Chemistry:Sulfasalazine

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Short description: Chemical compound
Sulfasalazine
Sulfasalazine.svg
Clinical data
Trade namesAzulfidine, Salazopyrin, Sulazine, others
Other namesSulphasalazine, SSZ
AHFS/Drugs.comMonograph
MedlinePlusa682204
License data
Pregnancy
category
Routes of
administration		By mouth
Drug classSulfonamides
ATC code
Legal status
Legal status
Pharmacokinetic data
Bioavailability<15%
Elimination half-life5-10 hours
Excretiondrug metabolites are excreted in urine and feces [4]
Identifiers
CAS Number
PubChem CID
DrugBank
ChemSpider
UNII
KEGG
ChEBI
ChEMBL
Chemical and physical data
FormulaC18H14N4O5S
Molar mass398.39 g·mol−1
3D model (JSmol)
Melting point240 to 245 °C (464 to 473 °F) (dec.)
 ☒N☑Y (what is this?)  (verify)

Sulfasalazine, sold under the brand name Azulfidine among others, is a medication used to treat rheumatoid arthritis, ulcerative colitis, and Crohn's disease.[5] It is considered by some to be a first-line treatment in rheumatoid arthritis.[6] It is taken by mouth or can be administered rectally.[5]

Significant side effects occur in about 25% of people.[6] Commonly these include loss of appetite, nausea, headache, and rash.[5] Severe side effects include bone marrow suppression, liver problems, Stevens–Johnson syndrome, and kidney problems.[6][7][4] It should not be used in people allergic to aspirin or sulfonamide.[6] Use during pregnancy appears to be safe for the baby.[5]

Sulfasalazine is in the disease-modifying antirheumatic drugs (DMARDs) family of medications.[5] It is unclear exactly how it works.[5] One proposed mechanism is the inhibition of prostaglandins, resulting in local anti-inflammatory effects in the colon.[4] The medication is broken down by intestinal bacteria into sulfapyridine and 5-aminosalicylic acid.[5]

Sulfasalazine was approved for medical use in the United States in 1950.[5] It is on the World Health Organization's List of Essential Medicines.[8] Sulfasalazine is available as a generic medication.[5] In 2020, it was the 284th most commonly prescribed medication in the United States, with more than 1 million prescriptions.[9][10]

Medical uses

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 and reactive arthritis).[11][3][2]

It is usually not given to children under two years of age.[3][2]

Side effects

Use of sulfasalazine is contraindicated in people with sulfa allergies and in those with urinary tract obstructions, intestinal obstructions, and severe liver or kidney problems.[4]

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 oligospermia and temporary infertility. Immune thrombocytopenia has been reported.[12]

Sulfasalazine inhibits dihydropteroate synthase, and can cause folate deficiency and megaloblastic anemia.[13][14][15] and various other undesirable effects.[16]

Sulfasalazine can cause hemolytic anemia in people with G6PD deficiency.[17]

Sulfasalazine can cause kidney stones.[18] Sulfasalazine may cause stomach upset, nausea, vomiting, loss of appetite, headache, dizziness, or unusual tiredness.[5] Skin and urine can become orange, with occasional allergic reactions.[19][5]

Sulfasalazine may cause sulfhemoglobinemia.[citation needed]

Pharmacology

Around 90% of a dose of sulfasalazine reaches the colon, where most of it is metabolized by bacteria into sulfapyridine and mesalazine (also known as 5-aminosalicylic acid or 5-ASA). Both metabolites are active; most of the sulfapyridine is absorbed and then further metabolized, but most mesalazine is not, and remains in the colon.[3]

A mix of unchanged, hydroxylated, and glucuronidated sulfapyridine is eliminated in urine, as is acetylated mesalazine and unmetabolized sulfasalazine.[3][2]

The mechanism of action is not clear, but it appears that sulfasalazine and its metabolites have immunosuppressive, antibacterial, and anti-inflammatory effects.[11][3] It also appears to inhibit the cystine-glutamate antiporter,[20] as well as sepiapterin reductase.[21]

Chemistry

It is a codrug which is a combination of sulfapyridine and 5-aminosalicylic acid coupled with an azo linkage.

Cost

In people with rheumatoid arthritis, the cost-effectiveness of sulfasalazine is improved by combining it with other drugs.[22] It is commonly used in treating inflammatory bowel disease in part due to its cost effectiveness.[23]

Research

Sulfasalazine has been studied in cirrhosis,[24] psoriasis,[25] idiopathic urticaria,[26] and amyloidosis.[27]

