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

Sulphasalazine (SASP), used in the treatment of inflammatory bowel disease, is split into sulphapyridine (SP) and 5-aminosalicylic acid (5-ASA) in the colon. Lower plasma levels of SASP and 5-ASA as compared to those of SP may be due to different absorption rates from the colon because of different pK values and pH dependent lipid-water partition coefficients. In this study we determined the pK values of 5-ASA and its major metabolite, N-acetyl amino-salicylic acid (AcASA), by 13C-NMR spectroscopy and compared the pH dependent apparent benzene-water partition coefficients (Papp) of SASP, SP and 5-ASA with respect to their different plasma levels. The COOH group of 5-ASA had a pK value of 3.0, the -NH3+ group had 6.0, the -OH group 13.9; the -COOH group of AcASA had 2.7 and the -OH group 12.9; The Papp of SASP (0.042 +/- 0.004) and 5-ASA (0.059 +/- 0.01) were significantly lower than that of SP (0.092 +/- 0.03) (at pH 5.5).
 ...
PMID:Determination of the pK values of 5-aminosalicylic acid and N-acetylaminosalicylic acid and comparison of the pH dependent lipid-water partition coefficients of sulphasalazine and its metabolites. 286 70

Sulphasalazine, devised by Dr Nana Svartz for the treatment of 'infective polyarthritis', has been used in the treatment of inflammatory bowel disease for more than 40 years. Many controlled trials have shown that sulphasalazine 4g daily will induce remissions in between one-half and three-quarters of patients with acute attacks of ulcerative colitis. When given in a dosage of 2g daily it will prevent relapses in quiescent colitis. Relapses are 5 times more likely in untreated patients. It is less effective in Crohn's disease, where it exerts only a transient benefit in patients with active colonic disease and fails to prevent relapse or recurrence. Sulphasalazine is absorbed from the small intestine, re-excreted in bile and carried to the colon, where its azo bond is split by bacteria to release sulphapyridine, which is absorbed and is responsible for most of the drug's side effects, and 5-aminosalicylic acid, which is the active therapeutic moiety of the drug and exerts a beneficial topical action on the colonic mucosa. Side effects are common but are mainly reversible and not serious. Those related to high concentrations of sulphapyridine and to poor acetylation of the drug include gastrointestinal intolerance, malaise, headache, arthralgia, drug fever, effects on red blood cells and reversible male infertility. More serious, idiosyncratic side effects are skin rashes, leucopenia and agranulocytosis. Rarely, neurotoxicity, hepatotoxicity, polyarteritis, pulmonary fibrosis, a lupus-like syndrome and haemorrhagic colitis are produced. It is possible to desensitise most patients with drug-induced skin rashes. A number of less toxic alternatives to sulphasalazine have been devised and are undergoing trial. They either convey 5-aminosalicylic acid in a coated tablet to the colon or, when conjugated to a non-toxic carrier, release 5-aminosalicylic acid by bacterial cleavage there. Sulphasalazine remains a most useful drug in the treatment of inflammatory bowel disease after 40 years of use.
 ...
PMID:Sulphasalazine: a review of 40 years' experience. 287 47

Purified intestinal macrophages obtained at resections for colonic neoplasms were investigated for chemotaxis to leukotriene B4 (LTB4) by the Millipore filter assay and leading front technique. Possible inhibition by drugs effective in the treatment of chronic inflammatory bowel disease (sulphasalazine, olsalazine, its active moiety 5-aminosalicylic acid (5-ASA), and the 5-ASA metabolite N-acetylated-5-ASA (ac-5-ASA)) was tested at therapeutic colonic concentrations of 0.01-10 mM. Leukotriene B4 at a dose of 10 nM was equipotent with casein (5 g litre-1) as regards chemoattraction of macrophages. Sulphasalazine, olsalazine and 5-ASA were potent inhibitors of macrophages chemotaxis to LTB4 with IC50 values of 0.43, 0.39 and 0.24 mM, respectively. These concentrations are below the lowest concentration of 5-ASA (2 mM) in the colonic lumen during conventional sulphasalazine treatment of patients with chronic inflammatory bowel disease. The inhibition of macrophage chemotaxis by these drugs may be important for this limitation of the local inflammatory process in chronic inflammatory bowel disease, and may in part explain the beneficial effect of systemic and local treatment with sulphasalazine. Leukotriene B4 appears to be an important inflammatory mediator for the activation of macrophages in colonic inflammation.
 ...
PMID:Inhibition of intestinal macrophage chemotaxis to leukotriene B4 by sulphasalazine, olsalazine, and 5-aminosalicylic acid. 290 54

