Sulfasalazine and 5-aminosalicylates in the treatment of inflammatory bowel disease
- Adam S Cheifetz, MD
Adam S Cheifetz, MD
- Associate Professor of Medicine
- Harvard Medical School
- Garret J Cullen, MD
Garret J Cullen, MD
- Consultant Gastroenterologist
- St. Vincent's University Hospital, Dublin
- Clinical Lecturer, University College Dublin School of Medicine and Medical Science
Salicylazosulfapyridine (sulfasalazine) was originally proposed as a treatment for rheumatoid arthritis. It was subsequently discovered that sulfasalazine was also efficacious in treating inflammatory bowel disease, particularly ulcerative colitis. The 5-aminosalicylic acid (5-ASA) medications were developed because many patients were intolerant of or allergic to sulfasalazine.
This topic will review the pharmacology of sulfasalazine and 5-ASAs, mechanism of action in inflammatory bowel disease, and side effects. The role of sulfasalazine and 5-ASAs in the treatment of inflammatory bowel disease and rheumatoid arthritis are discussed in detail separately. (See "Overview of the medical management of mild to moderate Crohn disease in adults" and "Management of mild to moderate ulcerative colitis in adults" and "Management of severe ulcerative colitis in adults" and "Sulfasalazine in the treatment of rheumatoid arthritis".)
Sulfasalazine is a prodrug composed of 5-aminosalicylic acid (5-ASA) linked to sulfapyridine through an azo bond (figure 1). Sulfasalazine is partially absorbed in the jejunum after oral ingestion. The remainder passes into the colon, where it is reduced by coliform bacterial enzyme, azoreductase, to sulfapyridine and 5-ASA .
The majority of absorbed sulfasalazine is excreted into bile; only a small fraction is excreted in the urine. 5-ASA is poorly absorbed from the colon and is largely excreted in the stool. Sulfapyridine is rapidly absorbed from the colon, metabolized by the liver, and excreted in the urine with only small amounts remaining in the stool.
5-ASA is primarily responsible for the efficacy of sulfasalazine, while sulfapyridine accounts for many of its side effects. Unconjugated 5-ASA (mesalamine) does not have the side effects associated with sulfapyridine, but is rapidly absorbed in the jejunum, allowing only 20 percent to reach the terminal ileum and colon. Therefore, a number of 5-ASA compounds have been developed to prevent absorption of 5-ASA in the proximal gastrointestinal tract, and thereby increase delivery to the colon (table 1).
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- 5-ASA formulations
- MECHANISM OF ACTION
- Inhibition of cytokine synthesis
- Inhibition of prostaglandin and leukotriene synthesis
- Free radical scavenging
- Immunosuppressive activity
- Impairment of white cell adhesion and function
- SIDE EFFECTS
- 5-aminosalicylic acid (5-ASA)
- INFORMATION FOR PATIENTS
- SUMMARY AND RECOMMENDATIONS