World Library  
Flag as Inappropriate
Email this Article
 

Metoclopramide

Metoclopramide (INN)
Systematic (IUPAC) name
4-Amino-5-chloro-N-(2-(diethylamino)ethyl)-2-methoxybenzamide
Clinical data
Pronunciation
Trade names list
AHFS/Drugs.com
MedlinePlus
Licence data US FDA:
Pregnancy
category
  • AU: A
  • US: B (No risk in non-human studies)
Legal status
Routes of
administration
Oral, intravenous, intramuscular
Pharmacokinetic data
Bioavailability 80±15% (oral)
Metabolism Hepatic
Biological half-life 5–6 hours
Excretion 70–85% renal, 2% faecal
Identifiers
CAS Registry Number  Y
ATC code A03
PubChem CID:
IUPHAR/BPS
DrugBank  Y
ChemSpider  Y
UNII  Y
KEGG  Y
ChEBI  Y
ChEMBL  Y
Chemical data
Formula C14H22ClN3O2
Molecular mass 299.80 g/mol
Physical data
Melting point 147.3 °C (297.1 °F)
 Y   

Metoclopramide is a medication used mostly for health system.[6]

Contents

  • Medical uses 1
    • Antiemetic 1.1
    • Gastroprokinetic 1.2
    • Other indications 1.3
  • Adverse effects 2
  • Cautions 3
    • Pregnancy 3.1
    • Infants 3.2
  • Mechanism of action 4
  • Brand names 5
  • Veterinary use 6
  • Contraindictions 7
  • See also 8
  • References 9
  • Further reading 10

Medical uses

Metoclopramide is commonly used to treat nausea - including that due to chemotherapy and that occurring postoperatively. Evidence also supports its use for gastroparesis, a condition that causes the stomach to empty poorly, and gastroesophageal reflux disease.[2] It is also used in pregnancy as a second choice for treatment of hyperemesis gravidarum (severe nausea and vomiting of pregnancy).[2]

Antiemetic

Metoclopramide 5-mg tablets (Pliva)

Metoclopramide treats nausea and vomiting associated with conditions such as uremia, radiation sickness, malignancy, labor, infection, migraine headaches, and emetogenic drugs.[7][8] In the setting of painful conditions such as migraine headaches, metoclopramide may be used in combination with paracetamol (acetaminophen) (available in the UK as Paramax, and in Australia as Metomax), or in combination with aspirin (MigraMax). It is also used preventatively by some EMS providers when transporting people who are conscious and spinally immobilized.[9]

The Rosemont Patient Information Leaflet of their sugar-free metoclopramide hydrochloride (5 mg/5 ml) oral solution states,

"Metoclopramide can be used to treat stomach upset including heartburn, wind, pain, indigestion, sickness and bile regurgitation, to stop nausea and vomiting, to relieve your symptoms of nausea and vomiting when you have a migraine, to help restore normal stomach emptying after an operation and during hospital tests such as a barium meal."

and

"In young adults and children, metoclopramide can be given for severe and long-lasting vomiting if the cause is known, to stop vomiting caused by cancer treatment such as radiotherapy and chemotherapy, to help in passing a tube into the stomach and intestine and to help stop feeling and being sick before having an operation." [10]

Gastroprokinetic

Metoclopramide increases peristalsis of the duodenum and jejunum, increases tone and amplitude of gastric contractions, and relaxes the pyloric sphincter and duodenal bulb, while simultaneously increasing lower esophageal sphincter tone. These gastroprokinetic effects make metoclopramide useful in the treatment of gastric stasis (for example: after gastric surgery or diabetic gastroparesis), as an aid in gastrointestinal radiographic studies by accelerating transit through the gastrointestinal system in barium studies, and as an aid in difficult intubation of the small intestine. It is also used in gastroesophageal reflux disease.[11]

Other indications

By inhibiting the action of dopamine, metoclopramide has sometimes been used to stimulate lactation.[12] It can also help with the pain of migraines.[3]

