Gastroenterolgy > Mechanism of Action of Aminosalicylates

Audience: Healthcare providers

Developed and produced for, a CME resource for physicians and healthcare providers.

Animation Description:
This animation explains the mechanism of action of aminosalicylates used for the treatment of inflammatory bowel disease (IBD). Aminosalicylates include sulfasalazine and 5-aminosalicylic acid (5-ASA). Sulfasalazine, a sulfa drug, inhibits folic acid synthesis. As such, folic acid supplements should be taken with sulfasalazine to reduce the risk of neural tube defects. Sulfasalazine exhibits anti-inflammatory properties when split by gut bacterium into its metabolites: sulfapyridine and 5-ASA (mesalamine). The anti-inflammatory benefits of sulfasalazine, are chiefly derived from 5-ASA, which has fewer side effects than sulfapyridine. As such, administration of 5-ASA alone may be preferred over sulfasalazine. 5-ASA is poorly absorbed by the intestines and systemic circulation, thus most remains in the terminal ileum and colon or is passed in the stool. 5-ASA within the lumen primarily exhibits a topical effect on the colonic epithelium. Absorbed 5-ASA is extensively metabolized to N-acetyl-5-ASA by N-acetyltransferase 1 (NAT1). N-acetyl-5-ASA then binds PPAR-gamma (peroxisome proliferator-activated receptor gamma) a nuclear hormone receptor. Binding of N-acetyl-5-ASA induces the translocation of PPAR-gamma from the cytoplasm to the cell nucleus and a conformational change in PPAR-gamma. This modification permits the recruitment of the co ...