||This article needs more medical references for verification or relies too heavily on primary sources. (July 2013)|
|Systematic (IUPAC) name|
|Pregnancy cat.||A (AU) B (US)|
|Legal status||Prescription Only (S4) (AU) POM (UK) ℞-only (US)|
|Routes||Oral, intravenous, intramuscular|
|Excretion||70–85% renal, 2% faecal|
|Mol. mass||299.80 g/mol|
|Melt. point||147.3 °C (297 °F)|
|(what is this?)|
Metoclopramide (INN) // 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.
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.
Metoclopramide treats nausea and vomiting associated with conditions such as uremia, radiation sickness, malignancy, labor, infection, migraine headaches, and emetogenic drugs. 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 (5 mg/5ml) oral solution states that " 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." 
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).
By inhibiting the action of dopamine, metoclopramide has sometimes been used to stimulate lactation. It can also help treat migraines in the setting of allodynia, where it is more effective than triptans.
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.
Metoclopramide may be the most common cause of drug-induced movement disorders. The risk of extrapyramidal effects is increased in people under 20 years of age, and with high-dose or prolonged therapy. 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. 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.
Mechanism of action
Metoclopramide was first described by Dr. Louis Justin-Besançon and C. Laville in 1964.
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. 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. The gastroprokinetic effect itself may also contribute to the antiemetic effect. Metoclopramide also increases the tone of the lower esophageal sphincter.
Contraindications and precautions
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. Also contraindicated with a suspected bowel obstruction.
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
Metoclopramide has long been used in all stages of pregnancy with no evidence of harm to the mother or unborn baby. In the USA, it has been assigned to pregnancy category B by the U.S. Food and Drug Administration (FDA). 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.  A large cohort study in Denmark found, in addition, no association between metoclopramide exposure and miscarriage. Metoclopramide is excreted into milk.
Metoclopramide is available world-wide under various trade names:
- Afipran (Takeda Nycomed, Norway)
- Maxolon (Shire/Valeant in Australia and the UK)
- Cerucal (AWD Pharma)
- Clopamon (Aspen, South Africa)
- Contromet (Adcock-Ingram, South Africa)
- Degan (Lek)
- Maxeran (Sanofi Aventis)
- Pasperan (Syrian Arab Republic)
- Plasil (Sanofi Aventis)
- Plazilin (Iran)
- Pramin (Rafa, Israel)
- Primperan (Sanofi Aventis)
- Pulin (Malaysia)
- Pylomid (Bosnalijek)
- Reglan (Schwarz Pharma in the USA)
- Tomit (Indonesia)
Metoclopramide is also commonly used to prevent vomiting in cats and dogs. It is also used as a gut stimulant in rabbits.
Metoclopramide is contraindicated in case of 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 phaeochromocytoma and in newborn babies.
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