Gastroparesis treatment options metoclopramide and prucalopride: analysis of the FDA Adverse Event Reporting System (FAERS) database.

BACKGROUND: We aimed to examine the common adverse drug reactions (ADRs) of metoclopramide, FDA-approved for treating many gastrointestinal conditions including gastroparesis, and prucalopride, FDA-approved for treating chronic idiopathic constipation but used off-label for other gastrointestinal conditions including gastroparesis. RESEARCH DESIGN AND METHODS: The FDA Adverse Event Reporting System (FAERS) was analyzed from January 2013 to December 2023. ADR reports regarding use of only metoclopramide or prucalopride were analyzed following exclusion of reports indicating use for treatment of non-gastrointestinal conditions. RESULTS: Analysis of 1,085 reports on metoclopramide revealed tardive dyskinesia (n = 393, 36.2%) and dystonia (n = 170, 15.7%) among the most reported ADRs in addition to QTc prolongation (n = 16, 1.5%) with progression to Torsade de pointes (n = 5, 0.5%) and triggering of pheochromocytoma crisis (n = 24, 2.2%). Analysis of 865 reports on prucalopride revealed headache (n = 120, 13.9%), diarrhea (n = 116, 13.4%), and abdominal pain (n = 100, 11.6%) as the most common ADRs with 22 reports (2.5%) of dystonia with the use of prucalopride. CONCLUSIONS: This FAERS database analysis shows post-marketing reports of ADRs from metoclopramide most frequently include tardive dyskinesia, dystonia, and tremor in addition to potentially fatal arrhythmias such as Torsade de pointes. Consumers of prucalopride may also be at risk of dystonia and other ADRs.

Pharmacokinetics, pharmacodynamics, safety, and tolerability of dopamine-receptor antagonists for the prevention of chemotherapy-induced nausea and vomiting.

INTRODUCTION: Dopamine (D)2,3-receptor antagonists (RAs) were the first antiemetics used in the prophylaxis of chemotherapy-induced nausea and vomiting (CINV). AREAS COVERED: Eight D2,3-RAs, amisulpride, domperidone, droperidol, haloperidol, metoclopramide, metopimazine, olanzapine and prochlorperazine are reviewed focusing on pharmacokinetics, pharmacodynamics, antiemetic effect and side effects. EXPERT OPINION: Since the introduction of D2,3-RAs, antiemetics such as corticosteroids, 5-hydroxytryptamine (5-HT)3-RAs and neurokinin (NK)1-RAs have been developed. The classical D2,3-RAs are recommended in the prophylaxis of CINV from low emetic risk chemotherapy, but not as a fixed component of an antiemetic regimen for moderately or highly (HEC) emetic risk chemotherapy. D2,3-RAs are also used in patients with breakthrough nausea and vomiting. It should be emphasized, that most of these drugs are not selective for dopamine receptors.The multi-receptor targeting agent, olanzapine, is recommended in the prophylaxis of HEC-induced CINV as part of a four-drug antiemetic regimen, including a 5-HT3-RA, dexamethasone and a NK1-RA. Olanzapine is the most effective agent to prevent chemotherapy-induced nausea.Side effects differ among various D2,3-RAs. Metopimazine and domperidone possess a low risk of extrapyramidal side effects. Domperidone and metoclopramide are prokinetics, whereas metopimazine delays gastric emptying and haloperidol does not influence gastric motility. Many D2,3-RAs increase the risk of prolonged QTc interval; other side effects include sedation and orthostatic hypotension.

Current and emerging pharmacotherapy for the treatment of gastroparesis.

INTRODUCTION: Gastroparesis is a chronic disorder characterized by decreased gastric emptying and presents with nausea, vomiting, and abdominal pain which impacts patients' quality of life greatly. The treatment modalities available for gastroparesis have been expanding over the past 2 decades. Currently, there are multiple options available for gastroparesis, albeit with only one FDA-approved medication until June 2021. AREAS COVERED: We review the different treatments available for gastroparesis and discuss the recently FDA-approved intranasal formulation of metoclopramide. This nasal spray guarantees metoclopramide absorption within 15 min of application bypassing first pass metabolism in the liver and overcoming the limitations of the oral formulation not passing into the small intestine for absorption because of a gastroparetic stomach or a patient unable to take the oral metoclopramide because of nausea and vomiting. EXPERT OPINION: We now find ourselves in an oasis after spending many years in a 'desert' regarding pharmacologic therapies available for gastroparesis. The expansion of the research involving dopamine receptor antagonists and delving into alternative mechanisms of alleviating gastroparesis symptoms has been crucial in the landscape of gastroparesis. This is especially true as our knowledge of gastroparesis has proven that simply improving gastric emptying does not necessarily translate to clinical improvement.

