Metoclopramide
Metoclopramide is a widely used **gastrointestinal prokinetic** and **antiemetic** agent in veterinary medicine. * **Prokinetic Effects**: It primarily targets the upper GI tract (stomach and small intestine) with minimal effect on the colon. It is used clinically for gastric stasis, gastroesophageal reflux, and post-operative ileus. * **Antiemetic Effects**: It is highly effective in dogs due to their abundance of dopaminergic receptors in the chemoreceptor trigger zone (CRTZ). Conversely, cats have fewer D2 receptors, making metoclopramide a less reliable antiemetic in felines (where alpha-2 antagonists or NK-1 antagonists like maropitant are often preferred). **Clinical Pearls**: * Often administered as a continuous rate infusion (CRI) for severe conditions like parvoviral enteritis or acute pancreatitis. * Because it crosses the blood-brain barrier, it can cause notable extrapyramidal side effects (e.g., tremors, restlessness, frenzied behavior), especially at higher doses or in sensitive species like horses.
Mechanism: Metoclopramide exerts its effects through both peripheral gastrointestinal and central nervous system mechanisms: * **Peripheral (GI Tract)**: Sensitizes upper GI smooth muscle to **acetylcholine** โ increases tone and amplitude of gastric contractions, relaxes the pyloric sphincter, and increases duodenal and jejunal peristalsis. It also increases lower esophageal sphincter (LES) pressure, reducing reflux. * **Central (CNS)**: Antagonizes **Dopamine (D2)** receptors in the **Chemoreceptor Trigger Zone (CRTZ)** โ blocks emetic signaling to the vomiting center, providing a potent central antiemetic effect. * **Additional Mechanisms**: At higher doses, it exhibits weak **5-HT3 (Serotonin)** receptor antagonism and **5-HT4** receptor agonism, further contributing to its antiemetic and prokinetic profiles.
Dosing by species
- As a prokinetic for adjunctive treatment of esophagitis ยท 0.2-0.4 mg/kg PO q8h ยท PO ยท q8h ยท Cisapride considered superior.
- General use ยท 0.2-0.4 mg/kg PO, SC 3-4 times daily; or as a continuous IV infusion (1-2 mg/kg per day) ยท PO/SC/IV ยท tid-qid or CRI
- General use ยท 0.2-0.5 mg/kg q8h PO or parenterally (may be given as a constant rate IV infusion at 0.01-0.02 mg/kg/hr) ยท PO/IV/IM/SC ยท q8h or CRI
- To increase bladder contractility ยท 0.2-0.5 mg/kg PO q8h ยท PO ยท q8h
- To induce milk let-down for secondary agalactia ยท 0.1-0.2 mg/kg SC q12h ยท SC ยท q12h ยท Used to promote milk production.
- To stimulate the gastrointestinal tract ยท 0.04 mg/kg/hr as a CRI ยท IV ยท CRI ยท ARCI UCGFS Class 4 Drug.
- For reflux esophagitis ยท 0.02-0.1 mg/kg SC q4-12 hours ยท SC ยท q4-12h ยท Horses may be prone to extrapyramidal neurologic side effects.
- General therapeutics (Rabbits) ยท 0.2-1 mg/kg PO or SC q6-8h ยท PO/SC ยท q6-8h
- To assist in removing gastric hairballs (Rabbits) ยท 0.5 mg/kg PO once a day (up to three times a day) ยท PO ยท sid to tid
Routes of administration
Contraindications
- GI hemorrhage
- GI obstruction or perforation
- Hypersensitivity to metoclopramide
- Seizure disorders (relatively contraindicated, lowers seizure threshold)
- Head trauma
- Pheochromocytoma (may induce hypertensive crisis)
- Concurrent phenothiazine therapy
- Dogs with pseudopregnancy (stimulates prolactin release)
- Gastrointestinal obstruction
- Gastrointestinal perforation
- Gastrointestinal hemorrhage
- Seizure disorders (epilepsy)
- Pheochromocytoma
Adverse effects
- Dogs: Changes in mentation and behavior (motor restlessness, involuntary spasms, aggression, hyperactivity to drowsiness/depression), constipation
- Cats: Frenzied behavior, disorientation, constipation
- Horses: Severe CNS effects (IV use), alternating sedation and excitement, behavioral changes, abdominal pain
- Extrapyramidal effects (tremors, rigid posture)
- Nausea and diarrhea
- Transient hypertension
- Elevated prolactin levels
- Extrapyramidal signs (tremors, twitching, hyperactivity, restlessness)
- Sedation
- Constipation or diarrhea
- Changes in mentation or behavior
Drug interactions
- Aspirin, Acetaminophen, Alcohol ยท Metoclopramide may enhance the absorption of these agents.
- Anesthetics ยท Acute hypotension has been reported if metoclopramide is used concurrently IV.
- Atropine (and anticholinergics) ยท May antagonize the GI motility effects of metoclopramide.
- Cephalexin ยท Oral metoclopramide increases cephalexin peak plasma concentrations and AUC in dogs.
- Cholinergic Drugs (e.g., bethanechol) ยท May enhance metoclopramide's GI effects.
- CNS Depressants ยท Metoclopramide may enhance CNS depressant effects. ยท moderate
- Cyclosporine ยท Metoclopramide increases the rate and extent of GI absorption.
- Opiate Analgesics ยท May antagonize the GI motility effects and enhance metoclopramide's CNS effects.
- MAO Inhibitors (e.g., amitraz, selegiline) ยท Could cause hypertension.
- Phenothiazines and Butyrophenones ยท May potentiate the extrapyramidal effects of metoclopramide.
- Propofol ยท Reduces induction requirements of propofol by 20-25%.
- SSRI Antidepressants ยท Potential for enhanced extrapyramidal effects.
Monitoring
- Clinical efficacy (resolution of vomiting, improved GI transit)
- Adverse effects (especially CNS and extrapyramidal signs)
- Clinical response (reduction in vomiting, improved gastric emptying)
- Hydration status and electrolyte balance
- Signs of extrapyramidal adverse effects (twitching, restlessness)
Overdose
The oral LD50 doses are very high (465-870 mg/kg in laboratory animals), making death from oral overdose unlikely in veterinary patients. **Clinical Signs of Toxicity**: * Sedation, ataxia, agitation * Extrapyramidal effects (tremors, rigidity, spasms) * Nausea, vomiting, constipation **Treatment**: * No specific antidote exists. * If ingestion was recent, empty the stomach using standard protocols. * **Anticholinergic agents** that enter the CNS (e.g., **diphenhydramine** at 2.2 mg/kg IV, or benztropine) are highly effective in controlling extrapyramidal effects. * Peritoneal dialysis or hemodialysis is not effective for drug removal.
VetSheet drug reference is intended for licensed veterinary professionals as a clinical decision-support aid, not a substitute for professional judgement or the manufacturerโs current label.