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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/01/19 03:42:15」(JST)
wiki en
| Systematic (IUPAC) name | |
|---|---|
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4-Amino-5-chloro-N-(2-(diethylamino)ethyl)-2-methoxybenzamide
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| Clinical data | |
| Pronunciation | /ˌmɛtəˈklɒprəmaɪd/ |
| Trade names | list |
| AHFS/Drugs.com | monograph |
| MedlinePlus | a684035 |
| Licence data | US FDA:link |
| Pregnancy category |
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| Legal status |
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| 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 Number | 364-62-5 Y |
| ATC code | A03FA01 |
| PubChem | CID: 4168 |
| IUPHAR/BPS | 241 |
| DrugBank | DB01233 Y |
| ChemSpider | 4024 Y |
| UNII | L4YEB44I46 Y |
| KEGG | D00726 Y |
| ChEBI | CHEBI:107736 Y |
| ChEMBL | CHEMBL86 Y |
| Chemical data | |
| Formula | C14H22ClN3O2 |
| Molecular mass | 299.80 g/mol |
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SMILES
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InChI
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| Physical data | |
| Melting point | 147.3 °C (297.1 °F) |
| (verify) | |
Metoclopramide is a medication used mostly for stomach and esophageal problems.[1] It is commonly used to treat nausea and vomiting, to help with emptying of the stomach in people with delayed stomach emptying due to either diabetes or following surgery, and to help with gastroesophageal reflux disease.[2] It is also used to treat migraine headaches.[3]
Common side effects include: feeling tired, diarrhea, and feeling restless. More serious side effects include: movement disorder like tardive dyskinesia, a condition called neuroleptic malignant syndrome, and depression.[2] It is thus rarely recommended that people take the medication for longer than twelve weeks.[2] It is pregnancy category B in the United States and category A in Australia, meaning no evidence of harm has been found after being taken by many pregnant women.[2][4] It belongs to the group of medications known as dopamine-receptor antagonists.[2]
In 2012, metoclopramide was one of the top 100 most prescribed medications in the United States.[5] It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.[6]
Contents
- 1 Medical uses
- 1.1 Antiemetic
- 1.2 Gastroprokinetic
- 1.3 Other indications
- 2 Adverse effects
- 3 Cautions
- 3.1 Pregnancy
- 3.2 Infants
- 4 Mechanism of action
- 5 Brand names
- 6 Veterinary use
- 7 Contraindictions
- 8 See also
- 9 References
- 10 Further reading
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:
- Afipran (Takeda Nycomed,[28] Norway)
- Maxolon (Shire/Valeant in Australia and the UK)
Maxolon 10MG Box, Tablet, Sheet
- Cerucal (AWD Pharma)
- Clopamon (Aspen, South Africa)[29]
- Contromet (Adcock-Ingram, South Africa)
- Degan (Lek)
- Emeprid (Ceva Animal Health, UK veterinary use)[30]
- Maxeran (Sanofi)
- Pasperan (Syrian Arab Republic)
- Plasil (Sanofi)
- Plazilin (Iran)
- Pramin (Rafa, Israel)
- Primperan (Sanofi)
- Pulin (Malaysia)
- Pylomid (Bosnalijek)
- Reglan (Schwarz Pharma in the USA)
- Reliveran (Novartis Laboratories, Argentina)
- Tomit (Indonesia)
- Perinorm (India)
- Meclodin (Iraq)
- Metpamid (Turkey)
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
- Benzamide, the chemical class to which metoclopramide belongs
- Bromopride, the bromo- analogue of metoclopramide
- Cisapride, a benzamide with a different mechanism of action
- Itopride, a newer benzamide with effects similar to those of metoclopramide
- Domperidone, another drug with antiemetic and prokinetic properties
References
- ^ "Metoclopramide". nlm.nih.gov. Retrieved 28 September 2014.
- ^ a b c d e f g h "Metoclopramide hydrochloride". Monograph. The American Society of Health-System Pharmacists. Retrieved 2014-09-27.
- ^ 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. doi:10.1002/14651858.CD008040.pub2. PMID 21069700.
- ^ "Prescribing medicines in pregnancy database". Australian Government. 3 March 2014. Retrieved 22 April 2014.
- ^ Bartholow, Michael. "Top 200 Drugs of 2012". Pharmacy Times. Retrieved 22 April 2014.
- ^ "WHO Model List of EssentialMedicines" (PDF). World Health Organization. October 2013. Retrieved 22 April 2014.
- ^ a b "Maxolon (Australian Approved Product Information)". Valeant Pharmaceuticals. 2000.
- ^ a b c d Rossi S., ed. (2006). Australian Medicines Handbook. Adelaide: Australian Medicines Handbook. ISBN 0-9757919-2-3.
