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The Science of the Total Environment Feb 2022Pharmaceuticals as ubiquitous organic pollutants in the aquatic environment represent substances whose knowledge of environmental fate is still limited. One such...
Pharmaceuticals as ubiquitous organic pollutants in the aquatic environment represent substances whose knowledge of environmental fate is still limited. One such compound is metoclopramide, whose direct and indirect photolysis and toxicological assessment have been studied for the first time in this study. Experiments were performed under solar radiation, showing metoclopramide as a compound that can easily degrade in different water matrices. The effect of pH-values showed the faster degradation at pH = 7, while the highly alkaline conditions at pH = 11 slowed photolysis. The highest value of quantum yield of metoclopramide photodegradation (ϕ = 43.55·10) was obtained at pH = 7. Various organic and inorganic substances (NO, Fe(III), HA, Cl, Br, HCO, SO), commonly present in natural water, inhibited the degradation by absorbing light. In all experiments, kinetics followed pseudo-first-order reaction with r greater than 0.98. The structures of the photolytic degradation products were tentatively identified, and degradation photoproducts were proposed. The hydroxylation of the aromatic ring and the amino group's dealkylation were two major photoproduct formation mechanisms. Calculated thermochemical quantities are in agreement with the experimentally observed stability of different photoproducts. Reactive sites in metoclopramide were studied with conceptual density functional theory and regions most susceptible to OH attack were characterized. Metoclopramide and its degradation products were neither genotoxic for bacteria Salmonella typhimurium in the SOS/umuC assay nor acutely toxic for bacteria Vibrio fischeri.
Topics: Density Functional Theory; Ferric Compounds; Kinetics; Metoclopramide; Pharmaceutical Preparations; Photolysis; Sunlight; Water Pollutants, Chemical
PubMed: 34600991
DOI: 10.1016/j.scitotenv.2021.150694 -
Critical Care (London, England) Sep 2014Regulatory agencies in North America and Europe recently re-evaluated the safety of metoclopramide. This re-evaluation resulted in recommendations and restrictions in... (Review)
Review
Regulatory agencies in North America and Europe recently re-evaluated the safety of metoclopramide. This re-evaluation resulted in recommendations and restrictions in order to minimise the risk of neurological and other adverse reactions associated with the use of metoclopramide. In the ICU, off-label prescription of metoclopramide is common. We have reviewed the evidence for safety, effectiveness and dosing of metoclopramide in critically ill patients. Furthermore, tachyphylaxis is addressed and alternatives are summarised. Finally, recommendations are presented not to abandon use of metoclopramide in ICU patients, because metoclopramide is considered effective in enhancing gastric emptying and facilitating early enteral nutrition.
Topics: Critical Illness; Dose-Response Relationship, Drug; Drug Prescriptions; Humans; Metoclopramide; Nervous System Diseases; Pharmacokinetics; Tachyphylaxis
PubMed: 25672546
DOI: 10.1186/s13054-014-0502-4 -
Endocrinologia, Diabetes Y Nutricion Apr 2023Primary bilateral macronodular adrenal hyperplasia (PBMAH) accounts for <2% of cases of Cushing's syndrome. The majority of patients present with no obvious steroid... (Review)
Review
Primary bilateral macronodular adrenal hyperplasia (PBMAH) accounts for <2% of cases of Cushing's syndrome. The majority of patients present with no obvious steroid excess it means with autonomous cortisol secretion (ACS). The classic treatment for patients with overt Cushing's syndrome is bilateral adrenalectomy, but unilateral resection of the larger adrenal gland can result in clinical and/or biochemical remission in >90% of cases, especially in cases of ACS. In this article, a series of 32 cases with PBMAH is described. Most of the cases of PBMAH had ACS, except for one case with overt Cushing's syndrome. A study of aberrant receptors was performed in six patients, being negative in three cases, positive in the metoclopramide test in two cases and positive in the metoclopramide test and in the mixed meal test in another patient. The patient with overt Cushing's syndrome was treated with adrenostatic therapy achieving biochemical control, while two patients with ACS underwent unilateral adrenalectomy with resection of the largest adrenal gland, demonstrating hypercortisolism remission and improvement of cardiovascular risk factors after surgery. This article describes a series of 32 cases of PBMAH and offers a comprehensive review of PBMAH.