Safety of prolonged use of metoclopramide and domperidone as treatment for chronic gastrointestinal dysmotility disorders in patients with systemic sclerosis.

Background: Metoclopramide and domperidone are prokinetic agents commonly used to treat gastrointestinal dysmotility disorders. This study aimed to evaluate the safety and associated side effects of prolonged-use metoclopramide and domperidone as treatment for chronic gastrointestinal dysmotility disorders in patients with systemic sclerosis (SSc). Methods: A quantitative observational survey was conducted by interview questionnaire in rheumatology outpatients at a tertiary teaching hospital in Riyadh, Saudi Arabia. The study included all patients aged 25-80 years diagnosed with SSc. All patients were on metoclopramide or domperidone for the treatment of chronic gastrointestinal dysmotility symptoms over at least 12 weeks. Results: Eighteen eligible patients were included. Most study participants were diagnosed with SSc complicated by interstitial lung disease (n = 13; 72.2 %). The most frequently reported side effect that occurred while taking prokinetic drugs was shortness of breath (n = 12; 66.7 %). None of the participants reported experiencing depression, galactorrhea, or syncope. CNS side effects were reported in 5.6 %. There were no differences in side effects based on the type and dosage of prokinetic drug used. Conclusions: Use of metoclopramide and domperidone for the treatment of chronic gastrointestinal dysmotility in SSc patients for 12 weeks or longer was not associated with any troublesome side effects. Further studies with more participants are needed to confirm our findings.

A green approach for metoclopramide quantification in pharmaceutical products: new HPLC and spectrophotometric methods.

Green spectrophotometric and HPLC methods have been developed for the quantification of metoclopramide. In the spectrophotometric method, it was determined by direct absorbance measurement at 273 nm wavelength using ultrapure water as solvent. The Extend C18 column was used for the HPLC method. The mobile phase system consisted of a combination of ethanol and formic acid solution (pH 2.0; 30:70 v/v). Isocratic elution was applied and the flow rate was set at 1.0 mL min-1. Metoclopramide was detected at 273 nm. The methods performed were economical, rapid, environmentally friendly, and simple, providing metoclopramide analysis within 5 min. The methods have been successfully applied in pharmaceutical products without matrix interference. The results of the application of the developed methods to pharmaceutical products were statistically compared and no significant difference was observed between the methods. In addition, the greenness assessment of the developed methods was performed using AGREE software. Our developed methods, based on the use of solvents such as ethanol and water, are proposed as a more environmentally and analyst-friendly option for the quantification of metoclopramide in pharmaceutical products than other methods currently in use.

The Use of Pre-Endoscopic Metoclopramide Does Not Prevent the Need for Repeat Endoscopy: A U.S. Based Retrospective Cohort Study.

BACKGROUND: Peptic ulcer disease (PUD) can cause upper gastrointestinal bleeding (UGIB), often needing esophagogastroduodenoscopy (EGD). Second-look endoscopies verify resolution, but cost concerns prompt research on metoclopramide's efficacy compared to erythromycin. METHODS: We analyzed the Diamond Network of TriNetX Research database, dividing UGIB patients with PUD undergoing EGD into three groups: metoclopramide, erythromycin, and no medication. Using 1:1 propensity score matching, we compared repeat EGD, post-EGD transfusion, and mortality within one month in two study arms. RESULTS: Out of 97,040 patients, 11.5% received metoclopramide, 3.9% received erythromycin, and 84.6% received no medication. Comparing metoclopramide to no medication showed no significant difference in repeat EGD (10.1% vs. 9.7%, p = 0.34), transfusion (0.78% vs. 0.86%, p = 0.5), or mortality (1.08% vs. 1.08%, p = 0.95). However, metoclopramide had a higher repeat EGD rate compared to erythromycin (9.4% vs. 7.5%, p = 0.003), with no significant difference in transfusion or mortality. CONCLUSIONS: The need to repeat EGD was not decreased with pre-EGD use of metoclopramide. If a prokinetic agent is to be used prior to EGD, erythromycin shows superior reduction in the need of repeat EGD as compared to metoclopramide.

