Water balance / Chloride secretion / Linaclotide
GC-C activator: LINACLOTIDE
Mechanism of action
- binds to and activates guanylyl cyclase-C on the luminal surface of intestinal epithelial cells
- increased intra- and extra-cellular cGMP activates the cystic fibrosis transmembrane conductance regulator (CFTR) → increased Cl- secretion
- results in 1-2 more bowel movements per week, within the first week of treatment; bowel movement frequency returns to normal within one week
- very little systemic absorption
Therapeutic uses
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LINACLOTIDE is used to treat chronic, idioptathic constipation and constipation-predominant IBS
Side effects
- diarrhea
- massive doses result in increased maternal death in rats, therefore considered a class C agent i.e., don't use in pregnant women
- increased mortality in juvenile mice, therefore contraindicated in pediatric patients