Ligand specificity GLP-2 and GLP-1 share high sequence similarity (69.7%) and have almost identical residues in two regions: the N-terminus (first six residues in GLP-2) that penetrates into the TMD core, and the C-terminus (residues 1833) that is recognized by the ECD and ECL1 of the receptor
doi: 10.1056/NEJMc2406233
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Chronic fissures are less likely to heal with conservative measures Increase fluid and fiber ingestion Sitz baths mineral oil or stool softener Topical application of nitrates and calcium channel blockers (CCBS) Leads to sphincter relaxation, vasodilation, improved blood flow Nitrates 0.1%, 0.2%, or 0.4% glyceryl trinitrate ointment Side effects: headache (occurs in 30% of treated patients) CCBs (e.g., diltiazem, nifedipine) Similar efficacy to nitrates Better side effect profile than nitrates Topical treatment preferred over oral treatment Botulinum toxin Similar results compared to topical therapies MOA: inhibit ACh at neuromuscular junction Temporary paralysis of the anal sphincter 20 100 IU will usually result in relaxation of the anal sphincter for 3 months Side effects: increased urinary residual volume, heart block, skin irritation, allergic reactions Lateral internal sphincterotomy (LIS) Most effective therapy to heal anal fissures Sustained partial relaxation of internal anal sphincter, resulting in decreased anal sphincter tone Can be offered first-line for patients with chronic anal fissures and no fecal incontinence
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