Intravenous metoclopramide for increasing endoscopic mucosal visualization in patients with acute upper gastrointestinal bleeding: a multicenter, randomized, double-blind, controlled trial.

Acute upper gastrointestinal hemorrhage (UGIH) is the most common emergency condition that requires rapid endoscopic treatment. This study aimed to evaluate the effects of pre-endoscopic intravenous metoclopramide on endoscopic mucosal visualization (EMV) in patients with acute UGIH. This was a multicenter, randomized, double-blind controlled trial of participants diagnosed with acute UGIH. All participants underwent esophagogastroduodenoscopy within 24 h. Participants were assigned to either the metoclopramide or placebo group. Modified Avgerinos scores were evaluated during endoscopy. In total, 284 out of 300 patients completed the per-protocol procedure. The mean age was 62.8 ± 14.3 years, and 67.6% were men. Metoclopramide group achieved a higher total EMV and gastric body EMV score than the other group (7.34 ± 1.1 vs 6.94 ± 1.6; P = 0.017 and 1.80 ± 0.4 vs 1.64 ± 0.6; P = 0.006, respectively). Success in identifying lesions was not different between the groups (96.5% in metoclopramide and 93.6% in placebo group; P = 0.26). In the metoclopramide group, those with active variceal bleeding compared with the control group demonstrated substantial improvements in gastric EMV (1.83 ± 0.4 vs 1.28 ± 0.8, P = 0.004), antral EMV (1.96 ± 0.2 vs 1.56 ± 0.6, P = 0.003), and total EMV score (7.48 ± 1.1 vs 6.2 ± 2.3, P = 0.02). Pre-endoscopic intravenous metoclopramide improved the quality of EMV in variceal etiologies of UGIH, which was especially prominent in those who had signs of active bleeding based on nasogastric tube assessment.Trial Registration: Trial was registered in Clinical Trials: TCTR 20210708004 (08/07/2021).

An Unusual Case of an Acute Episode of Restless Leg Syndrome Following Oral Metoclopramide Therapy.

Restless leg syndrome (RLS) is a chronic disorder characterized by a compulsive urge to move the legs, accompanied by various subjective symptoms and a distinctive nyctimeral pattern. A negligent entity is drug-induced RLS, which may be challenging to recognize by practitioners due to its rarity. Among various drugs that can induce or exacerbate RLS, metoclopramide is notable; however, the literature primarily describes cases related to its intravenous forms. In this case presentation, a 33-year-old male experienced drug-related gastrointestinal (GI) symptoms after starting semaglutide for weight loss. Semaglutide was discontinued, and oral metoclopramide was administered to manage the GI symptoms. Subsequently, he developed RLS-like symptoms, which resolved within 48 hours of stopping metoclopramide. His family history included chronic RLS. Laboratory tests were normal. The case highlights a potential link between drug administration and transient RLS symptoms. This case suggests that RLS can be a rare, reversible side effect of oral metoclopramide. It emphasizes the need for careful monitoring of RLS symptoms in patients using this drug and highlights the variability of side effects depending on the method of drug administration. The case serves as a reminder of the unpredictable nature of drug reactions and the importance of vigilance in pharmacotherapy.

Review of Dopamine Antagonists for Nausea and Vomiting in Palliative Care Patients.

