Irritable Bowel Syndrome (IBS)
A functional gastrointestinal disorder characterised by abdominal pain and altered bowel habits. Linaclotide and plecanatide (guanylate cyclase-C agonist peptides) are approved for IBS with constipation, working by stimulating intestinal fluid secretion and reducing visceral pain.
Technical Context
IBS subtypes: IBS-C (constipation-predominant), IBS-D (diarrhoea-predominant), IBS-M (mixed). Linaclotide and plecanatide act on guanylate cyclase-C (GC-C) receptors on intestinal epithelial luminal surface → increased intracellular and extracellular cGMP → CFTR chloride channel activation → intestinal fluid secretion + accelerated transit. cGMP also reduces visceral pain signalling (activating visceral afferent nerve inhibition). Linaclotide (Linzess): 290μg daily for IBS-C, 72μg for chronic constipation. Plecanatide (Trulance): 3mg daily for IBS-C and chronic constipation. Both are oral peptides that act locally in the GI tract (minimal systemic absorption). Diarrhoea is the main side effect (pharmacological — excessive secretion). These represent rare examples of orally administered peptide drugs that work without systemic absorption.