References

  1. ↑ "Sulfasalazine Use During Pregnancy". 9 November 2018. https://www.drugs.com/pregnancy/sulfasalazine.html. 
  2. ↑ 2.0 2.1 2.2 2.3 "Sulfasalazine 250mg/5ml Oral Suspension - Summary of Product Characteristics (SmPC)". 13 September 2019. https://www.medicines.org.uk/emc/product/413/smpc. 
  3. ↑ 3.0 3.1 3.2 3.3 3.4 3.5 "Salazopyrin Tablets - Summary of Product Characteristics". electronic medicines compendium (emc). February 2014. https://www.medicines.org.uk/emc/medicine/3344. 
  4. ↑ 4.0 4.1 4.2 4.3 Davis's drug guide for nurses (Fourteenth ed.). Philadelphia. 5 June 2014. ISBN 978-0-8036-4085-6. OCLC 881473728. 
  5. ↑ 5.00 5.01 5.02 5.03 5.04 5.05 5.06 5.07 5.08 5.09 5.10 "Sulfasalazine". The American Society of Health-System Pharmacists. https://www.drugs.com/monograph/sulfasalazine.html. 
  6. ↑ 6.0 6.1 6.2 6.3 WHO Model Formulary 2008. World Health Organization. 2009. pp. 41, 45. ISBN 9789241547659. 
  7. ↑ Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. 2015. p. 464. ISBN 9781284057560. 
  8. ↑ World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. 2019. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO. 
  9. ↑ "The Top 300 of 2020". https://clincalc.com/DrugStats/Top300Drugs.aspx. 
  10. ↑ "Sulfasalazine - Drug Usage Statistics". https://clincalc.com/DrugStats/Drugs/Sulfasalazine. 
  11. ↑ 11.0 11.1 "Azulfidine- sulfasalazine tablet". 8 May 2019. https://dailymed.nlm.nih.gov/dailymed/drugInfo.cfm?setid=ddbe69f3-bd55-45f3-a64f-f60226c744c4. 
  12. ↑ "Sulfasalazine-induced immune thrombocytopenia". Postgraduate Medical Journal 83 (980): e1. June 2007. doi:10.1136/pgmj.2006.055194. PMID 17551063. 
  13. ↑ Inflammatory Bowel Disease~workup at eMedicine
  14. ↑ Women With Autoimmune Diseases: Medications During Pregnancy and Lactation: Sulfasalazine; "Women with Autoimmune Diseases: Medications During Pregnancy and Lactation: Sulfasalazine". http://www.medscape.org/viewarticle/720225_7. 
  15. ↑ "Folic acid antagonists during pregnancy and the risk of birth defects". The New England Journal of Medicine 343 (22): 1608–1614. November 2000. doi:10.1056/NEJM200011303432204. PMID 11096168. 
  16. ↑ "Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis". eLife 3: e02523. May 2014. doi:10.7554/eLife.02523. PMID 24844246. 
  17. ↑ "SulfaSALAzine: Drug Information Provided by Lexi-Comp". Merck & Co., Inc.. Jan 2012. https://www.merckmanuals.com/professional/appendixes/brand-names-of-some-commonly-used-drugs?search=sulfasalazine. 
  18. ↑ "An Unusual Type of Kidney Stone". Clinical Laboratory 62 (1–2): 235–239. 2016. doi:10.7754/Clin.Lab.2015.150605. PMID 27012055. https://biblio.ugent.be/publication/6847821. 
  19. ↑ "Sulfasalazine". http://www.webmd.com/drugs/2/drug-6260/sulfasalazine-oral/details. 
  20. ↑ "System xc⁻ cystine/glutamate antiporter: an update on molecular pharmacology and roles within the CNS". British Journal of Pharmacology 165 (1): 20–34. January 2012. doi:10.1111/j.1476-5381.2011.01480.x. PMID 21564084. 
  21. ↑ "Analgesia by inhibiting tetrahydrobiopterin synthesis". Current Opinion in Pharmacology 12 (1): 92–99. February 2012. doi:10.1016/j.coph.2011.10.019. PMID 22178186. 
  22. ↑ "Cost effectiveness analysis of disease-modifying antirheumatic drugs in rheumatoid arthritis. A systematic review literature". International Journal of Rheumatology 2011: 845496. 2011. doi:10.1155/2011/845496. PMID 22162693. 
  23. ↑ (in en) Crohn's Disease and Ulcerative Colitis: From Epidemiology and Immunobiology to a Rational Diagnostic and Therapeutic Approach. Springer. 2017. p. 395. ISBN 978-3-319-33703-6. https://books.google.com/books?id=zLE-DgAAQBAJ&dq=Sulfasalazine+cost&pg=PA395. 
  24. ↑ "Inhibition of inhibitor of kappaB kinases stimulates hepatic stellate cell apoptosis and accelerated recovery from rat liver fibrosis". Gastroenterology 128 (1): 108–120. January 2005. doi:10.1053/j.gastro.2004.10.003. PMID 15633128. 
  25. ↑ "Sulfasalazine improves psoriasis. A double-blind analysis". Archives of Dermatology 126 (4): 487–493. April 1990. doi:10.1001/archderm.1990.01670280071013. PMID 1690970. 
  26. ↑ "Successful treatment of recalcitrant chronic idiopathic urticaria with sulfasalazine". Archives of Dermatology 142 (10): 1337–1342. October 2006. doi:10.1001/archderm.142.10.1337. PMID 17043190. 
  27. ↑ "Inhibition by small-molecule ligands of formation of amyloid fibrils of an immunoglobulin light chain variable domain". eLife 4: e10935. November 2015. doi:10.7554/eLife.10935. PMID 26576950. 

External links



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