Combination Of Metoclopramide Research Articles

Comparison of metoclopramide–dexamethasone combination and metoclopramide alone for prophylaxis of postoperative nausea vomiting in laparoscopic cholecystectomy

BACKGROUND & OBJECTIVE: Post operative nausea and vomiting (PONV) is an important concern in laparoscopic surgeries. Aim of this study is to identify the role of metoclopramide dexamethasone combination for prophylactic management of post laparoscopic cholecystectomy nausea and vomiting in comparison to metoclopramide alone.
 METHODOLOGY: The study group comprised of 150 patients. These were the patients with symptomatic gallstones for whom elective laparoscopic cholecystectomy was planned. Study was conducted from 15-04-2018 to 15-07-2019. Non-probability consecutive sampling technique was used.Two groups were generated by simple random method. Group M was given injection metoclopramide only, whereas patients in Group D+M were injected with both dexamethasone and metoclopramide, intravenously, before induction of anesthesia. Parameters observed for 24 hours during postoperative period included; nausea, episodes of vomiting, requirement for rescue antiemetic drugs and total duration of hospital stay after the surgical procedure.
 RESULTS: In Group D+M (dexamethasone+metoclopramide), out of total 75 patients, 8% developed nausea while 5.33% had both nausea along with emesis. While in group M (metoclopramide), 16% out of the total 75 patients had nausea only but 18.7% patients had complaints of nausea and emesis. Three patients out of 75, that is 4% from group (D+M) had extended duration of in hospital admission (> 24 hours), while in groupM, this percentage was 13.33% (n=10) patients.
 CONCLUSION: A combination of metoclopramide with dexamethasone for prophylaxis against PONV in laparoscopic cholecystectomy patients is preferred to metoclopramide alone.

COMPARATIVE STUDY OF METOCLOPRAMIDE AND ONDANSETRON WITH PANTOPRAZOLE IN ELECTIVE CAESEREAN SECTION UNDER SPINAL ANAESTHESIA FOR ASPIRATION PNEUMONITIS PROPHYLAXIS.

BACKGROUND- Caesarean delivery, one of the most commonly performed surgical procedure. The choice of anaesthesia is spinal blockade for elective caeserean-section,unless general anaesthesia is specically indicated. Aspiration pneumonitis remains an important cause of morbidity and mortality in anaesthesia practise,particularly in obstetric patients,prophylaxis against it is paramount importance in pre-anaesthetic management. AIMS AND OBJECTIVES- The aim of this study was to compare pH and volume of gastric contents after administration of combination of metoclopramide and pantoprazole versus ondansetron and pantoprazole during elective caesarean section under spinal anaesthesia for prophylaxis against aspiration pneumonitis. METHODS: It is a prospective study where 100 parturient women, ASA 1 and 2 scheduled for elective caesarean section. They were divided into 2 groups: ondansetron(4mg) and pantoprazole(40mg),and metoclopramide(10mg), pantoprazole(40mg) administered intravenously 2hours before surgery. Gastric aspirate was taken in various positions before giving spinal anaesthesia and at the end of operation. Patients at risk were according to criteria of gastric volume more than 0.4ml/kg with pH <2.5. RESULTS:Patients at risk were 7(14%) in metoclopramide group and 1(2%) in ondansetron group before giving spinal anaesthesia(p=0.027) and 6(12%) in metoclopramide group and 0(0%) in ondansetron group at end of operation(p=0.012) . Since p-value was less than 0.05 there was signicant difference between two groups. CONCLUSION: As there was signicant difference between ondansetron and metoclopramide , it is recommended to use ondansetron and pantoprazole for prophylaxis against aspiration pneumonitis.

Management of primary headaches during pregnancy, postpartum, and breastfeeding: A systematic review.

