Metoclopramide adverse effects

Metoclopramide crosses the BBB and has centrally-mediated adverse effects. Young children and the elderly are especially susceptible to these effects, which include somnolence, reduced mental acuity, anxiety, depression, and EPS (akathisia, dystonia, and tardive dyskinesia).30 The overall incidence of adverse effects is estimated to be 10% to 20%.1... 

Domperidone minimally crosses the BBB it acts in the CTZ which lies outside of the BBB. As such, domperidone is less likely to cause the centrally-mediated adverse effects seen with metoclopramide and has an estimated overall incidence of 5% to 10%.1,30 However, domperidone has been associated with prolonged QT intervals, cardiac arrhythmias, and sudden death.31 It should not be used for patients with underlying long QT interval or for those on other medications that prolong the QT interval. Both metoclopramide and domperidone can cause hyperprolactinemia, galactorrhea, and gynecomastia. 

Symptomatic gastroesophageal reflux 10 to 15 mg orally up to 4 times daily 30 minutes before each meal and at bedtime. If symptoms occur only intermittently or at specific times of the day, single doses up to 20 mg prior to the provoking situation may be preferred rather than continuous treatment. Occasionally, patients who are more sensitive to the therapeutic or adverse effects of metoclopramide (eg, elderly) will require only 5 mg/dose. Guide therapy directed at esophageal lesions by endoscopy. Therapy longer than 12 weeks has not been evaluated and cannot be recommended. 

As first choice treatment a well-established antihistamine such as meclozine is recommended. Promethazine is another antihistamine which reduces nausea, but sedation is a not always desired adverse effect. Metoclopramide increases intestinal motility and could be used short term also early in pregnancy. A neuroleptic such as prochlorperazine reduces nausea but should only be used for shortterm treatment due to the risk of extrapyramidal adverse reactions. Serotonin receptor antagonists can be used in post-operahve nausea and during treatment with cytostatics. 

Adverse effects of cisapride in causing cardiac dysrhythmias have led to withdrawal from general use. Metoclopramide and domperidone are well described as occasionally causing dyskinesias, particularly in younger people. Treatment is generally licensed for short term typically six week prescription. 

Metoclopramide can cause adverse effects such as sedation, akathisia (motor restlessness), involuntary movements, diarrhea, and dizziness. The extrapyramidal reactions, which are more common in patients < 30 years old, can be relieved by intravenous or oral diphenhydramine or benztropine (Cogentin). 

Concomitant use of drugs with extrapyramidal adverse effects GI hemorrhage, obstruction (mechanical), or perforation Hypersensitivity to metoclopramide products Pheochromocytoma Seizure disorders... 

Hepatic adverse effects secondary to antiemetic therapy are usually asymptomatic. Metoclopramide has been reported as causing cholestasis and the formation of arteriovenous shunts in the liver [12]. The 5HTj-receptor antagonists have all been documented as occasionally causing mild increases in liver fimction tests. Cholestatic jaundice has been reported with cyclizine, prochlorperazine and promethazine, and hepatitis has been reported with cyclizine. 

Metoclopramide could be used in an older patient, but as this patient is only 14 years old it should be avoided, where possible, because of the increased incidence of extrapyramidal effects in children, young adults and females. In an older patient, an initial dose of 10 mg three times a day could be used and then titrated against response and adverse effects. 

Acute hemorrhagic colitis without pseudomembranes has been reported after oral cefuroxime (SEDA 21, 261). In mice, some cephalosporins accelerated gastric emptying, in some instances even more effectively than erythromycin or metoclopramide (93). The relevance of this to the gastrointestinal adverse effects of cephalosporins, such as nausea and vomiting, is uncertain. 

Domperidone is a neuroleptic antiemetic, a dopamine receptor antagonist. It produces the expected range of dystonic and extrapyramidal adverse effects (1), which seem, as with metoclopramide, to be more likely to occur in children (2). It is difficult to accept that claims for lower frequencies than with metoclopramide are justified, particularly when one reads a report of neuroleptic malignant sjmdrome (3). Like its congeners, domperidone has repeatedly been shown to cause sjmptoms attributable to hyperprolactinemia (galactorrhea, amenorrhea, and breast tenderness), despite claims that there is a lower incidence of effects on prolactin concentrations. However, a study in patients with Parkinson s disease using domperidone did not suggest that the adverse effects are especially problematical in these patients (4). 

