Domperidone antiemetic effects

DOMPERIDONE, METOCLOPRAMIDE ANTIMUSCARINICS i efficacy of domperidone on gut motility by antimuscarinics Some effects of metodopramide are considered to be due to t release of ACh and t sensitivity of the cholinergic receptors to ACh. Antimuscarinics prevent the effects on muscarinic receptors The gastrointestinal effects of metodopramide will be impaired, while the antiemetic effects may not be. Thus, concurrent use with antimuscarinics is not advised because of effects on the gastrointestinal system... 

Less serious reactions to contrast agents are nausea and vomiting, mild skin reactions (hives) and more serious generalized skin reactions with urticaria. Nausea and vomiting rarely require treatment with antiemetics, for example domperidone. Skin reactions can be treated with oral or intravenous antihistamines, which also have an antiemetic effect. Intravenous corticosteroids may be required for serious urticaria. 

Metoclopramide may be considered as a prototype 5-HT3 antagonist because its antiemetic efficacy both in animals and man could not be adequately explained by D2-dopamine blockade. In fact, metoclopramide was considerably weaker as a D2-antagonist than haloperidol or domperidone and yet it was effective against emesis induced by anticancer agents both in animals [43, 80] and cancer patients [135]. 

Butyrophenones Haloperidol, droperidol and domperidone act by blocking dopamine receptors. The butyrophenones are moderately effective antiemetics, but high-dose haloperidol was found to... 

All antiemetics are hepatically metabolised to a lesser or greater degree. Domperidone and prochlorperazine in particular have a very high first-pass effect and are extensively metabolised by the liver. 

Domperidone may be the antiemetic of choice in this patient. Despite being extensively metabolised by the liver it has few adverse effects and does not cross the blood-brain barrier. 

Domperidone may be the antiemetic of choice in this patient. Despite being extensively metabolised by the Hver it has few adverse effects and does not cross the blood-brain barrier. The bioavailability is hkely to be increased as first-pass metabolism will be reduced because of portal hypertension. There may also be accumulation of domperidone owing to reduced metabolic capacity. Consequently the dose should be reduced to 50% and titrated up to 10 mg three times a day if necessary. 

Domperidone may be the antiemetic of choice, but as the patient has very little metabolic and synthetic liver function, owing to massive hepatocellular necrosis secondary to the hepatotoxic effects of the paracetamol overdose, accumulation of the domperidone may occur. However, it may be of benefit as a pro-kinetic agent. 

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). 

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. 

Domperidone (100 mg p.o.) is an antiemetic agent that blocks selectively peripheral dopamine receptors in the chemoreceptor trigger zone for emesis, as well as those in the GI tract. Unlike metoclopramide, domperidone does not pass across the blood-brain barrier, and hence it is thought to be devoid of any extrapyramidal side effects. Clinical evidence indicates that domperidone, by blocking dopamine receptors in the wall of the Gl tract, enhances normal synchronized Gl peristalsis and motility in the proximal portion of the Gl tract (see also Figure 73). 

Morphine appears to antagonise the effects of metoclopramide on gastric emptying. As a reduction in gastric motility occurs with all opioids they would all be expected to interact with metoclopramide, and other motility stimulants such as domperidone. However, these drugs are commonly used together and the clinical significance of such effects is not clear. Consider also Opioids + Antiemetics Ondansetron , below. 

The hypotensive adverse effects of apomorphine may possibly be increased by alcohol. The concurrent use of other drugs used for erectile dysfunction or dopamine agonists or antagonists is not recommended. However, domperidone, and prochlorperazine are said not to interact when apomorphine is used for erectile dysfunction, and domperidone is the recommended antiemetic when apomorphine is used for Parkinson s disease. There is evidence that antidepressants, antiepileptics, and ondansetron do not interact adversely. 

Note that prochlorperazine should not be given if apomorphine is used for Parkinson s disease, as its dopamine antagonist actions can worsen the disease (see also Levodopa + Antiemetics , p.682). Because apomorphine is highly emetogenic at the doses required for the treatment of Parkinson s disease (1 to 4 mg/hour by subcutaneous infusion), patients with Parkinson s disease requiring apomorphine should be pretreated with domperidone 20 mg three times daily for at least 2 days. Rare reports of extrapyramidal adverse effects have been reported with ondansetron, which may be of relevance in patients with Parkinson s Disease. 

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