Adverse effects

Plastic ampoule of metoclopramide

Common adverse drug reactions (ADRs) associated with metoclopramide therapy include restlessness (akathisia), and focal dystonia. Infrequent ADRs include hypertension, hypotension, hyperprolactinaemia leading to galactorrhea, constipation, depression, headache, and extrapyramidal effects such as oculogyric crisis. Rare but serious ADRs associated with metoclopramide therapy include agranulocytosis, supraventricular tachycardia, hyperaldosteronism, neuroleptic malignant syndrome, akathisia and tardive dyskinesia.[8]

Metoclopramide may be the most common cause of drug-induced movement disorders.[13] The risk of extrapyramidal effects is increased in people under 20 years of age, and with high-dose or prolonged therapy.[7][8] Tardive dyskinesia may be persistent and irreversible in some patients. The majority of reports of tardive dyskinesia occur in people who have used metoclopramide for more than three months.[13] Consequently, the US Food and Drug Administration (FDA) recommends that metoclopramide be used for short-term treatment, preferably less than 12 weeks. In 2009, the FDA required all manufacturers of metoclopramide to issue a black box warning regarding the risk of tardive dyskinesia with chronic or high-dose use of the drug.[13]

Dystonic reactions may be treated with benzatropine, diphenhydramine, trihexyphenidyl, or procyclidine. Symptoms usually subside with diphenhydramine injected intramuscularly.[14] Agents in the benzodiazepine class of drugs may be helpful, but benefits are usually modest and side effects of sedation and weakness can be problematic.[15]

In some cases, the akathisia effects of metoclopramide are directly related to the infusion rate when the drug is administered intravenously. Side effects were usually seen in the first 15 minutes after the dose of metoclopramide.[16]

Cautions

Metoclopramide is contraindicated in pheochromocytoma. It should be used with caution in Parkinson's disease since, as a dopamine antagonist, it may worsen symptoms. Long-term use should be avoided in patients with clinical depression, as it may worsen one's mental state.[8] Also, it is contraindicated in patients with a suspected bowel obstruction.[2]

Patients with a history of ADHD, restless legs syndrome, hyperprolactinaemia, and Parkinson's disease should be closely monitored when using dopamine antagonists for treatment of emesis. Patients who take antipsychotics are recommended not to take metoclopramide.

Pregnancy

Metoclopramide has long been used in all stages of pregnancy with no evidence of harm to the mother or unborn baby.[17] In the USA, it has been assigned to pregnancy category B by the US FDA.[18] A large cohort study of babies born to Israeli women exposed to metoclopramide during pregnancy found no evidence that the drug increases the risk of congenital malformations, low birth weight, preterm birth, or perinatal mortality. [19] A large cohort study in Denmark found, in addition, no association between metoclopramide exposure and miscarriage.[20] Metoclopramide is excreted into milk.[17]

Infants

A systematic review found a wide range of reported outcomes for treatment of gastroesophageal reflux disease (GERD) in infants and concluded a "poor" rating of evidence and "inconclusive" rating of safety and efficacy for the treatment of GERD in infants.[21]

Mechanism of action

Metoclopramide was first described by Dr. Louis Justin-Besançon and C. Laville in 1964.[22]

It appears to bind to dopamine D2 receptors with nanomolar affinity (Ki 28.8 nM),[23] where it is a receptor antagonist, and is also a mixed 5-HT3 receptor antagonist/5-HT4 receptor agonist.

The antiemetic action of metoclopramide is due to its antagonist activity at D2 receptors in the chemoreceptor trigger zone in the central nervous system — this action prevents nausea and vomiting triggered by most stimuli.[24] At higher doses, 5-HT3 antagonist activity may also contribute to the antiemetic effect.

