3, 4 and 6 months was not reported. Only one study (metoclopramide) reported on the outcome of infant weight, finding little or no difference (mean difference (MD) 23.0 grams, 95% confidence interval (CI) -47.71 to 93.71; 1 study, 20 participants; low-certainty evidence). Three studies (metoclopramide, domperidone, sulpiride) reported on milk volume, finding pharmacological galactagogues may increase milk volume (MD 63.82 mL, 95% CI 25.91 to 101.72; I² = 34%; 3 studies, 151 participants; low-certainty evidence). Subgroup analysis indicates there may be increased milk volume with each drug, but with varying CIs. There was limited reporting of adverse effects, none of which could be meta-analysed. Where reported, they were limited to minor complaints, such as tiredness, nausea, headache and dry mouth (very low-certainty evidence). No adverse effects were reported for infants. Natural galactagogues Twenty-seven studies compared natural oral galactagogues (banana flower, fennel, fenugreek, ginger, ixbut, levant cotton, moringa, palm dates, pork knuckle, shatavari, silymarin, torbangun leaves or other natural mixtures) with placebo or no treatment. One study (Mother's Milk Tea) reported breastfeeding rates at six months with a concluding statement of "no significant difference" (no data and no measure of significance provided, 60 participants, very low-certainty evidence). Three studies (fennel, fenugreek, moringa, mixed botanical tea) reported infant weight but could not be meta-analysed due to substantial clinical and statistical heterogeneity (I = 60%, 275 participants, very low-certainty evidence). Subgroup analysis shows we are very uncertain whether fennel or fenugreek improves infant weight, whereas moringa and mixed botanical tea may increase infant weight compared to placebo. Thirteen studies (Bu Xue Sheng Ru, Chanbao, Cui Ru, banana flower, fenugreek, ginger, moringa, fenugreek, ginger and turmeric mix, ixbut, mixed botanical tea, Sheng Ru He Ji, silymarin, Xian Tong Ru, palm dates; 962 participants) reported on milk volume, but meta-analysis was not possible due to substantial heterogeneity (I = 99%). The subgroup analysis for each intervention suggested either benefit or little or no difference (very low-certainty evidence). There was limited reporting of adverse effects, none of which could be meta-analysed. Where reported, they were limited to minor complaints such as mothers with urine that smelled like maple syrup and urticaria in infants (very low-certainty evidence). Galactagogue versus galactagogue Eight studies (Chanbao; Bue Xue Sheng Ru, domperidone, moringa, fenugreek, palm dates, torbangun, moloco, Mu Er Wu You, Kun Yuan Tong Ru) compared one oral galactagogue with another. We were unable to perform meta-analysis because there was only one small study for each match-up, so we do not know if one galactagogue is better than another for any outcome.
AUTHORS' CONCLUSIONS
Due to extremely limited, very low certainty evidence, we do not know whether galactagogues have any effect on proportion of mothers who continued breastfeeding at 3, 4 and 6 months. There is low-certainty evidence that pharmacological galactagogues may increase milk volume. There is some evidence from subgroup analyses that natural galactagogues may benefit infant weight and milk volume in mothers with healthy, term infants, but due to substantial heterogeneity of the studies, imprecision of measurements and incomplete reporting, we are very uncertain about the magnitude of the effect. We are also uncertain if one galactagogue performs better than another. With limited data on adverse effects, we are uncertain if there are any concerning adverse effects with any particular galactagogue; those reported were minor complaints. High-quality RCTs on the efficacy and safety of galactagogues are urgently needed. A set of core outcomes to standardise infant weight and milk volume measurement is also needed, as well as a strong basis for the dose and dosage form used.
Topics: Administration, Oral; Body Weight; Breast Feeding; Domperidone; Female; Galactogogues; Humans; Infant; Infant, Newborn; Lactation; Metoclopramide; Milk, Human; Mothers; Phytotherapy; Plant Extracts; Randomized Controlled Trials as Topic; Sulpiride; Thyrotropin-Releasing Hormone
PubMed: 32421208
DOI: 10.1002/14651858.CD011505.pub2 -
British Journal of Clinical Pharmacology Oct 2021Concerns exist regarding the cardiovascular safety of domperidone. However, many of the previous studies addressing this issue had important limitations. We aimed to... (Meta-Analysis)
Meta-Analysis Review
AIMS
Concerns exist regarding the cardiovascular safety of domperidone. However, many of the previous studies addressing this issue had important limitations. We aimed to examine domperidone and the risks of sudden cardiac death and ventricular arrhythmia through a systematic review and meta-analysis of observational studies, including an in-depth methodological assessment.
METHODS
We systematically searched MEDLINE, PubMed, EMBASE, Scopus and CINAHL Plus to identify observational studies examining the association of domperidone and sudden cardiac death and/or ventricular arrhythmia. We assessed study quality in duplicate using the ROBINS-I tool supplemented by an assessment of specific biases and the GRADE (Grading of Recommendations, Assessment, Development and Evaluations) approach. Data were pooled across studies using DerSimonian and Laird random-effects models.
