Loperamide

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Loperamide
Systematic (IUPAC) name
4-[4-(4-chlorophenyl)- 4-hydroxy-1-piperidyl]- N,N-dimethyl- 2,2-diphenyl-butanamide
Identifiers
CAS number	53179-11-6 34552-83-5 (with HCl)
ATC code	A07DA03 A07 DA05
PubChem	3955
DrugBank	APRD00275
Chemical data
Formula	C₂₉H₃₃Cl N₂O₂
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	GSL(UK) OTC(US) Over the counter (OTC) in Canada
Routes	oral, possible insufflation

"Imodium" redirects here. For the Nirvana song once called "Imodium", see Breed (song).

Loperamide, usually as hydrochloride, is a drug effective against diarrhea resulting from gastroenteritis or inflammatory bowel disease. In most countries it is available generically under brand names such as Lopex®, Imodium®, Dimor® and Pepto® Diarrhea Control. It was discovered at Janssen Pharmaceutica in 1969.

1 Mode of action
2 Contraindications
3 Crossing the blood-brain barrier
4 Side-effects
5 See also
6 References
7 External links

[edit] 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.^[1]

Loperamide does not cross the blood-brain barrier and has no analgesic properties. 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]}

[edit] 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.

[edit] 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.^[2]

Concurrent administration of P-glycoprotein inhibitors with loperamide has been found to produce respiratory depression, indicative of central opiod action. ^[3]

Also, it may be possible for loperamide to bypass the blood brain barrier through insufflation.^[4]

[edit] Side-effects

Side effects can include the following: drowsiness, constipation, abdominal pain or discomfort, dry mouth, fatigue, and in rare cases toxic megacolon.