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Loperamide: Wikis

  

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Loperamide
Systematic (IUPAC) name
4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]- N,N-dimethyl-2,2-diphenylbutanamide
Identifiers
CAS number 53179-11-6 34552-83-5 (with HCl)
ATC code A07DA03 A07DA05
PubChem 3955
DrugBank APRD00275
ChemSpider 3818
Chemical data
Formula C 29H33ClN2O2  
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. B[1] [2]
Legal status  ? (CA) GSL (UK) OTC (US)
Routes oral, insufflation
 Yes check.svgY(what is this?)  (verify)

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.

Contents

Mode of action

Loperamide is an opioid-receptor agonist and acts on the μ-opioid receptors in the myenteric plexus large intestines; by itself it does not affect the central nervous system like other opioids.

It works by decreasing the activity of the myenteric plexus, which, like morphine, decreases the tone of the longitudinal smooth muscles but increases tone of circular 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 or euphoric 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 has been shown to cause a mild physical dependence during preclinical studies, specifically in mice, rats, and rhesus monkeys. Symptoms of mild opiate withdrawal have been observed following abrupt discontinuation of long-term therapy with loperamide.[5][6]

Contraindications

Treatment should be avoided in the presence of fever or if the stool is bloody (dysentery).[7] It is of no value in diarrhoea caused by cholera, Shigella or Campylobacter.[7] Treatment is not recommended for patients that 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

Concurrent administration of P-glycoprotein inhibitors such as quinidine and its other isomer quinine (although much higher doses must be used), PPIs like omeprazole (Prilosec OTC), venlafaxine (Effexor), and even black pepper (piperine as the active ingredient) could potentially allow loperamide to cross the blood-brain barrier. It should however be noted that only quinidine with loperamide was found to produce respiratory depression, indicative of central opioid action.[8]

See also

References

  1. ^ loperamide medical facts from Drugs.com
  2. ^ SafeFetus.com
  3. ^ US National Cancer Institute, Drug Dictionary
  4. ^ Katzung, Bertram G. Basic and Clinical Pharmacology, 9th ed. (2004). ISBN 0-07-141092-9
  5. ^ Yanagita T, Miyasato K, Sato J (1979). "Dependence potential of loperamide studied in rhesus monkeys". NIDA Research Monograph 27: 106–13. PMID 121326.  
  6. ^ Nakamura H, Ishii K, Yokoyama Y, et al. (November 1982). "[Physical dependence on loperamide hydrochloride in mice and rats]" (in Japanese). Yakugaku Zasshi 102 (11): 1074–85. PMID 6892112.  
  7. ^ a b Butler T (October 2008). "Loperamide for the treatment of traveler's diarrhea: broad or narrow usefulness?". Clinical Infectious Diseases 47 (8): 1015–6. doi:10.1086/591704. PMID 18781871.  
  8. ^ Sadeque AJ, Wandel C, He H, Shah S, Wood AJ (September 2000). "Increased drug delivery to the brain by P-glycoprotein inhibition". Clinical Pharmacology and Therapeutics 68 (3): 231–7. doi:10.1067/mcp.2000.109156. PMID 11014404.  

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