Addition of a metoclopramide constant rate infusion to prevent ptyalism, regurgitation and vomiting in brachycephalic dogs undergoing spinal surgery.

OBJECTIVE: To assess whether adding metoclopramide to a protocol of maropitant and pantoprazole would reduce incidence of ptyalism, vomiting and regurgitation in brachycephalic dogs undergoing thoracolumbar spinal surgery. STUDY DESIGN: Randomized blinded controlled trial. ANIMALS: A total of 43 brachycephalic dogs undergoing thoracolumbar spinal surgery. METHODS: In addition to a standardized anaesthetic regimen, dogs were randomized to be administered either a 2 mg kg-1 day-1 metoclopramide constant rate infusion (CRI) or a saline solution at an equivalent infusion rate, started after anaesthetic induction and discontinued 5 hours after tracheal extubation. The presence of vomiting, regurgitation and pytalism, and short form of the Glasgow Composite Pain Scale pain scores were assessed by a blinded observer hourly for 4 hours, starting 1 hour postextubation. RESULTS: Regurgitation occurred in six dogs postoperatively; three dogs were in the placebo group and three in the metoclopramide group. The odds ratio (OR) of regurgitation after surgery did not differ between groups [OR: 0.76, 95% confidence interval (CI): 0.13-4.3, p = 0.76]. The odds of observing ptyalism at 3 and 4 hours was approximately 15 times less than 1 hour postoperatively (both OR: 15.4, 95% CI: 1.8-130.7, p = 0.012) and did not differ based on the addition of metoclopramide (OR: 0.73, 95% CI: 0.07-8.0, p = 0.79). The odds of observing pain did not change over time and did not differ based on the addition of metoclopramide (OR: 0.71, 95% CI: 0.12-4.2, p = 0.71). Vomiting did not occur during the study (0.0%, 95% CI: 0.0-8.2%). No adverse effects were observed during the study period in either group. CONCLUSIONS AND CLINICAL RELEVANCE: The addition of a metoclopramide CRI to maropitant and pantoprazole did not result in a significant reduction in ptyalism or regurgitation in brachycephalic dogs undergoing thoracolumbar spinal surgery.

Influence of selected non-antibiotic pharmaceuticals on antibiotic resistance gene transfer in Escherichia coli.

BACKGROUND: Antibiotic resistance genes (ARGs) transfer rapidly among bacterial species all over the world contributing to the aggravation of antibiotic resistance crisis. Antibiotics at sub-inhibitory concentration induce horizontal gene transfer (HRT) between bacteria, especially through conjugation. The role of common non-antibiotic pharmaceuticals in the market in disseminating antibiotic resistance is not well studied. OBJECTIVES: In this work, we indicated the effect of some commonly used non-antibiotic pharmaceuticals including antiemetic (metoclopramide HCl) and antispasmodics (hyoscine butyl bromide and tiemonium methyl sulfate) on the plasmid-mediated conjugal transfer of antibiotic resistance genes between pathogenic E. coli in the gastric intestinal tract (GIT). METHODS: Broth microdilution assay was used to test the antibacterial activity of the tested non-antibiotic pharmaceuticals. A conjugation mating system was applied in presence of the studied non-antibiotic pharmaceuticals to test their effect on conjugal transfer frequency. Plasmid extraction and PCR were performed to confirm the conjugation process. Transmission electron microscopy (TEM) was used for imaging the effect of non-antibiotic pharmaceuticals on bacterial cells. RESULTS: No antibacterial activity was reported for the used non-antibiotic pharmaceuticals. Plasmid-mediated conjugal transfer between isolates was induced by metoclopramide HCl but suppressed by hyoscine butyl bromide. Tiemonium methylsulfate slightly promoted conjugal transfer. Aggregation between cells and periplasmic bridges was clear in the case of metoclopramide HCl while in presence of hyoscine butyl bromide little affinity was observed. CONCLUSION: This study indicates the contribution of non-antibiotic pharmaceuticals to the dissemination and evolution of antibiotic resistance at the community level. Metoclopramide HCl showed an important role in the spread of antibiotic resistance.

Evaluation of pharmacokinetics of metoclopramide administered via subcutaneous bolus and intravenous constant rate infusion to adult horses.