The gastroprokinetic activity of metoclopramide is mediated by muscarinic activity, D2 receptor antagonist activity and 5-HT4 receptor agonist activity.[25][26] The gastroprokinetic effect itself may also contribute to the antiemetic effect. Metoclopramide also increases the tone of the lower esophageal sphincter.[27]

Brand names

Metoclopramide is available world-wide under various trade names:

Veterinary use

Metoclopramide is also commonly used to prevent vomiting in cats and dogs. It is also used as a gut stimulant in rabbits.[31]

Contraindictions

Metoclopramide is contraindicated in epilepsy, if a stomach operation has been performed in the previous three or four days, if the patient has ever had bleeding, perforation or blockage of the stomach, in cases of pheochromocytoma, and in newborn babies.[10]

See also

References

  1. ^ "Metoclopramide". nlm.nih.gov. Retrieved 28 September 2014. 
  2. ^ a b c d e f g h "Metoclopramide hydrochloride". Monograph. The American Society of Health-System Pharmacists. Retrieved 2014-09-27. 
  3. ^ a b Derry, S; Moore, RA; McQuay, HJ (Nov 10, 2010). "Paracetamol (acetaminophen) with or without an antiemetic for acute migraine headaches in adults.". The Cochrane database of systematic reviews (11): CD008040.  
  4. ^ "Prescribing medicines in pregnancy database". Australian Government. 3 March 2014. Retrieved 22 April 2014. 
  5. ^ Bartholow, Michael. "Top 200 Drugs of 2012". Pharmacy Times. Retrieved 22 April 2014. 
  6. ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014. 
  7. ^ a b "Maxolon (Australian Approved Product Information)". Valeant Pharmaceuticals. 2000. 
  8. ^ a b c d Rossi S., ed. (2006). Australian Medicines Handbook. Adelaide: Australian Medicines Handbook.  
  9. ^ "Ambulance Victoria Clinical Guideline A0701"http://www.ambulance.vic.gov.au/media/docs/Adult%20CPG%20wm-a01f0e1e-4fc0-405c-bc83-3136adf4a723-0.pdf
  10. ^ a b http://xpil.medicines.org.uk/ViewPil.aspx?DocID=8068
  11. ^ "METOCLOPRAMIDE (metoclopramide hydrochloride) injection, solution [Hospira, Inc.]" http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=373ba08b-33ad-49fc-28a7-928e89a65314#nlm34089-3
  12. ^ "Metoclopramide". lowmilksupply.org. 
  13. ^ a b c "FDA requires boxed warning and risk mitigation strategy for metoclopramide-containing drugs" (Press release). U.S. Food and Drug Administration. 2009-02-26. Retrieved 2009-06-11.  "Lay Summary – WebMD". 
  14. ^ "Metoclopramide (metoclopramide hydrochloride) injection, solution [Hospira, Inc.]" http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=373ba08b-33ad-49fc-28a7-928e89a65314#nlm34089-3
  15. ^ Olanow C, Schapira AV. Chapter 372. Parkinson's Disease and Other Movement Disorders. In: Longo DL, Fauci AS, Kasper DL, Hauser SL, Jameson J, Loscalzo J. eds. Harrison's Principles of Internal Medicine, 18e. New York, NY: McGraw-Hill; 2012.
  16. ^ Parlak, I; Atilla, R; Cicek, M; Parlak, M; Erdur, B; Guryay, M; Sever, M; Karaduman, S (Sep 2005). "Rate of metoclopramide infusion affects the severity and incidence of akathisia.". Emergency medicine journal : EMJ 22 (9): 621–4.  
  17. ^ a b Briggs, G. G.; Freeman, R. K.; Yaffe, S. J. (2008). Drugs in Pregnancy and Lactation (8th ed.). Philadelphia: Lippincott Williams & Wilkins. pp. 1197–1200.  
  18. ^ http://www.drugs.com/metoclopramide.html
  19. ^ Matok, I.; Gorodischer, R.; Koren, G.; Sheiner, E.; Wiznitzer, A.; Levy, A. (2009). "The Safety of Metoclopramide Use in the First Trimester of Pregnancy" (pdf). New England Journal of Medicine 360 (24): 2528–2535.  
  20. ^ Pasternak, B. R.; Svanström, H.; Mølgaard-Nielsen, D.; Melbye, M.; Hviid, A. (2013). "Metoclopramide in Pregnancy and Risk of Major Congenital Malformations and Fetal Death". JAMA 310 (15): 1601–1611.  
  21. ^ Hibbs, AM; Lorch, SA (Aug 2006). "Metoclopramide for the treatment of gastroesophageal reflux disease in infants: a systematic review.". Pediatrics 118 (2): 746–52.  
  22. ^ Justin-Besancon, L.; Laville, C. (1964). "Antiemetic Action of Metoclopramide with Respect to Apomorphine and Hydergine". Comptes Rendus des Séances de la Société de Biologie et de ses Filiales (in French) 158: 723–727.  
  23. ^ Prediction of Catalepsies Induced by Amiodarone, Aprindine and Procaine: Similarity in Conformation of Diethylaminoethyl Side Chain http://jpet.aspetjournals.org/content/287/2/725.full.pdf
  24. ^ Rang, H. P.; Dale, M. M.; Ritter, J. M.; Moore, P. K. (2003). Pharmacology (5th ed.). Edinburgh: Churchill Livingstone.  
  25. ^ Sweetman S., ed. (2004). Martindale: The Complete Drug Reference (34th ed.). London: Pharmaceutical Press.  
  26. ^ Tonini, M.; Candura, S. M.; Messori, E.; Rizzi, C. A. (1995). "Therapeutic Potential of Drugs with Mixed 5-HT4 Agonist/5-HT3 Antagonist Action in the Control of Emesis". Pharmacological Research 31 (5): 257–260.  
  27. ^ Feldman, M.; Friedman, L. S.; Brandt, L. J., eds. (2010). "Ch. 43: Gastroesophageal Reflux Disease". Sleisenger and Fordtran's Gastrointestinal and Liver Disease (9th ed.). Philadelphia: Saunders.  
  28. ^ felleskatalogen.no
  29. ^ Snyman, J.R., ed. (June 2010). MIMS (Monthly Index of Medical Specialities) (Vol. 50 no. 6 ed.). Johannesburg: Avusa Media Ltd. 
  30. ^ "Summary of Product Characteristics (Emeprid 1mg/ml)". DEFRA Veterinary Medicines Directorate. 
  31. ^ Mikota, S. K.; Plumb, D. C. (June 2003). "Metoclopramide HCl". The Elephant Formulary. Elephant Care International. 

