This MedLibrary.org supplementary page on Loperamide is provided directly from the open source Wikipedia as a service to our readers. Please see the note below on authorship of this content, as well as the Wikipedia usage guidelines. To search for other content from our encyclopedia supplement, please use the form below:
Related Sponsors
 |
|
|
Loperamide
|
|
| Systematic (IUPAC) name | |
| 4-[4-(4-chlorophenyl)- 4-hydroxy-1-piperidyl]- N,N-dimethyl- 2,2-diphenyl-butanamide | |
| Identifiers | |
| CAS number | 34552-83-5 (with HCl) |
| ATC code | A07 A07DA05 |
| PubChem | |
| DrugBank | |
| Chemical data | |
| Formula | C29H33ClN2O2 |
| Mol. mass | 477.037 g/mol (513.506 with HCl) |
| Pharmacokinetic data | |
| Bioavailability | Not significantly absorbed from the gut |
| Protein binding | 97% |
| Metabolism | hepatic |
| Half life | 9.1 to 14.4 hours (average 10.8 hours) |
| Excretion | ? |
| Therapeutic considerations | |
| Pregnancy cat. | |
| Legal status | |
| Routes | oral, possible insufflation |
Loperamide, a synthetic piperidine derivative[3], is a 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.
Contents |
Mode of action
Loperamide is an opioid receptor agonist and acts on the 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 muscles 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.[4]
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.citation needed
Contraindications
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 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.[5]
Concurrent administration of P-glycoprotein inhibitors such as quinidine with loperamide has been found to produce respiratory depression, indicative of central opioid action. [6]
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
References
- ^ loperamide medical facts from Drugs.com
- ^ SafeFetus.com
- ^ US National Cancer Institute, Drug Dictionary
- ^ Katzung, Bertram G. Basic and Clinical Pharmacology, 9th ed. (2004). ISBN 0-07-141092-9
- ^ That's Poppycock! - Loperamide : From controlled substance to over-the-counter wonder
- ^ Clinical Pharmacology & Therapeutics - Abstract of article: Increased drug delivery to the brain by P-glycoprotein inhibition[ast]
External links
|
||||||||||||||||||||
Wikipedia content modification information:
- This page was last modified on 30 June 2008, at 22:10.
Wikipedia Authorship and Review
Wikipedia content provided here is not reviewed directly by MedLibrary.org. Wikipedia content is authored by an open community of volunteers and is not produced by or in any way affiliated with MedLibrary.org.
Wikipedia Usage Guidelines
This article is licensed under the GNU Free Documentation License. It uses material from the Wikipedia article on "Loperamide".
The URL for this specific entry is:
All Wikipedia text is available under the terms of the GNU Free Documentation License. (See Copyrights for details). Wikipedia® is a registered trademark of the Wikimedia Foundation, Inc.