Topics: Humans; Cushing Syndrome; Hyperplasia; Metoclopramide; Hydrocortisone; Adrenal Glands
PubMed: 37116968
DOI: 10.1016/j.endien.2023.04.005 -
The Cochrane Database of Systematic... Jan 2015Enteral nutrition by feeding tube is a common and efficient method of providing nutritional support to prevent malnutrition in hospitalised patients who have adequate... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Enteral nutrition by feeding tube is a common and efficient method of providing nutritional support to prevent malnutrition in hospitalised patients who have adequate gastrointestinal function but who are unable to eat. Gastric feeding may be associated with higher rates of food aspiration and pneumonia than post-pyloric naso-enteral tubes. Thus, enteral feeding tubes are placed directly into the small intestine rather than the stomach, and the use of metoclopramide, a prokinetic agent, has been recommended to achieve post-pyloric placement, but its efficacy is controversial. Moreover, metoclopramide may include adverse reactions, which with high doses or prolonged use may be serious and irreversible.
OBJECTIVES
To determine the effect of intravenous metoclopramide on post-pyloric placement of the naso-enteral tube in adults.
SEARCH METHODS
Trials were identified by searching the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 10) which includes the CUGPD group's specialised register of trials, MEDLINE (1996 to 21 October 2014), EMBASE (1988 to 21 October 2014), LILACS (2005 to 21 October 2014) We did not confine our search to English language publications. Searches in all databases were updated originally in January 2005, then in November 2008 and again in October 2014. No new studies were found in 2008 or in 2014.
SELECTION CRITERIA
We selected randomised controlled trials of adults needing enteral nutrition, who received intravenous or intramuscular metoclopramide to aid placement of transpyloric naso-enteral feeding tubes, compared to placebo or no intervention.
DATA COLLECTION AND ANALYSIS
We used standard methodological procedures expected by The Cochrane Collaboration. All analyses were performed according to the intention-to-treat method. We present risk ratios (RR) with 95% confidence intervals (CI).
MAIN RESULTS
Four studies, with a total of 204 participants were included and analysed. The trials compared metoclopramide with placebo (two trials) or with no intervention (two trials). Metoclopramide was investigated at doses of 10 mg (two trials) and 20 mg (two trials). There was no statistically significant difference between metoclopramide versus placebo or no intervention administered to promote tube placement (RR 0.82, 95% CI 0.61 to 1.10). Metoclopramide at doses of 10 mg (RR 0.82, 95% CI 0.60 to 1.11) and 20 mg (RR 0.62, 95% CI 0.15 to 2.62) were equally ineffective in facilitating post-pyloric intubation when compared with placebo or no intervention.
AUTHORS' CONCLUSIONS
In this review, we found only four studies that fitted our inclusion criteria. These were small, underpowered studies, in which metoclopramide was given at doses of 10 mg and 20 mg. Our analysis showed that metoclopramide did not assist post-pyloric placement of naso-enteral feeding tubes.Ideally randomised clinical trials should be performed that have a significant sample size, administering metoclopramide against control, however, given the lack of efficacy revealed by this review it is unlikely that further studies will be performed.
