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==Overview==
==Overview==
'''Ondansetron''' ([[International Nonproprietary Name|INN]]) ([[International Phonetic Alphabet|IPA]]: {{IPA|[ɒnˈdænsɛˌtrɒn]}}) is a [[serotonin]] [[5-HT3 antagonist|5-HT<sub>3</sub> receptor antagonist]] used mainly to treat [[nausea]] and [[vomiting]] following [[chemotherapy]]. Its effects are thought to be on both peripheral and central nerves. One part is to reduce the activity of the [[vagus nerve]], which is a nerve that activates the vomiting center in the [[medulla oblongata]], the other is a blockage of serotonin receptors in the [[chemoreceptor trigger zone]]. It does not have much effect on vomiting that is due to motion sickness. This drug does not have any effect on [[dopamine]] receptors or [[Muscarinic acetylcholine receptor|muscarinic receptor]]s.
'''Ondansetron''' ([[International Nonproprietary Name|INN]]) ([[International Phonetic Alphabet|IPA]]: {{IPA|[ɒnˈdænsɛˌtrɒn]}}) is a [[serotonin]] [[5-HT3 antagonist|5-HT<sub>3</sub> receptor antagonist]] used mainly to treat [[nausea]] and [[vomiting]] following [[chemotherapy]]. Its effects are thought to be on both peripheral and central nerves. One part is to reduce the activity of the [[vagus nerve]], which is a nerve that activates the vomiting center in the [[medulla oblongata]], the other is a blockage of serotonin receptors in the [[chemoreceptor trigger zone]]. It does not have much effect on vomiting that is due to motion sickness. This drug does not have any effect on [[dopamine]] receptors or [[Muscarinic acetylcholine receptor|muscarinic receptor]]s.
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[[Category:Antiemetics]]
[[Category:Antiemetics]]

Revision as of 14:30, 20 August 2012

Ondansetron (oral)
Error creating thumbnail: File missing
Clinical data
Pregnancy
category
  • AU: B1
  • US: B (No risk in non-human studies)
Routes of
administration
Oral, rectal, IV, IM
ATC code
Legal status
Legal status
  • AU: S4 (Prescription only)
  • UK: POM (Prescription only)
  • US: ℞-only
Pharmacokinetic data
Bioavailability~60%
Protein binding70%-76%
MetabolismHepatic (CYP3A4, CYP1A2, CYP2D6)
Elimination half-life5.7 hours
ExcretionRenal
Identifiers
CAS Number
PubChem CID
DrugBank
E number{{#property:P628}}
ECHA InfoCard{{#property:P2566}}Lua error in Module:EditAtWikidata at line 36: attempt to index field 'wikibase' (a nil value).
Chemical and physical data
FormulaC18H19N3O
Molar mass325.9 g/mol

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Overview

Ondansetron (INN) (IPA: Template:IPA) is a serotonin 5-HT3 receptor antagonist used mainly to treat nausea and vomiting following chemotherapy. Its effects are thought to be on both peripheral and central nerves. One part is to reduce the activity of the vagus nerve, which is a nerve that activates the vomiting center in the medulla oblongata, the other is a blockage of serotonin receptors in the chemoreceptor trigger zone. It does not have much effect on vomiting that is due to motion sickness. This drug does not have any effect on dopamine receptors or muscarinic receptors.

The drug is administered 1–3 times daily, depending on the severity of nausea and/or vomiting. The normal oral dose for adults and children over the age of 12, is 8 mg initially, followed by a second dose of 8 mg, eight hours later. The drug is then administered once every 12 hours, usually not for more than 2-3 days. Following oral administration, it takes about 1.5–2 hours to reach maximum plasma concentrations. This drug is removed from the body by the liver and kidneys.

It is currently marketed by GlaxoSmithKline (GSK) under the trade name Zofran; other manufacturers include Cipla Ltd. (Emeset), Gedeon Richter Ltd. (Emetron), and Zentiva a.s. (Ondemet). On May 29, 2006, Baxter Healthcare received tentative approval [1] to market its own label of Ondansetron Injection, USP, 8 mg/50 mL and 32 mg/50 mL iso-osmotic sodium chloride solution, after GSK's patent expired on December 24, 2006.

