Drugs Used in the Treatment of Gastrointestinal Diseases 1099

channel (CIC-2) in the small intestine. This increases chloride-

rich fluid secretion into the intestine, which stimulates intestinal
motility and shortens intestinal transit time. Over 50% of patients
experience a bowel movement within 24 hours of taking one dose.
A dose of 24 meg orally twice daily is the recommended dose for
treatment of chronic constipation. There appears to be no loss of
efficacy with long-term therapy. After discontinuation of the drug,
constipation may return to its pretreatment severity. Lubiprostone
has minimal systemic absorption but is designated category C for
pregnancy because of increased fetal loss in guinea pigs. Lubipro-
stone may cause nausea in up to 30% of patients due to delayed
gastric emptying.

Linaclotide and plecanatide are minimally absorbed, short

amino acid peptides that stimulate intestinal chloride secre-
tion through a different mechanism by binding to and acti-
vating guanylate cyclase-C on the luminal surface. This leads
to increased intracellular and extracellular cyclic guanosine
monophosphate (CGMP) with activation of the cystic fibrosis
transmembrane conductance regulator (CFTR), followed by
chloride-rich secretion and acceleration of intestinal transit.
Both agents are approved for the treatment of chronic constipa-
tion (linaclotide 145 mcg orally once daily; plecanatide 3 mg
orally once daily); linaclotide is also approved for the treatment
of irritable bowel syndrome with constipation (290 mcg orally

once daily). These agents result in an average increase of 1-2

bowel movements per week that usually occurs within the first
week C f treatment. | oF DON a iSCO} ntis nu atic n of the drug, bowel
movement fr quency returns to No mal within aq week. The
most common side effect is diarrhea, which occurs in up to

)% of pati Ww. vere diarrhea in 2%. These drugs have

of reports of increased
tion. (Crofelemer is 2
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