Topics: Antiemetics; Duodenum; Enteral Nutrition; Gastric Emptying; Humans; Injections, Intravenous; Intubation, Gastrointestinal; Jejunum; Metoclopramide; Pylorus; Randomized Controlled Trials as Topic
PubMed: 25564770
DOI: 10.1002/14651858.CD003353.pub2 -
Intensive Care Medicine Jul 2019
Topics: Critical Illness; Double-Blind Method; Enteral Nutrition; Humans; Macrocyclic Compounds; Metoclopramide
PubMed: 31127326
DOI: 10.1007/s00134-019-05635-9 -
Molecular Psychiatry Sep 2023Antipsychotic-induced sialorrhea carries a significant burden, but evidence-based treatment guidance is incomplete, warranting network meta-analysis (NMA) of... (Meta-Analysis)
Meta-Analysis
Antipsychotic-induced sialorrhea carries a significant burden, but evidence-based treatment guidance is incomplete, warranting network meta-analysis (NMA) of pharmacological interventions for antipsychotic-related sialorrhea. PubMed Central/PsycInfo/Cochrane Central database/Clinicaltrials.gov/WHO-ICTRP and the Chinese Electronic Journal Database (Qikan.cqvip.com) were searched for published/unpublished RCTs of antipsychotic-induced sialorrhea (any definition) in adults, up to 06/12/2023. We assessed global/local inconsistencies, publication bias, risk of bias (RoB2), and confidence in the evidence, conducting subgroup/sensitivity analyses. Co-primary efficacy outcomes were changes in saliva production (standardized mean difference/SMD) and study-defined response (risk ratios/RRs). The acceptability outcome was all-cause discontinuation (RR). Primary nodes were molecules; the mechanism of action (MoA) was secondary. Thirty-four RCTs entered a systematic review, 33 NMA (n = 1958). All interventions were for clozapine-induced sialorrhea in subjects with mental disorders. Regarding individual agents and response, metoclopramide (RR = 3.11, 95% C.I. = 1.39-6.98), cyproheptadine, (RR = 2.76, 95% C.I. = 2.00-3.82), sulpiride (RR = 2.49, 95% C.I. = 1.65-3.77), propantheline (RR = 2.39, 95% C.I. = 1.97-2.90), diphenhydramine (RR = 2.32, 95% C.I. = 1.88-2.86), benzhexol (RR = 2.32, 95% C.I. = 1.59-3.38), doxepin (RR = 2.30, 95% C.I. = 1.85-2.88), amisulpride (RR = 2.23, 95% C.I. = 1.30-3.81), chlorpheniramine (RR = 2.20, 95% C.I. = 1.67-2.89), amitriptyline (RR = 2.09, 95% C.I. = 1.34-3.26), atropine, (RR = 2.03, 95% C.I. = 1.22-3.38), and astemizole, (RR = 1.70, 95% C.I. = 1.28-2.26) outperformed placebo, but not glycopyrrolate or ipratropium. Across secondary nodes (k = 28, n = 1821), antimuscarinics (RR = 2.26, 95% C.I. = 1.91-2.68), benzamides (RR = 2.23, 95% C.I. = 1.75-3.10), TCAs (RR = 2.23, 95% C.I. = 1.83-2.72), and antihistamines (RR = 2.18, 95% C.I. = 1.83-2.59) outperformed placebo. In head-to-head comparisons, astemizole and ipratropium were outperformed by several interventions. All secondary nodes, except benzamides, outperformed the placebo on the continuous efficacy outcome. For nocturnal sialorrhea, neither benzamides nor atropine outperformed the placebo. Active interventions did not differ significantly from placebo regarding constipation or sleepiness/drowsiness. Low-confidence findings prompt caution in the interpretation of the results. Considering primary nodes' co-primary efficacy outcomes and head-to-head comparisons, efficacy for sialorrhea is most consistent for the following agents, decreasing from metoclopramide through cyproheptadine, sulpiride, propantheline, diphenhydramine, benzhexol, doxepin, amisulpride, chlorpheniramine, to amitriptyline, and atropine (the latter not for nocturnal sialorrhea). Shared decision-making with the patient should guide treatment decisions regarding clozapine-related sialorrhea.
Topics: Adult; Humans; Antipsychotic Agents; Clozapine; Sulpiride; Amisulpride; Sialorrhea; Doxepin; Amitriptyline; Network Meta-Analysis; Propantheline; Trihexyphenidyl; Metoclopramide; Chlorpheniramine; Astemizole; Randomized Controlled Trials as Topic; Cyproheptadine; Diphenhydramine; Ipratropium; Atropine Derivatives
PubMed: 37821573
DOI: 10.1038/s41380-023-02266-x -
The Cochrane Database of Systematic... May 2016Hyperemesis gravidarum is a severe form of nausea and vomiting in pregnancy affecting 0.3% to 1.0% of pregnancies, and is one of the most common indications for... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hyperemesis gravidarum is a severe form of nausea and vomiting in pregnancy affecting 0.3% to 1.0% of pregnancies, and is one of the most common indications for hospitalization during pregnancy. While a previous Cochrane review examined interventions for nausea and vomiting in pregnancy, there has not yet been a review examining the interventions for the more severe condition of hyperemesis gravidarum.
