Aminosalicylic acid adverse effects

Maintenance therapy with sulfasalazine reduces relapse rate. However a considerable number of patients experience adverse effects which are by the sulfa component of sulfasalazine. Then preparations of 5-aminosalicylic acid can be used. 

Sulfasalazine is absorbed in the proximal intestine and is then excreted unchanged in the bile. In consequence most of orally administred sulfasalzine reaches the colon as such. It is then split by the intestinal flora into its components sulfapyridine, a sulfonamide antimicrobial agent, and 5-aminosalicylic acid (5-ASA). It has been proven that in inflammatory bowel disease 5-ASA is responsible for the beneficial effects while the sulpha component only contributes to the adverse reaction profile. Although some 5-ASA is absorbed and excreted in urine with a half-life of 0.5-1.5 hours, most is eliminated unchanged in the faeces. Sulfapyridine is to a major extend reabsorbed, metabolized in the liver and excreted in the urine with a half-life, depending on the acetylator phenotype, between 5 and 15 hours. 

Sulfasalazine has been used for the management of RA and ankylosing spondylitis with apparently similar effectiveness as penicillamine and with less toxicity. While 5-aminosalicylic acid is the active agent in inflammatory bowel disease, it is believed that sulfapyridine is mostly responsible for the antirheumatoid effects. Gastrointestinal complaints, dizziness and photosensitivity are the most frequently observed adverse events. With levamisole and also with sulfasalazine and olsalazine a delay of 2-3 months is to be expected before positive responses will be observed. 

The systemic adverse effects of corticosteroids make them inappropriate as maintenance treatments and the first line treatments are the aminosalicylates. The original drug sulfasalazine is a chemical combination of sulfapyridine and 5 aminosalicylic acid. Following the discovery that the active... 

Schworer H, Ramadori G. Akute Pankreatitis-unerwunschte Wirkung von Aminosalicylsaure (Mesalazin) in verschiedenen galenischen Applikationsformen. [Acute pancreatitis—adverse effect of 5-aminosalicylic acid (mesa-lazine) in various galenic dosage forms.] Dtsch Med Wochenschr 2000 125(44) 1328-30. 

Apart from classic analgesic nephropathy, this chapter will also handle the possible nephrotoxic role of 5-aminosalicylic acid (5-ASA) used in patients with chronic inflammatory bowel disease (IBD). During the last decade, 5-ASA replaced sulfasalazine as first-line therapy for mildly to moderately active IBD. For decades, sulphasalazine, an azo-compound derived from sulphapyridine and 5-aminosalicylic acid (5-ASA), has been the only valuable non-corticosteroid drug in the treatment of inflammatory bowel disease. Azad Kahn et al. [25] showed that the pharmacologically active moiety in sulphasalazine for the treatment of these diseases was 5-ASA. Consequently, this resulted in a number of new 5-ASA formulations (mesalazine, olsalazine, balsalazine) for topical and oral use. Since the metabolite sulphapyridine was largely responsible for the side effects of sulfasalazine, the primary advantage of the newer 5-ASA agents is their improved adverse effect profile. 

A study found that aminosalicylic acid significantly increased the plasma levels of isoniazid at 4 and 6 hours after administration by 32% and 114%, respectively in fast acetylators of isoniazid, and by 21% and 39%, respectively in slow acetylators. The half-life of isoniazid was increased from 1.32 to 2.89 hours in fast acetylators and from 3.05 to 4.27 hours in slow acetylators (see Genetic factors , (p.4), for more information about acetylator status). The effects were probably due to the inhibition of isoniazid metabolism by aminosalicylic acid. There seem to be no reports of isoniazid toxicity arising from this interaction, but the manufacturers of isoniazid warn that adverse effects are more likely in the presence of aminosalicylic acid. ... 

Two reports from India again stressed the fact that serious dermatological adverse effects are not uncommon with this compound. Bhagi et al. (50 -) reported a case of severe acute epidermal necrolysis developing in a 25-year-old woman treated for 6 weeks with streptomycin and isoniazid followed by 15 days of thiacetazone (150 mg daily) and isoniazid. The patient recovered on withdrawal of the drugs and local and systemic treatment with corticosteroids, and was subsequently treated satisfactorily with a combination of isoniazid and para-aminosalicylic acid. 

An interesting and unusual adverse effect attributed to pyrazinamide was described in a paper from the United States (54 ). A patient was described who suffered several attacks of acute intermittent porphyria whilst under treatment for tuberculosis. The first attack occurred after 18 months therapy with isoniazid and ethambutol. The second episode occurred after 14 days treatment with rifampicin, 7 days treatment with pyrazinamide and 3 days treatment with streptomycin. The patient was subsequently treated successfully with a combination of rifampicin, ethambutol and capreomycin. The compounds were investigated for their capacity to induce hepatic delta-aminolaev-ulinic acid synthesis in an in vitro preparation of rat Uver. The results showed that pyrazinamide had a greater potential for inducing the enzyme activity than any of the other compounds. It is worthy of note, however, that in this in vitro system para-aminosalicylic acid, rifampicin, cycloserine and ethionamide all induced increased delta-aminolaevulinic acid synthesis. 

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