Loperamide
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Loperamide
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| Systematic (IUPAC) name | |
| 4-[4-(4-chlorophenyl)-4-hydroxypiperidin-1-yl]- N,N-dimethyl-2,2-diphenylbutanamide | |
| Identifiers | |
| CAS number | 34552-83-5 (with HCl) |
| ATC code | A07 A07 |
| PubChem | |
| DrugBank | |
| ChemSpider | |
| Chemical data | |
| Formula | C29H33ClN2O2 |
| 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 | |
| Routes | oral |
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 in 1969.
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[edit] 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 (anal sphincter) 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 can cause a mild physical dependence. Symptoms of mild 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 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.
[edit] Crossing the blood-brain barrier
Concurrent administration of P-glycoprotein inhibitors such as quinidine with loperamide has been found to produce respiratory depression, indicative of central opioid action. [5] Other P-GP.I.'s include grapefruit juice, black pepper, and most proton pump inhibitors.
[edit] Side-effects
Side-effects can include drowsiness, constipation, abdominal pain or discomfort, dry mouth, fatigue, and, in rare cases, toxic megacolon, mild euphoria, and mild stimulation (at high doses).[citation needed]
[edit] See also
[edit] References
- ^ loperamide medical facts from Drugs.com
- ^ SafeFetus.com
- ^ US National Cancer Institute, Drug Dictionary
- ^ Katzung, Bertram G. Basic and Clinical Pharmacology, 9th ed. (2004). ISBN 0-07-141092-9
- ^ http://www.nature.com/clpt/journal/v68/n3/abs/clpt2000101a.html
[edit] External links
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