The semen of 11 patients with inflammatory bowel disease treated with sulphasalazine (Salazopyrin) was analysed and compared with that of 6 men with similar disease not treated with the drug. The treated group had significantly reduced sperm population density and motility compared with the untreated group. Both groups had high numbers of abnormal spermatozoa compared with the standard for our laboratory, but there was no significant difference between the two groups for this parameter. Sulphasalazine has a deleterious effect on spermatogenesis.
 ...
PMID:Sulphasalazine and spermatogenesis. 612 57

Sulphasalazine treatment for inflammatory bowel disease in man causes oligospermia, reduced sperm motility and an increased proportion of abnormal forms. On withdrawal of sulphasalazine these effects are found to be reversible and 15 pregnancies occurred at a median of 2.5 months after stopping sulphasalazine therapy. Seminal plasma concentrations of acid phosphatase fructose and PGE2 as well as the hormone profiles of patients on sulphasalazine for three months were found to be within normal limits. Sulphasalazine fed to male Sprague Dawley rats caused a dose dependent and reversible infertility with a significant reduction in litter size. Rats fed the metabolite sulphapyridine also had a reduced litter size when mated, while those fed the metabolite 5'aminosalicylic acid and a polymer of 5'aminosalicylic acid did not. It seems likely that the sulphapyridine moiety of sulphasalazine is responsible for the infertility seen, the effect being mediated at a late stage in sperm maturation.
 ...
PMID:Reversible male infertility due to sulphasalazine: studies in man and rat. 614 93

Sulphasalazine is an effective drug for the treatment of rheumatoid arthritis in adults. In paediatric patients, the drug has been used to treat inflammatory bowel disease and is currently under investigation for the treatment of juvenile chronic arthritis. Although sulphasalazine has a rather low incidence of serious side effects, one of the most common is skin rash, thought to be an allergic reaction. In adults, sulphasalazine desensitization programmes have proven to be effective for the treatment of this side effect. We present the case of a 7-year-old boy suffering from HLA-B 27 positive juvenile chronic arthritis. After initiation of treatment with sulphasalazine he developed an allergic skin rash, but tolerated the drug well after completion of a desensitization programme. To our knowledge, this is the first report of a paediatric patient with juvenile chronic arthritis successfully desensitized with sulphasalazine.
 ...
PMID:Sulphasalazine desensitization in a paediatric patient with juvenile chronic arthritis. 748 28

Thiopurine drugs are used in the treatment of inflammatory bowel disease--as are sulphasalazine and its metabolite 5-aminosalicylic acid (ASA). S-Methylation catalyzed by thiopurine methyltransferase (TPMT) is a major pathway in the metabolism of thiopurines. The hypothesis was tested that TPMT might be inhibited by sulphasalazine or isomers of ASA. Sulphasalazine as well as 3-, 4- and 5-ASA inhibited recombinant human TPMT, with IC50 values of 78, 99, 2600 and 1240 microM, respectively. Kinetic studies demonstrated that the inhibition of TPMT by sulphasalazine and ASA isomers was non-competitive with regard to the thiopurine substrate, 6-MP, and was uncompetitive with regard to the methyl donor for the reaction, S-adenosyl-L-methionine. Our observations raise the possibility of a clinically significant drug-drug interaction in patients treated simultaneously with sulphasalazine and thiopurine drugs.
 ...
PMID:Sulphasalazine inhibition of thiopurine methyltransferase: possible mechanism for interaction with 6-mercaptopurine and azathioprine. 764 Jan 56