Symptoms of nausea and vomiting are common in palliative care and hospice patients. One of the many classes of medications used for the treatment of nausea and vomiting is dopamine receptor antagonists which are particularly helpful for treating nausea mediated by the chemoreceptor trigger zone (CTZ) and impaired gastrointestinal function. While dopamine antagonists can be very effective treatments for nausea they should be used with caution as they carry the risk of QTc prolongation, have a FDA black box warning for tardive dyskinesia (TD), and increased risk of precipitating psychosis and death in patients with dementia. This review will cover haloperidol, olanzapine, prochlorperazine, and metoclopramide for treatment of nausea and vomiting including evidence of efficacy, pharmacokinetics, and pharmacodynamics to improve safe and effective utilization in clinical practice. This includes medication receptor site affinities at histaminic, muscarinic, serotonergic, and alpha-adrenergic receptors which can help providers anticipate potential adverse effects and risk of extrapyramidal symptoms (EPS), TD, and QTc prolongation. This review also includes considerations for dose adjustments based on renal function, hepatic function, and age. Understanding the pharmacology of dopamine antagonists can help providers choose the best treatment for control of nausea and vomiting and subsequently improve patients' quality of life.

Palliative Management of Inoperable Malignant Bowel Obstruction: Prospective, Open Label, Phase 2 Study at an NCI Comprehensive Cancer Center.

CONTEXT: Malignant bowel obstruction (MBO) is a common complication of intra-abdominal cancer, frequently seen in advanced gastrointestinal and gynecologic cancer. Management of MBO can be challenging, particularly if the patient is not a surgical candidate. No consensus exists on how best to manage these patients medically. Retrospective studies suggest that the combination of dexamethasone, octreotide and metoclopramide may lead to relief of obstruction and improvement in symptoms associated with the obstruction. OBJECTIVES: This study seeks to prospectively evaluate the combination of drug "triple therapy" dexamethasone 4 mg BID, metoclopramide 10 mg Q6 and octreotide 300 mcg TID to assess tolerability, safety, and effect on symptoms and deobstruction. METHODS: Adults admitted at Roswell Park Comprehensive Cancer Center with malignant bowel obstruction were eligible. Eligible patients who constented to the study were started on the triple therapy with close monitoring of symptoms and for adverse effects. RESULTS: A total of 15 patients enrolled in the study. Two patients experienced bradycardia as adverse effect and there was no incidence of bowel perforation. All patients who completed the study had complete resolution of their nausea, and improvement in other symptoms including pain, constipation, tolerance of oral intake and resumption of bowel movements. Only two of the 15 patients were alive to complete the six-month post study follow up. CONCLUSION: "Triple therapy" with dexamethasone, metoclopramide, and octreotide for management of nonsurgical MBO in this small sample size appears safe and well tolerated however a diagnosis of inoperable MBO remains associated with poor prognosis and death within months.

Comparison of the Effects of Govarcin Herbal Capsule and Metoclopramide for Alleviating Gastrointestinal Symptoms in Patients with Functional Dyspepsia: A Randomized Double-blind Clinical Trial.

BACKGROUND: Functional dyspepsia (FD) is felt as a discomfort or pain on the center line or upper abdomen. In this study, we aimed to compare the effects of Govarcin herbal capsule and Metoclopramide for alleviating gastrointestinal symptoms in patients with FD. METHODS: Totally, 106 patients enrolled in a double-blind, clinical trial study. The participants had FD and were divided into two groups receiving Govarcin and Metoclopramide by block randomization. The patients were treated for four weeks, taking one Govarcin capsule or Metoclopramide tablet after each meal. The rate of improvement in patients was assessed by mitigation of clinical symptoms, including epigastric pain, fullness, discomfort, nausea, vomiting and heartburn. Also, before and after intervention, we used Nepin questionnaire and ROME III. SPSS statistics 25 software was used for data analyzing. RESULTS: Clinical symptom score changes between Govarcin and Metoclopramide patients' groups showed that there was no significant difference in any of the clinical symptom scores (except for heartburn, p-value=0.012) between the study groups. Nepean score in Govarcin group before and after treatment were 19.3±4.8 and 8.9±2.8, respectively (p-value<0.001). For Metoclopramide group, these values were 19.8±3.5 and 9.4±2.1 respectively (p-value<0.001). No significant difference was found in terms of Nepean score between the Govarcin and Metoclopramide groups (p-value=0.995). CONCLUSION: Govarcin herbal capsule can be used to remedy symptoms in patients with FD. It seems that Govarcin is as effective as Metoclopramide in fighting symptoms of FD as no significant difference in efficacy has been demonstrated between them.