Primary headaches (migraine, tension headache, cluster headache, and other trigeminal autonomic cephalgias) are common in pregnancy and postpartum. It is unclear how to best and most safely manage them. We conducted a systematic review (SR) of interventions to prevent or treat primary headaches in women who are pregnant, attempting to become pregnant, postpartum, or breastfeeding. We searched Medline, Embase, Cochrane CENTRAL, CINAHL, ClinicalTrials.gov, Cochrane Database of SRs, and Epistemonikos for primary studies of pregnant women with primary headache and existing SRs of harms in pregnant women regardless of indication. No date or language restrictions were applied. We assessed strength of evidence (SoE) using standard methods. We screened 8549 citations for studies and 2788 citations for SRs. Sixteen studies (mostly high risk of bias) comprising 14,185 patients (total) and 26 SRs met the criteria. For prevention, we found no evidence addressing effectiveness. Antiepileptics, venlafaxine, tricyclic antidepressants, benzodiazepines, β-blockers, prednisolone, and oral magnesium may be associated with fetal/child adverse effects, but calcium channel blockers and antihistamines may not be (1 single-group study and 11 SRs; low-to-moderate SoE). For treatment, combination metoclopramide and diphenhydramine may be more effective than codeine for migraine or tension headache (1 randomized controlled trial; low SoE). Triptans may not be associated with fetal/child adverse effects (8 nonrandomized comparative studies; low SoE). Acetaminophen, prednisolone, indomethacin, ondansetron, antipsychotics, and intravenous magnesium may be associated with fetal/child adverse effects, but low-dose aspirin may not be (indirect evidence; low-to-moderate SoE). We found insufficient evidence regarding non-pharmacologic treatments. For prevention of primary headache, calcium channel blockers and antihistamines may not be associated with fetal/child adverse effects. For treatment, combination metoclopramide and diphenhydramine may be more effective than codeine. Triptans and low-dose aspirin may not be associated with fetal/child adverse effects. Future research should identify effective and safe interventions in pregnancy and postpartum.

Metoclopramide increased cell proliferation in HepG2 cell line and sorafenib attenuated the effect

Aim: Metoclopramide is an antiemetic drug used for treating postoperative or chemotherapy-induced emesis. Sorafenib is a kinase inhibitor drug and is approved for the treatment of advanced primary liver cancer, renal cell carcinoma, thyroid cancer, and acute myeloid leukemia. Hepatocellular cancer is a common cause of cancer-related death and its treatment may require coadministration of an antiemetic medication. The study aims to investigate the effect of metoclopramide on hepatocellular cancer cell proliferation alone or in combination with sorafenib. Material and Methods: Metoclopramide doses of 0.17 µM to 25 µM alone or in combination with sorafenib were administered to human hepatocellular cancer cell line, HepG2. Cell viability and proliferation test was used to determine the possible effects on proliferation. Hematoxylin and Eosin staining was performed to visualize the morphological effects of the treatments. Results: Metoclopramide doses of 0.58 µM, 25µM increased cell proliferation when compared to the control group. Metoclopramide combination groups with 9.9 µM sorafenib were compared with control and sorafenib groups. Each combination group was comparable with the control group. Metoclopramide increased proliferation in certain doses. Safety concerns about its use in hepatocellular cancer should be confirmed in clinical trials Each combination group was comparable with the control group. Conclusion: Metoclopramide increased proliferation in certain doses. Sorafenib inhibited the effect. Safety concerns about its use in hepatocellular cancer should be addressed in clinical trials.

Comparing the Therapeutic Effects of Dexamethasone-Metoclopramide with Ketorolac in Relieving Headache in Patients with Acute Migraine Attacks Presenting to the Emergency Department.

Introduction:Migraine is a frequent chief complaint of patients in the emergency department. A wide range of treatments are used for acute migraine. Objective:This study aimed to compare the therapeutic effects of a combination of metoclopramide + dexamethasone with those of ketorolac for treatment of acute migraine in the emergency department. Method:This quasi-experimental study enrolled patients identified as migraine headache cases admitted to the emergency departments of Shohadaye Tajrish and Sina hospitals, Tehran, Iran. The patients were divided into two groups and treated with either 8 mg Dexamethasone + 10 mg Metoclopramide or 60 mg ketorolac, and then compared regarding the rate of pain control based on visual analogue scale (VAS) on arrival and 1 and 2 hours afterward.Results:Overall, 86 patients were recruited, of whom 50 were male (58.1%). Their mean age was 37.6 ± 10.3 years. Thirty-five (40.7%) were in the ketorolac group and 51 (59.3%) were in the dexamethasone + metoclopramide group. Treatment success was defined as a reduction of at least 3 points in pain severity in comparison to the admission time. One hour after administration of medications, the reported pain intensity was 4.7 ± 2.0 and 6.2 ± 2.3 in ketorolac group and dexamethasone + metoclopramide group, respectively. By the second hour, pain intensity was 3.4 ± 1.2 and 2.9 ± 1.3 in ketorolac group and dexamethasone + metoclopramide group, respectively. The two groups did not show a significant difference in terms of the reported pain at this time (p= 0.04).Conclusion:Based on our findings, the pain reduction time was relatively shorter for ketorolac in acute migraine, but the final response was identical in the two groups.

