Systematic (IUPAC) name | |
---|---|
4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]- N,N-dimethyl-2,2-diphenylbutanamide | |
Clinical data | |
Trade names | Imodium |
AHFS/Drugs.com | monograph |
MedlinePlus | a682280 |
Pregnancy cat. | B[1] |
Legal status | ? (CA) GSL (UK) OTC (US) |
Routes | oral, insufflation |
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) |
Identifiers | |
CAS number | 53179-11-6 34552-83-5 (with HCl) |
ATC code | A07DA03 A07DA05 |
PubChem | CID 3955 |
DrugBank | DB00836 |
ChemSpider | 3818 |
UNII | 6X9OC3H4II |
KEGG | D08144 |
ChEBI | CHEBI:6532 |
ChEMBL | CHEMBL841 |
Chemical data | |
Formula | C29H33ClN2O2 |
Mol. mass | 477.037 g/mol (513.506 with HCl) |
SMILES | eMolecules & PubChem |
|
|
(verify) |
(what is this?)
Loperamide ( /loʊˈpɛrəmaɪd/; R-18553), a synthetic piperidine derivative,[2] is an opioid drug used 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.[3]
Contents |
Loperamide is effective for the treatment of a number of types of diarrhea.[4]
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, unless extremely high doses are taken (in which case it can produce psychoactive effects on its own).
It works by decreasing the activity of the myenteric plexus, which, like morphine, decreases the tone of the longitudinal smooth muscles but increases the 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.[5]
Many physicians and pharmacists believe that loperamide does not cross the blood–brain barrier. In fact, however, loperamide does cross this barrier, although it is immediately pumped back out into non–central nervous system (CNS) circulation by P-glycoprotein. While this mechanism effectively shields the CNS from exposure (and thus risk of CNS addiction) to loperamide, many drugs are known to inhibit P-glycoprotein and may thus render the CNS vulnerable to opiate agonism by loperamide.[6]
Only when very high doses are taken does enough accumulate in the brain to produce typical opioid effects, lasting for a number of hours (just as typical opioids would). 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.[7][8]
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.[9] In 1990, all pediatric formulations of the antidiarrheal loperamide (Imodium and others) were banned in Pakistan.[10]
Treatment should be avoided in the presence of fever or if the stool is bloody (dysentery).[11] It is of no value in diarrhea caused by cholera, Shigella or Campylobacter.[11] 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.
Loperamide treatment is not used in symptomatic C. difficile infections, as it increases the risk of toxin retention and precipitation of toxic megacolon.
Adverse drug reactions (ADRs) associated with Loperamide include abdominal pain and bloating, nausea, vomiting and constipation. Rare side-effects associated with Loperamide are paralytic ileus, dizziness and rashes.[12]
It is not recommended for use in hepatic failure since it can precipitate hepatic encephalopathy.[12]
In Pakistan, seven infants died in 1989 and 1990 after parents treated their babies' diarrhea with Imodium, a medicine sold by a subsidiary of Johnson & Johnson.
Since 1980, the World Health Organization has warned doctors of developing countries not to use Imodium because it can paralyze a child's intestines. For months a local doctor begged the company to pull the product from stores, but it didn't do so until a British television program broadcast footage of dying babies.[13]
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) 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.[14]
|