RESULTS
Six case-control studies, 1 case-crossover study and 1 retrospective cohort study were included (n = 480 395). Based on ROBINS-I, 3 studies had moderate risk of bias, 4 had serious risk, and 1 had critical risk. The overall GRADE rating is moderate. When data were pooled across nonoverlapping studies, domperidone was associated with an increased risk of composite endpoint of sudden cardiac death or ventricular arrhythmia compared to nonuse (adjusted odds ratio: 1.69; 95% confidence interval: 1.46, 1.95; I : 0%; τ : 0). This association persisted when restricted to higher-quality studies (odds ratio: 1.60; 95% confidence interval: 1.30, 1.97; I : 0%; τ : 0).
CONCLUSION
Domperidone is associated with an increased risk of sudden cardiac death and ventricular arrhythmia compared to nonuse. Further investigation comparing domperidone to an active comparator and in younger populations are warranted.
Topics: Antiemetics; Arrhythmias, Cardiac; Cross-Over Studies; Death, Sudden, Cardiac; Domperidone; Humans; Retrospective Studies
PubMed: 33439512
DOI: 10.1111/bcp.14737 -
RSC Advances Aug 2022Domperidone is a powerful peripheral dopamine receptor antagonist; however, a systematic review of the synthetic methods and processes of this drug has not been reported... (Review)
Review
Domperidone is a powerful peripheral dopamine receptor antagonist; however, a systematic review of the synthetic methods and processes of this drug has not been reported so far. This review summarizes the synthetic strategies, synthetic routes and reaction processes of domperidone in detail. Domperidone can be synthesized from the coupling reaction of two benzimidazolone derivatives (intermediates 1 and 2). Intermediate 1 can be prepared by two synthetic routes: the cyclization of -phenylenediamine with carbonyl reagents followed by coupling with 1,3-dihalopropane, and the coupling reaction of o-halo or o-amino substituted nitrobenzene with 1,3-disubstituted propane followed by reduction and cyclization. The latter route avoids the production of di-substituted by-products and has higher reaction selectivity. Intermediate 2 is synthesized by coupling substituted nitrobenzene with 4-aminopiperidine followed by reduction and cyclization, which is similar to the synthetic route of intermediate 1. Understanding the advantages and drawbacks of these synthetic methodologies would provide insights for the development of new strategies to prepare domperidone. Moreover, the methods used to synthesize domperidone can provide alternative approaches in the preparation of drugs or compounds with similar structure.
PubMed: 36105951
DOI: 10.1039/d2ra03777g -
The British Journal of General Practice... Sep 2017
Topics: Breast Feeding; Domperidone; Female; Galactogogues; Humans; Lactation; Risk Assessment
PubMed: 28860289
DOI: 10.3399/bjgp17X692345 -
Clinics (Sao Paulo, Brazil) Feb 2016
Topics: Animals; Death, Sudden, Cardiac; Domperidone; Dopamine Antagonists; Humans; Mice; Models, Animal; Parkinson Disease
PubMed: 26934232
DOI: 10.6061/clinics/2016(02)01 -
Journal of Clinical Medicine Sep 2022The aims of gastroesophageal reflux disease (GERD) treatment are symptom relief and healing of oesophagitis. Besides proton pump inhibitors (PPIs), prokinetic agents are... (Review)
Review
Efficacy and Safety of Domperidone in Combination with Proton Pump Inhibitors in Gastroesophageal Reflux Disease: A Systematic Review and Meta-Analysis of Randomised Controlled Trials.
The aims of gastroesophageal reflux disease (GERD) treatment are symptom relief and healing of oesophagitis. Besides proton pump inhibitors (PPIs), prokinetic agents are also commonly prescribed to treat GERD. Domperidone, a well-known antiemetic, is an example of a prokinetic agent. It is a dopaminergic blocker that increases lower oesophagus sphincter pressure and activates gastric motility. We carried out a systematic review and meta-analysis to explore the benefits of domperidone in addition to PPI therapy for GERD. We searched for publications comparing PPI plus domperidone to PPI monotherapy in terms of symptom improvement in GERD (until 21 April 2022) on PubMed, Scopus, Google Scholar, Web of Science, Cochrane Library, WHO's International Clinical Studies Registry Platform, and ClinicalTrials.gov without restricting date, language, or study design. The protocol was registered in PROSPERO (CRD42021242076). This meta-analysis incorporated 11 studies with a total of 841 participants (419 in the PPI plus domperidone group and 422 in the PPI monotherapy group). The combination of a PPI and domperidone resulted in a significant reduction in global GERD symptoms. Adverse events associated with PPI plus domperidone treatment were similar to those associated with PPI monotherapy. In conclusion, the combination of domperidone and a PPI is generally safe and effective in treating GERD as compared with that of PPI alone.
PubMed: 36142915
DOI: 10.3390/jcm11185268