Metoclopramide

Metoclopramide
Systematic (IUPAC) name
4-amino-5-chloro-N-(2-(diethylamino)ethyl)-
2-methoxybenzamide
Clinical data
Trade names Reglan
AHFS/Drugs.com monograph
MedlinePlus a684035
Pregnancy cat. A (Au), B (U.S.)
Legal status S3/S4 (Au), POM (UK), ℞-only (U.S.)
Routes Oral, intravenous, intramuscular
Pharmacokinetic data
Bioavailability 80±15% (oral)
Metabolism Hepatic
Half-life 5–6 hours
Excretion 70–85% renal, 2% faecal
Identifiers
CAS number 364-62-5 YesY
ATC code A03FA01
PubChem CID 4168
IUPHAR ligand 241
DrugBank DB01233
ChemSpider 4024 YesY
UNII L4YEB44I46 YesY
KEGG D00726 YesY
ChEBI CHEBI:107736 N
ChEMBL CHEMBL86 YesY
Chemical data
Formula C14H22ClN3O2 
Mol. mass 299.80 g/mol
SMILES eMolecules & PubChem
Physical data
Melt. point 147.3 °C (297 °F)
 N(what is this?)  (verify)

Metoclopramide (INN) (play /ˌmɛtəˈklɒprəmd/) is an antiemetic and gastroprokinetic agent. It is commonly used to treat nausea and vomiting, to facilitate gastric emptying in people with gastroparesis, and as a treatment for the gastric stasis often associated with migraine headaches.

Contents

Medical uses

Metoclopramide is commonly used to treat nausea including that which is due to chemotherapy and that occurring post operatively. Evidence also supports its use for gastroparesis (poor stomach emptying) and gastroesophageal reflux disease.[1]

Antiemetic

Metoclopramide 5mg tablets (Pliva)

Metoclopramide commonly treats nausea and vomiting associated with conditions such as uremia, radiation sickness, malignancy, labor, infection, migraine headaches, and emetogenic drugs.[2][3] 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).

Gastroprokinetic

Metoclopramide increases peristalsis of the jejunum and duodenum, increases tone and amplitude of gastric contractions, and relaxes the pyloric sphincter and duodenal bulb. These gastroprokinetic effects make metoclopramide useful in the treatment of gastric stasis (e.g. 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 (GERD).

Other indications

By inhibiting the action of dopamine, metoclopramide has sometimes been used to stimulate lactation. It can also be used in the treatment of migraines in the setting of allodynia, where it is more effective than triptans.[4]

Adverse effects

Plastic ampoule of metoclopramide

Common adverse drug reactions (ADRs) associated with metoclopramide therapy include restlessness, drowsiness, dizziness, fatigue, 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.[3]

Recent research suggests that metoclopramide may be the most common cause of drug-induced movement disorders.[5] The risk of extrapyramidal effects is increased in people under 20 years of age, and with high-dose or prolonged therapy.[2][3] 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.[5] Consequently, the USFDA recommends that metoclopramide be used for short term treatment, preferably less than 12 weeks. In 2009, the USFDA 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.[5]

Dystonic reactions may be treated with benztropine, diphenhydramine, trihexyphenidyl or procyclidine.

Mechanism of action

Metoclopramide was first described by Dr. Louis Justin-Besançon and C. Laville in 1964.[6]

It appears to bind to dopamine D2 receptors where it is a receptor antagonist, and is also a mixed 5-HT3 receptor antagonist/ 5-HT4 receptor agonist.

The anti-emetic action of metoclopramide is due to its antagonist activity at D2 receptors in the chemoreceptor trigger zone (CTZ) in the central nervous system (CNS)—this action prevents nausea and vomiting triggered by most stimuli.[7] At higher doses, 5-HT3 antagonist activity may also contribute to the anti-emetic effect.

The gastroprokinetic activity of metoclopramide is mediated by muscarinic activity, D2 receptor antagonist activity and 5-HT4 receptor agonist activity.[8][9] The gastroprokinetic effect itself may also contribute to the anti-emetic effect.

Contraindications and precautions

Metoclopramide is contraindicated in phaeochromocytoma. 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 mental state.[3] Also contraindicated with a suspected bowel obstruction.[1]

Use in pregnancy

Metoclopramide has long been used in all stages of pregnancy with no evidence of harm to the mother or unborn baby.[10] 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. [11] Metoclopramide is excreted into milk.[10]

Brand names

It is available under various trade names including Maxolon in the UK (Shire/Valeant), Reglan in the USA (Schwarz Pharma), Degan (Lek), Maxeran (Sanofi Aventis), Primperan (Sanofi Aventis), Pylomid (Bosnalijek), Cerucal (AWD Pharma), Pramin (Generic)).