Effect of L-arginine on the resolution rate of postoperative ileus in patients with urgent abdominal pathology

Background. Postoperative ileus is widespread in the postoperative period and occurs not only after extended operations on the abdominal cavity, retroperitoneal cavity, but also after minor surgical interventions, including laparoscopic operations [1, 2]. The aim of this study is to increase the effectiveness of intensive care after urgent abdominal surgeries by developing a drug correction for bowel motility disorders based on studying of the motor and evacuator function of the gastrointestinal tract, inflammatory markers, hemodynamic parameters and electrolyte blood composition.
 Materials and methods. 51 patients were examined, who underwent urgent surgical interventions with laparotomy access for infringed hernias, acute intestinal obstruction, perforation of duodenal ulcers. Depending on the variant of drug correction of postoperative intestinal motility disorder, patients were divided into 2 groups. The first (control) group (n = 27). In the postoperative period, the pharmacological correction of the motor-evacuator function of the gastrointestinal tract was performed by combining a solution of 0,5% metoclopramide and neostigmine bromide. The second (main) group (n = 24). In the postoperative period, the pharmacological correction of the motor-evacuator function of the gastrointestinal tract was performed by combining 0.5% metoclopramide solution and L-arginine (Tivortin, Yuriya-Farm, Ukraine). Motorevacuation disorders of the gastrointestinal tract (the frequency of development of bloating, nausea, vomiting, delay in the escape of gases, an independent moving of gases, measurement of intra-abdominal pressure), parameters of hemodynamics, the level of systolic, diastolic, mean arterial pressure, cardiac index, stroke volume, total peripheral vascular resistance, heart rate, minute volume of blood circulation and left ventricular power, markers of inflammation (leukocyte count, fibrinogen, IL-lα, TNFα, IL-10, calculation of leukocyte intoxication index, the study of electrolytes of blood serum (Na+, K+, Ca2+, Cl- ) were studied before and after 1st, 3rd and 7th days after the operation.
 Results. The use of L-arginine leads to a decrease in the phenomena of peripheral vasospasm, which, improving the microcirculation of the intestinal wall leads to a faster recovery of the motor-evacuation function of the gastrointestinal tract. With standard prokinetic therapy (combination of metoclopramide with neostigmine bromide), the number of patients with elevated intra-abdominal pressure increases in 92,1%, оn the second day after surgery, the number of patients with elevated intra-abdominal pressure exceeds the norm in 100%. The resumption of intestinal motility 3 days after the operation is accompanied by the normalization of intra-abdominal pressure in 55% of patients. Against the backdrop of the use of L-arginine with metoclopramide on day 1 after the operation, the number of patients with an increase in intra-abdominal pressure does not exceed 50%. 37,5% of them have elevated intra-abdominal pressure, 8,3% have abdominal hypertension of the 1st degree. On the second day of the observation, intraabdominal pressure in 41,7% patients normalized, abdominal hypertension of 1 degree was noted in 16,7%. of them. On the 3rd day after surgery, intra-abdominal pressure corresponded to the norm in 79,2% of patients, abdominal hypertension of 1st degree was registered in 8,3% of patients.
 Сonclusions. The use of a combination of metoclopramide with L-arginine reduces the stress on the myocardium, activates - anti-inflammatory link of the cytokine system, accelerates the normalization of intra-abdominal pressure, increases the rate of self-evacuation, independent defecation, and reduces the patients’ stay in the intensive care, which makes it possible to recommend it as the most optimal remedy for resuming motor activity intestines after urgent operations in abdominal surgery.

Prophylaxis of radiation-induced nausea and vomiting: a systematic review and meta-analysis of randomized controlled trials.

The aim of this article was to systematically review the efficacy and safety of various antiemetics in prophylaxis of radiation-induced nausea and vomiting (RINV). A literature search of Ovid MEDLINE, EMBASE and Cochrane CENTRAL was performed to identify randomized controlled trials (RCTs) that evaluated the efficacy of prophylaxis for RINV in patients receiving radiotherapy to abdomen/pelvis, including total body irradiation (TBI). Primary endpoints were complete control of nausea and complete control of vomiting during acute and delayed phases. Secondary endpoints included use of rescue medication, quality of life (QoL) and incidence of adverse events. Seventeen RCTs were identified. Among patients receiving radiotherapy to abdomen/pelvis, our meta-analysis showed that prophylaxis with a 5-hydroxytryptamine-3 receptor antagonist (5HT3 RA) was significantly more efficacious than placebo and dopamine receptor antagonists in both complete control of vomiting [OR 0.49; 95% confidence interval (CI): 0.33-0.72 and OR 0.17; 95% CI: 0.05-0.58 respectively] and complete control of nausea (OR 0.43; 95% CI: 0.26-0.70 and OR 0.46; 95% CI: 0.24-0.88 respectively). 5HT3 RAs were also more efficacious than rescue therapy and dopamine receptor antagonists plus dexamethasone. The addition of dexamethasone to 5HT3 RA compared to 5HT3 RA alone provides a modest improvement in prophylaxis of RINV. Among patients receiving TBI, 5HT3 RA was more effective than other agents (placebo, combination of metoclopramide, dexamethasone and lorazepam). 5HT3 RAs are more effective than other antiemetics for prophylaxis of RINV in patients receiving radiotherapy to abdomen/pelvis and TBI. Future RCTs should investigate the efficacy of newer agents such as substance P neurokinin 1 receptor antagonists in addition to 5HT3 RAs in prophylaxis of RINV during both acute and delayed phases.

