Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:APRD00152 (Sulphasalazine)
 152 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effect of 5-ASA and 4-ASA, drugs used for the treatment of inflammatory bowel disease, on modulation of experimental colitis and on colonic generation of interleukin-1 was evaluated. Three weeks of treatment with 5-ASA or 4-ASA (50 micrograms/kg) and one week of treatment with 5-ASA significantly decreased colonic interleukin-1 generation and the extent and severity of inflammation in a rat model of colitis induced by trinitrobenzene sulphonic acid. Colonic biopsies were obtained from patients with active ulcerative colitis and organ cultured 24 hours in the absence or presence of the following drugs: sulphasalazine, sulphapyridine, 5-ASA and 4-ASA (25-100 micrograms/ml). Interleukin-1 content in tissue cultured in the presence of 5-ASA (100 micrograms/ml) was two-thirds of its content in tissue cultured in drug free medium and its release into the medium was decreased by 50%. Sulphasalazine 50 micrograms/ml significantly decreased by 33% the tissue content but did not affect interleukin-1 release and a higher dose was not more effective. Sulphapyridine and 4-ASA in doses up to 100 micrograms/ml did not affect either interleukin-1 colonic content or its release into the culture medium. We conclude that pharmacological suppression of colonic interleukin-1 generation may be one, although not the sole mechanism to explain the therapeutic efficacy of 5-ASA in the treatment of inflammatory bowel disease.
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PMID:Effect of aminophenols (5-ASA and 4-ASA) on colonic interleukin-1 generation. 135 43

Sulphasalazine has been shown to have an effect in patients with spondyloarthropathies, but the clinical indication for its use is controversial and its long term effect has not yet been evaluated. Treatment with sulphasalazine was analysed retrospectively in a group of 372 patients with a wide range of spondyloarthropathies to determine subsets of patients showing differential effects of the drug. One hundred and one patients received sulphasalazine at a mean daily dose of 2 g (ankylosing spondylitis, 54 patients; psoriatic arthritis, 21 patients; reactive arthritis, four patients; arthritis related to inflammatory bowel disease, six patients; undifferentiated spondyloarthropathy, 16 patients). A comparison between treated and untreated patients suggests that only patients with active and severe disease were treated whatever the precise diagnosis or the amount of axial disease in the spondyloarthropathy. After six months of treatment improvement was noted in 59 patients unrelated to their subgroup or amount of axial disease. After a mean follow up of 20 months, 37 patients were still receiving treatment, 33 had discontinued the drug because of inefficacy, 14 because of side effects, six because of remission of the disease, and 11 for other reasons. Comparison between the beginning and end of treatment showed a statistically significant decrease in morning stiffness, erythrocyte sedimentation rate, and daily dose of non-steroidal anti-inflammatory drugs (NSAIDs). It is concluded that: (a) a low percentage of patients with spondyloarthropathy have active disease requiring treatment with sulphasalazine despite the use of NSAIDs (27% in this study); (b) in this subgroup of patients sulphasalazine seems to be of clinically relevant benefit in 59%; and (c) this benefit does not seem to be correlated with either the precise diagnosis of spondyloarthropathy or the amount of axial disease.
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PMID:Evaluation of sulphasalazine in the treatment of spondyloarthropathies. 135 38