Veterinary use

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

See also

References

  1. ^ a b "Metoclopramide hydrochloride". Monograph. The American Society of Health-System Pharmacists. http://www.drugs.com/monograph/metoclopramide-hydrochloride.html. Retrieved 2011-04-03. 
  2. ^ a b "Maxolon (Australian Approved Product Information)". Valeant Pharmaceuticals. http://www.mydr.com.au/medicines/cmis/maxolon-tablets. 
  3. ^ a b c d Rossi S., ed (2006). Australian Medicines Handbook. Adelaide: Australian Medicines Handbook. ISBN 0-9757919-2-3. 
  4. ^ Snow, V.; Weiss, K.; Wall, E. M.; Mottur-Pilson, C.; American Academy of Family Physicians; American College of Physicians-American Society of Internal Medicine (2002). "Pharmacologic management of acute attacks of migraine and prevention of migraine headache" (pdf). Annals of internal medicine 137 (10): 840–849. PMID 12435222. http://www.annals.org/content/137/10/840.full.pdf.  edit
  5. ^ 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. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm149533.htm. Retrieved 2009-06-11.  "Lay summary–WebMD". http://www.webmd.com/digestive-disorders/news/20090227/metoclopramide-drugs-get-black-box-warning. 
  6. ^ Justin-Besancon, L.; Laville, C. (1964). "Antiemetic Action of Metoclopramide with Respect to Apomorphine and Hydergine" (in french). Comptes rendus des seances de la Societe de biologie et de ses filiales 158: 723–727. PMID 14186927.  edit
  7. ^ Rang, H.P.; Dale, M. M.; Ritter, J. M.; Moore, P. K. (2003). Pharmacology (5th ed.). Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4. 
  8. ^ Sweetman S., ed (2004). Martindale: The complete drug reference (34th ed.). London: Pharmaceutical Press. ISBN 0-85369-550-4. 
  9. ^ 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. ISSN 1043-6618. PMID 7479521.  edit
  10. ^ 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. ISBN 0-7817-7876-X. http://books.google.com/books?id=YOEV2w3XTxsC&pg=PA1197. Retrieved 2009-06-11. 
  11. ^ 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. doi:10.1056/NEJMoa0807154. PMID 19516033. http://www.nejm.org/doi/pdf/10.1056/NEJMoa0807154.  edit

Further reading

  • Brenner, G. M. (2000). Pharmacology. London: Saunders. ISBN 0-7216-7757-6. 
  • Compendium of Pharmaceuticals and Specialties 2011. Toronto: Canadian Pharmacists Association. 2011. ISBN 978-1-894402-54-5. 

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Look at other dictionaries:

  • Metoclopramide — Métoclopramide Métoclopramide Général Nom IUPAC …   Wikipédia en Français

  • Métoclopramide — Général Nom IUPAC …   Wikipédia en Français

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  • metoclopramide — ˌmed.əˈklōprəˌmīd noun ( s) Etymology: International Scientific Vocabulary methoxy + chlor + procainamide; originally formed as French métoclopramide : an antiemetic drug C14H22ClN3O2 administered in the form of its hydrochloride …   Useful english dictionary

  • metoclopramide — /met oh kloh preuh muyd /, n. Pharm. a white crystalline substance, C14H22ClN3O2, used primarily in the symptomatic treatment of certain upper gastrointestinal tract problems, and as an antiemetic. [met(h)o(benzamide) a component + C(H)LO(RO) 2 + …   Universalium

  • metoclopramide — noun A gastrokinetic drug with antiemetic properties …   Wiktionary

  • metoclopramide — met·o·clo·pra·mide .met ə klō prə .mīd n an antiemetic drug administered in the form of its hydrated hydrochloride C14H22ClN3O2·HCl·H2O * * * n. a drug that antagonizes the actions of dopamine; it is used to treat nausea, vomiting, indigestion,… …   Medical dictionary

  • metoclopramide — met·o·clo·pra·mide …   English syllables

  • metoclopramide — n. a drug that antagonizes the actions of dopamine; it is used to treat nausea and vomiting, particularly when associated with gastrointestinal disorders. It is administered by mouth or injection; high doses may cause drowsiness and muscle spasms …   The new mediacal dictionary

  • metoclopramide — A drug that increases the motility (movements and contractions) of the stomach and upper intestine. It is used to treat certain stomach problems and nausea and vomiting caused by chemotherapy. It belongs to the families of drugs called… …   English dictionary of cancer terms


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