OBJECTIVES
To assess the effectiveness and safety, of all interventions for hyperemesis gravidarum in pregnancy up to 20 weeks' gestation.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register and the Cochrane Complementary Medicine Field's Trials Register (20 December 2015) and reference lists of retrieved studies.
SELECTION CRITERIA
Randomized controlled trials of any intervention for hyperemesis gravidarum. Quasi-randomized trials and trials using a cross-over design were not eligible for inclusion.We excluded trials on nausea and vomiting of pregnancy that were not specifically studying the more severe condition of hyperemesis gravidarum.
DATA COLLECTION AND ANALYSIS
Two review authors independently reviewed the eligibility of trials, extracted data and evaluated the risk of bias. Data were checked for accuracy.
MAIN RESULTS
Twenty-five trials (involving 2052 women) met the inclusion criteria but the majority of 18 different comparisons described in the review include data from single studies with small numbers of participants. The comparisons covered a range of interventions including acupressure/acupuncture, outpatient care, intravenous fluids, and various pharmaceutical interventions. The methodological quality of included studies was mixed. For selected important comparisons and outcomes, we graded the quality of the evidence and created 'Summary of findings' tables. For most outcomes the evidence was graded as low or very low quality mainly due to the imprecision of effect estimates. Comparisons included in the 'Summary of findings' tables are described below, the remaining comparisons are described in detail in the main text.No primary outcome data were available when acupuncture was compared with placebo, There was no clear evidence of differences between groups for anxiodepressive symptoms (risk ratio (RR) 1.01, 95% confidence interval (CI) 0.73 to 1.40; one study, 36 women, very low-quality evidence), spontaneous abortion (RR 0.48, 95% CI 0.05 to 5.03; one study, 57 women, low-quality evidence), preterm birth (RR 0.12, 95% CI 0.01 to 2.26; one study, 36 women, low-quality evidence), or perinatal death (RR 0.57, 95% CI 0.04 to 8.30; one study, 36 women, low-quality evidence).There was insufficient evidence to identify clear differences between acupuncture and metoclopramide in a study with 81 participants regarding reduction/cessation in nausea or vomiting (RR 1.40, 95% CI 0.79 to 2.49 and RR 1.51, 95% CI 0.92 to 2.48, respectively; very low-quality evidence).In a study with 92 participants, women taking vitamin B6 had a slightly longer hospital stay compared with placebo (mean difference (MD) 0.80 days, 95% CI 0.08 to 1.52, moderate-quality evidence). There was insufficient evidence to demonstrate a difference in other outcomes including mean number of episodes of emesis (MD 0.50, 95% CI -0.40 to 1.40, low-quality evidence) or side effects.A comparison between metoclopramide and ondansetron identified no clear difference in the severity of nausea or vomiting (MD 1.70, 95% CI -0.15 to 3.55, and MD -0.10, 95% CI -1.63 to 1.43; one study, 83 women, respectively, very low-quality evidence). However, more women taking metoclopramide complained of drowsiness and dry mouth (RR 2.40, 95% CI 1.23 to 4.69, and RR 2.38, 95% CI 1.10 to 5.11, respectively; moderate-quality evidence). There were no clear differences between groups for other side effects.In a single study with 146 participants comparing metoclopramide with promethazine, more women taking promethazine reported drowsiness, dizziness, and dystonia (RR 0.70, 95% CI 0.56 to 0.87, RR 0.48, 95% CI 0.34 to 0.69, and RR 0.31, 95% CI 0.11 to 0.90, respectively, moderate-quality evidence). There were no clear differences between groups for other important outcomes including quality of life and other side effects.In a single trial with 30 women, those receiving ondansetron had no difference in duration of hospital admission compared to those receiving promethazine (MD 0.00, 95% CI -1.39 to 1.39, very low-quality evidence), although there was increased sedation with promethazine (RR 0.06, 95% CI 0.00 to 0.94, low-quality evidence) .Regarding corticosteroids, in a study with 110 participants there was no difference in days of hospital admission compared to placebo (MD -0.30, 95% CI -0.70 to 0.10; very low-quality evidence), but there was a decreased readmission rate (RR 0.69, 95% CI 0.50 to 0.94; four studies, 269 women). For other important outcomes including pregnancy complications, spontaneous abortion, stillbirth and congenital abnormalities, there was insufficient evidence to identify differences between groups (very low-quality evidence for all outcomes). In other single studies there were no clear differences between groups for preterm birth or side effects (very low-quality evidence).For hydrocortisone compared with metoclopramide, no data were available for primary outcomes and there was no difference in the readmission rate (RR 0.08, 95% CI 0.00 to 1.28;one study, 40 women).In a study with 80 women, compared to promethazine, those receiving prednisolone had increased nausea at 48 hours (RR 2.00, 95% CI 1.08 to 3.72; low-quality evidence), but not at 17 days (RR 0.81, 95% CI 0.58 to 1.15, very low-quality evidence). There was no clear difference in the number of episodes of emesis or subjective improvement in nausea/vomiting. There was insufficient evidence to identify differences between groups for stillbirth and neonatal death and preterm birth.