[11C]metoclopramide is a sensitive radiotracer to measure moderate decreases in P-glycoprotein function at the blood-brain barrier.

The efflux transporter P-glycoprotein (P-gp) at the blood-brain barrier limits the cerebral uptake of various xenobiotics. To assess the sensitivity of [11C]metoclopramide to measure decreased cerebral P-gp function, we performed [11C]metoclopramide PET scans without (baseline) and with partial P-gp inhibition by tariquidar in wild-type, heterozygous Abcb1a/b(+/-) and homozygous Abcb1a/b(-/-) mice as models with controlled levels of cerebral P-gp expression. Brains were collected to quantify P-gp expression with immunohistochemistry. Brain uptake of [11C]metoclopramide was expressed as the area under the brain time-activity curve (AUCbrain) and compared with data previously obtained with (R)-[11C]verapamil and [11C]N-desmethyl-loperamide. Abcb1a/b(+/-) mice had intermediate P-gp expression compared to wild-type and Abcb1a/b(-/-) mice. In baseline scans, all three radiotracers were able to discriminate Abcb1a/b(-/-) from wild-type mice (2.5- to 4.6-fold increased AUCbrain, p ≤ 0.0001). However, only [11C]metoclopramide could discriminate Abcb1a/b(+/-) from wild-type mice (1.46-fold increased AUCbrain, p ≤ 0.001). After partial P-gp inhibition, differences in [11C]metoclopramide AUCbrain between Abcb1a/b(+/-) and wild-type mice (1.39-fold, p ≤ 0.001) remained comparable to baseline. There was a negative correlation between baseline [11C]metoclopramide AUCbrain and ex-vivo-measured P-gp immunofluorescence (r = -0.9875, p ≤ 0.0001). Our data suggest that [11C]metoclopramide is a sensitive radiotracer to measure moderate, but (patho-)physiologically relevant decreases in cerebral P-gp function without the need to co-administer a P-gp inhibitor.

[Nutrition (therapy) in gastrointestinal failure]. / Gastrointestinales Versagen ­ Ernährung bei Reflux und Darmatonie.

BACKGROUND: The presence of gastrointestinal dysfunction is an outcome-relevant complication in critically ill ICU patients. AIMS, MATERIALS AND METHODS: The following review aims to show the importance of gastrointestinal dysfunction. Multimodal therapy for gastroparesis and paralytic ileus is discussed. CONCLUSION: Erythromycin and metoclopramide are options for gastroparesis, while neostigmine is commonly used for paralytic ileus.

Comparative Analysis of Oral Ondansetron, Metoclopramide, and Domperidone for Managing Vomiting in Children With Acute Gastroenteritis.

Background Acute gastroenteritis (AGE) is a major health concern in pediatric populations because of its associated vomiting, which worsens dehydration and the severity of illness. Objective The purpose of the research was to compare the relative effectiveness of oral ondansetron in treating AGE in children's vomiting when compared to oral domperidone and oral metoclopramide. Methodology A clinical investigation involving 120 pediatric patients diagnosed with AGE was conducted in Pakistan from November 2022 to April 2023 using a single-blind randomized design and convenience sampling. The participants received oral suspensions of ondansetron, metoclopramide, and domperidone, with doses of 0.15 mg/kg, 0.1-0.2 mg/kg, and 0.5 mg/kg, respectively, adjusted according to their body weight. The outcome in different groups was analyzed using the Statistical Package for the Social Sciences (SPSS) (version 20.0; IBM SPSS Statistics for Windows, Armonk, NY). Results At six hours, vomiting cessation rates were 80.0% for ondansetron (n=32), 72.5% for domperidone (n=29), and 67.5% for metoclopramide (n=27; p=0.29). By 24 hours, ondansetron exhibited significantly higher efficacy (92.5%; n=37) compared to domperidone (82.5%; n=33) and metoclopramide (77.5%; n=31; p=0.03). Adverse effects were minimal and comparable across groups. Conclusion Oral ondansetron demonstrated superior efficacy in managing AGE-related vomiting in children within 24 hours compared to metoclopramide and domperidone.

