Tx

5-aminosalicyclic acid (5-ASA) is released in the colon and is not absorbed. It acts locally as an anti-inflammatory. The mechanism of action is not fully understood but 5-ASA may inhibit prostaglandin synthesis

Sulphasalazine

• a combination of sulphapyridine (a sulphonamide) and 5-ASA
• many side-effects are due to the sulphapyridine moiety: rashes, oligospermia, headache, Heinz body anaemia, megaloblastic anaemia, lung fibrosis
• other side-effects are common to 5-ASA drugs (see mesalazine)

Mesalazine

• a delayed release form of 5-ASA
• sulphapyridine side-effects seen in patients taking sulphasalazine are avoided
• mesalazine is still however associated with side-effects such as GI upset, headache, agranulocytosis, pancreatitis, interstitial nephritis

Olsalazine

• two molecules of 5-ASA linked by a diazo bond, which is broken by colonic bacteria

Aminosalicylates are associated with a variety of haematological adverse effects, including agranulocytosis - FBC is a key investigation in an unwell patient taking them.

• pancreatitis is 7 times more common in patients taking mesalazine than sulfasalazine

• Acute exacerbations = steroids (IV methylprednisolone or PO Budesonide) Budesonide has a strong local effect; is largely cleared by the liver in a first-pass effect; limits the amount of systemic toxicity
• To maintain remission = 5-ASA derivatives such as mesalamine
  • Rowasa (enema for rectal disease, preferred for UC); Asacol (preferred for UC because it releases in large bowel); Pentasa (preferred for Chron's because it releases in both upper and lower bowel)
  • Balsalazide and olsalazine are also used occasionally (only active in the colon)
  • Sulfasalazine was used in the past but has many adverse effects
• Use Ciclosporin if poor response to steroids, then consider Azathioprine and 6-mercaptopurine as steroid-sparing agents for the long-term
  • Thiopurine s-methyltransferase (TPMT) testing is essential prior to starting therapy with azathioprine to reduce the risk of toxicity.
• Everyone needs calcium and Vitamin D.
• Perianal CD is treated with Ciprofloxacin and metronidazole.