530P_PR Evaluation of quality of supportive care in cancer patients receiving chemotherapy: An experience from a developing country

Background Supportive care is essential in cancer patients to prevent and manage drug related toxicities. This study was conducted to assess the quality of supportive care prescribed to patients on cancer chemotherapy. Methods This was a prospective study conducted for a period of six months at a private cancer center. Medical records of the patients on chemotherapy were reviewed and patients were interviewed during the study period to study the prescribed supportive care. Evaluation of supportive care included reviewing use of anti-emetics, colony stimulating factors (CSF), analgesics, antibiotics and protein supplements. Use of supportive care was reviewed with respect to standard recommendations and clinicians’ consensus of the study hospital. Results A total of 850 patients were enrolled in this study. The majority of patients on highly emetogenic regimen (48%) were prescribed with a combination of metoclopramide and dexamethasone followed by combination of ondansetron and dexamethasone (46%). Use of neurokinin receptor antagonist was highly restricted (6%) due to their unaffordability to patients. Only 144 (30%) of 480 patients who were on highly myelosuppressive chemotherapy were prescribed with prophylaxis with filgrastim or pegfilgrastim. CSF is not reimbursed for patients under government schemes and so its use was highly restricted (28 of 294 patients) despite the need. The majority of the patients were prescribed with tramadol with or without non-steroidal analgesics (86%) for cancer related pain. Use of opioids like morphine was limited due to drug shortages at pharmacy. Ceftriaxone and cefoparazone were commonly used antibiotics for prevention and actual treatment of neutropenic fever. Protein supplements were prescribed fairly (76%) for patients under private insurance whereas they were prescribed rarely (14%) for patients under government insurance schemes. Conclusions Poor supportive care delayed treatment schedules due to drug toxicities in our patients. The majority of patients treated under government schemes had poor quality of supportive care while on chemotherapy due to highly restricted provision for the use of supportive care which informs the need for improving the treatment policies at government level. Legal entity responsible for the study N/A Funding N/A Disclosure All authors have declared no conflicts of interest.

Medical treatment of 145 cases of gastric dilatation in rabbits

Gastric dilatation is an acute and life-threatening condition in pet rabbits commonly caused by an intestinal obstruction with pellets of compressed hair. Surgery is normally considered to be the treatment...

Black tea extract and its thearubigins relieve the sildenafil-induced delayed gut motility in mice: a possible role of nitric oxide.

In this study we hypothesize that a standardized black tea aqueous extract (BTE) and thearubigins, its main polyphenolic pigments, will improve sildenafil-induced delay in gastric emptying (GE) and small intestinal transit (SIT) in mice. Twenty groups of mice (n = 8) were given a phenol red meal, and three sets of experiments were performed. In the first and second sets, effects of different concentrations of BTE, thearubigins (TRs), and sildenafil (SLD), alone and in combinations, on GE and SIT were measured. In the third set, influence of nω -Nitro-l-arginine methyl ester hydrochloride (l-NAME) pretreatment on effects of these treatments was tested. Black tea extract (3% and 4.5%) and thearubigins (50 and 60 mg/kg) dose-dependently increased GE and SIT, whereas BTE 6% and thearubigins 70 mg/kg did not affect them. Sildenafil dose-dependently reduced both GE and SIT. Combination of metoclopramide, BTE 4.5%, thearubigins 60, or l-NAME with sildenafil (5 mg/kg) reversed its motility-delaying effects. Pretreatment with l-NAME followed by BTE 4.5%, thearubigins 60, BTE 4.5% + sildenafil 5, or thearubigins 60 + sildenafil 5 only partially affected the accelerating effects of BTE 4.5% and thearubigins 60. In conclusion, a standardized BTE and its thearubigins improve the sildenafil-induced delayed gut motility in mice. This improvement was partially blocked by l-NAME suggesting a possible role of nitric oxide. Thus, BTE 4.5% or TRs 60 mg/kg solution could be considered a reliever therapy for the sildenafil-induced dyspepsia.

