You ate Taco Bell for lunch, and your stomach is rumbling, you run for the nearest bathroom.

You make it barely in time. You cannot have loose stools for the rest of the day, what will you do? You drive to the nearest gas station and pick up a pack of Imodium (Loperamide.) Will it bring relief? If it does make you feel better at what cost?

What Is Imodium and What Is Its Mechanism of Action?

Loperamide is a piperidine derivative and opioid that relieves diarrhea. 1 Most opioids like codeine and morphine are known to cause constipation in people, and this is the why loperamide was originally proposed to treat people with diarrhea. 2

Loperamide works by decreasing the peristaltic activity of the myenteric plexus muscle of the large intestine and decreases muscle tone in the intestinal wall. This increases the amount of time that feces stay in the intestines allowing greater hydration, which bulks up the fecal matter. Finally, it decreases MMC function mainly the gastrocolic reflex. 3 4

What Are The Issues Associated With Its Use?

Loperamide sounds like a good idea in theory. It soothes an overactive MMC and slows down motility so that diarrhea lessens. The main problem with this is that diarrhea is a defensive mechanism by the body to expel substances that irritate and damage the intestinal tract including: pathogens, toxins, and metals. 5

Endotoxins that gram-negative bacteria produce in large amounts over-activate the TRPV-1 / serotonin receptors of the gastrointestinal tract causing diarrhea. Too many endotoxins, however, can ablate TRPV-1 receptors from extreme over-activation causing severe side effects like toxic megacolon and necrolysis from increased inflammatory responses, infection, and cytokine storms. Healthy TRPV-1 receptors are very important for the proper regulation of inflammation within the body. 6 7

Increased endotoxin load is why Imodium is associated with causing toxic megacolon in gram-negative bacterial infections including C. diff, E. coli O157:H7, Shigella, MAP, or Campylobacter infection. Imodium should be used very carefully with suspected food poisoning because of increased endotoxin and cytolethal distending toxin load that are produced by certain opportunistic bacteria associated with the condition. It is rarely recommended by the medical community anymore for food poisoning or people with IBD. 8 9 10

Loperamide, unlike other opioids, is blocked by the blood-brain barrier because of P-glycoprotein. The blockage of the drug by the blood-brain barrier causes no pain relieving benefits or any of the neurological side effects of standard opioids so that it can be used long term without these drawbacks. Some drugs and spices cause the P-glycoprotein to lose its effectiveness like quinine, PPI’s, and piperine. Large dosages of Imodium may deplete P-glycoprotein production in the brain and may weakly cause standard opioid side effects. Even with P-glycoprotein protection in the brain, mild opiate withdrawal in animals has been observed with long-term use of loperamide. The known information about loperamide causing opioid side effects or addiction is mixed and weak at best, but should be noted until more studies can be performed in humans. 11 12 13

Loperamide is not recommended for pregnant or nursing women or people with liver impairment. Loperamide should not be used in children under two because of the increased risk of the fatal condition known as paralytic ileus syndrome. 14

Common side effects associated with Loperamide treatment are abdominal pain and bloating, nausea, vomiting and constipation. It has been rarely implicated in causing paralytic ileus, dizziness, rashes, and systemic allergic reactions. 15

If you are suffering from diarrhea activated charcoal might be a better way to try to find some relief.

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