Loperamide

Class

• Synthetic piperidine derivative (opioid) antidiarrhoeal

Indications

• Diarrhoea resulting from gastroenteritis or inflammatory bowel disease

• Reducing the volume of discharge from ileostomies

Administration/Absorption

• Oral

• Not significantly absorbed from the gut

Dosage

Distribution

• Does cross the blood-brain barrier

  • However it is immediately pumped back out into non–central nervous system (CNS) circulation by P-glycoprotein

  • This mechanism effectively shields the CNS from exposure (and thus risk of CNS addiction) to loperamide

• NB many drugs are known to inhibit P-glycoprotein and may thus render the CNS vulnerable to opiate agonism by loperamide

Mechanism

• Opioid-receptor agonist

  • Acts on the μ-opioid receptors in the myenteric plexus of the large intestine

• Decreases the activity of the myenteric plexus

  • 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

Excretion

• Unchanged in faeces

• Half life 9.1 to 14.4 hours (average 10.8 hours)

Side effects

• Abdominal pain and bloating, nausea, vomiting and constipation

Interactions

• Concurrent administration of P-glycoprotein inhibitors could potentially allow loperamide to cross the blood-brain barrier

  • Quinidine and its other isomer quinine (although much higher doses must be used)

  • PPIs like omeprazole

  • Black pepper (piperine as the active ingredient)

Contraindications

• Children under 2 years

  • There have been rare reports of fatal paralytic ileus associated withabdominal distention

• 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 orCampylobacter

• Should not be used if there is a suspicion of diarrhea associated with organisms that can penetrate the intestinal walls

  • E. coli O157:H7 or salmonella

• Loperamide treatment is not used in symptomatic C. difficile infections

  • Increases the risk of toxin retention and precipitation of toxic megacolon