Parenteral Treatment of Episodic Tension‐Type Headache: A Systematic Review

Tension-type headache is highly prevalent in the general population and is a consistent if not frequent cause of visits to acute care settings. Analgesics such as nonsteroidal anti-inflammatory drugs, acetaminophen, and salicylates are considered first-line therapy for treatment of tension-type headache. For patients who present to an acute care setting with persistent tension-type headache despite analgesic therapy, it is not clear which parenteral agent should be administered. We performed a systematic review of the medical literature to determine whether parenteral therapies other than salicylates or nonsteroidals are efficacious for acute tension-type headache. We performed a systematic review of Medline, EMBASE, CINAHL, Google scholar, and the Cochrane Central Registry of Controlled Trials from inception through August, 2012 using the search terms "tension-type headache" and "parenteral or subcutaneous or intramuscular or intravenous." Our goal was to identify randomized trials in which one parenteral treatment was compared to another active comparator or to placebo for the acute relief of tension-type headache. Parenteral was defined as intravenous, intramuscular, or subcutaneous administration. We only included studies that distinguished tension-type headache from other primary headache disorders, such as migraine. The primary outcome for this review was measures of efficacy one hour after medication administration. Data abstraction was performed by two authors. Disagreements were resolved by a third author. We assessed the internal validity of trials using the Cochrane Collaboration risk of bias tool. Because of the small number of trials identified, and the substantial heterogeneity among study design and medications, we decided that combining data and reporting summary statistics would serve no useful function. The results of individual studies are presented using Number Needed to Treat (NNT) with 95%CI when dichotomous outcomes were available and continuous outcomes otherwise. Our search returned 640 results. One hundred eighty-seven abstracts were reviewed, and 8 studies involving 486 patients were included in our analysis. The most common reasons for exclusion of abstracts were no assessment of acute pain relief, use of nonparenteral medications only, and no differentiation of headache type. Risk of bias ranged from low to high. The following medications were more effective than placebo for acute pain (NNT, 95%CI): metamizole (4, 2-26), chlorpromazine (4, 2-26), and metoclopramide (2, 1-3). The combination of metoclopramide + diphenhydramine was superior to ketorolac (4, 2-8) The following medications were not more effective than placebo: mepivacaine, meperidine + promethazine, and sumatriptan. Various parenteral medications other than salicylates or nonsteroidals provide acute relief of tension-type headache. Comparative efficacy studies are needed.

Postoperative nausea and vomiting prophylaxis: The efficacy of a novel antiemetic drug (palonosetron) combined with dexamethasone

BackgroundPalonosetron is a new, potent, and long-acting 5HT3-receptors antagonist that had been approved by the FDA for use in postoperative nausea and vomiting (PONV) prophylaxis. This study is designed to evaluate its efficacy combined with dexamethasone in PONV prophylaxis in highrisk patients scheduled for laparoscopic surgeries.MethodsIn this double-blind, active-controlled study, 150 patients aged 20–55 years, ASA I–II, and with Apfel’s PONV score 2–4 were equally randomized to receive dexamethasone 8 mg before anesthesia induction and saline 30 min before the end of surgery (group D + S), dexamethasone 8 mg before anesthesia induction and metoclopramide 25 mg 30 min before the end of surgery (group D + M), or dexamethasone 8 mg combined with palonosetron 0.075 mg before anesthesia induction and saline 30 min before the end of surgery (group D + P). Incidences of early and late PONV, complete response, adverse events from antiemetics used, and overall patients’ satisfaction were recorded.ResultsThe incidence of PONV was comparable in the three groups 0–6 h postoperatively. Palonosetron–dexamethasone and dexamethasone–metoclopramide combination therapies significantly reduced the incidence of PONV at 6–12 h postoperatively compared to dexamethasone monotherapy (12% and 16%, vs. 36%, respectively, with P < 0.05). Moreover, palonosetron–dexamethasone combination therapy significantly reduced the incidence of PONV at 12–24 h postoperatively compared to both dexamethasone monotherapy (16% vs. 48%, P < 0.01), and dexamethasone–metoclopramide combination therapy (16% vs. 40%, P < 0.05). The incidence of adverse drug effects was comparable in the three groups. The overall patients’ satisfaction was significantly higher in palonosetron–dexamethasone combination therapy compared to other groups.ConclusionPalonosetron–dexamethasone combination is effective and safe in PONV (early and late) prophylaxis in high-risk patients undergoing laparoscopic surgeries with known high-risk of PONV.

