Alosetron (Lotronex) - Making life a little less crappy

  • used to treat the symptoms associated with the diarrhea-predominant form of irritable bowel syndrome (IBS-D), a wonderful functional bowel disorder that features gut pain and the sloppy poops
  • blocks a specific subtype of serotonin receptor (5-HT3) that is found in a number of locations in the body including the gastrointestinal (GI) tract
    • serotonin is a neurotransmitter involved in, among other things, the transmission of neural signals that control the initiation of peristalsis, GI secretory reflexes, enteric nervous system (ENS) function, and feedback to the brain and spinal cord
      • the ENS is a special little nervous system that the GI tract has all to itself
    • is thought that the 5-HT3 receptor subtype has a role in the pathophysiology of IBS, which is why this drug was developed
  • has a structure that is similar to ondansetron, a 5-HT3 blocker that is used to treat the nausea and vomiting associated with chemotherapy (alosetron does not share this antiemetic effect)
  • for some strange and utterly mysterious reason, this drug only improves IBS-D symptoms in females (tough luck, dudes)
  • the big issue with this drug is that it has two particularly terrible and potentially life-threatening GI side effects:
    1. constipation with serious complications including obstruction, perforation (my personal favourite), impaction, toxic megacolon, and secondary colonic ischemia (which is essentially #2 caused by the constipation)
    2. ischemic colitis
  • although these conditions are fairly rare, they are serious enough that the drug was removed from the US market in 2000 (it was reintroduced in 2002 with greater restrictions on its use and availability)
Gallo-Torres H, Brinker A, Avigan M. Alosetron: ischemic colitis and serious complications of constipation. Am J Gastroenterol. 2006 May;101(5):1080-3.

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