Metoclopramide

From Drugs Prescribing Information
Jump to: navigation, search

Contents

[edit] BRAND NAMES

[edit] STRUCTURE

File:Metoclopramide.jpg

[edit] MECHANISM OF ACTION

Metoclopramide acts as:

  • Competitive antagonist at dopamine D2 receptors (anti-emetic effect): metoclopramide crosses the blood-brain barrier (BBB) ​​and acts as an antagonist at D2 receptors in the chemoreceptor trigger zone (CTZ) of the central nervous system. This activity blocks the nausea and vomiting.
  • Antagonist at serotonin 5-HT3 receptor (antiemetic effect): Serotonin is one of the most important mediators of nausea and vomiting. 5-HT3 receptors are located peripherally on vagal afferent nerve terminals and in certain areas of the brain (area postrema). Serotonin binding to 5HT3 receptors, activates the emetic reflex and metoclopromide antagonizes it.
  • Agonist at serotonin 5-HT4 receptor (prokinetic effect), mainly expressed in peripheral neurons of the gastrointestinal tract. The activation of these receptors indirectly stimulates the release of acetylcholine, the main neurotransmitter promoting intestinal motility, ie facilitating the gastrointestinal transit , digestion, and evacuation of the bowels.

[edit] INDICATIONS

  • To prevent or treat nausea and vomiting, including nausea and vomiting that may result from anticancer medicines or radiation treatment, surgery, or an attack of migraine.
  • Relief of Symptomatic Gastroesophageal Reflux

[edit] DOSAGE

[edit] CONTRAINDICATIONS

For all formulations:

  • Hypersensitivity to Metoclopramide or to any of the excipients
  • Intestinal obstruction, Hemorrhage, or Perforation.
  • Confirmed or suspected pheochromocytoma, due to the risk of severe hypertension episodes
  • History of neuroleptic or metoclopramide-induced tardive dyskinesia
  • Known Sensitivity or Intolerance
  • Epilepsy (increased crises frequency and intensity)
  • Concomitant Medications with Extrapyramidal Reactions
  • Parkinson’s disease
  • Combination with levodopa or dopaminergic agonists
  • Use in children less than 1 year of age due to an increased risk of extrapyramidal disorders

For rectal formulations

  • Recent history of proctitis or rectal bleeding
  • Use in children below 18 years of age

[edit] WARNINGS AND PRECAUTIONS

  • Tardive Dyskinesia: Treatment with metoclopramide can cause tardive dyskinesia, a serious movement disorder that is often irreversible, characterized by spasmodic or repetitive motions or lack of coordination. The risk of developing tardive dyskinesia increases with duration of treatment and total cumulative dose. In some patients, symptoms may lessen or resolve after metoclopramide treatment is stopped. Treatment with metoclopramide for longer than 12 weeks should be avoided in all but rare cases where therapeutic benefit is thought to outweigh the risk of developing tardive dyskinesia.
  • Acute Dystonic Reactions, Drug-induced Parkinsonism and Other Extrapyramidal Symptoms: Extrapyramidal symptoms (EPS), manifested primarily as acute dystonic reactions, occur in approximately 1 in 500 patients treated with the usual adult dosages of 30 to 40 mg/day of metoclopramide. These usually are seen during the first 24 to 48 hours of treatment with metoclopramide, occur more frequently in pediatric patients and adult patients less than 30 years of age and are even more frequent at higher doses. These symptoms may include involuntary movements of limbs and facial grimacing, torticollis, oculogyric crisis, rhythmic protrusion of tongue, bulbar type of speech, trismus, or dystonic reactions resembling tetanus. Rarely, dystonic reactions may present as stridor and dyspnea, possibly due to laryngospasm. If these symptoms occur, inject 50 mg diphenhydramine hydrochloride intramuscularly. Benztropine mesylate, 1 to 2 mg intramuscularly, may also be used to reverse these reactions.
  • Neuroleptic Malignant Syndrome: There have been rare reports of an uncommon but potentially fatal symptom complex sometimes referred to as Neuroleptic Malignant Syndrome (NMS) associated with metoclopramide. Clinical manifestations of NMS include hyperthermia, muscle rigidity, altered consciousness, and evidence of autonomic instability (irregular pulse or blood pressure, tachycardia, diaphoresis and cardiac arrhythmias).
  • Depression: Depression associated with metoclopramide use has occurred in patients with and without a history of depression. Symptoms ranged from mild to severe and included suicidal ideation and suicide. For those patients with a prior history of depression, metoclopramide should only be given if the expected benefits outweigh the potential risks.
  • Hypertension: caution should be exercised when metoclopramide is used in patients with hypertension.
  • Congestive Heart Failure and Ventricular Arrhythmia: Since metoclopramide produces a transient increase in plasma aldosterone, patients with cirrhosis or congestive heart failure may be at risk of developing fluid retention and volume overload. If these side effects occur at any time in any patients during metoclopramide therapy, the drug should be discontinued.
  • Withdrawal from Metoclopramide: Adverse reactions, especially those involving the nervous system, may occur after stopping the use of metoclopramide. A small number of patients may experience withdrawal symptoms after stopping that could include dizziness, nervousness, and/or headaches.

[edit] INTERACTIONS

  • Anticholinergic drugs: Antagonize effects of metoclopramide.
  • Narcotic analgesic drugs: May increase sedation
  • Monoamine oxidase inhibitors: May cause hypertensive crisis (due to catecholamine release)
  • Altered drug absorption: May decrease absorption of drugs from the stomach and increase absorption of drugs from the small bowel
  • Insulin: Changes in food transit time may require adjustment of insulin dose or timing to avoid hypoglycemia
  • Antidepressants, Antipsychotics, and Neuroleptics: Concomitant use with metoclopramide is associated with increased risk of tardive dyskinesia and Neuroleptic Malignant Syndrome.

[edit] PREGNANCY AND LACTATION

  • Pregnancy Category B (US). Metoclopramide should be used during pregnancy only if clearly needed
  • Nursing Mothers: Metoclopramide is excreted in human milk. Caution should be exercised when metoclopramide is administered to a nursing mother. Because of the potential for serious adverse reactions from metoclopramide in nursing infants and because of the potential for tumorigenicity (including tumor promoting potential in rats), a decision should be made whether to discontinue nursing or to discontinue the drug, taking into account the importance of the drug to the mother

[edit] SIDE EFFECTS

The most common adverse reactions are headache, fatigue, and somnolence

[edit] RELATED LINKS

[edit] BIBLIOGRAPHY

[edit] REFERENCES

Antiemetics
5-HT3 receptor antagonists Dolasetron   Granisetron   Ondansetron   Palonosetron   Tropisetron
Dopamine antagonists Alizapride   Bromopride   Clebopride   Domperidone   Metoclopramide   Prochlorperazine   Thiethylperazine
H1 antagonists Dimenhydrinate   Meclizine
NK1 receptor antagonists‎ Aprepitant   Fosaprepitant   Maropitant
Motion sickness‎ Cinnarizine   Dimenhydrinate   Meclizine   Meclizine/Pyridoxine   Scopolamine (Patch)
Pregnancy Meclizine/Pyridoxine   Ondansetron
Veterinary Maropitant