Postoperative nausea and vomiting management in maxillofacial procedures: Dexamethasone combined with metoclopramide

BackgroundEfficient prevention and management of postoperative nausea and vomiting (PONV) continues to be a concern that needs to be addressed. There was a persistently high incidence of PONV despite prophylaxis with, metoclopramide, droperidol, dimenhydrinate or ondansetron when each was used alone in ‘at risk’ patients. Dexamethasone was also used as a stand alone drug in patients undergoing surgery. However, the current opinion questions the role of monotherapy. Drug combinations are deemed to be more useful for balanced anti-emesis. The aim of this study was to evaluate the prophylactic antiemetic effects of the combination dexamethasone–metoclopramide in patients undergoing maxillofacial procedures.Patients and methodsIn this placebo-controlled, double-blind study, 208 outpatients under standardized anesthetic technique were randomized to receive dexamethasone 8 mg before anesthesia induction and metoclopramide, 10 mg at the end of surgery (Group A), dexamethasone 8 mg before anesthesia induction and placebo at the end of surgery (Group B), placebo before anesthesia induction and metoclopramide, 10 mg at the end of surgery (Group C) or placebo before anesthesia induction and at the end of surgery (Group D). Complete response to prophylactic antiemetic medication was defined as no vomiting, no sustained moderate nausea and no requesting of antiemetic drug.ResultsDuring predischarge period, the number of patients with complete response to prophylactic antiemetic medication was significantly higher in Groups B (90.4%) and A (86.5%) in comparison with Groups D (55.8%) and C (75%). At the 24 h follow-up evaluation, complete response was higher in Group A (96.2%) in comparison with Groups C (67.3%) and D (78.8%).ConclusionsDexamethasone–metoclopramide combination is not more effective than administration of dexamethasone alone in the prophylaxis of (PONV).

Antinociception by metoclopramide, ketamine and their combinations in mice

BackgroundMetoclopramide is a centrally acting antiemetic and ketamine is a general anesthetic used with sedatives, tranquilizers and analgesics. Metoclopramide has analgesic effects and its combination with ketamine causes sedation and hypnosis. The contribution of metoclopramide to the analgesic effect of ketamine is not known. The purpose of the present study was to explore the anal-gesic effects of metoclopramide and ketamine alone or in combination in mice. MethodsThe up-and-down method was used to determine the median effective analgesic dosages (ED50s) of metoclopramide and ketamine administered intraperitoneally (ip) either alone or concomitantly in male albino Swiss mice. Analgesia was measured by using a hot plate. The ED50s of both drugs were analyzed isobolographically to determine the type of interaction between them. The analgesic effect of metoclopramide-ketamine combination (62.3and 4.3mg/kg, ip) was also monitored by the hot plate and acetic acid writhing methods. ResultsThe analgesic ED50s for metoclopramide and ketamine in mice were 30.15and 2.15mg/kg, ip, respectively. Concomitant administration of the drugs reduced their ED50s to 10.17and 0.68mg/kg, ip, respectively. Isobolographic analysis of these ED50s for both drugs revealed synergistic analgesic effect. Further, the combination of the drugs was effective analgesic as seen by the hot plate test and by another analgesic test paradigm, the acetic acid-induced writhings in mice. ConclusionsThe data suggest that the combination of metoclopramide and ketamine synergistically controls acute pain in mice. This combination could be used clinically for restraint and minor surgical interventions in mice.

Rescue Therapy for Acute Migraine, Part 3: Opioids, NSAIDs, Steroids, and Post‐Discharge Medications