- ^ "Ambulance Victoria Clinical Guideline A0701"http://www.ambulance.vic.gov.au/media/docs/Adult%20CPG%20wm-a01f0e1e-4fc0-405c-bc83-3136adf4a723-0.pdf
- ^ a b http://xpil.medicines.org.uk/ViewPil.aspx?DocID=8068
- ^ "METOCLOPRAMIDE (metoclopramide hydrochloride) injection, solution [Hospira, Inc.]" http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=373ba08b-33ad-49fc-28a7-928e89a65314#nlm34089-3
- ^ "Metoclopramide". lowmilksupply.org.
- ^ 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".
- ^ "Metoclopramide (metoclopramide hydrochloride) injection, solution [Hospira, Inc.]" http://dailymed.nlm.nih.gov/dailymed/lookup.cfm?setid=373ba08b-33ad-49fc-28a7-928e89a65314#nlm34089-3
- ^ 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.
- ^ 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. doi:10.1136/emj.2004.014712. PMC 1726928. PMID 16113179.
- ^ 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. Retrieved 2009-06-11.
- ^ http://www.drugs.com/metoclopramide.html
- ^ 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.
- ^ 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. doi:10.1001/jama.2013.278343. PMID 24129464.
- ^ Hibbs, AM; Lorch, SA (Aug 2006). "Metoclopramide for the treatment of gastroesophageal reflux disease in infants: a systematic review.". Pediatrics 118 (2): 746–52. doi:10.1542/peds.2005-2664. PMID 16882832.
- ^ 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. PMID 14186927.
- ^ 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
- ^ Rang, H. P.; Dale, M. M.; Ritter, J. M.; Moore, P. K. (2003). Pharmacology (5th ed.). Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4.
- ^ Sweetman S., ed. (2004). Martindale: The Complete Drug Reference (34th ed.). London: Pharmaceutical Press. ISBN 0-85369-550-4.
- ^ 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. doi:10.1016/1043-6618(95)80029-8. ISSN 1043-6618. PMID 7479521.
- ^ 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. ISBN 978-1-4160-6189-2.
- ^ felleskatalogen.no
- ^ Snyman, J.R., ed. (June 2010). MIMS (Monthly Index of Medical Specialities) (Vol. 50 no. 6 ed.). Johannesburg: Avusa Media Ltd.
- ^ "Summary of Product Characteristics (Emeprid 1mg/ml)". DEFRA Veterinary Medicines Directorate.
- ^ 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. ISBN 0-7216-7757-6.
- Compendium of Pharmaceuticals and Specialties 2011. Toronto: Canadian Pharmacists Association. 2011. ISBN 978-1-894402-54-5.
- 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.
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UpToDate Contents
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- 1. 吃逆の概要 overview of hiccups
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- 3. 成人における片頭痛の急性期治療 acute treatment of migraine in adults
- 4. 遅発性ジスキネジア：病因および疫学 tardive dyskinesia etiology and epidemiology
- 5. 制吐剤の特性 characteristics of antiemetic drugs
English Journal
- Efficacy and Mechanism of Action of Yiru Tiaojing Granule Against Hyperprolactinemia In Vitro and In Vivo.
- Wei Y1, Wang X1, Yu Z2, Zhou W3, Wang L1, Qin F1, Wang C1, Hou L1.
- Planta medica.Planta Med.2015 Aug 7. [Epub ahead of print]
- Yiru Tiaojing Granule, a traditional Chinese medicine formula, is used to treat hyperprolactinemia. This study was conducted to evaluate the mechanism of action and pharmacological activity of Yiru Tiaojing Granule on prolactin secretion. The animal model of hyperprolactinemia was induced by metoclo
- PMID 26252831
- Neuroleptic Malignant Syndrome Associated With Metoclopramide Use in a Boy: Case Report and Review of the Literature.
- Wittmann O1, Sadot E, Bisker-Kassif O, Scolnik D, Tavor O, Glatstein MM.
- American journal of therapeutics.Am J Ther.2015 Aug 1. [Epub ahead of print]
- Neuroleptic malignant syndrome (NMS), an idiosyncratic reaction comprising muscular rigidity, altered level of consciousness, and autonomic dysfunction, is a rare but serious medical condition. It is most commonly precipitated by major tranquilizers such as butyrophenones, phenothiazines, and thioxa
- PMID 26241559
- Adverse effects reported in the use of gastroesophageal reflux disease treatments in children: a 10 years literature review.
- Cohen S1,2,3, Bueno de Mesquita M1,2, Mimouni FB2,3,4.
- British journal of clinical pharmacology.Br J Clin Pharmacol.2015 Aug;80(2):200-8. doi: 10.1111/bcp.12619. Epub 2015 Jun 11.
- Gastroesophageal reflux (GER) is commonly observed in children, particularly during the first year of life. Pharmacological therapy is mostly reserved for symptomatic infants diagnosed with GER disease (GERD), usually as defined in a recent consensus statement. The purpose of the present article was
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