Efficacy of metoclopramide for prevention of gastric regurgitation during endotracheal intubation in the emergency department: A randomized controlled trial.

Background: Gastric content regurgitation and aspiration are the dreaded complications of securing the airway. Cricoid pressure hinders intubation and causes lower esophageal sphincter (LES) relaxation. A recent study suggests no added benefit of cricoid pressure in preventing pulmonary aspiration of gastric contents. Metoclopramide increases LES tone, prevents gastroesophageal reflux, and increases antral contractions. Hence, we wanted to study the efficacy of metoclopramide for preventing gastric regurgitation during endotracheal intubation (ETI) in patients presenting to the emergency department (ED). Methods: This study was a randomized controlled trial in patients requiring ETI in the ED. The study participants were randomized to receive either metoclopramide (intervention) 10 mg/2 ml intravenous (IV) bolus or a placebo of normal saline (placebo) 2 ml IV bolus 5 min before rapid sequence induction and intubation. The outcome of the study was the visualization of gastric regurgitation at the glottic opening during direct laryngoscopy at the time of intubation. Results: Seventy-four study participants were randomized and allocated to the metoclopramide group (n = 37) or placebo group (n = 37). Gastric regurgitation at the glottis was noted in three study participants (8%) in the metoclopramide group, and six (16%) in the placebo group (odds ratio [OR] - 0.456; 95% confidence interval [CI] of 0.105-1.981; P = 0.295). The study participants who were intubated in the first attempt had less gastric regurgitation compared to ≥2 attempts (OR 0.031; 95% CI of 0.002-0.511; P = 0.015). Conclusion: There was no decrease in regurgitation with metoclopramide as compared to placebo during ETI in study participants presenting to the ED.

Intravenous ketorolac versus metoclopramide in adult patients with migraine headaches: An updated systematic review and meta-analysis.

BACKGROUND: Intravenous ketorolac and metoclopramide are common emergency treatments for adult patients with migraine headaches. The comparison between ketorolac and metoclopramide for migraine treatment is an intriguing issue for research and clinical practice. OBJECTIVES: To provide an updated systematic review and meta-analysis of randomized clinical trials (RCTs) to help determine which treatment has better effects for migraine patients. MATERIAL AND METHODS: Intravenous ketorolac and metoclopramide were compared to evaluate whether intravenous ketorolac is associated with significant benefits for pain intensity, short-term headache relief and sustained headache relief among adult patients with migraines. Adverse effects were also analyzed. Five studies with a total of 674 adult patients were included in the analysis, which focused on the outcomes of pain intensity, short-term headache relief, sustained headache relief, and adverse effects. RESULTS: The meta-analysis showed that the only modest but statistically significant difference was present in short-term headache relief when comparing intravenous ketorolac with intravenous metoclopramide. There were no significant differences between intravenous ketorolac and metoclopramide in terms of pain intensity, sustained headache relief or adverse effects. CONCLUSION: The results suggest that there are no significant differences in most treatment effects (aside from short-term headache relief) and adverse effects when comparing intravenous ketorolac with intravenous metoclopramide. However, the paucity of literature on this topic might have limited the interpretation of the current results. Thus, more relevant studies are warranted.

Total Intravenous Anaesthesia for Laparoscopic Cholecystectomy in a Patient With Congenital Long QT Syndrome: A Case Report.

Long QT syndrome (LQTS) is characterised by QT interval prolongation and ventricular arrhythmia, leading to sudden cardiac death. Patients with acquired or congenital LQTS pose special challenges to anaesthetists perioperatively due to the risk of developing life-threatening arrhythmia. A variety of medications, including commonly used volatile anaesthetic agents are known to prolong QT interval and there has been growing evidence of using total intravenous anaesthesia (TIVA) instead of volatile agents for such patients.  This is a case report of a 30-year-old patient with congenital LQTS and subcutaneous implantable cardioverter defibrillator (SICD) in situ who underwent laparoscopic cholecystectomy and endoscopic retrograde cholangiopancreatography (ERCP) under TIVA safely within two months. There were no arrhythmic events observed perioperatively.  This case highlights the importance of comprehensive planning and meticulous preparation to avoid all possible QT-prolonging conditions during the perioperative period, especially in patients with acquired or congenital LQTS.

