塩酸メトクロプラミド

関: metoclopramide

WordNet

a complex consisting of an organic base in association with hydrogen chloride

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/07/30 09:55:00」(JST)

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Metoclopramide (INN) /ˌmɛtəˈklɒprəmaɪd/ is an antiemetic and gastroprokinetic agent. It belongs to a group of medicines called ´dopaminergic´ blockers. 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.

Medical uses[edit]

Clinicians commonly use metoclopramide to treat nausea - including that due to chemotherapy and that occurring post-operatively. Evidence also supports its use for gastroparesis (poor stomach emptying) and gastroesophageal reflux disease.^[1]

Antiemetic[edit]

Metoclopramide 5mg tablets (Pliva)

Metoclopramide can treat 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).

The Rosemont Patient Information Leaflet of their sugar free metoclopramide hydrochloride (5mg/5ml) oral solution states that " Metaclopramide 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 which has been cause 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." ^[4]

Gastroprokinetic[edit]

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 (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 (GERD).

Other indications[edit]

By inhibiting the action of dopamine, metoclopramide has sometimes been used to stimulate lactation.^[5] It can also help treat migraines in the setting of allodynia, where it is more effective than triptans.^[6]

Adverse effects[edit]

Plastic ampoule of metoclopramide

Common adverse drug reactions (ADRs) associated with metoclopramide therapy include restlessness (akathisia), 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]

Metoclopramide may be the most common cause of drug-induced movement disorders.^[7] 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.^[7] 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.^[7]

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

Mechanism of action[edit]

Metoclopramide was first described by Dr. Louis Justin-Besançon and C. Laville in 1964.^[8]

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 antiemetic 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.^[9] 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.^[10]^[11] The gastroprokinetic effect itself may also contribute to the antiemetic effect. Metoclopramide also increases the tone of the lower esophageal sphincter.^[12]

Contraindications and precautions[edit]

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 mental state.^[3] Also contraindicated with a suspected bowel obstruction.^[1]

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.

Use in pregnancy[edit]

Metoclopramide has long been used in all stages of pregnancy with no evidence of harm to the mother or unborn baby.^[13] In the USA, it has been assigned to pregnancy category B by the U.S. Food and Drug Administration (FDA).^[14] 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. ^[15] Metoclopramide is excreted into milk.^[13]

Brand names[edit]

It is available under various trade names including Maxolon in Australia and the UK (Shire/Valeant), Reglan in the USA (Schwarz Pharma), Degan (Lek), Maxeran (Sanofi Aventis), Primperan (Sanofi Aventis), Pylomid (Bosnalijek), Plazilin (Iran), "'Tomit'" (Indonesia), Cerucal (AWD Pharma), Pramin (Rafa, Israel)), Plasil (Sanofi Aventis), Pulin(Malaysia) , Pasperan (Syrian Arab Republic)

Veterinary use[edit]

Metoclopramide is also commonly used to prevent vomiting in cats and dogs. It is also used as a gut stimulant in rabbits.^[16]

Use[edit]

Metoclopramide is contraindicated in case of epilepsy, after a stomach operation in the previous three or four days, have ever had bleeding, perforation or blockage of the stomach and phaeochromocytoma and newborn babies ^[17]

References[edit]

^ ^a ^b "Metoclopramide hydrochloride". Monograph. The American Society of Health-System Pharmacists. Retrieved 2011-04-03.
^ ^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.
^ http://xpil.medicines.org.uk/ViewPil.aspx?DocID=8068
^ "Metoclopramide". lowmilksupply.org.
^ 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. edit
^ ^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".
^ 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. edit
^ 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. ISSN 1043-6618. PMID 7479521. edit
^ 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.
^ ^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. edit
^ Mikota, S. K.; Plumb, D. C. (June 2003). "Metoclopramide HCl". The Elephant Formulary. Elephant Care International.
^ http://xpil.medicines.org.uk/ViewPil.aspx?DocID=8068

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Comparative evaluation of gastric pH and volume in morbidly obese and lean patients undergoing elective surgery and effect of aspiration prophylaxis.

Mahajan V1, Hashmi J1, Singh R2, Samra T3, Aneja S1.
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Quantitative Structure-Activity Relationship Analysis of the Effect of Metoclopramide and Related Compounds on the Surface Ionization of Fumed Silica.