OBJECTIVE: To determine the pharmacokinetics (PK) of metoclopramide administered via intravenous continuous rate infusion (IV CRI) and subcutaneous (SC) bolus and evaluate for gastrointestinal motility and adverse side effects. STUDY DESIGN: Experimental study; randomized, crossover design. ANIMALS: Six healthy adult horses. METHODS: Each horse received metoclopramide via IV CRI (0.04 mg/kg/h for 24 h) and SC bolus (0.08 mg/kg once), with ≥1 week washout period between. Plasma was analyzed by UPLC-MS/MS. Compartmental modeling was used to determine PK parameters for each treatment; nonparametric superposition was used to simulate multiple SC bolus regimens. Gastrointestinal motility and evidence of adverse effects were monitored. RESULTS: Tmax (h) for SC bolus was 0.583 ± 0.204 versus 17.3 ± 6.41 for IV CRI, while Cmax (ng/mL) was 27.7 ± 6.38 versus 43.6 ± 9.97, respectively. AUC (h × ng/mL) was calculated as 902 ± 189 for 24 h IV CRI versus 244 ± 37.4 simulated for 0.08 mg/kg SC bolus every 8 h. Simulations revealed similar exposure between groups with administration of 0.96 mg/kg/day SC bolus, divided into three, four, or six doses. SC bolus bioavailability was estimated as 110 ± 11.5%. No clear trends in motility alteration were identified. No adverse effects were noted. CONCLUSION: Repeated SC boluses of metoclopramide at 0.08 mg/kg would result in lower total drug exposure and Tmax than IV CRI administration but would be highly bioavailable. CLINICAL SIGNIFICANCE: Higher and/or more frequent SC bolus doses are needed to achieve a similar AUC to IV CRI. No adverse effects were noted; however, evaluation of alternative dosing strategies is warranted.

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.

Formulation of Metoclopramide Hydrochloride-Loaded Lipid Carriers by QbD Approach for Combating Nausea: Safety and Bioavailability Evaluation in New Zealand Rabbit.

The focus of the research was to overcome the limitations of metoclopramide (MTC) when administered intranasally. The aim was to improve its bioavailability, increase patient compliance, and prolong its residence time in the nasal cavity. MTC-loaded liposomes were prepared by applying the film hydration method. A study was conducted to determine how formulation variables affected encapsulation efficiency (EE %), mean particle size (MPS), and zeta potential (ZP). The MTC-liposomes were further loaded into the in situ gel (gellan gum) for longer residence times following intranasal administration. pH, gelling time, and in vitro release tests were conducted on the formulations produced. In vivo performance of the MTC-loaded in situ gels was appraised based on disparate parameters such as plasma peak concentration, plasma peak time, and elimination coefficient compared to intravenous administration. When the optimal liposome formulation contained 1.98% of SPC, 0.081% of cholesterol, 97.84% of chloroform, and 0.1% of MTC, the EE of MTC was 83.21%, PS was 107.3 nm. After 5 h, more than 80% of the drug was released from MTC-loaded liposome incorporated into gellan gum in situ gel formulation (Lip-GG), which exhibited improved absorption and higher bioavailability compared to MTC loaded into gellan gum in situ gel (MTC-GG). Acceptable cell viability was also achieved. It was found out that MTC-loaded liposomal in situ gel formulations administered through the nasal route could be a better choice than other options due to its ease of administration, accurate dosing, and higher bioavailability in comparison with MTC-GG.

The effectiveness of parenteral agents for pain reduction in patients with migraine presenting to emergency settings: A systematic review and network analysis.

