Pharmacology of Aminosalicylates

Aminosalicylates are medicines used predominantly in the treatment of ulcerative colitis. Here, we review the role of aminosalicyates in the treatment of inflammatory disorders – how they work, what side effects they cause, and what they interact with.

Examples of aminosalicylates include:

  • Mesalamine – also known as mesalazine, or 5-aminosalicylic acid (5-ASA)
  • Sulfasalazine
  • Olsalazine
  • Balsalazide

The medicines are used to treat mild-to-moderate ulcerative colitis. Sulfasalazine is composed of 5-ASA – the active ingredient of aminosalicylates – linked to sulfapyridine. The harsh side effect profile of sulfasalazine is due to the sulfapyridine group, though this later group shows efficacy in the treatment of rheumatoid arthritis.

Ulcerative colitis and Crohn’s disease are two members of inflammatory bowel disease.

DIFFERENCES

  • Crohn’s disease affects both the small and large intestine, as well as the mouth, esophagus, stomch and anus.
  • Ulcerative colitis affects the colon and rectum only.
  • Ulcerative colitis affects the epithelial lining of the gut, whereas Crohn’s disease affects the full thickness of the bowel wall.

The aminosalicylate medicines are therapeutic only for ulcerative colitis, not for Crohn’s disease.

Common symptoms of ulcerative colitis include:

  • Diarrhea – often mixed with blood or mucus
  • Weight loss
  • Anemia
  • Abdominal pain

Medicines used to treat ulcerative colitis include aminosalicylates, steroid medicines, and immunosuppressant drugs. Where patients do not respond to treatment, TNF-inhibitors – such as infliximab – may be used. Iron supplementation may be required to offset the loss of iron from the gastrointestinal tract.

Here though, we focus on aminosalicylates pharmacology. Let’s quickly review how precisely they work.

Mechanism of action

5-aminosalicyclic acid (5-ASA) is the active ingredient of aminosalicylates.

5-ASA has anti-inflammatory and immunosuppressive effects, though the precise mechanism by which it achieves these effects is not fully understood. Remember – ulcerative colitis is an inflammatory condition that impacts the colon and rectum only. Preparations are designed to administer the drug to that part of the body.

Previously, sulfasalazine was the original means to treat ulcerative colitis. However, it is associated with an unpleasant side effect profile – such as nausea, rash, headache, loss of appetite, bone marrow suppression, liver toxicity and kidney problems – all of which are attributed to the sulfapyridine moiety of the sulfasalazine compound. Its therapeutic effects come from 5-ASA.

When it was learned that 5-ASA was the active ingredient, the later aminosalicylate medicines – such as mesalamine – were discovered. This meant that the medicines could deliver an anti-inflammatory effect without having the unpleasant side effect profile that comes with the sulfapyridine moiety.

Side effects

Side effects associated with aminosalicylates include:

  • Gastrointestinal upset
  • Headache
  • Liver enzyme changes
  • Rash
  • Abdominal cramps

More rarely, mesalamine is linked to myelosuppression, oligospermia and serious hypersensitivity reactions.

Clinical considerations

When we talk about the clinical pharmacology of aminosalicylates, we need to think about the following factors:

  • That both mesalamine and sulfasalazine are salicylates, the same family of medicines that aspirin derives from. Avoid aminosalicylates in patients who have an established allergy to aspirin.
  • That oral preparations of mesalamine come with enteric coatings, to prevent their degradation. Alterations in pH can disturb the integrity of the coating. For example – proton-pump inhibitors and H2 receptor antagonists reduce gastric acid and increase stomach pH. Lactulose is known to reduce stool pH etc.

Aminosalicylates remain important medicines in the treatment of ulcerative colitis. Through lifestyle changes, the disease has become more prevalent since the 1950s and is likely to rise further – particularly in Europe and North America – in coming decades.

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