Loperamide

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Loperamide

File:Loperamide.svg
File:Loperamide2mg.JPG
Systematic (IUPAC) name
4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]- N,N-dimethyl-2,2-diphenylbutanamide
Clinical data
Pregnancy category	B
Routes of administration	oral, insufflation
Legal status
Legal status	CA: (OTC) UK: General sales list (GSL, OTC) US: OTC
Pharmacokinetic data
Bioavailability	Not significantly absorbed from the gut
Protein binding	97%
Metabolism	hepatic
Biological half-life	9.1 to 14.4 hours (average 10.8 hours)
Identifiers
CAS Number	53179-11-6 34552-83-5 (with HCl)
ATC code	A07DA03 (WHO) A07DA05
PubChem	CID 3955
DrugBank	APRD00275
ChemSpider	3818
Chemical data
Formula	C29H33ClN2O2
Molar mass	477.037 g/mol (513.506 with HCl)[[]]
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Loperamide (pronounced /loʊˈpɛrəmaɪd/) a synthetic piperidine derivative, is an opioid 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, Fortasec and Pepto Diarrhea Control. It was developed at Janssen Pharmaceutica.

History

Loperamide was approved in the United States by the FDA in 1976, when it was also placed on schedule V. It was descheduled in 1982, and became available over the counter in 1988.

Mechanism of action

Loperamide is an opioid-receptor agonist and acts on the μ-opioid receptors in the myenteric plexus of the large intestine; 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.

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.

Contraindications

The use of Loperamide (Imodium) in children under 2 years is not recommended. There have been rare reports of fatal paralytic ileus associated with abdominal distention. Most of these reports occurred in the setting of acute dysentery, overdose, and with very young children less than two years of age. In 1990, all pediatric formulations of the antidiarrheal loperamide (Imodium and others) were banned in Pakistan.

Treatment should be avoided in the presence of fever or if the stool is bloody (dysentery). It is of no value in diarrhoea caused by cholera, Shigella or Campylobacter. 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.

Effectiveness

Studies have shown loperamide to be more effective than diphenoxylate, attapulgite or bismuth subsalicylate for the treatment of acute diarrhea. For the treatment of chronic diarrhea, loperamide was found to be as effective as, or slightly more so than, diphenoxylate.

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.

See also

• Simethicone - an anti-flatulent frequently combined with Loperamide in medications
• Gastroenteritis
• Traveler's diarrhea

External links

• Imodium Website

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