An increased incidence of colonic cancer is associated with chronic inflammatory bowel disease. Sulphasalazine, metronidazole and more recently, modified forms of 5-aminosalicylic acid are used for maintenance therapy of inflammatory bowel disease. In a series of experiments, we used the 1,2-dimethylhydrazine animal model of colonic cancer in conjunction with these drugs, to study the effect on the development of colon cancer. Inbred male Wistar rats were divided into groups receiving orally: metronidazole 18 mg Kg-1 dy-1; sulphasalazine 60 mg Kg-1 dy-1; 5-aminosalicylic acid 30 and 60 mg Kg-1 dy-1 and olsalazine 60 mg Kg-1 dy-1 administered daily. Half of each group also received weekly injections of DMH 40 mg Kg-1. Metronidazole, sulphasalazine and 30 mg Kg-1 dy-1 5-aminosalicylic acid were co-carcinogenic, increasing either the number of cancers or tumour size. In contrast 60 mg Kg-1 dy-1 5-aminosalicylic acid inhibited tumour size and olsalazine had no effect. These results may have a bearing on long term maintenance therapy in inflammatory bowel disease.
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PMID:The effect of therapeutic drugs used in inflammatory bowel disease on the incidence and growth of colonic cancer in the dimethylhydrazine rat model. 810 63

Sulphasalazine is an active agent in the treatment of chronic inflammatory bowel disease, but there are a number of well-known side effects, including pancreatitis. The newer 5-ASA agents are thought to be equally effective but less toxic. Here we describe a patient who developed a pancreatitis due to mesalamine; this was confirmed at rechallenge.
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PMID:Pancreatitis induced by mesalamine. 140 43

The effects of sulphasalazine, 5-aminosalicylic acid (5-ASA), and sulphapyridine on peroxidation of red cell membrane lipids, measured as malondialdehyde production, were assessed. Sulphasalazine and 5-ASA, at concentrations of 10(-5)-10(-3) M significantly inhibit lipid peroxidation, suggesting an antioxidant action that may explain the efficacy of these drugs in treating inflammatory bowel disease. Sulphapyridine, which is not effective in inflammatory bowel disease inhibited malondialdehyde production at a concentration of 10(-3) M only.
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PMID:Inhibition of red cell membrane lipid peroxidation by sulphasalazine and 5-aminosalicylic acid. 168 30

The in vitro action of sulphasalazine, BW 755-C and indomethacin on phytohemagglutinin P-induced human peripheral blood mononuclear cell activation was studied. Sulphasalazine increased, while indomethacin and BW 755-C decreased, prostaglandin E2 (PGE2) accumulation in activated cultures. When used together with indomethacin or BW 755-C, sulphasalazine did not counteract the inhibition of PGE2 caused by the other two. Sulphasalazine inhibited phytohemagglutinin P-induced cell activation in a concentration-dependent manner even when used together with indomethacin or BW 755-C. BW 755-C inhibited cell activation at 350 microM, whereas at 11 microM it only increased sulphasalazine-induced inhibition. The implications of these findings on the etiopathology of inflammatory bowel disease are discussed.
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PMID:The effect of sulphasalazine on the in vitro activation of human peripheral blood mononuclear cells by phytohemagglutinin P. 257 59

The effect of sulphasalazine on two mast cell populations and human peripheral leukocytes is reported. Sulphasalazine inhibited histamine release from mouse and rat mast cells, but it caused a potentiation of secretion in human peripheral leukocytes. The drug alone did not induce histamine release when administered without an anaphylactic stimulus. The results are discussed in terms of a possible mode of action of sulphasalazine in the treatment of inflammatory bowel disease.
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PMID:Inhibition of IgE-mediated mast cell degranulation by sulphasalazine. 257 29

1. The effects of anti-inflammatory drugs on eicosanoid formation and colonic damage in a chronic model of inflammatory bowel disease (IBD) in the rat were investigated. 2. A single colonic instillation of the hapten, trinitrobenzene sulphonic acid (TNB) resulted in ulceration and inflammation which persisted for 3 weeks. 3. The macroscopic colonic damage, present 3 weeks after TNB, was correlated with an increase in immunoreactive 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) and leukotriene B4 (LTB4) synthesis by the rat colon. 4. Anti-inflammatory drugs were administered 2 weeks after TNB, when there was substantial colonic damage, and continued for a week. The experimental drug BW755C inhibited the increased formation of 6-keto-PGF1 alpha and LTB4 by the inflamed colon. Indomethacin and aspirin markedly inhibited prostanoid formation in both inflamed and control colon. Sulphasalazine or prednisolone also inhibited the formation of 6-keto-PGF1 alpha but the effects were less marked. 5. None of the anti-inflammatory drugs significantly reduced the colonic damage induced by TNB. 6. The results suggest that eicosanoids, including LTB4, have only a minor role in maintaining the chronic macroscopic damage induced in the rat colon by TNB. The role of such eicosanoids in the underlying infiltration and activity of inflammatory cells in this model of IBD, however, is not known.
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PMID:The effect of anti-inflammatory drugs on eicosanoid formation in a chronic model of inflammatory bowel disease in the rat. 284 Sep 94

