5-aminosalicylic acid prevention

McKenzie, S.M., Doe, W.F., and Buffinton, G.D. (1999). 5-aminosalicylic acid prevents oxidant mediated damage of glyceraldehyde-3-phosphate dehydrogenase in colon epithelial cells. Gut 44, 180-5. 

After 3 h in the presence of riboflavin (formula [38]) and light, the electrophoretic mobility of Cat-3 increased similar to other catalases. The presence of singlet oxygen quenchers such as histidine and 5-aminosalicylic acid prevented this change. 

The three standard drugs used in the treatment of tuberculosis were streptomycin (considered above), -aminosalicylic acid (PAS) and isoniazid (isonicotinylhydrazide, INH synonym, isonicotinic acid hydrazine, INAH). The tubercle bacillus rapidly becomes resistant to streptomycin, and the role of PAS was mainly that of preventing this development of resistance. The current approach is to treat tuberculosis in two phases an initial phase where a combination of three dmgs is used to reduce the bacterial level as rapidly as possible, and a continuation phase in which a combination of... 

Baughan, C.A., Canney, P.A., Buchanan, R.B. and Pickering, R.M. (1993). A randomised trial to assess the efficacy of 5-aminosalicylic acid for the prevention of radiation enteritis. Clin. Oncol. Roy. Coll. Radiol. 5, 19-24. 

Amylose, another natural polysaccharide, prepared under appropriate conditions, is not only able to produce films, but is also found to be resistant to the action of pancreatic a-amylase while remaining vulnerable to the colonic flora [82]. However, incorporation of ethylcellulose was necessary to prevent premature drug release through simple diffusion [83], In vitro release of 5-aminosalicylic acid from pellets coated with a mixture of amylose-ethylcellulose in a ratio of 1 4 was complete after 4 hr in a colonic fermenter. By contrast, it took more than 24 hr to release only 20% of the drug under conditions that mimic that of the stomach and of the small intestine. 

Sulfasalazine. Salicylazosulfapyridine or Azulfadine [599-79-1] (2-hydroxy-5-[[4[(2-pyridylamino)sulfonyl]-phenyl]azo] benzoic acid) (15) is a light brownish yellow-to-bright yellow fine powder that is practically tasteless and odorless. It melts at ca 255°C with decomposition, is very slightly soluble in ethanol, is practically insoluble in water, diethyl ether, chloroform, and benzene, and is soluble in aqueous solutions of alkali hydroxides. Sulfasalazine may be made by the synthesis described in Reference 13. It is not used as an antidiarrheal as such, but is indicated for the treatment of inflammatory bowel diseases such as ulcerative colitis and Crohn s disease. Its action is purported to result from the breakdown in the colon to 5-aminosalicylic acid [89-57-6] (5-AS A) and sulfapyridine [144-83-2]. It may cause infertility in males, as well as producing idiosyncratic reactions in some patients these reactions have been attributed to the sulfa component of the compound. The mechanism of 5-ASA is attributed to inhibition of the arachidonic acid cascade preventing leukotriene B4 production and the ability to scavenge oxygen free radicals. The active component appears to be 5-aminosalicylic acid. 

CHEMISTRY, MECHANISM OF ACTION, AND PHARMACOLOGICAL PROPERTIES First-line therapy for mild-to-moderate ulcerative colitis generally involves mesalamine (5-aminosalicylic acid, or 5-ASA). The archetype for this class of medications is sulfasalazine (azulfidine), which consists of 5-ASA linked to sulfapyridine by an azo bond. Sulfasalazine represents one of the first examples of an oral drug that is delivered effectively to the distal GI tract. The azo linkage in sulfasalazine prevents absorption in the stomach and small intestine, and the individual components are not liberated for absorption until colonic bacteria cleave the bond. 5-ASA is now regarded as the therapeutic agent, with little, if any, contribution by sulfapyridine. 

A well documented and clinically important interaction. Separating the administration of the two drugs by 8 to 12 hours to prevent their mixing in the gut has been suggested as an effective way to prevent this interaction. An alternative is to give aminosalicylic acid preparations that do not contain bentonite. 

A study in rats found that colestyramine binds with sulfasalazine so that the azo-bond is protected against attack by the bacteria within the gut. As a result the active 5-aminosalicylic acid is not released and the faecal excretion of intact sulfasalazine increases 30-fold. It seems possible that this interaction could also occur in humans, but confirmation of this is lacking. Separating the drug dosages to prevent their admixture in the gut has proved effective with other drugs that bind with colestyramine. Standard advice is to avoid other drugs for one hour before, and 4 to 6 hours after colestyramine. 

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