|Systematic (IUPAC) name|
|Pregnancy cat.||B3 (AU) C (US)|
|Legal status||Pharmacy Only (S2) (AU) OTC (CA) GSL (UK) OTC (US)|
|Excretion||Faeces (30-40%), urine (1%)|
34552-83-5 (with HCl)
|Mol. mass||477.037 g/mol (513.506 with HCl)|
|(what is this?)|
Loperamide //, a piperidine derivative, is a drug used against diarrhoea resulting from gastroenteritis or inflammatory bowel disease. It was developed by Janssen in 1971. In most countries it is available generically and under brand names such as Lopex, Imodium, Dimor, Fortasec, Lopedium, Gastro-Stop and Pepto Diarrhea Control. It was developed at Janssen Pharmaceutica.
Loperamide is effective for the control of acute nonspecific diarrhea, mild traveler's diarrhea, irritable bowel syndrome, chronic diarrhea due to bowel resection, and chronic diarrhea secondary to inflammatory bowel disease. It is also useful for reducing ileostomy output. Of note, Loperamide is not useful in preventing traveler's diarrhea. Off Label uses for loperamide also include chemotherapy induced diarrhea, especially related to irinotecan use. Loperamide should not be used in cases of bloody diarrhea, acute exacerbation of ulerative colitis, or bacterial enterocolitis.
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. A systematic review and meta-analysis examined control trials of loperamide in children under 12 years old, and found that serious adverse events occurred only in children under 3 years old. The study reported that the use of loperamide should be contraindicated in children under 3 years old, systemically ill, malnourished, moderately dehydrated, or have bloody diarrhea. In 1990, all pediatric formulations of the antidiarrheal loperamide (Imodium and others) were banned in Pakistan.
Treatment should be avoided in the presence of high fever or if the stool is bloody (dysentery). It is of no value in diarrhea 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.
Loperamide is not recommended in the UK for use during pregnancy nor by nursing mothers. In the US, loperamide is classified by the FDA as pregnancy category C. Studies in rat models have shown no teratogenicity, but there have not been sufficient studies in humans.  One controlled, prospective study of 89 women exposed to loperamide during the first trimester showed no increased risk of malformations. This, however, was only one study with a small sample size.
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.In high doses, loperamide in conjunction with Cimetadine, can cause ventricular fibrillation and death.
The most frequent symptoms of loperamide overdose are drowsiness, vomiting and abdominal pain or burning.
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. It works similarly to morphine, by decreasing the activity of the myenteric plexus, which in turn decreases the tone of the longitudinal and 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.
Ability to cross the blood–brain barrier
It is a misconception that loperamide does not cross the blood–brain barrier. 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 tolerance/dependence) to loperamide, many drugs are known to inhibit P-glycoprotein and may thus render the CNS vulnerable to opiate agonism by loperamide.
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.
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.
- Methylnaltrexone - a Mu opioid antagonist (in contrast to the Mu opioid agonist loperamide) that does not cross the blood brain barrier so as to not affect CNS
- Simethicone - an anti-gas frequently combined with loperamide in medications
- Traveler's diarrhea
- Activated carbon
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