OBJECTIVES: To assess the comparative effectiveness and safety of parenteral agents for pain reduction in patients with acute migraine. BACKGROUND: Parenteral agents have been shown to be effective in treating acute migraine pain; however, the comparative effectiveness of different approaches is unclear. METHODS: Nine electronic databases and gray literature sources were searched to identify randomized clinical trials assessing parenteral agents to treat acute migraine pain in emergency settings. Two independent reviewers completed study screening, data extraction, and Cochrane risk-of-bias assessment, with differences being resolved by adjudication. The protocol of the review was registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42018100096). RESULTS: A total of 97 unique studies were included, with most studies reporting a high or unclear risk of bias. Monotherapy, as well as combination therapy, successfully reduced pain scores prior to discharge. They also increased the proportion of patients reporting pain relief and being pain free. Across the pain outcomes assessed, combination therapy was one of the higher ranked approaches and provided robust improvements in pain outcomes, including lowering pain scores (mean difference -3.36, 95% confidence interval [CI] -4.64 to -2.08) and increasing the proportion of patients reporting pain relief (risk ratio [RR] 2.83, 95% CI 1.74-4.61). Neuroleptics and metoclopramide also ranked high in terms of the proportion of patients reporting pain relief (neuroleptics RR 2.76, 95% CI 2.12-3.60; metoclopramide RR 2.58, 95% CI 1.90-3.49) and being pain free before emergency department discharge (neuroleptics RR 4.8, 95% CI 3.61-6.49; metoclopramide RR 4.1, 95% CI 3.02-5.44). Most parenteral agents were associated with increased adverse events, particularly combination therapy and neuroleptics. CONCLUSIONS: Various parenteral agents were found to provide effective pain relief. Considering the consistent improvements across various outcomes, combination therapy, as well as monotherapy of either metoclopramide or neuroleptics are recommended as first-line options for managing acute migraine pain. There are risks of adverse events, especially akathisia, following treatment with these agents. We recommend that a shared decision-making model be considered to effectively identify the best treatment option based on the patient's needs.

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.

Efficacy of acupoint injection of metoclopramide for post-chemotherapy vomiting: A systematic review and meta-analysis.

BACKGROUND: Vomiting is one of the most common adverse events of chemotherapy. The purpose of this study was to systematically review the clinical efficacy of acupoint injection of metoclopramide in the treatment of post-chemotherapy vomiting. METHODS: We searched 4 general English databases and 4 conventional Chinese databases, all with a time frame from database creation to December 2022. The retrieved clinical trials of acupoint injection of metoclopramide for post-chemotherapy vomiting were then subjected to meta-analysis and trial sequential analysis. RESULTS: A total of 12 studies were included, with a total sample size of 965 cases. Meta-analysis showed that acupoint injection of metoclopramide was effective in improving anti-vomiting effective rate [odds ratio = 5.67, 95% confidence interval = (3.80,8.47), P < .00001] compared with intramuscular/intravenous injection, and trial sequential analysis showed that this benefit was conclusive. Subgroup analysis demonstrated that acupoint injection significantly improved the anti-vomiting effective rate at doses of 10 mg qd, 20 mg qd, and 30 mg qd, as well as at durations of 1 day and 5 days. Subgroup analysis also indicated that injection at the Zusanli acupoint significantly increased the anti-vomiting effective rate, while injection at the Neiguan acupoint had an anti-vomiting effective rate comparable to that of the control group. Harbord regression showed no significant publication bias (P = .730). CONCLUSION: Acupoint injection of metoclopramide for post-chemotherapy vomiting is more effective than intramuscular and intravenous injections and is not limited by dose or duration of treatment, which may be the preferred way of administration.

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).

Novel Lactation Induction Protocol for a Transgender Woman Wishing to Breastfeed: A Case Report.

Background: Lactation induction in transgender women is a clinical and research priority in the field of breastfeeding medicine. To date, there are four case reports detailing successful induced lactation in transgender patients who wished to breastfeed. The Academy of Breast Feeding Medicine does not formally recommend a specific medication regimen for transgender patients due to lack of high-quality research. Case Presentation: A 50-year-old transgender woman with a hypercoagulable disorder who was able to lactate and breastfeed with novel hormone regimen management at a gender care clinic. Her baseline hormone treatment was an estradiol 0.3 mg transdermal patch every 72 hours and micronized progesterone 200 mg daily. Results: Within four weeks of initiating a modified hormone regimen (estradiol 0.4 mg patch every 72 hours, progesterone 300 mg daily, metoclopramide 10 mg three times daily), the patient was lactating spontaneously. On multiple occasions, she breastfed and expressed up to 30 mL of milk through pumping. Conclusion: This report offers a new effective hormone regimen for transgender patients who wish to lactate and cannot access domperidone-the galactagogue used in previous case reports. It also provides a review of previously published case reports on this subject. Future research in this field should prioritize cohort studies of transgender patients who desire lactation to further assess patient attitudes, experiences, and outcomes.

The Management of Nausea and Vomiting in Pregnancy and Hyperemesis Gravidarum (Green-top Guideline No. 69).

