Loperamide
293758
222745174
2008-06-30T22:10:11Z
Malendras
548125
[[WP:UNDO|Undid]] revision 222670056 by [[Special:Contributions/92.2.19.159|92.2.19.159]] ([[User talk:92.2.19.159|talk]])(agonist is the correct term)
{{drugbox
| IUPAC_name = 4-[4-(4-chlorophenyl)- 4-hydroxy-1-piperidyl]- N,N-dimethyl- 2,2-diphenyl-butanamide
| image = Loperamide.svg
| CAS_number = 53179-11-6
| CAS_supplemental = {{CAS|34552-83-5}} (with HCl)
| ATC_prefix = A07
| ATC_suffix = DA03
| ATC_supplemental = {{ATC|A07|DA05}}
| PubChem = 3955
| smiles Clc1ccc(cc1)C1(O)CCN(CCC(c2ccccc2)(c2ccccc2)C(=O)N(C)C)CC1
| DrugBank = APRD00275
| C=29 | H=33 | Cl=1 | N=2 | O=2
| molecular_weight = 477.037 g/mol (513.506 with HCl)
| bioavailability = Not significantly absorbed from the gut
| protein_bound = 97%
| metabolism = [[hepatic]]
| elimination_half-life = 9.1 to 14.4 hours (average 10.8 hours)
| excretion =
| pregnancy_category = B<ref>[http://www.drugs.com/mtm/loperamide.html loperamide medical facts from Drugs.com<!-- Bot generated title -->]</ref> <ref>[http://www.safefetus.com/DrugDetail.asp?DrugId=204&TradeName=Loperamide&TradeId=2543 SafeFetus.com<!-- Bot generated title -->]</ref>
| legal_status = Over the counter (OTC) in Canada
| legal_US = OTC
| legal_UK = GSL
| routes_of_administration = oral, possible insufflation
}}
{{redirect|Imodium|the [[Nirvana (band)|Nirvana]] song once called "Imodium"|Breed (song)}}
'''Loperamide''', a synthetic [[piperidine]] derivative<ref>[http://www.cancer.gov/Templates/drugdictionary.aspx?CdrID=41911 US National Cancer Institute, Drug Dictionary]</ref>, is a [[medication|drug]] effective against [[diarrhea]] resulting from [[gastroenteritis]] or [[inflammatory bowel disease]]. In most countries it is available generically and under brand names such as '''Lopex''', '''Imodium''', '''Dimor''' and '''Pepto''' Diarrhea Control. It was discovered at [[Janssen Pharmaceutica]] in [[1969]].
==Mode of action==
Loperamide is an [[opioid]] receptor agonist and acts on the [[Mu Opioid receptor|μ-opioid receptors]] in the [[myenteric plexus]] large intestines; it does not affect the [[central nervous system]] like other opioids.
It works by decreasing the activity of the [[myenteric plexus]] which decreases the motility of the circular and longitudinal [[smooth muscle]]s of the intestinal wall. This increases the amount of time substances stay in the intestine, allowing for more water to be absorbed out of the fecal matter. Loperamide also decreases colonic mass movements and suppresses the [[gastrocolic reflex]].<ref>Katzung, Bertram G. ''Basic and Clinical Pharmacology'', 9th ed. (2004). ISBN 0-07-141092-9</ref>
Loperamide molecules do not cross the [[blood-brain barrier]] in significant amounts, and thus it has no [[analgesic]] properties. Any that do cross the blood-brain barrier are quickly exported from the brain by [[P-glycoprotein]] (Pgp), also known as multidrug resistance protein (MDR1). Tolerance in response to long-term use has not been reported.
However, loperamide can cause [[physical dependence]]. Symptoms of opiate withdrawal have been observed in patients abruptly discontinuing long-term therapy with loperamide. For this reason, the drug was briefly classified as a Schedule V [[controlled substance]] upon its introduction.{{Fact|date=February 2007}}
==[[Contraindication]]s==
Treatment should be avoided in the presence of [[fever]] or if the stool is bloody. Treatment is not recommended for patients who could suffer detrimental effects from rebound [[constipation]]. If there is a suspicion of diarrhea associated with organisms that can penetrate the intestinal walls, such as [[Escherichia coli O157:H7|E. coli O157:H7]] or [[salmonella]], loperamide is contraindicated.
==Crossing the blood-brain barrier==
When loperamide is taken by itself, it cannot readily cross the [[blood-brain barrier]]; however, when loperamide-containing nanoparticles are coated with [[polysorbate 80]] and injected, the results were the same as typical opiates and opioids -- long, effective [[analgesia]]. A solution prepared using loperamide coated with polysorbate 80 resulted in a very short duration of action and less effective analgesic effect. The same study concluded that loperamide does not cause any analgesic effects when taken by itself.<ref>[http://www.thatspoppycock.com/articles/2006_11_29_otc_ops.htm That's Poppycock! - Loperamide : From controlled substance to over-the-counter wonder]</ref>
Concurrent administration of P-glycoprotein inhibitors such as [[quinidine]] with loperamide has been found to produce respiratory depression, indicative of central opioid action. <ref>[http://www.nature.com/clpt/journal/v68/n3/abs/clpt2000101a.html;jsessionid=DF4E10E08776A89B889FC05B3DB509CF Clinical Pharmacology & Therapeutics - Abstract of article: Increased drug delivery to the brain by P-glycoprotein inhibition[ast]<!-- Bot generated title -->]</ref>
==Side-effects==
Side effects can include drowsiness, constipation, abdominal pain or discomfort, dry mouth, fatigue, and in rare cases [[toxic megacolon]], mild euphoria and mild stimulation (at high doses).
==See also==
* [[Gastroenteritis]]
* [[Traveler's diarrhea]]
==References==
<references/>
==External links==
[[Category:Antidiarrhoeals]]
[[Category:Opioids]]
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{{Antidiarrheals, intestinal anti-inflammatory/anti-infective agents}}
[[Category:Opioids]]
[[Category:Piperidines]]
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