The efficacy and adverse effects of domperidone and metoclopramide have been compared in a double-bhnd, multicenter, randomized trial in 93 insuhn-dependent diabetics with symptomatic gastroparesis (7). Domperidone 20 mg qds and metoclopramide 10 mg qds, for 4 weeks, were equally effective in alleviating sjmptoms of gastroparesis. Somnolence, akathisia, anxiety, and depression were more... 

Granisetron and tropisetron appear to have the same safety profile as ondansetron (6). Their adverse reactions include mild rises in transaminases (up to 17%), slight headache (8-42%), transient diarrhea (2-5%), which may be followed during longer-term therapy by constipation, dizziness (5%), and dry mouth (5-17%) the incidence of xerostomia is higher than with metoclopramide. Other reported adverse effects include anorexia, paresthesia, constipation or abdominal discomfort, changes in blood pressure, fever, facial edema, leg cramps, hot flushes, and enlargement of the spleen (7). 

The antiemetic effect of combined intravenous ondansetron 8 mg, oral dexamethasone 20 mg, and oral lorazepam 0.5 mg was significantly better than that of intravenous metoclopramide 10 mg, dexamethasone 20 mg, and oral lorazepam 0.5 mg in 30 patients receiving chemotherapy for ovarian cancer in a randomized trial (23). All the antiemetics were given 30 minutes before and 6 hours after chemotherapy. Significantly more patients given metoclopramide (40% versus 13%) complained of adverse effects. The most frequent adverse effects with both regimens were sedation and headache. 

Although metoclopramide has lost some ground to newer congeners, it has been the most widely used of the neuroleptic-type antiemetic drugs and is therefore the one for which the clearest picture of adverse effect, typically neuroleptic and endocrine effects, has emerged. Reactions are generally short-lived provided treatment is withdrawn the duration of reactions does not always seem to be explained by simple pharmacokinetic considerations. 

Adverse reactions Well tolerated with few side effects. Headache, especially at higher doses, is the most common adverse effect. Others include dizziness, fatigue, constipation, Gl upset, and elevations in hepatic transaminases. Metoclopramide and prochlorperazine may cause dystonic reactions or EPS at high doses. High doses of droperidol may cause QT(- prolongation. Others include sedation, dizziness, and dry mouth. 

Thirty randomized, controlled trials from 1975 to 1996 were analyzed to quantify the antiemetic efficacy and adverse effects of cannabis when given to 1366 patients receiving chemotherapy. Oral nabUone, oral dronabinol, and intramuscular levonantradol were compared with conventional antiemetics (prochlorperazine, metoclopramide, chlor-promazine, thiethylperazine, haloperidol, domperidone, and aliza-pride) or placebo. Across all trials, cannabinoids were slightly more effective than active comparators and placebo when the chemotherapy regimen was of moderate emetogenic potential, and patients preferred them. No dose-response relationships were evident to the authors. The cannabinoids were also more toxic side effects included euphoria, drowsiness, sedation, somnolence, dysphoria, depression, hallucinations, and paranoia. The efficacy of cannabinoids as compared to SSRls has not been studied. Use of these agents should be considered when other regimens do not provide desired efficacy. 

Adverse Effects The major side effects of metoclopramide include extrapyramidal effects. Dystonias, usually occurring acutely after intravenous administration, and parkinsonian-like symptoms that may occur several weeks after initiation of therapy generally respond to treatment with antichohn-eigic or antihistaminic drugs and are reversible upon metoclopramide discontinuation. Tardive dyskinesia also can occur with chronic treatment (months to years) and may be irreversible. Metoclopramide can elevate prolactin levels by blocking the inhibitory effect of dopamine on pituitary lactotropes. Methemoglobinemia has been reported in premature and fuU-term neonates receiving metoclopramide. 

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