An objective and validated index of nausea and vomiting such as the Pregnancy-Unique Quantification of Emesis (PUQE) and HyperEmesis Level Prediction (HELP) tools can be used to classify the severity of NVP and HG. [Grade C] Ketonuria is not an indicator of dehydration and should not be used to assess severity. [Grade A] There are safety and efficacy data for first line antiemetics such as anti (H1) histamines, phenothiazines and doxylamine/pyridoxine (Xonvea®) and they should be prescribed initially when required for NVP and HG (Appendix III). [Grade A] There is evidence that ondansetron is safe and effective. Its use as a second line antiemetic should not be discouraged if first line antiemetics are ineffective. Women can be reassured regarding a very small increase in the absolute risk of orofacial clefting with ondansetron use in the first trimester, which should be balanced with the risks of poorly managed HG. [Grade B] Metoclopramide is safe and effective and can be used alone or in combination with other antiemetics. [Grade B] Because of the risk of extrapyramidal effects metoclopramide should be used as second-line therapy. Intravenous doses should be administered by slow bolus injection over at least 3 minutes to help minimise these. [Grade C] Women should be asked about previous adverse reactions to antiemetic therapies. If adverse reactions occur, there should be prompt cessation of the medications. [GPP] Normal saline (0.9% NaCl) with additional potassium chloride in each bag, with administration guided by daily monitoring of electrolytes, is the most appropriate intravenous hydration. [Grade C] Combinations of different drugs should be used in women who do not respond to a single antiemetic. Suggested antiemetics for UK use are given in Appendix III. [GPP] Thiamine supplementation (either oral 100 mg tds or intravenous as part of vitamin B complex (Pabrinex®)) should be given to all women admitted with vomiting, or severely reduced dietary intake, especially before administration of dextrose or parenteral nutrition. [Grade D] All therapeutic measures should have been tried before considering termination of pregnancy. [Grade C].

Performance and Sensitivity of [99mTc]Tc-sestamibi Compared with Positron Emission Tomography Radiotracers to Measure P-glycoprotein Function in the Kidneys and Liver.

P-glycoprotein (P-gp, encoded in humans by the ABCB1 gene and in rodents by the Abcb1a/b genes) is a membrane transporter that can restrict the intestinal absorption and tissue distribution of many drugs and may also contribute to renal and hepatobiliary drug excretion. The aim of this study was to compare the performance and sensitivity of currently available radiolabeled P-gp substrates for positron emission tomography (PET) with the single-photon emission computed tomography (SPECT) radiotracer [99mTc]Tc-sestamibi for measuring the P-gp function in the kidneys and liver. Wild-type, heterozygous (Abcb1a/b(+/-)), and homozygous (Abcb1a/b(-/-)) Abcb1a/b knockout mice were used as models of different P-gp abundance in excretory organs. Animals underwent either dynamic PET scans after intravenous injection of [11C]N-desmethyl-loperamide, (R)-[11C]verapamil, or [11C]metoclopramide or consecutive static SPECT scans after intravenous injection of [99mTc]Tc-sestamibi. P-gp in the kidneys and liver of the mouse models was analyzed with immunofluorescence labeling and Western blotting. In the kidneys, Abcb1a/b() mice had intermediate P-gp abundance compared with wild-type and Abcb1a/b(-/-) mice. Among the four tested radiotracers, renal clearance of radioactivity (CLurine,kidney) was significantly reduced (-83%) in Abcb1a/b(-/-) mice only for [99mTc]Tc-sestamibi. Biliary clearance of radioactivity (CLbile,liver) was significantly reduced in Abcb1a/b(-/-) mice for [11C]N-desmethyl-loperamide (-47%), [11C]metoclopramide (-25%), and [99mTc]Tc-sestamibi (-79%). However, in Abcb1a/b(+/-) mice, CLbile,liver was significantly reduced (-47%) only for [99mTc]Tc-sestamibi. Among the tested radiotracers, [99mTc]Tc-sestamibi performed best in measuring the P-gp function in the kidneys and liver. Owing to its widespread clinical availability, [99mTc]Tc-sestamibi represents a promising probe substrate to assess systemic P-gp-mediated drug-drug interactions and to measure renal and hepatic P-gp function under different (patho-)physiological conditions.

[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.

Is enhanced recovery after surgery essential?