History

Ondansetron was developed around 1984 by scientists working at Glaxo's laboratories in London. After several attempts the company successfully filed for U.S. patent protection for the drug in 1986. U.S. Patent 4,695,578 was granted in September 1987 while U.S. Patent 4,753,789 was granted in June 1988. U.S. Patent 5,578,628, a divisional patent of U.S. Patent 4,753,789, was granted in November 26, 1996. Ondansetron was granted Food and Drug Administration (FDA) approval as Zofran in January 1991. Glaxo did pediatric research on Zofran's uses, and gained patent extension as a result. Consequently U.S. exclusivity ended December 24, 2006. The FDA subsequently approved the first generic versions in December 2006, with marketing approval granted to Teva Pharmaceuticals USA and SICOR Pharmaceuticals.

Clinical uses

Template:Seealso The 5-HT3 receptor antagonists are the primary drugs used to treat and prevent chemotherapy-induced nausea and vomiting (CINV). Many times they are given intravenously about 30 minutes before beginning therapy. Ondansetron is also effective in controlling post-operative (PONV) and post-radiation nausea and vomiting, and is a possible therapy for nausea and vomiting due to acute or chronic medical illness or acute gastroenteritis.

Although it is highly effective, its high cost limits its use to controlling PONV and CINV. It is also used off-label to treat hyperemesis gravidarum in pregnant women, but there is no conclusive data available on its safety in pregnancy, especially during the first trimester. It is also often used to treat cyclic vomiting syndrome; although there have been no formal trials to confirm efficacy, case reports suggest it can be helpful in some cases.

The clinical effect of ondansetron (and other drugs from the same group) can be potentiated by combining it with dexamethasone.

Investigational

A 2006 double-blind, randomized controlled trial indicated that ondansetron may have value in the treatment of schizophrenia, as an adjunct to haloperidol. The study found the combination to significantly improve negative schizophrenia symptoms, and people taking both drugs experienced fewer of the adverse effects commonly associated with haloperidol;[1] an earlier, smaller, open-label trial had found ondansetron to be useful in treating antipsychotic-induced tardive dyskinesia in people with schizophrenia, and the study patients also showed significant improvement in the disease's symptoms.[2][3]

Early studies have also examined ondansetron as a possible treatment for psychosis resulting from advanced Parkinson's disease.[4] Its ability to be of benefit despite lacking any significant antagonistic properties at dopamine receptors or the 5-HT2A receptor raises interesting questions about the etiology of psychosis.

Adverse effects

Ondansetron is a well-tolerated drug with few side effects. Headache, constipation, and dizziness are the most commonly reported side effects associated with its use. There have been no significant drug interactions reported with this drug's use. It is broken down by the hepatic cytochrome P450 system and it has little effect on the metabolism of other drugs broken down by this system.

See also

References


Template:5-HT3 antagonists

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Template:WikiDoc Sources

  1. Zhang ZJ, Kang WH, Li Q, Wang XY, Yao SM, Ma AQ (2006). "Beneficial effects of ondansetron as an adjunct to haloperidol for chronic, treatment-resistant schizophrenia: a double-blind, randomized, placebo-controlled study". Schizophr Res. 88 (1–3): 102–10. doi:10.1016/j.schres.2006.07.010. PMID 16959472.
  2. Zullino DF, Eap CB, Voirol P (2001). "Ondansetron for tardive dyskinesia". Am J Psychiatry. 158 (4): 657–8. PMID 11282718.
  3. Sirota P, Mosheva T, Shabtay H, Giladi N, Korczyn AD (2000). "Use of the selective serotonin 3 receptor antagonist ondansetron in the treatment of neuroleptic-induced tardive dyskinesia". Am J Psychiatry. 157 (2): 287–9. PMID 10671405. Free full text
  4. Zoldan J, Friedberg G, Livneh M, Melamed E (1995). "Psychosis in advanced Parkinson's disease: treatment with ondansetron, a 5-HT3 receptor antagonist". Neurology. 45 (7): 1305–8. PMID 7617188.