1. Mice, whose drinking water contained sulphasalazine, sulphapyridine or 5-amino-salicylic acid, received an antigenic challenge by cholera toxin administered either orally or systemically. 2. Sulphasalazine treated mice made less specific antibody of IgA class provided the antigen also was administered orally (P = 0.009 for days 7-28). When the antigen was administered systemically, there was a vigorous anti-cholera toxin antibody response of IgG class, and a lesser IgM but only a weak IgA response. The effect of sulphasalazine in this case was confined to the IgG response, which was significantly suppressed on day 28 (P = 0.008). 3. Sulphapyridine and 5-amino salicylic acid had no significant effect on the anti-cholera toxin (CT) responses of all three classes. 4. It therefore appears that in this model, only sulphasalazine is capable of influencing the humoral immune system, the antibody class affected depending on the route of entry of antigen. This may have implications for conditions such as rheumatoid arthritis and chronic inflammatory bowel disease, for which sulphasalazine has been found useful.
 ...
PMID:Comparison of the effect of oral sulphasalazine, sulphapyridine and 5-amino-salicylic acid on the in vivo antibody response to oral and systemic antigen. 809 1

Sulphasalazine and other 5-aminosalicylic acid (5-ASA)-containing drugs are used in the treatment of acute inflammatory bowel disease and in the maintenance of clinical remission. Despite their use for over 50 years, the mechanism of action of this class of drugs remains uncertain, although a number of possibilities are discussed in this review. It seems likely that the aminosalicylates are important free radical scavengers, can reduce leukotriene production and can inhibit the cellular release of interleukin-1, all of which are likely to be important in reducing the acute inflammatory response in inflammatory bowel disease. The effects of these drugs on prostaglandin production are more contentious, but it appears that 10(-5) to 10(-4) M concentrations stimulate production of prostaglandins which may be cytoprotective, while higher doses of these drugs inhibit prostaglandin production. The aminosalicylates may maintain remission in inflammatory bowel disease by preventing leucocyte recruitment into the bowel wall. The drugs inhibit the chemotactic response to leukotriene B4, reduce the synthesis of platelet activating factor and also inhibit leucocyte adhesion molecule upregulation.
 ...
PMID:Review article: the mode of action of the aminosalicylates in inflammatory bowel disease. 810 84

Gut inflammation plays a crucial role in the pathogenesis of spondylarthropathies (SpA) since ileocolonoscopic studies have demonstrated the presence of gut inflammation in different forms of this concept: in ankylosing spondylitis (AS) (60%), in enterogenic (90%) and urogenital reactive arthritis (20%), in undifferentiated SpA (65%), in the pauciarticular and axial forms of psoriatic arthritis (16%), in late onset pauciarticular juvenile chronic arthritis (80%) and in acute anterior uveitis (66%). The strong relationship between gut and joint inflammation was demonstrated by performing a second ileocolonoscopy: remission of the joint inflammation was always connected with a disappearance of gut inflammation, whereas persistence of locomotor inflammation was mostly associated with the persistence of gut inflammation. During further evolution 20% of the non-ankylosing spondylitis SpA patients can develop AS. About 6% of the total group SpA patients, in whom inflammatory bowel disease (IBD) was excluded, developed Crohn's disease 5 to 9 years later. All these patients initially presented with gut inflammation, which indicates that this finding has prognostic value. The high prevalence of evolution to IBD in SpA patients confirms the thesis that both disease entities bear common pathogenic mechanisms, and confirms the place of IBD in the concept of SPA. Sulphasalazine (SASP), a successful drug in the treatment of IBD, has demonstrated its effectiveness in the treatment of SpA. The beneficial effect of the drug in this disease entity could be due to its anti-inflammatory effect on the gut wall, by normalizing its permeability and by preventing the entrance of antigens through the defective gut wall. However, SASP could not prevent the evolution to IBD.
 ...
PMID:Course of gut inflammation in spondylarthropathies and therapeutic consequences. 867 45


<< Previous 1 2 3 Next >>