Metoclopramide sedation

Most common Sedation, restlessness, diarrhea (metoclopramide), agitation, central nervous system depression Less common Extrapyramidal effects (more frequent with higher doses), hypotension, neuroleptic syndrome, supraventricular tachycardia (with intravenous administration)... 

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. 

Metoclopramide is a dopamine antagonist that centrally inhibits stimulation of the CTZ. By improving gastric emptying, it can decompress the stomach, thereby decreasing a peripherally associated stimulation of the emetic center. Metoclopramide may precipitate ex-trapyramidal reactions and sedation. For further details, see earlier section, Drugs that Increase GI Motility. 

B. Two medicines, ipecac and apomorphine, induce vomiting. Metoclopramide is a prokinetic with antiemetic properties and therefore would have the opposite of the desired effect. Morphine is an opioid with analgesic and sedating properties. Promethazine and ondansetron are also antiemetics, not emetics. 

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). 

Prochlorperazine (Compazine, and others) can be effective for prevention of vomiting due to cancer chemotherapy, but is generally less so than dexamethasone or metoclopramide. Phenothiazines can cause orthostatic hypotension, sedation, dystonic reactions, and akathisia. 

In a randomized, placebo-controlled trial inl40 patients a combination of metoclopramide 10 mg and droperidol 1.25 mg or two doses of droperidol provided a more effective antiemetic effect than metoclopramide alone (9). The level of sedation was significantly greater in the patients who received two doses of droperidol (8/35) and metoclopramide followed by droperidol (7/35) than in those who received only placebo (0/35) or metoclopramide followed by placebo (0/35). 

Alcohol Metoclopramide increases the rate of absorption and blood levels of alcohol and increases alcohol-related sedation. 

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. 

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. 

In high dose, injection of metoclopramide can cause sedation and facial muscle spasms due to effects on dopamine receptors in the brain. This is similar to the adverse reactions seen with antipsychotic drugs (see Chapter 11). 

Domperidone is an alternative to metoclopramide. It too acts on dopamine (D2) receptors in the chemotrigger zone of the medulla. It does not penetrate other areas of the brain, therefore it is less likely to cause sedation and muscle spasms. 

Metoclopramide (Reglan) suppresses emesis by blocking the dopamine and serotonin receptors in the CTZ. High doses can cause sedation and diarrhea. The occurrence of EPS is more prevalent in children than adults. 

There is some evidence that metoclopramide can increase the rate of absorption of alcohol, raise maximum blood-alcohol levels, and possibly increase alcohol-related sedation. 

Metoclopramide increases the rate of absorption of oral morphine and increases its rate of onset and sedative effects. However, opioids may antagonise the effects of metoclopramide on gastric emptying. The use of droperidol with opioids can be beneficial, but an increase in sedation appears to occur. 

Metoclopramide increases the rate of gastric emptying so that the rate of morphine absorption from the small intestine is increased. An alternative idea is that both drugs act additively on opiate receptors to increase sedation. Droperidol may also enhance adverse effects such as sedation, and in some cases respiratory depression, possibly through opioid and other receptor sites in the CNS. In one case the respiratory depression was not reversed by naloxone, suggesting that the droperidol was at least partially if not completely responsible. ... 

The effect of metoclopramide on oral morphine absorption is an established interaction that can be usefully exploited in anaesthetic practice, but the increased sedation may also represent a problem if the morphine is being given long-term. The morphine-sparing effect of droperidol is also a useful interaction, but the increased sedation and possible respiratory depression and hypotension should be borne in mind. One manufacturer of fentanyl specifically warns that concurrent use with droperidol can result in a higher incidence of hypotension. ... 

Common adverse events sedation, respiratory depression, pruritus, nausea/vomiting, constipation, and urinary retention, which are treated with a naloxone 40-80 pg IV bolus followed by an infusion of 50-100 pg/h. However, these adverse events are relatively less commonly observed with epidural hydromorphone than with neuraxial morphine regimens. Pruritus is treated with a naloxone infusion of 50-100 pg/h, diphenhydramine 12.5-50 mg or propofol infusion of 10 mg/h. Nausea and vomiting is best treated with either ondansetron (4-8 mg IV), low-dose droperidol (0.625-1.25 mg IV), metoclopramide (10 mg IV every 4-6 h), or transdermal scopolamine patch during the first 10 hours following administration. 

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