Saudi Journal of Gastroenterology
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Year : 2001  |  Volume : 7  |  Issue : 3  |  Page : 122-123

Room 908, 9th floor, Victoria Building, QE II Health Sciences Centre, 1278 Tower Road, Halifax, Nova Scotia, Canada B3H 2Y9

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Date of Submission25-Apr-2001
Date of Acceptance13-Jun-2001

How to cite this article:
Williams C N. Aminosalicylates . Saudi J Gastroenterol 2001;7:122-3

How to cite this URL:
Williams C N. Aminosalicylates . Saudi J Gastroenterol [serial online] 2001 [cited 2021 Dec 7];7:122-3. Available from:

In the 1940s, sulphasalazine was developed as a drug to be used in patients with rheumatoid arthritis. At the time it never gained wide acceptance with the development of the powerful corticosteroids. However, it was noted that the sulphasalazine was useful in treating patients with inflammatory bowel disease, both Crohn's disease and ulcerative colitis. Its use was widespread and quickly became the first line drug to be used in this situation. This drug remained the mainstay of treatment until it was realized that the active principle was 5­aminosalicylic acid (5-ASA). Sulphasazaline consists of one molecule of 5-ASA and one molecule of sulphapyridine, held together with an azo-bond. After oral ingestion, the pro-drug is inactive until bacteria in the colon containing azo­reductases cleave off the 5-ASA and allow its absorption. It was quickly realized that the sulpha moiety was the one mainly responsible for the side effects associated with sulphasalazine. In the '70's, there was a rapid explosion of the compounds developed in which the main constituent only 5­ASA. These included enteric-coated capsules allowing pH-dependent release (Salofalk, Asacol), the development of microencapsulated, time-release 5-ASA in compressed form (Pentasa), and the development of other pro-drugs containing two molecules of 5-ASA attached via an azo-bond, olsalazine (Dipentum) or 5-ASA attached via an azo bond to an inert substance, Balsalazide [Table - 1].

Multiple studies have shown that the action of 5­aminosalicylic acid in inflammatory bowel disease is complex. It acts on two parts of the prostaglandin pathway and has predominant action in binding free oxygen radicals. Both oral and topical preparations were developed. Topical preparations included enemas and suppositories. Ulcerative colitis is a chronic inflammatory bowel disease leading to superficial inflammation, initially affecting the rectum and in different subsets spreading proximally in continuity, with small proportion having the whole colon involved. 5-ASA suppositories have found their main indication when the disease is limited to the rectum. 5-ASA enemas work very well in patients with proctosigmoiditis. Absorption is minimal and side effects are unusual with both these topical medications. Oral preparations (tablets) are useful for more extensive disease above the rectosigmoid junction or in proctosigmoiditis, when the topical preparations have not been acceptable. The anticipated time to induce remission of the topical preparations is within three to six weeks, with improvement starting within a few days. With the oral preparations there is a similar timeframe. The recommended dose for treating an acute flare-up of pan colitis is four grams a day in divided doses, the enema doses are four grams (usually taken at night time) and the suppositories at least one gram per day to bring proctitis under control. Ulcerative colitis tends to relapse and maintenance treatment has been shown to be effective in the initial studies in a dose of half the dose that induced emission. However, in subsequent studies, with experience gained with the safety of four grams a day these initial doses are now used for better maintenance of remission.

In Crohn's disease, 5-ASA preparations act best when the disease is confined to the colon where similar oral doses of four grams a day are used for both induction and maintenance of remission. When the rectum is involved with Crohn's disease, topical preparations are used, but may take up to three months to induce remission. Oral 5-ASA preparations are generally not effective when the ileum is involved. When the proximal small bowel is involved, slow release microgranules of Pentasa, which starts being released in the duodenum, is of a benefit. The pH-dependent enteric-coated preparations are not released in the proximal small bowel. Similarly, the pro-drugs would not be effective as there are no bacteria present with the appropriate enzymes to release the preparation in the proximal small bowel.

The original sulphasalazine, with increasing doses to effective therapeutic levels was only tolerated by 70% of the patients. Significant side effects were seen with the sulphapyridine part of the drug., which included headaches, nausea, vomiting, fever, allergic rashes, bone marrow suppression, pancreatitis and hepatitis, and rarely worsening of colitis. Olsalazine has less allergic side effects and is well tolerated, except that in a percentage of patients with increasing doses, there is a dose-dependent diarrhea. The enteric-coated and slow-release preparations of 5-ASA are much more expensive, but much better tolerated, with less side effects. Appropriate doses can be maintained indefinitely in most patients. There are no dangerous side effects seen with 5­ASA group. Some patients find these unacceptable because of induced headaches, nausea, vomiting, rashes, a rare case of pancreatitis or worsening of colitis. Theoretically, high doses of aminosalicylates could lead to renal damage. However, this is rarely seen in practice and is not a concern with the usual therapeutic doses used in patients with normal renal function.

In the year 2001, aminosalicylates worldwide are the first-line drugs for treatment of choice in patients with both ulcerative colitis and Crohn's disease.[9]

   References Top

1.Svartz NS. A new Sulfanilamide preparation. Acta Med Scand, 1942,110:577-98.  Back to cited text no. 1    
2.Azad Khan KA, Piris T, Truelove SC. An experiment to determine the active therapeutic moiety of sulphasalazine. Lancet 1973, ii: 892-5.  Back to cited text no. 2    
3.Dew FM, Ebden P, Kidwai NS, Lee G et al. Comparison of absorption and metabolism of sulphasalazine and acrylic­coated 5-aminosalicylic acid in normal subjects and in patients with colitis. Br J Pharmacol 1984,17:474-6.  Back to cited text no. 3    
4.Habal FM, Greenberg GR. Oral 5-aminosalicyclic acid in the treatment of ulcerative colitis. Gastroenterology 1985, 88: 1409.  Back to cited text no. 4    
5.Snitsky CA, Cort DH, Shanchan E et al. Oral mesalamine (Asacol) for mildy to moderately active ulcerative colitis. A multicentre study. Ann Int Med 1991,115:350-5.  Back to cited text no. 5    
6.Hanauer S. Schwatz J, Robinson M et al. Mesalamine capsules for treatment of active ulcerative colitis. Results of control trial. Amer J Gastroenterol 1993, 118:9  Back to cited text no. 6    
7.Williams CN. Clinical experience with 5-aminosalicylate preparations in the inflammatory bowel disease- A review. Can J Gastroenterol 1987, 1: 28-32.  Back to cited text no. 7    
8.Williams CN, Haber G, Aquino JA. Double blind, placebo­controlled evaluation of 5-ASA suppositories in the treatment of patients with active distal proctitis: measurement of extent of spread using 99m Tc-5­ASAsuppositories. Dig Dis Sci 1987,32: 715-55 (supplement).  Back to cited text no. 8    
9.Camma C, Giuntz M, Rosseli M, Cottone M. Mesalamine in the maintenance treatment of Crohn's disease: A meta­analysis adjusted for confounding variables. Gastroenterol 1997,113:1465-73.  Back to cited text no. 9    

Correspondence Address:
C Noel Williams
Room 908, 9th floor, Victoria Building, QE II Health Sciences Centre, 1278 Tower Road, Halifax, Nova Scotia, Canada B3H 2Y9

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Source of Support: None, Conflict of Interest: None

PMID: 19861782

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