AUTHORS' CONCLUSIONS
On the basis of this review, there is little high-quality and consistent evidence supporting any one intervention, which should be taken into account when making management decisions. There was also very limited reporting on the economic impact of hyperemesis gravidarum and the impact that interventions may have.The limitations in interpreting the results of the included studies highlights the importance of consistency in the definition of hyperemesis gravidarum, the use of validated outcome measures, and the need for larger placebo-controlled trials.
Topics: Acupuncture Therapy; Adrenal Cortex Hormones; Antiemetics; Female; Humans; Hydrocortisone; Hyperemesis Gravidarum; Metoclopramide; Ondansetron; Placebo Effect; Prednisolone; Pregnancy; Promethazine; Pyridoxine
PubMed: 27168518
DOI: 10.1002/14651858.CD010607.pub2 -
Clinical and Translational... Jan 2022Optimizing the accuracy of colon capsule endoscopy (CCE) requires high completion rates. To prevent incomplete CCE, we aimed to identify predictors associated with slow...
INTRODUCTION
Optimizing the accuracy of colon capsule endoscopy (CCE) requires high completion rates. To prevent incomplete CCE, we aimed to identify predictors associated with slow CCE transit times.
METHODS
In this population-based study, participants received CCE with a split-dose polyethylene glycol bowel preparation and booster regimen (0.5 L oral sulfate solution and 10 mg metoclopramide if capsule remained in stomach for > 1 hour). The following predictors were assessed: age, sex, body mass index (BMI), smoking, coffee and fiber intake, diet quality, physical activity, dyspeptic complaints, stool pattern, history of abdominal surgery, medication use, and CCE findings. Multivariable logistic and linear regressions with backward elimination were performed.
RESULTS
We analyzed 451 CCE procedures with a completion rate of 51.9%. The completion rate was higher among older participants (odds ratio [OR] 1.54, 95% confidence interval [CI] 1.04-2.28, P = 0.03) and participants with a changed stool pattern (OR 2.27, 95% CI 1.20-4.30, P = 0.01). Participants with a history of abdominal surgery had a lower completion rate (OR 0.54, 95% CI 0.36-0.80, P = 0.003). Participants with higher BMI had faster stomach, small bowel, and total transit times (β = -0.10, P = 0.01; β = -0.14, P = 0.001; β = -0.12, P = 0.01). A faster small bowel transit was found in participants with a changed stool pattern (β = -0.08, P = 0.049) and the use of metoclopramide (β = -0.14, P = 0.001). Participants with high fiber intake had a slower colonic transit (β = 0.11, P = 0.03).
DISCUSSION
Younger age, unchanged stool pattern, history of abdominal surgery, low BMI, and high fiber intake resulted in slower CCE transit times and lower completion rates. In future practice, these factors can be considered to adjust preparation protocols.
Topics: Capsule Endoscopy; Colon; Colonoscopy; Gastrointestinal Transit; Humans; Metoclopramide
PubMed: 35584543
DOI: 10.14309/ctg.0000000000000498 -
Veterinary Anaesthesia and Analgesia Mar 2018To evaluate whether subcutaneous (SC) metoclopramide (0.2 mg kg) administered 30 minutes prior to (T30) or simultaneously with (T0) intramuscular (IM) morphine... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
To evaluate whether subcutaneous (SC) metoclopramide (0.2 mg kg) administered 30 minutes prior to (T30) or simultaneously with (T0) intramuscular (IM) morphine (0.2 mg kg) and dexmedetomidine (0.003 mg kg) reduces the incidence of nausea and emesis in healthy dogs.
