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The role of mesalamine in the treatment of ulcerative colitis.

Karagozian R, Burakoff R - Ther Clin Risk Manag (2007)

Bottom Line: Newer formulations of salicylates based drugs with fewer side-effects have been developed.In the setting of left-sided distal colitis (proctitis), topical (rectal) formulations have been found to be superior to oral aminosalicylates at inducing remission.Mesalamine has been shown to be safe in short term use with a dose-response efficacy without dose-related toxicity.

View Article: PubMed Central - PubMed

Affiliation: Brigham and Women’s Hospital, Harvard Medical School Boston, MA, USA.

ABSTRACT
Ulcerative colitis (UC) is a chronic inflammatory condition of unclear etiology affecting the large bowel, most commonly the rectum and extending proximally in a continuous fashion. The overall principle in the pathophysiolgy of ulcerative colitis is the dysregulation of the normal immune system against an antigenic trigger leading to a prolonged mucosal inflammatory response. The diagnosing of UC is made by combining the clinical picture, tissue biopsy with the endoscopic appearance of mucosal ulceration, friable, edematous, erythematous granular appearing mucus. The approach to therapy of UC has been dependent on severity of symptoms with frontline therapy being salicylate based sulfasalazine. Newer formulations of salicylates based drugs with fewer side-effects have been developed. These are free of the sulphur component and are composed of 5-ASA, without the sulfapyridine carrier molecule. Mesalamine is one of these 5-ASA based agents that are currently available and indicated for treatment of UC. In mild/moderate active disease mesalamine has response rates between 40%-70% and remission rates of 15%-20%. Considering that the efficacy of 5-ASA is dose dependent, 4.8 g/day and 2.4 g/day have been shown to be the optimal dosages for mild-moderate distal active disease and for maintenance therapy, respectively. Patients with moderately active ulcerative colitis treated with 4.8 g/d of mesalamine are significantly more likely to achieve overall improvement at week 6 compared to patients treated with 2.4 g/d. In the setting of left-sided distal colitis (proctitis), topical (rectal) formulations have been found to be superior to oral aminosalicylates at inducing remission. Mesalamine has been shown to be safe in short term use with a dose-response efficacy without dose-related toxicity.

No MeSH data available.


Related in: MedlinePlus

Chemical structures of 5-ASA preparations.
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fig2: Chemical structures of 5-ASA preparations.

Mentions: Sulfasalazine (Pharmacia & Upjohn Company, Kalamazoo, MI, USA), first developed in 1942, has been the parent aminosalicylate in use for over 60 years (Hanauer 2004) and consists of 5-aminosalyclic acid linked by an azo bond to sulfapyridine (Figure 2). It combines an antibacterial agent (sulfapyridine) with an anti-inflammatory component (5-ASA). The sulfonamide moiety acts as a carrier to deliver the active component 5-ASA to the colon where it is released by bacterial action. Sulfasalazine is metabolized by colonic bacterial enzymes to produce the two active byproducts. Sulfapyraidine is metabolized by the liver and excreted in the urine whereas the 5-ASA component is acetylated by the colonic epithelium (Rochester and Abreu 2005). The original indication for 5-ASA was for rheumatoid arthritis, however it was subsequently found to be efficacious in ulcerative colitis. Misiewicz et al (1965) published the first placebo controlled maintenance trial in 1965 randomizing patients to receive sulfasalazine or placebo for one year. Seventy three percent of patients taking placebo relapsed compared to 21% taking the active drug, thus showing sulfasalazine to be highly efficacious for the treatment of ulcerative colitis.


The role of mesalamine in the treatment of ulcerative colitis.

Karagozian R, Burakoff R - Ther Clin Risk Manag (2007)

Chemical structures of 5-ASA preparations.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376091&req=5

fig2: Chemical structures of 5-ASA preparations.
Mentions: Sulfasalazine (Pharmacia & Upjohn Company, Kalamazoo, MI, USA), first developed in 1942, has been the parent aminosalicylate in use for over 60 years (Hanauer 2004) and consists of 5-aminosalyclic acid linked by an azo bond to sulfapyridine (Figure 2). It combines an antibacterial agent (sulfapyridine) with an anti-inflammatory component (5-ASA). The sulfonamide moiety acts as a carrier to deliver the active component 5-ASA to the colon where it is released by bacterial action. Sulfasalazine is metabolized by colonic bacterial enzymes to produce the two active byproducts. Sulfapyraidine is metabolized by the liver and excreted in the urine whereas the 5-ASA component is acetylated by the colonic epithelium (Rochester and Abreu 2005). The original indication for 5-ASA was for rheumatoid arthritis, however it was subsequently found to be efficacious in ulcerative colitis. Misiewicz et al (1965) published the first placebo controlled maintenance trial in 1965 randomizing patients to receive sulfasalazine or placebo for one year. Seventy three percent of patients taking placebo relapsed compared to 21% taking the active drug, thus showing sulfasalazine to be highly efficacious for the treatment of ulcerative colitis.

Bottom Line: Newer formulations of salicylates based drugs with fewer side-effects have been developed.In the setting of left-sided distal colitis (proctitis), topical (rectal) formulations have been found to be superior to oral aminosalicylates at inducing remission.Mesalamine has been shown to be safe in short term use with a dose-response efficacy without dose-related toxicity.

View Article: PubMed Central - PubMed

Affiliation: Brigham and Women’s Hospital, Harvard Medical School Boston, MA, USA.

ABSTRACT
Ulcerative colitis (UC) is a chronic inflammatory condition of unclear etiology affecting the large bowel, most commonly the rectum and extending proximally in a continuous fashion. The overall principle in the pathophysiolgy of ulcerative colitis is the dysregulation of the normal immune system against an antigenic trigger leading to a prolonged mucosal inflammatory response. The diagnosing of UC is made by combining the clinical picture, tissue biopsy with the endoscopic appearance of mucosal ulceration, friable, edematous, erythematous granular appearing mucus. The approach to therapy of UC has been dependent on severity of symptoms with frontline therapy being salicylate based sulfasalazine. Newer formulations of salicylates based drugs with fewer side-effects have been developed. These are free of the sulphur component and are composed of 5-ASA, without the sulfapyridine carrier molecule. Mesalamine is one of these 5-ASA based agents that are currently available and indicated for treatment of UC. In mild/moderate active disease mesalamine has response rates between 40%-70% and remission rates of 15%-20%. Considering that the efficacy of 5-ASA is dose dependent, 4.8 g/day and 2.4 g/day have been shown to be the optimal dosages for mild-moderate distal active disease and for maintenance therapy, respectively. Patients with moderately active ulcerative colitis treated with 4.8 g/d of mesalamine are significantly more likely to achieve overall improvement at week 6 compared to patients treated with 2.4 g/d. In the setting of left-sided distal colitis (proctitis), topical (rectal) formulations have been found to be superior to oral aminosalicylates at inducing remission. Mesalamine has been shown to be safe in short term use with a dose-response efficacy without dose-related toxicity.

No MeSH data available.


Related in: MedlinePlus