Overview
Clinical Meaning
Advanced IBS pharmacotherapy requires subtype specific prescribing guided by the predominant bowel pattern (IBS C, IBS D, IBS M) and the primary symptom driver (pain, diarrhea,...
Advanced IBS pharmacotherapy requires subtype-specific prescribing guided by the predominant bowel pattern (IBS-C, IBS-D, IBS-M) and the primary symptom driver (pain, diarrhea, constipation, bloating). The gut-brain axis is the therapeutic target: visceral hypersensitivity (augmented afferent pain signaling from the gut via dorsal horn neurons to the brain), dysmotility (serotonin-mediated — 95% of body serotonin is in the GI tract), altered intestinal secretion, and microbiome dysbiosis each respond to different pharmacological mechanisms. IBS-C agents: linaclotide and plecanatide are guanylate cyclase-C (GC-C) agonists that increase intraluminal cGMP, stimulating chloride/bicarbonate secretion and accelerating transit while simultaneously reducing visceral pain through extracellular cGMP — this dual mechanism is unique and advantageous. Lubiprostone activates type-2 chloride channels (ClC-2) on apical enterocyte membranes, increasing chloride-rich fluid secretion. Tegaserod (5-HT4 agonist) enhances peristalsis but is restricted to women <65 without cardiovascular risk. IBS-D agents: eluxadoline is a mixed mu-opioid receptor agonist / delta-opioid antagonist / kappa-opioid agonist — it slows motility without complete constipation (unlike loperamide). Rifaximin (non-absorbable antibiotic) modifies the gut microbiome and reduces bacterial gas production. Alosetron (5-HT3 antagonist) is highly effective but restricted to...