indication

For the treatment of gastroesophageal reflux disease (GERD). It is also used in treating nausea and vomiting, and to increase gastric emptying.

pharmacology

Metoclopramide, although chemically related to procainamide, does not possess local anesthetic or antiarrhythmic properties. Metoclopramide is used to enhance GI motility, to treat diabetic gastroparesis, as an antinauseant, and to facilitate intubation of the small bowel during radiologic examination. Metoclopramide may be used to treat chemotherapy-induced emesis and as a radiosensitizing agents in the treatment of non-small cell lung carcinoma and glioblastomas in the future.

mechanism of action

Metoclopramide inhibits gastric smooth muscle relaxation produced by dopamine, therefore increasing cholinergic response of the gastrointestinal smooth muscle. It accelerates intestinal transit and gastric emptying by preventing relaxation of gastric body and increasing the phasic activity of antrum. Simultaneously, this action is accompanied by relaxation of the upper small intestine, resulting in an improved coordination between the body and antrum of the stomach and the upper small intestine. Metoclopramide also decreases reflux into the esophagus by increasing the resting pressure of the lower esophageal sphincter and improves acid clearance from the esophagus by increasing amplitude of esophageal peristaltic contractions. Metoclopramide's dopamine antagonist action raises the threshold of activity in the chemoreceptor trigger zone and decreases the input from afferent visceral nerves. Studies have also shown that high doses of metoclopramide can antagonize 5-hydroxytryptamine (5-HT) receptors in the peripheral nervous system in animals.

toxicity

Oral, mouse LD₅₀: 280 mg/kg. Signs of overdose include drowsiness, disorientation, and extrapyramidal reactions.

biotransformation

Hepatic

absorption

Rapidly and well absorbed (oral bioavailability 80±15.5%).

half life

5-6 hr

route of elimination

Approximately 85% of the radioactivity of an orally administered dose appears in the urine within 72 hours.

drug interactions

Cyclosporine: Metoclopramide increases serum levels of cyclosporine

Levodopa: Levodopa decreases the effect of metoclopramide

Paliperidone: Metoclopramide may increase the risk of extrapyramidal side effects of paliperidone. Concomitant therapy should be avoided.

Tacrolimus: Metoclopramide may increase the concentration of Tacrolimus in the blood. Monitor for changes in the therapeutic/toxic effects of Tacrolimus if Metoclopramide therapy is initiated, discontinued or altered.

Venlafaxine: Possible serotoninergic syndrome with this combination

Vilazodone: Seek alternatives to this combination when possible. Monitor patients receiving metoclopramide with selective serotonin reuptake inhibitors for signs of extrapyramidal symptoms, neuroleptic malignant syndrome, and serotonin syndrome.

Zuclopenthixol: Additive dopamine D2 receptor antagonism may cause dopaminergic imbalance in the nigrostriatal (dopamine D1 receptors) and striatopallidal (dopamine D2 receptors). Increased risk of extrapyramidal reactions and neuroleptic malignant syndrome. Concomitant therapy should be avoided.