Further reading

  • Brenner, G. M. (2000). Pharmacology. London: Saunders.  
  • Compendium of Pharmaceuticals and Specialties 2011. Toronto: Canadian Pharmacists Association. 2011.  
  • Anderson, E. P.; Freeman, E. B. (May 2004). "Recognition of Movement Disorders and Extrapyramidal side effects - would you recognize them if you see them?" (pdf). Practical Gastroenterology: 14. 
This article was sourced from Creative Commons Attribution-ShareAlike License; additional terms may apply. World Heritage Encyclopedia content is assembled from numerous content providers, Open Access Publishing, and in compliance with The Fair Access to Science and Technology Research Act (FASTR), Wikimedia Foundation, Inc., Public Library of Science, The Encyclopedia of Life, Open Book Publishers (OBP), PubMed, U.S. National Library of Medicine, National Center for Biotechnology Information, U.S. National Library of Medicine, National Institutes of Health (NIH), U.S. Department of Health & Human Services, and USA.gov, which sources content from all federal, state, local, tribal, and territorial government publication portals (.gov, .mil, .edu). Funding for USA.gov and content contributors is made possible from the U.S. Congress, E-Government Act of 2002.
 
Crowd sourced content that is contributed to World Heritage Encyclopedia is peer reviewed and edited by our editorial staff to ensure quality scholarly research articles.
 
By using this site, you agree to the Terms of Use and Privacy Policy. World Heritage Encyclopedia™ is a registered trademark of the World Public Library Association, a non-profit organization.
 



Copyright © World Library Foundation. All rights reserved. eBooks from World eBook Library are sponsored by the World Library Foundation,
a 501c(4) Member's Support Non-Profit Organization, and is NOT affiliated with any governmental agency or department.