BACKGROUND: The enhanced recovery after surgery (ERAS) method is designed for the patient to recover quickly, have less pain and have a more comfortable period after the surgery; that includes preoperative, intra and postoperative processes. ERAS has been started to be applied in cesarean section surgeries as the patients need to recover quickly. In the literature, there is no study about the results of ERAS in cesarean section about pain scores and complications. OBJECTIVES: It is aimed to compare the results of cesarean section patients using the ERAS method completely in patients who have had cesarean section without meeting some of the postoperative conditions of the ERAS criteria. STUDY DESIGN: It is a prospective study designed as postoperative metoclopramide, enema and routine opioids in group 1, enema and metoclopramide in group 2, metoclopramide only in group 3 and nothing in group 4. Postoperative pain scoring was done by using visual analog scale (VAS). Analysis of variance tests and t tests were used for results. RESULTS: There was no difference between groups according to age, parity, and birth weight. As a result, although there was no difference between the groups in terms of discharge time and complications, the VAS score used in pain scoring was found to be significantly lower in group 3 compared to the other groups (p: 0.000). Only metoclopramide group (group 3) had lowest VAS score. CONCLUSION: It has been revealed that the ERAS procedure does not need to be so detailed in the postoperative period, and the addition of metoclopramide may be sufficient. Since pain can be a subjective factor, other randomized studies are needed in terms of other criteria.

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.

Hipo persistente: una rara complicación de una inyección epidural transforaminal de corticoides / Persistent hiccup: a rare complication of a transforaminal epidural corticoid injection / Soluços persistentes: uma complicação rara da injeção peridural transforaminal de corticosteroide

Se describe el caso de un paciente que instaló un hipo persistente luego de recibir una inyección epidural transforaminal lumbar de corticoides. Se destaca que es una complicación raramente reportada y por ende poco conocida por quienes practican intervencionismo en dolor. Se discuten los posibles mecanismos por los que puede presentarse, se reseña la evolución observada, y se describe el tratamiento instituido. Se señala el impacto que el hipo puede tener sobre la calidad de vida.

The case of a patient who installed a persistent hiccup after receiving a lumbar transforaminal epidural injection of corticosteroids is described. It is highlighted that it is a rarely reported complication and little known by those who practice interventional pain medicine. Possible mechanisms by which it may occur are discussed, the evolution observed and the treatment instituted are reviewed. The impact that hiccups can have on quality of life is pointed out.

Descrevemos o caso de um paciente que desenvolveu soluços persistentes após receber uma injeção peridural transforaminal lombar de corticosteróides. Ressalta-se que é uma complicação pouco relatada e, portanto, pouco conhecida por quem pratica o intervencionismo na dor. Discutem-se os possíveis mecanismos pelos quais pode ocorrer, revisa-se a evolução observada e descreve-se o tratamento instituído. O impacto que os soluços podem ter na qualidade de vida é apontado.

Development and optimization of metoclopramide containing polymeric patches: impact of permeation enhancers

Abstract The study is aimed to develop a monolithic controlled matrix transdermal patches containing Metoclopramide as a model drug by solvent casting method. Eudragit L100, Polyvinylpyrrolidone K-30, and Methylcellulose were used in different ratios and Polyethylene glycol 400 added as a plasticizer. Resulting patches were evaluated for their physicochemical characters like organoleptic characters, weight variation, folding endurance, thickness, swelling index, flatness, drug content, swelling index, percentage erosion, moisture content, water vapor transmission rate and moisture uptake. Formed patches were also evaluated through Fourier transform spectroscopy (FT-IR), X-ray diffraction (XRD), Differential Scanning calorimetry (DSC) and Scanning Electron Microscopy (SEM). Results of SEM unveiled smooth surface of drug-loaded patches. In-vitro dissolution studies were conducted by using dissolution medium phosphate buffer saline pH 7.4. Effect of natural permeation enhancers was elucidated on two optimized formulations (Z4 and Z9). Different concentrations (5%-10 %) of permeation enhancers i.e. Olive oil, Castor oil and Eucalyptus oil were evaluated on Franz diffusion cell using excised abdominal rat skin. Z4-O2 (Olive oil 10%) had enhanced sustain effect and flux value (310.72) close to the desired flux value. Z4-O2 followed Higuchi release model (R2= 0.9833) with non-fickian diffusion release mechanism (n=0.612)

An attempt to enhance solubility of metoclopramide base by Solid dispersion strategy and its application on development of Transdermal device