The final section of this 3-part review analyzes published reports involving the acute treatment of migraine with opioids, non-steroidal anti-inflammatory drugs (NSAIDs), and steroids in the emergency department (ED), urgent care, and headache clinic settings, as well as post-discharge medications. In the Conclusion, there is a general discussion of all the therapies presented in the 3 sections. Using the terms ("migraine" AND "emergency") AND ("therapy" OR "treatment"), the author searched MEDLINE for reports from ED and urgent care settings that involved all routes of medication delivery. Reports from headache clinic settings were included only if medications were delivered by a parenteral route. Seventy-five reports were identified that compared the efficacy and safety of multiple acute migraine medications for rescue. Of the medications reviewed in Part 3, opioids, NSAIDs, and steroids all demonstrated some effectiveness. When used alone, nalbuphine and metamizole were superior to placebo. NSAIDs were inferior to the combination of metoclopramide and diphenhydramine. Meperidine was arguably equivalent when compared with ketorolac and dihydroergotamine (DHE) but was inferior to chlorpromazine and equivalent to the other dopamine antagonists. Steroids afford some protection against headache recurrence after the patient leaves the treatment center. All 3 opioids most frequently studied - meperidine, tramadol, and nalbuphine - were superior to placebo in relieving migraine pain, although meperidine combined with promethazine was not. Opioid side effects included dizziness, sedation, and nausea. With ketorolac being the most frequently studied drug in the class, NSAIDs were generally well tolerated, and they may provide benefit even when given late in the migraine attack. The rate of headache recurrence within 24-72 hours after discharge from the ED can be greater than 50%. Corticosteroids can be useful in reducing headache recurrence after discharge. As discussed in Parts 1, 2, and 3, there are effective medications for provider-administered "rescue" in all the classes discussed. Prochlorperazine and metoclopramide are the most frequently studied of the anti-migraine medications in the emergent setting, and their effectiveness is superior to placebo. Prochlorperazine is superior or equivalent to all other classes of medications in migraine pain relief. Although there are fewer studies involving sumatriptan and DHE, relatively "migraine-specific" medications, they appear to be equivalent to the dopamine antagonists for migraine pain relief. Lack of comparisons with placebo and the frequent use of combinations of medications in treatment arms complicate the comparison of single agents to one another. When used alone, prochlorperazine, promethazine, metoclopramide, nalbuphine, and metamizole were superior to placebo. Droperidol and prochlorperazine were superior or equal in efficacy to all other treatments, although they also are more likely to produce side effects that are difficult for a patient to tolerate (especially akathisia). Metoclopramide was equivalent to prochlorperazine, and, when combined with diphenhydramine, was superior in efficacy to triptans and NSAIDs. Meperidine was arguably equivalent when compared with ketorolac and DHE but was inferior to chlorpromazine and equivalent to the other neuroleptics. Sumatriptan was inferior or equivalent to the neuroleptics and equivalent to DHE when only paired comparisons were considered. The overall percentage of patients with pain relief after taking sumatriptan was equivalent to that observed with droperidol or prochlorperazine.

Postoperative vomiting in patients after laparoscopic surgery

BACKGROUND: Postoperative nausea and vomiting (PONV) is common after anaesthesia and surgery. We decided to evaluate metoclopramide, dexamethasone, and their combination in preventing PONV in patients under going laparoscopic surgery. METHOD: 396 patients were studied. Four groups were created: group received metoclopramide postoperatively; group 2 received dexamethasone following anaesthesia; and group 3 received dexamethasone following anaesthesia and metoclopramide before end of anaesthesia. Results were compared to group without anti-emetic. PONV incidence, basal and active mean visual analogue pain scores, time to first analgesia request, side effects, and well-being score were recorded at first 24 h postoperatively. RESULTS: Literature total incidence of PONV was 60% in control group de void of anti-emetic but 45% of PONV was seen in Group 1 with metoclopramide, Group 2 -23% with dexamethasone, and Group 3-12% with the combination of dexamethasone and metoclopramide. Anti-emetic rescue was not required in dexamethasone plus metoclopramide group or group with only dexamethasone, compared with four patients in the metoclopramide group and six patients in the control group. CONCLUSION: Dexamethasone or dexamethasone + metoclopramide combination was more effective in preventing PONV than metoclopramide or lack of anti-emetic. Scripta Scientifica Medica 2011;V.43(1):27-30

Antiemetic efficacy of metoclopramide and diphenhydramine added to patient-controlled morphine analgesia: a randomised controlled trial

the objective of this study was to assess whether antiemetic drugs metoclopramide and diphenhydramine, administered together as opposed to alone, can have better efficacy in preventing postoperative nausea and vomiting when added to patient-controlled morphine analgesia. during the period July 2007 to August 2008, 200 women scheduled for abdominal total hysterectomy were randomised to one of four postoperative, patient-controlled analgesia regimens: group 1, morphine 1 mg ml; group 2, morphine 1 mg ml with metoclopramide 0.5 mg ml; group 3, morphine 1 mg ml with diphenhydramine 0.6 mg ml; and group 4, morphine 1 mg ml with metoclopramide 0.5 mg ml and diphenhydramine 0.6 mg ml. Dexamethasone 4 mg was administered to all patients in all groups after anaesthesia induction as a prophylactic antiemetic medication, and prochlorperazine 5 mg was administered by intramuscular injection as necessary as a salvage/rescue therapy. Nausea, vomiting, pruritus, level of sedation, pain and morphine consumption were compared between the four groups. the incidence of nausea was significantly (P < 0.05) lower in group 4 compared to the other groups. In addition, there was a significant (P = 0.006) difference in the incidence of vomiting between groups 1 and 4. Repeated measurement analysis showed that numeric rating scale scores for group 4 were significantly (P < 0.001) lower than those for the other groups. results of this study showed that a combination of metoclopramide with diphenhydramine in patients treated with dexamethasone at anaesthesia induction decreased postoperative nausea and vomiting compared to metoclopramide or diphenhydramine in these patients, when added to patient-controlled anaesthesia with morphine.