There is accumulating clinical evidence that 5-aminosalicylic acid (5-ASA) represents the therapeutic moiety of sulphasalazine in the treatment of inflammatory bowel disease. For more than 4 decades, the active metabolite, 5-ASA, has been administered in the form of the 'prodrug' sulphasalazine; however, in contrast to sulphasalazine, the pharmacokinetics of 5-ASA were unknown until recently. Sulphasalazine itself is poorly absorbed (3 to 12%) and its elimination half-life of about 5 to 10 hours is probably affected by the absorption process. The major part of sulphasalazine is split by bacterial azo-reduction in the colon into 5-ASA and sulphapyridine, the latter accounting for most of the adverse effects of sulphasalazine. The effective cleavage of sulphasalazine depends on an intact colon and transit time. It is markedly reduced in patients taking antibiotics and after removal of the large bowel. The formed sulphapyridine is almost completely absorbed and eliminated by hydroxylation, glucuronidation and polymorphic acetylation. Depending on the genetic phenotype, the elimination half-life and apparent oral clearance of sulphapyridine are approximately 14 hours and 40 ml/min (slow acetylators) or 6 hours and 150 ml/min (fast acetylators), respectively. Of the 5-ASA released from its 'vehicle' sulphapyridine in the colon, at least 25% is absorbed and after acetylation is subsequently excreted in the urine. At least 50% is eliminated in the faeces. Recently, 5-ASA has also been administered directly in the form of enemas, suppositories and oral slow-release preparations. While the elimination half-life of 5-ASA is short (0.5 to 1.5 h), its major acetylated metabolite (which may be active) exhibits a half-life of 5 to 10 hours. During therapy with sulphasalazine or 5-ASA, steady-state plasma concentrations of 5-ASA are relatively low (less than or equal to 2 micrograms/ml); thus its mode of action appears to be topically rather than systemically. Another approach to deliver the active 5-ASA to the gastrointestinal tract is accomplished with novel 'prodrugs' of 5-ASA, in which the carrier molecule sulphapyridine is replaced by 5-ASA itself (azodisalicylate) or other compounds.
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PMID:Clinical pharmacokinetics of sulphasalazine, its metabolites and other prodrugs of 5-aminosalicylic acid. 286 55

Sulphasalazine impairs folic acid absorption and metabolism but rarely leads to folate deficiency in inflammatory bowel disease (IBD). In rheumatoid arthritis (RA), however, serum and red cell folate concentrations are often low and sulphasalazine might stress folate metabolism. In a prospective study, 2 g sulphasalazine was compared with 500 mg penicillamine daily in 30 patients over 24 weeks. Pre-treatment serum and red cell folate concentrations were low-normal. Improvements in disease activity and haemoglobin occurred in both treatment groups, but MCV increased only in patients taking sulphasalazine. Serum and red cell folate concentrations did not change in either group. Increased MCV with sulphasalazine might therefore reflect reticulocytosis secondary to drug-induced haemolysis. The mechanisms by which sulphasalazine antagonizes folate metabolism are dose-dependent and, consequently, higher doses might precipitate folate deficiency.
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PMID:Does sulphasalazine cause folate deficiency in rheumatoid arthritis? 286 41


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