Metoclopramide works as a 5HT serotonin receptor antagonist the chemoreceptor trigger zone of the brain to prevent nausea and vomiting.
Metoclopramide is helpful in gastroparesis and GERD, as it increases duodenal and jejunal peristalsis, improving the tone and amplitude of gastric contractions. This medication also increases the lower esophageal sphincter (LES) tone. It is important to also note it does these actions without increasing gastric secretions.
Gastroprokinetic activity with metoclopramide is due to increased resting tone of gastric contractions. The tone and amplitude of gastric contractions are increased, with relaxation of the pyloric sphincter and duodenal bulb. These effects combine to result in improved motility of gastric contents.
This drug works as an antagonist at dopaminergic D2 receptors, has serotonergic blocking activity in the chemoreceptor zone, as well as enhancing responsiveness to acetylcholine of gastric tissue. D2 antagonism, combined with 5HT3 inhibition in higher doses, blocks receptors in the chemoreceptor trigger zone (CTZ) of the CNS from causing nausea and vomiting. Furthermore, D2 antagonism contributes to gastroprokinetic activity, but an enhancement of Ach leads to increased gastric emptying, though without an increase of gastric secretions.
As this medication is a dopaminergic antagonist, patients may display parkinsonian symptoms, such as involuntary muscle movements, facial grimaces and dystonic reactions.
Patients taking metoclopramide may experience galactorrhea. This occurs because by blocking dopamine, there is no negative inhibition of prolactin release from the anterior pituitary. Thus, patients taking this medication develop hyperprolactinemia, which can present with galactorrhea.
In a situation where improved gastric motility may be harmful, such as a small bowel obstruction, metoclopramide is contraindicated.
As this medication is a dopaminergic antagonist, it should be contraindicated or used very cautiously in patients with Parkinson's disease. Administration of metoclopramide may worsen symptoms in patients with Parkinson's disease.
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