STUDY DESIGN
Prospective, randomized and blinded study.
ANIMALS
A total of 45 dogs scheduled for elective procedures.
METHODS
Dogs were assigned randomly to three groups to be administered SC metoclopramide (0.2 mg kg) 30 minutes before (group M30) or simultaneously (group M0) to IM morphine (0.2 mg kg) and dexmedetomidine (0.003 mg kg). Dogs in the control group (group C) were administered SC saline at T30 and T0. Dogs were observed for 30 minutes after premedication to evaluate signs of nausea (continuous lip-licking and sialorrhoea) and emesis. Signs of pain or discomfort caused by SC injections were also recorded.
RESULTS
There were no statistical differences amongst groups for age, body weight and sex. More dogs developed continuous lip-licking in group C (12/15, 80.0%) compared to dogs in group M30 (1/15, 6.7%) and dogs in group M0 (5/15, 33.3%; p = 0.0001 and p = 0.01, respectively). More dogs developed sialorrhoea in group M0 (8/15, 53.3%) and in group C (10/15, 66.7%) compared to dogs in group M30 (2/15, 13.3%; p = 0.03 and p = 0.004, respectively). More dogs vomited in group M0 (4/15, 26.7%) and in group C (9/15, 60.0%) compared to dogs in group M30 (0/15, 0.0%; p = 0.05 and p = 0.0003, respectively). None of the dogs demonstrated signs of pain or discomfort during SC metoclopramide injection.
CONCLUSIONS AND CLINICAL RELEVANCE
Subcutaneous metoclopramide at 0.2 mg kg may reduce IM morphine and dexmedetomidine-induced nausea and emesis if administered 30 minutes in advance. It is effective in reducing lip-licking even when administered concurrently with IM morphine-dexmedetomidine.
Topics: Analgesics, Opioid; Animals; Antiemetics; Dexmedetomidine; Dogs; Dopamine Antagonists; Female; Male; Metoclopramide; Morphine; Nausea; Premedication; Single-Blind Method; Vomiting
PubMed: 29409803
DOI: 10.1016/j.vaa.2017.09.042 -
Journal of Clinical Medicine Sep 2019The aim of this study was to investigate the prescribing cascade phenomenon of dopaminergic drugs such as levodopa in the management of gastroprokinetic drugs induced...
The aim of this study was to investigate the prescribing cascade phenomenon of dopaminergic drugs such as levodopa in the management of gastroprokinetic drugs induced parkinsonism. Based on the Korea National Health Insurance Service (NHIS)-Senior Cohort Database, we analyzed patients aged ≥65 years, between 2009 and 2013, who obtained new prescriptions for levodopa through the NHIS during this period. Those who were prescribed levodopa from 2002 to 2008 were excluded, only patients who were prescribed metoclopramide and levosulpiride within 90 days of receiving the levodopa prescription were included. Those who did not receive levodopa were used as a control group for 1:3 age and sex matching. We assessed 1824 and 1197 levodopa cases for metoclopramide and levosulpiride use, respectively. The matched controls for each levodopa case were 5472 and 3591, respectively. We used conditional logistic regression to determine the odds ratio (OR) for initiation of levodopa therapy in patients using metoclopramide and levosulpiride, relative to nonusers, after adjusting for age, sex, and exposure to antipsychotic medication. Both metoclopramide (OR = 3.04; 95% confidence interval, CI, 2.46-3.77) and levosulpiride (OR = 3.32; 95% CI, 2.56-4.3) users were three times more likely to begin using medication containing levodopa, compared to nonusers. Metoclopramide and levosulpiride were frequently prescribed within 90 days of receiving a prescription for levodopa. Before prescribing levodopa, it should be considered whether the adverse event is actually a side effect caused by metoclopramide and levosulpiride.
PubMed: 31546900
DOI: 10.3390/jcm8091496