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  1. Pharmacology. Metoclopramide is a dopamine antagonist with antiemetic activity at the chemoreceptor trigger zone. It also accelerates GI motility and facilitates gastric emptying. The onset of effect is 1–3 minutes after intravenous administration, and therapeutic effects persist for 1–2 hours after a single dose regardless of route. The drug is excreted primarily by the kidneys. The elimination half-life is about 5–6 hours but may be as long as 14.8 hours in patients with renal insufficiency and 15.4 hours in patients with cirrhosis.

  2. Indications

    1. Metoclopramide is used to prevent and control persistent nausea and vomiting, particularly when vomiting can compromise the ability to administer activated charcoal (eg, treatment of theophylline poisoning) or another oral antidotal therapy (eg, acetylcysteine for acetaminophen poisoning).

    2. Theoretic (unproven) use to stimulate bowel activity in patients with ileus who require repeat-dose activated charcoal or whole-bowel irrigation.

  3. Contraindications

    1. Known hypersensitivity to the drug; possible cross-sensitivity with procainamide.

    2. Mechanical bowel obstruction, active gastrointestinal hemorrhage, or intestinal perforation.

    3. Pheochromocytoma (metoclopramide may cause hypertensive crisis by enhancing tumor catecholamine secretion).

    4. Patients with seizure disorders (the frequency and severity of seizures may be increased).

    5. Patients receiving other drugs that are likely to cause extrapyramidal reactions (consider using selective 5-HT3 receptor antagonists as alternatives in these patients).

  4. Adverse effects

    1. Sedation, restlessness, fatigue, and diarrhea may occur.

    2. Extrapyramidal reactions may result, particularly with high-dose treatment. Pediatric patients and adults younger than 30 years appear to be more susceptible. These reactions may be treated or prevented with diphenhydramine.

    3. Parenteral formulations that contain sulfite preservatives may precipitate bronchospasm in susceptible individuals.

    4. Use in pregnancy. FDA Category B. Not likely to cause harm when used as short-term therapy (Table II–66).

  5. Drug or laboratory interactions

    1. Additive sedation in the presence of other CNS depressants.

    2. Due to an increased risk for extrapyramidal reactions in the presence of other dopamine antagonist agents (eg, haloperidol and other antipsychotic agents), concurrent use is contraindicated.

    3. In one study involving hypertensive patients, metoclopramide enhanced the release of catecholamines. As a result, the manufacturer advises cautious use in hypertensive patients and suggests that the drug should not be used in patients taking monoamine oxidase inhibitors.

    4. Agitation, diaphoresis, and extrapyramidal movement disorder were reported in two patients taking selective serotonin reuptake inhibitors (sertraline, venlafaxine) who received IV metoclopramide.

    5. The drug may enhance the absorption of ingested drugs by promoting gastric emptying.

    6. Anticholinergic agents may inhibit bowel motility effects.

    7. Numerous IV incompatibilities: calcium gluconate, sodium bicarbonate, cimetidine, furosemide, and many antibiotic agents (eg, ampicillin, chloramphenicol, erythromycin, penicillin G potassium, tetracycline).

  6. Dosage and method of administration

    1. Low-dose therapy. Effective for mild nausea and vomiting. Give 10–20 mg IM, orally, sublingually, or slowly IV (children: 0.1 mg/kg per dose). Doses of 10 mg or less can be given by IV push undiluted over 1–2 minutes.

    2. High-dose therapy. For control of severe or persistent vomiting. For adults and children, give a 1- to 2-mg/kg IV infusion over 15 minutes in 50 mL of saline or dextrose. May ...

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