Metoclopramide Levodopa

The effects of metoclopramide are antagonized by concurrent administration of anticholinergics or narcotic analgesics. Metoclopramide may decrease the absorption of digoxin and cimetidine and increase absorption of acetaminophen, tetracyclines, and levodopa Metoclopramide may alter die body s insulin requirements. 

Clinically important, potentially hazardous interactions with guanethidine, levodopa, metoclopramide, piperazine... 

Drugs that may affect metoclopramide include levodopa, anticholinergics, and narcotic analgesics. Drugs that may be affected by metoclopramide include alcohol, cimetidine, cyclosporine, digoxin, levodopa, MAO inhibitors, and succinylcholine. 

Levodopa or dopamine agonists produce diverse dyskinesias as a dose-related phenomenon in patients with Parkinson s disease dose reduction reverses them. Chorea may also develop in patients receiving phenytoin, carbamazepine, amphetamines, lithium, and oral contraceptives, and it resolves with discontinuance of the offending medication. Dystonia has resulted from administration of dopaminergic agents, lithium, serotonin reuptake inhibitors, carbamazepine, and metoclopramide and postural tremor from theophylline, caffeine, lithium, valproic acid, thyroid hormone, tricyclic antidepressants, and isoproterenol. 

Vomiting is triggered in the chemoreceptor trigger zone of the medulla, and nearly all dopamine receptor agonists (e.g. bromocriptine), and agents that increase dopamine in the brain (e.g. levodopa), cause vomiting. Conversely, many dopamine receptor antagonists (e.g. metoclopramide, and phenothiazines, e.g. chlorpromazine and prochlorperazine) have antiemetic activity. 

Clinically important, potentially hazardous interactions with alcohol, amiodarone, anticholinergics, antihistamines, barbituates, cisapride, dofetilide, doxazosin, erythromycin, guanethidine, hydralazine, levodopa, lithium, methyldopa, metoclopramide, moxifloxacin, piperazine, quinidine, sibutramine, sotalol, thiazide diuretics, thioridazine... 

The antiemetic properties of metoclopramide appear to be a result of its antagonism of central and peripheral dopamine receptors. Dopamine produces nausea and vomiting by stimulation of the medullary chemoreceptor trigger zone (CTZ), and metoclopramide blocks stimulation of the CTZ by agents like levodopa or apomorphine that are known to increase dopamine levels or to possess dopaminelike effects. Metoclopramide also inhibits the central and peripheral effects of apomorphine and abolishes the slowing of gastric emptying caused by apomorphine. 

Metoclopramide increases gastric transit time, enhancing the absorption of substances absorbed in the small intestine (e.g., ethanol, cyclosporin) and decreasing the absorption of substances absorbed in the stomach (e.g., cimetidine, digoxin). Anticholinergic drugs and dopamine-function-enhancing substances such as levodopa reduce the effectiveness of metoclopramide. Because metoclopramide releases catecholamine, it should be used cautiously with monoamine oxidase inhibitors such as tranylcypromine. Because metoclopramide inhibits plasma cholinesterase, it increases the effectiveness of succinylcholine, a skeletal muscle relaxant. 

Antihistamines, dronabinol, glucocorticoids, and metoclopramide have antiemetic actions that are useful in the management of vomiting caused by anticancer drugs. Levodopa causes nausea because it is converted to dopamine, which activates dopamine receptors in the emetic center. The answer is (C). 

Domperidone is a dopamine antagonist similar to metoclopramide. However, since it acts on the dopamine receptors in the stomach wall, and unlike metoclopramide, it does not readily cross the blood-brain barrier, it does not appear to oppose the effects of levodopa within the brain, although some extrapyramidal symptoms have been observed. It may even slightly increase the bioavailability and effects of levodopa (by stimulating gastric emptying). Domperidone can therefore be used to control the nausea and vomiting associated with levodopa treatment of Parkinson s disease. 

Taisy D, Parices JD, Marsden CD. Metoclopramide and pimozide in Paridnson s disease and levodopa-induced dyskinesias. /AfeMro/A/ Mro5w Psychiatry (1975) 38,331-5. 

Absorption of digoxin in the stomach may be diminished. Absorption of oral medication (e.g. acetaminophen, levodopa, tetracycline, and ethanol) in the small bowel may be increased. Insulin dosage may require adjustment because the action of metoclopramide will influence the dehvery of food to the intestines and thus the rate of absorption. Metoclopramide increases the effect of succinylcholine and the serum levels of cyclosporine. 

A 79-year-old man underwent colonic resection for bowel obstruction. He had a history of Parkinson s disease and associated dementia, hypertension, type-2 diabetes and occasional constipation. His current medications included carbidopa-levodopa extended release, lisinopril, furosemide, isophane insulin and polyethylene glycol (as needed for constipation). He was treated with metoclopramide (10 mg i.v., every 6 h) for stimulating gastric motility. After receiving the first three doses of metoclopramide, the patient developed mental deterioration until he became xmre-sponsive, and could not be aroused. An electroencephalogram displayed a pattern of diffuse slowing of the background rhythm, which was consistent with acute metabolic encephalopathy. Metoclopramide was discontinued, and... 

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