Aspiration: Metoclopramide

METOCLOPRAMIDE

Mechanism of Action

Metoclopramide acts peripherally as a cholinomi-metic (ie, facilitates acetylcholine transmission at selective muscarinic receptors) and centrally as a dopamine receptor antagonist. Its action as a proki-netic agent in the upper gastrointestinal (GI) tract is not dependent on vagal innervation but is abol-ished by anticholinergic agents. It does not stimulate secretions.

Clinical Uses

By enhancing the stimulatory effects of acetyl-choline on intestinal smooth muscle, metoclopramide increases lower esophageal sphincter tone, speeds gastric emptying, and lowers gastric fluid volume. These properties account for its efficacy in the treatment of patients with diabetic gastroparesis and GERD, as well as prophylaxis for those at risk for aspiration pneumonia. Metoclopramide does not affect the secretion of gastric acid or the pH of gas-tric fluid.

Metoclopramide produces an antiemetic effect by blocking dopamine receptors in the chemore-ceptor trigger zone of the central nervous system. However, at doses used clinically during the periop-erative period, the drug’s ability to reduce postop-erative nausea and vomiting is negligible.

Side Effects

Rapid intravenous injection may cause abdominal cramping, and metoclopramide is contraindicated in patients with complete intestinal obstruction. It can induce a hypertensive crisis in patients with pheo-chromocytoma by releasing catecholamines from the tumor. Sedation, nervousness, and extrapyramidal signs from dopamine antagonism (eg, akathisia) are uncommon and reversible. Nonetheless, metoclo-pramide is best avoided in patients with Parkinson’s disease. Metoclopramide-induced increases in aldo-sterone and prolactin secretion are probably inconse-quential during short-term therapy. Metoclopramide may rarely result in hypotension and arrhythmias.

Dosage

An adult dose of 10–20 mg of metoclopramide (0.25 mg/kg) is effective orally, intramuscularly, or intravenously (injected over 5 min). Larger doses (1–2 mg/kg) have been used to prevent emesis during chemotherapy. The onset of action is much more rapid following parenteral (3–5 min) than oral (30–60 min) administration. Because metoclo-pramide is excreted in the urine, its dose should be decreased in patients with renal dysfunction.

Drug Interactions

Antimuscarinic drugs (eg, atropine, glycopyr-rolate) block the GI effects of metoclopramide. Metoclopramide decreases the absorption of orally administered cimetidine. Concurrent use of pheno-thiazines or butyrophenones (droperidol) increases the likelihood of extrapyramidal side effects.