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Loperamide

Trade name Imodium.

Pregnancy category C

Oral OTC agent

Bioavailability 0.3%.

Protein binding@ 97%.

Metabolism extensively In liver.

Biological half-life 9-14 hours.

Excretion via feces at 30-40%, urine at 1%.

An oral medication used to decrease the frequency of diarrhea.

It is often used in gastroenteritis, inflammatory bowel disease, and short bowel syndrome.

Common side effects include: abdominal pain, constipation, sleepiness, vomiting, and a dry mouth.

It may increase the risk of toxic megacolon.

It appears to be safe in breastfeeding.

An opioid with no significant absorption from the gut.

Does not cross the blood brain barrier when used at normal doses.

An opioid for relief of diarrhea is loperamide which is only an agonist of the μ opioid receptors in the large intestine and does not have opioid affects in the central nervous system as it doesn’t cross the blood–brain barrier in significant amounts. 

Slows the contractions of the intestines.

Loperamide is effective for the treatment of a number of types of diarrhea including: acute nonspecific diarrhea, traveler’s diarrhea, irritable bowel syndrome, chronic diarrhea due to bowel resection, and chronic diarrhea secondary to inflammatory bowel disease.

Useful for reducing ileostomy output, chemotherapy induced diarrhea, especially related to irinotecan.

Should not be used as the primary treatment in cases of bloody diarrhea, acute exacerbation of ulcerative colitis, or bacterial enterocolitis.

Compared to diphenoxylate it is more effective and has lower neural side effects.

Adverse drug reactions are constipation, in 1.7%-5.3% of cases, dizziness in up to 1.4%. nausea in 0.7%-3.2%, and abdominal cramps in 0.5%-3.0%.

Rare, but more serious, side-effects include: toxic megacolon, paralytic ileus, angioedema, anaphylaxis/allergic reactions, toxic epidermal necrolysis, Stevens-Johnson syndrome, erythema multiforme, urinary retention, and heat stroke.

The most frequent symptoms are drowsiness, vomiting and abdominal pain or burning.

High doses may result in heart problems such as abnormal heart rhythms.

Should be avoided in the presence of high fever or if the stool is bloody.

Treatment is not recommended for people that could have negative effects from rebound constipation.

Should not be used If there is a suspicion of diarrhea associated with organisms that can penetrate the intestinal walls, such as E. coli O157:H7 or salmonella.

Not used in symptomatic C. difficile infections, as it increases the risk of toxin retention and precipitation of toxic megacolon.

Should be administered with caution to people with liver failure due to reduced first pass metabolism.

Should be used with caution when treating people with advanced HIV as there have been cases of both viral and bacterial toxic megacolon.

If abdominal distension is noted, therapy should be discontinued.

Use of loperamide in children under 2 years is not recommended.

Rarely fatal paralytic ileus associated with abdominal distention can occur.

Serious adverse events occur only in children under 3 years old, and its use should be contraindicated in children under 3 years old, systemically ill, malnourished, moderately dehydrated, or have bloody diarrhea.

It is not recommended in children as it may cross the immature blood–brain barrier and cause toxicity.

Classified by the FDA as pregnancy category C.

Can be present in breast milk, and is not recommended for breast feeding mothers.

A substrate of P-glycoprotein; therefore, the concentration of loperamide will increase when given with a P-glycoprotein inhibitor.

Common P-glycoprotein inhibitors include quinidine, ritonavir, and ketoconazole.

Is capable of decreasing the absorption of some other drugs.

Saquinavir concentrations can decrease by half when given with loperamide.

An anti-diarrheal agent which decreases intestinal movement.

When combined with other antimotility drugs, (opioids, antihistamines, antipsychotics, and anticholinergics, increases the risk of constipation.

An opioid-receptor agonist and acts on the μ-opioid receptors in the myenteric plexus of the large intestine.

Works similarly to morphine, decreasing the activity of the myenteric plexus, which decreases the tone of the longitudinal and circular smooth muscles of the intestinal wall.

It increases the time material stays in the intestine, allowing more water to be absorbed from the fecal matter, and decreases colonic mass movements and suppresses the gastrocolic reflex.

Its circulation in the bloodstream is limited by efflux as P-glycoprotein in the intestinal wall reduces passage of loperamide, and the fraction of drug crossing is then further reduced through first pass metabolism by the liver.

Efflux by P-glycoprotein also prevents circulating loperamide from effectively crossing the blood–brain barrier, affecting the central nervous system.

Concurrent administration of P-glycoprotein inhibitors such as quinidine potentially allows it to cross the blood–brain barrier and produce central morphine-like effects, and produce respiratory depression, indicative of central opioid action.

Deemed to have a relatively low risk of misuse.

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