Buyuktimkin T1, Wurster DE1.
Journal of pharmaceutical sciences.J Pharm Sci.2015 Aug;104(8):2566-73. doi: 10.1002/jps.24529. Epub 2015 Jun 10.
Potentiometric titration curves were generated for fumed silica with various concentrations of dissolved metoclopramide. The effects of various benzamide analogs of metoclopramide, which are positively charged in the titration medium and differ solely by their aromatic substituents, as well as lidoc
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Japanese Journal

Particle Condition Change in Emulsion Admixture Evaluated by in Situ Flow Particle Imaging Analysis

Ohkawa Tomoyo,Uchino Tomonobu,Sasakura Daisuke [他],Miyazaki Yasunori,Kagawa Yoshiyuki
Chemical and Pharmaceutical Bulletin 61(3), 333-339, 2013
… A binary mixture of Ropion® and normal saline (NS), and a ternary admixture of Ropion®, NS, and Gaster® injection (famotidine: Gaster®) or Primperan® injection (metoclopramide hydrochloride: Primperan®) were prepared and the change in emulsion particle state was analyzed using FPIA under in situ condition. …
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トラマドール塩酸塩／アセトアミノフェン配合錠の変形性膝関節症に対する臨床的有用性について

那須耀夫
日本関節病学会誌 31(4), 499-502, 2012
… Objective: The tramadol hydrochloride/acetaminophen combination tablet (Tramcet) is a nonnarcotic analgesic and is expected to have efficacy for relief of chronic pain in patients who have failed to respond well to nonsteroidal anti-inflammatory drugs (NSAIDs). … All patients were simultaneously administered metoclopramide to prevent nausea and emesis, side effects that were anticipated to occur most frequently. …
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脊椎疾患に対するトラマドール・アセトアミノフェン合剤の使用経験

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中国・四国整形外科学会雑誌 24(1), 113-117, 2012
… Tramadol hydrochloride/acetaminophen is a combination drug containing tramadol hydrochloride 37.5 mg and acetaminophen 325 mg. … To evaluate the effect of this tramadol hydrochloride/acetaminophen combination (Tramcet®) on pain in patients with spinal disease, we tested 40 consecutive patients who had been receiving NSAIDs for more than one month without any effective pain relief. …
NAID 130004438597

「塩酸メトクロプラミド」

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 (US)
Legal status	Prescription Only (S4) (AU) POM (UK) ℞-only (US)
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
ATC code	A03FA01
PubChem	CID 4168
IUPHAR ligand	241
DrugBank	DB01233
ChemSpider	4024
UNII	L4YEB44I46
KEGG	D00726
ChEBI	CHEBI:107736
ChEMBL	CHEMBL86
Chemical data
Formula	C14H22ClN3O2
Mol. mass	299.80 g/mol
	SMILES Clc1cc(c(OC)cc1N)C(=O)NCCN(CC)CC;
	InChI InChI=1S/C14H22ClN3O2/c1-4-18(5-2)7-6-17-14(19)10-8-11(15)12(16)9-13(10)20-3/h8-9H,4-7,16H2,1-3H3,(H,17,19) ; Key:TTWJBBZEZQICBI-UHFFFAOYSA-N ;
Physical data
Melt. point	147.3 °C (297 °F)
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　　[★]

英: metoclopramide hydrochloride
関: メトクロプラミド

「hydrochloride」

　　[★] 塩酸塩、ハイドロクロライド　

[AHFS-1] "Metoclopramide hydrochloride". Monograph. The American Society of Health-System Pharmacists. Retrieved 2011-04-03.

[Maxolon-2] "Maxolon (Australian Approved Product Information)". Valeant Pharmaceuticals. 2000.

[AMH2006-3] Rossi S., ed. (2006). Australian Medicines Handbook. Adelaide: Australian Medicines Handbook. ISBN 0-9757919-2-3.

[4] ttp://xpil.medicines.org.uk/ViewPil.aspx?DocID=8068

[5] "Metoclopramide". lowmilksupply.org.

[Snow2002-6] 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. edit

[FDA2009-7] "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".

[Justin1964-8] 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. edit

[Rang2003-9] Rang, H. P.; Dale, M. M.; Ritter, J. M.; Moore, P. K. (2003). Pharmacology (5th ed.). Edinburgh: Churchill Livingstone. ISBN 0-443-07145-4.

[Sweetman2004-10] Sweetman S., ed. (2004). Martindale: The Complete Drug Reference (34th ed.). London: Pharmaceutical Press. ISBN 0-85369-550-4.

[Tonini1995-11] 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

[Feldman2010-12] 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.

[Briggs2008-13] 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.

[14] ttp://www.drugs.com/metoclopramide.html

[Matok2009-15] 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. edit

[16] Mikota, S. K.; Plumb, D. C. (June 2003). "Metoclopramide HCl". The Elephant Formulary. Elephant Care International.

[17] ttp://xpil.medicines.org.uk/ViewPil.aspx?DocID=8068

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metoclopramide hydrochloride