METOCLOPRAMIDE
Metoclopramide is a dopamine receptor antagonist with antiemetic and prokinetic properties. It has multiple applications in anesthesia and perioperative care, which contribute to its importance in this field:
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Prevention and treatment of postoperative nausea and vomiting (PONV): Metoclopramide is used to prevent and treat PONV, a common and uncomfortable complication that can occur after surgery. PONV can lead to patient distress, delayed recovery, prolonged hospital stays, and increased healthcare costs. By blocking dopamine receptors in the chemoreceptor trigger zone (CTZ), metoclopramide reduces the incidence and severity of PONV.
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Gastric emptying enhancement: Metoclopramide promotes gastric emptying and accelerates intestinal transit due to its prokinetic properties. This can be beneficial in the perioperative period, especially for patients at risk of aspiration or those with delayed gastric emptying.
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Multimodal approach to PONV management: Metoclopramide can be used in combination with other antiemetic agents, such as ondansetron, dexamethasone, or droperidol, to enhance their effectiveness in preventing PONV. This multimodal approach to PONV management can provide superior results compared to using a single antiemetic agent.
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Migraine treatment: Metoclopramide is sometimes used to treat migraine headaches, which can be relevant for patients with a history of migraines who are undergoing surgery. The drug's antiemetic and analgesic-enhancing properties can help alleviate migraine symptoms.
The mechanism of action of metoclopramide involves both central and peripheral actions on dopamine (D2) receptors and serotonin (5-HT3) receptors. Here are the main steps in metoclopramide's mechanism of action:
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Central action – D2 receptor antagonism: In the central nervous system, metoclopramide acts as a dopamine D2 receptor antagonist, particularly in the chemoreceptor trigger zone (CTZ) of the area postrema in the brainstem. By blocking dopamine receptors in the CTZ, metoclopramide reduces the input from the CTZ to the vomiting center, thus decreasing the frequency and severity of nausea and vomiting.
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Central action – 5-HT3 receptor antagonism: Metoclopramide also exerts antiemetic effects by antagonizing serotonin 5-HT3 receptors in the CTZ, further inhibiting the transmission of nausea and vomiting signals to the vomiting center.
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Peripheral action – D2 receptor antagonism: In the gastrointestinal tract, metoclopramide antagonizes dopamine D2 receptors on smooth muscle cells and enteric nerves. This action increases the release of acetylcholine, which stimulates gastrointestinal motility and accelerates gastric emptying.
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Peripheral action – 5-HT4 receptor agonism: Metoclopramide also acts as a 5-HT4 receptor agonist in the gastrointestinal tract, which enhances the release of acetylcholine and promotes coordinated contractions of the smooth muscle in the stomach and upper small intestine. This effect contributes to the prokinetic activity of metoclopramide, improving gastric emptying and overall gastrointestinal motility.
Key points about Metoclopramide
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It readily crosses the blood-brain barrier and may have direct effects on the vomiting center because of its antidopaminergic effect.
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Stimulates the gastrointestinal tract via cholinergic mechanism.
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Causes contraction of the lower esophageal sphincter.
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Increases gastric and small intestinal motility.
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Decreases muscle activity in the pylorus and duodenum when stomach contracts.
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Because of its antidopaminergic activity, metoclopramide should be used with caution if at all in patients with Parkinson’s disease.
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Akathisia, a feeling of unease and restlessness in the lower extremities, may follow the IV administration.
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Dystonic extrapyramidal reactions (opisthotonos, trismus, torticollis, tardive dyskenesia) occur in less than 1% of patients.