Pharmacology of Aminosalicylates

Aminosalicylates are used in the treatment of inflammatory bowel disease. Examples include balsalazide, mesalazine, olsalazine and sulfasalazine. Inflammatory bowel disease is a family term for a wide variety of inflammatory conditions: such as Crohn’s disease and ulcerative colitis. Ulcerative colitis only affects the colon and rectum, in contrast to Crohn’s disease which affects the colon, but also many other parts of the gastrointestinal tract. The effect of drugs, too, depends on the condition involved – as mesalazine is more effective in the treatment of ulcerative colitis than Crohn’s disease. First, though, let's take a closer look at the pharmacology of aminosalicylates - how and why they work.

Pharmacology of Aminosalicylates

The pharmacology of aminosalicylates can be reduced to one important detail – that the active component of all aminosalicylates is 5-aminosalicylic acid (5-ASA). In other words, all aminosalicylates are formulated to deliver 5-ASA to the lower bowel of patients – where it can exert its therapeutic effect.

Let’s consider sulfasalazine – one of the first aminosalicylates considered effective for treating IBD. Sulfasalazine is cleaved in vivo to two compounds: sulfapyridine and 5-ASA. The unwanted effects of sulfasalazine – such as depression, infertility, thrombocytopenia, and anaemia – are attributable to the presence of sulfapyridine, and not 5-ASA.

Aminosalicylates

5-ASA is also referred to as mesalazine, as is the active component in the treatment of IBD. Its mechanism of action is not entirely understood, but is thought to involve:

  • Reduced cytokine formation
  • Reduced free radical formation
  • Inhibited prostaglandin production
  • Inhibited leucocyte chemotaxis

Mesalazine is more effective in the treatment of ulcerative colitis than Crohn’s disease. Indeed, it is usually limited to use in mild-to-moderate Crohn’s disease.

Pharmacokinetics

Gut bacteria are key in the transformation of sulfasalazine into its constituent by-products, though some is absorbed through the gut itself. In fact, approximately 20 percent of 5-ASA, along with sulfapyridine, is absorbed through the colon – thereafter going on toward hepatic metabolism. Both of these metabolites have half-lives ranging between 5 and 10 hours. Sulfasalazine isn’t the only formulation by which 5-ASA can reach the colon, as more tolerable agents are also available.

Mesalazine has been formulated as enteric-coated and modified-release preparations. Olsalazine is a drug comprising of two 5-ASA molecules – themselves joined by an azo bond. Colonic flora are required to split this azo bond and release active 5-ASA into the gut. Balsalazide is another drug, this time composed of 5-ASA attached to 4-amino-benzoyl-β-alanine – this attachment, again, manifesting in an azo bond. Mesalazine and sulfasalazine are also available by suppository/enema to treat distal colon disease.

Adverse Effects

The diverse pharmacology of aminosalicylates means that adverse effects enormously depend on the formulation of 5-ASA used. Patients taking sulfasalazine, for example, are three times more likely to experience adverse effects compared to mesalazine. These adverse effects include gastrointestinal effects: nausea, vomiting, and abdominal pain. Patients may also experience headache, rash, blood dyscrasias (particularly agranulocytosis and thrombocytopenia), fever and oligospermia (with sulfasalazine).

The pharmacology of aminosalicylates is quite simple - drugs which use 5-ASA, in the lower bowel, to alleviate symptoms brought on by inflammatory bowel disease. They have proven effective in terms of treatment and management, but are far removed from a cure from this ever growing ailment.

By | 2016-12-05T18:18:41+00:00 October 19th, 2015|Pharmacology Guides|0 Comments

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