Pharmacokinetic interaction between fluoxetine and metoclopramide in healthy volunteers

The pharmacokinetic interaction of fluoxetine with metoclopramide in healthy volunteers was evaluated. A dose of 20 mg metoclopramide in combination with 60 mg fluoxetine was administered to 24 healthy male volunteers in a two treatment study design, separated by 8 days in which the fluoxetine alone was administered as a single p.o. dose daily. Plasma concentrations of metoclopramide were determined during a 24 h period following drug administration. Metoclopramide plasma concentrations were determined by a validated HPLC method. Pharmacokinetic parameters of metoclopramide were calculated using non-compartmental analysis. In the two periods of treatment, the mean peak plasma concentrations (Cmax) were 44.02 ng/ml (metoclopramide alone) and 62.72 ng/ml (metoclopramide after pre-treatment with fluoxetine). The times taken to reach Cmax and tmax, were 1.15 h and 1.06 h, respectively. The total areas under the curve (AUC(0-infinity)) were 312.61 ng.h/ml and 590.62 ng.h/ml, respectively. The half-life values (t1/2) were 5.52 h and 8.47 h. Statistically significant differences were observed for both AUC(0-infinity) and t1/2 of metoclopramide when administered alone or after 8 days treatment with fluoxetine. The experimental data demonstrate the pharmacokinetic interaction between fluoxetine and metoclopramide and suggest that the observed interaction may be clinically significant, but its relevance has to be confirmed.

Metoclopramide and dexamethasone in prevention of postoperative nausea and vomiting after inhalational anaesthesia

Because of its complex profile of action (binding to dopamine, serotonin and histamine receptors), low rate of adverse effects and low cost as a medicinal preparation, metoclopramide is an interesting substance for the prophylaxis of post-operative nausea and vomiting (PONV). As a single substance its antiemetic effects are slight at the usual dose, so the aim was to test the efficacy of a combination of metoclopramide and dexamethasone for the prevention of PONV on a group of patients with the same operative trauma. All patients (n = 204) were recruited prospectively (January-October 2002) and were to undergo a lumbar disc operation. The anaesthetic was administered according to a standard procedure as a balanced anaesthetic with fentanyl and isoflurane in oxygen/air. 60 min before the end of the operation, all patients were given 10 mg of metoclopramide and 8 mg of dexamethasone intravenously. The Würzburg-Oulu-Score served as an instrument for comparison, because no placebo group has been included. 24 hours after the operation, all patients were asked to report on nausea and vomiting, stating the time and the degree of discomfort (quantification by means of an analogue numerical scale from 0-10). The influence of age, height, weight, duration of the anaesthetic, operating position and increased dexamethasone dose was analyzed in addition to the risk factors according to the score. The cost analysis was based on the purchase prices of the hospital dispensary. The expected PONV incidence was 35.8%; 10% nausea (average intensity 4.3) and 3% emesis (4.8) was reported for the 24-hour period. The rescue medication (dimenhydrinate) was requested 8 times. Nausea was mainly during the early part of the period (0-6 hours). Of 42 patients with a history of PONV, 71% had no symptoms. The Odds Ratios for female sex (2.9), non-smoker status (2.0) and post-operative opioid administration (1.9) correspond to the data given in the literature; it was not possible to determine the significance of a history of PONV as an independent risk factor. None of the other factors investigated had a significant influence on PONV. For the chosen combination of antiemetic drugs the number-needed-to-treat is 3.9 (95% CI: 3.3-4.7). The direct costs of the PONV prophylaxis are 0.65 euro per patient. The metoclopramide/dexamethasone combination proved to be effective and inexpensive, on the basis of these findings it is used prophylactically at our hospital if only one PONV risk factor exists.

Prevention of postoperative nausea and vomiting after laparoscopic gynaecological surgery. Combined antiemetic treatment with tropisetron and metoclopramide vs. metoclopramide alone

Female patients undergoing gynaecological procedures, especially laparoscopically, are at high risk of postoperative nausea and vomiting. No available antiemetic is entirely effective. This double-blinded randomized trial examines the efficacy and safety of tropisetron and metoclopramide in combination and compares the results with metoclopramide alone in laparoscopic gynaecological surgery. One hundred and twenty female patients scheduled for minor gynaecological laparoscopy, aged 27-43 years, were randomly allocated to receive pretreatment with metoclopramide 10 mg intravenously (n=57) or tropisetron 5 mg with metoclopramide 5 mg (n=63). Fewer patients in the combined treatment group experienced postoperative nausea and vomiting (14% vs. 37%, P=0.008) or needed rescue antiemetic treatment (3% vs. 16%, P=0.038). No significant adverse events were observed. The combination of the antiemetics was superior, which is probably explained by the fact that the two drugs have different sites of action, thus preventing emesis by blocking different pathways.