|Systematic (IUPAC) name|
|Biological half-life||5-10 hours|
|Molar mass||398.394 g/mol|
|(what is this?)|
Sulfasalazine (brand name Azulfidine in the U.S., Salazopyrin and Sulazine in Europe and Hong Kong) was developed in the 1950s specifically to treat rheumatoid arthritis. It was believed at the time that bacterial infections were the cause of rheumatoid arthritis. Sulfasalazine is a sulfa drug, a derivative of mesalazine, and is formed by combining sulfapyridine and salicylate with an azo coupling. It may be abbreviated SSZ.
It is on the World Health Organization's List of Essential Medicines, a list of the most important medication needed in a basic health system.
Sulfasalazine is used in the treatment of inflammatory bowel disease, including ulcerative colitis and Crohn's disease. It is also indicated for use in rheumatoid arthritis and used in other types of inflammatory arthritis (e.g. psoriatic arthritis) where it has a beneficial effect. It is often well tolerated compared to other DMARDs.
In clinical trials for the treatment of chronic alcoholics, sulfasalazine has been found to reverse the scarring associated with liver cirrhosis. A study at Newcastle University found that the drug may act to aid the healing of cirrhosis of the liver. Cells called myofibroblasts, which contribute to scar tissue in a diseased liver, also appear to secrete proteins that prevent the breakdown of the scar tissue. Sulfasalazine appears to retard this secretion.
It is usually not given to children under 2 years of age.
The use of sulfasalazine in inflammatory bowel disease has declined due mainly to the fact that it yields the metabolite sulfapyridine which gives rise to side-effects such as agranulocytosis and hypospermia. However, the other metabolite of sulfasalazine, 5-aminosalicylic acid (5-ASA) is credited with causing the drug's therapeutic effect. Therefore, 5-ASA and other derivatives of 5-ASA, are now usually preferred and given alone (as mesalazine), despite their increased cost, due to their more favourable side-effect profile.
Sulfasalazine metabolizes to sulfapyridine. Serum levels should be monitored every three months, and more frequently at the outset. Serum levels above 50 μg/l are associated with side effects. In rare cases, Sulfasalazine can cause severe depression in young males. It can also cause temporary infertility. Immune thrombocytopenia has been reported.
Mechanism of action
Sulfasalazine, and its metabolite 5-ASA, are poorly absorbed from the small intestine. Its main mode of action is therefore believed to be inside the intestine.Approximately one third of a dose of sulfasalazine is absorbed from the small intestine. The remaining two thirds passes into the colon where it is split by bacteria into 5-ASA and SP. SP is well absorbed from the colon (estimated bioavailability 60%); 5-ASA is less well absorbed (estimated bioavailability 10% to 30%).
In Crohn's disease and ulcerative colitis, it is thought to be an antinflammatory drug that provides topical relief inside the intestine. It does this via a number of mechanisms such as reducing the synthesis of inflammatory mediators known as eicosanoids and inflammatory cytokines. However, compared to glucocorticoids (another class of drug used in the treatment in inflammatory bowel disease), sulfasalazine is only a mild immunosuppressant.
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When treatment for arthritis is successful, pain, joint swelling and stiffness will be reduced and this may slow down or stop the development of joint damage.[tone] The precise reasons why sulfasalazine are effective in various forms of arthritis is not clearly understood.[tone] However, sulfasalazine is thought to work by inhibiting NF-κB.
Because sulfasalazine and its metabolite mesalazine (or 5-aminosalicylic acid (5-ASA)) are poorly absorbed into the bloodstream, it is surprising that the drug is effective against symptoms outside of the intestine. One possible explanation is that, given that ulcerative colitis produces arthritic symptoms, the arthritic symptoms resolved by sulfasalazine are actually[tone] a product of [clarify] ulcerative colitis, which is effectively treated with sulfasalazine.
The other metabolite, sulfapyridine, is absorbed into the blood, and is believed to be the source of the side-effects discussed above. It is possible that the sulfapyridine is responsible for some of the anti-arthritic effects of sulfasalazine.
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