Chemotherapy induced nausea and vomiting (CINV) is an issue, which usually occurs in cancer patient. Despite high bioavailability of oral and intravenous administration, these have some drawbacks. The oral route causes hepatic first pass metabolism and intravenous route is invasive in nature. Hence, antiemetic drug by means of transdermal route is necessary to administer in such cases. The aim of the present investigation is to develop suitable Transdermal Therapeutic System (TTS) with an objective to enhance solubility and skin permeability properties of metoclopramide base. Preformulation study begins with an approach to enhance solubility of 40 metoclopramide base by solid dispersion technique. transdermal films were prepared with 41 the solid dispersion as well as with pure drug. Phase solubility study at various temperatures reveals binding constants (Ka, 95-350 M-1 for PVP K30; 56-81 M-1 for HPßCD). Spontaneity of solubilization was justified by AL type linear profiles. The films showed satisfactory diffusion (%), permeation rate and flux after 8 h study. The transdermal patches as prepared were analyzed under FTIR, DSC and SEM. Both solubility and permeability rate in this investigation have been enhanced. So, it can be affirmed that this route would effectively enhance bioavailability

Effect of acupuncture on the prevention of nausea and vomiting after laparoscopic cholecystectomy: a randomized clinical trial / Efeitos da acupuntura para a prevenção de náuseas e vômitos após colecistectomia laparoscópica: estudo clínico randomizado

Abstract Background and objectives: Postoperative nausea and vomiting (PONV) is a common and undesirable complication observed after laparoscopic cholecystectomy (LC). We investigated the effects of auriculoacupuncture (AA) on the prevention of postoperative nausea and vomiting in the immediate postoperative period of uncomplicated laparoscopic cholecystectomy. Methods: Sixty-eight patients were randomly divided into two groups, auriculoacupuncture (n = 35) and control (n = 33), and then they were evaluated prospectively. The needle was placed before anaesthesia induction and remained for 20 minutes. Nausea intensity was evaluated using an analogic visual scale and PONV events were registered immediately after anaesthesia care unit admission and in the second, fourth and sixth hours after the surgery. Results: The auriculoacupuncture group had a significantly smaller incidence of nausea and vomiting than the control group throughout the whole postoperative period (16/35 vs. 27/33, p= 0.03 and 4/35 vs. 15/33, p= 0.005, respectively); the AA group had fewer nausea events 2 h (p= 0.03) and 6 h (p= 0.001) after surgery and fewer vomiting events 2 h (p= 0.01) and 6 h (p= 0.02) after surgery. Conclusions: Auriculoacupuncture can partially prevent postoperative nausea and vomiting when compared to metoclopramide alone after uncomplicated laparoscopic cholecystectomy. Auriculoacupuncture can be recommended as an adjuvant therapy for postoperative nausea and vomiting prevention in selected patients.

Resumo Justificativa e objetivos: Náuseas e vômitos são complicações comuns e indesejáveis no pós-operatório de colecistectomia laparoscópica (CL). Nós investigamos os efeitos da auriculoacupuntura (AA) para a prevenção de náuseas e vômitos no período pós-operatório (NVPO) imediato da CL não complicada. Métodos: 68 pacientes foram aleatoriamente divididos em dois grupos, auriculoacupuntura (n = 35) e controle (n = 33), e foram avaliados prospectivamente. A agulha foi aplicada antes da indução anestésica e permaneceu no lugar por 20 minutos. A intensidade da náusea foi avaliada mediante escala visual analógica e episódios de NVPO foram registrados imediatamente após a admissão na unidade de recuperação anestésica e duas, quatro e seis horas após a cirurgia. Resultados: O grupo AA apresentou significativamente menos episódios de NVPO do que o grupo controle durante todo o período pós-operatório (16/35 vs. 27/33, p = 0,03 e 4/35 vs. 15/33, p = 0,005, respectivamente). O grupo auriculoacupuntura apresentou episódios de náuseas menos intensos às 2 horas (p = 0,03) e 6 horas (p = 0,001) após a cirurgia e menos episódios de vômitos 2 horas (p = 0,01) e 6 horas (p = 0,02) após a cirurgia. Conclusão: A auriculoacupuntura aliviou náuseas e vômitos no pós-operatório em número significante de pacientes, mas não foi capaz de prevenir náuseas e vômitos no pós-operatório em todos os pacientes. Ela pode ser recomendada como terapia adjuvante para prevenção de náuseas e vômitos no pós-operatório no pós-operatório de colecistectomia laparoscópica em pacientes selecionados.