Sustainable eco-friendly ratio-based spectrophotometric and HPTLC-densitometric methods for simultaneous analysis of co-formulated anti-migraine drugs with overlapped spectra.

Considering the green chemistry perspective and improving the environmental impact of quality control labs; two direct techniques with less hazardous solvents, less waste production and less energy consumption were developed for simultaneous analysis of Aspirin and Metoclopramide in bulk powder and pharmaceutical formulation. The ratio between the two drugs in their co-formulated preparation is very challenging; (90: 1, Aspirin: Metoclopramide). The first technique is spectrophotometry using simple mathematical operations; ratio difference and derivative ratio-zero crossing. The second technique is high-performance thin-layer chromatography (HPTLC) -densitometry which used a mobile phase consisting of cyclo-hexane: methanol: methylene chloride in a ratio of (1:4:1, v/v/v). The greenest solvents which give acceptable resolution were chosen. Following the International Conference on Harmonization (ICH) guidelines, the methods were found to be accurate, precise, and selective. Those methods were statistically compared to the reported spectrophotometric method and the results proved that there is no significant difference in accuracy and precision. Furthermore, the developed methods were assessed using the Analytical Eco-scale, Green Analytical Procedure Index (GAPI) and the Analytical Greenness calculator (AGREE), which gave a full image about their greenness profile. The spectrophotometry was found to be an excellent green technique compared to HPTLC with was considered an acceptable green one. The developed HPTLC-densitometric method was used for the first time for the analysis of this binary mixture. The two proposed spectrophotometric methos have advantages over the published methods as they used easy manipulation steps and are applied on the market pharmaceutical formulation. Owing to the advantages of the developed techniques; being green, do not require expensive sophisticated equipment or large volume of solvents; they could be used for routine analysis in quality control aspects.

The efficacy of prophylactic metoclopramide in preventing nausea and vomiting in patients with acute pain treated with intravenous tramadol: a randomized double-blinded, placebo-controlled trial.

OBJECTIVE: To examine the clinical efficacy of prophylactic metoclopramide in reducing the incidence of nausea and vomiting in emergency department (ED) patients with acute pain who were treated with intravenous tramadol. RESULTS: We conducted a single-center randomized, double-blinded, placebo-controlled trial. A total of 99 ED patients presented with acute pain were recruited. Sixty-four patients were randomized, 31 patients in the treatment arm and 33 in the control arm. Overall, there were no significant differences in baseline characteristics between treatment arm and control arm. Only one patient within each arm reported having nausea symptom. No patients reported vomiting episode. There was no statistically significant difference in the proportion of patients with nausea or vomiting symptoms between the two groups (3.2% in the treatment arm vs. 3.0% in the control arm, p = 1.000). The administration of prophylactic metoclopramide may not provide additional benefit in reducing the occurrence of nausea and/or vomiting episode in ED patients with acute pain treated with intravenous tramadol. Trial registration Randomized clinical trial TCTR20220525001; registration date: 21 October 2021. Retrospectively registered.

Case report: metoclopramide induced acute dystonic reaction in adolescent CYP2D6 poor metabolizers.

Metoclopramide is indicated for the management of gastroesophageal reflux, gastric stasis, nausea, and vomiting. Metoclopramide-induced acute dystonic reactions (MIADRs), along with repetitive involuntary protrusion of the tongue, are well-known phenomena in children and young adults that may appear after the first dose. The drug is primarily metabolized via oxidation by the cytochrome P450 enzyme CYP2D6 and to a lesser extent by CYP3A4 and CYP1A2. A recommendation to decrease metoclopramide dosing in patients with severely limited to no CYP2D6 activity (i.e., poor metabolizers, PMs) is included in the drug label. It is important to note, however, that a requirement or recommendation for pre-emptive testing for CYP2D6 metabolizer status is not included in the drug label. We present two cases of acute dystonia in two non-consanguineous male adolescents: one following metoclopramide and cimetidine administration in a 14-year-old to treat gastroesophageal reflux, and another following metoclopramide and pantoprazole administration in a 17-year-old with acute gastroenteritis. A retrospective pharmacogenetic analysis revealed both patients as CYP2D6 PMs.