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Sulfasalazine

September 02, 2023

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.[5]

Sulfasalazine
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
  • 2-hydroxy-5-[(E)-2-{4-[(pyridin-2-yl)sulfamoyl]phenyl}diazen-1-yl]benzoic acid
CAS Number
  • 599-79-1 Y
PubChem CID
  • 5339
DrugBank
  • DB00795 Y
ChemSpider
  • 10481900 Y
UNII
  • 3XC8GUZ6CB
KEGG
  • D00448 Y
  • C07316 Y
ChEBI
  • CHEBI:9334
ChEMBL
  • ChEMBL421 N
CompTox Dashboard (EPA)
  • DTXSID0021256
ECHA InfoCard100.009.069
Chemical and physical data
FormulaC18H14N4O5S
Molar mass398.39 g·mol−1
3D model (JSmol)
  • Interactive image
Melting point240 to 245 °C (464 to 473 °F) (dec.)
  • C1=CC=NC(=C1)NS(=O)(=O)C2=CC=C(C=C2)N=NC3=CC(=C(C=C3)O)C(=O)O
  • InChI=1S/C18H14N4O5S/c23-16-9-6-13(11-15(16)18(24)25)21-20-12-4-7-14(8-5-12)28(26,27)22-17-3-1-2-10-19-17/h1-11,23H,(H,19,22)(H,24,25) Y
  • Key:NCEXYHBECQHGNR-UHFFFAOYSA-N Y
 NY (what is this?)  (verify)

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 Edit

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 Edit

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 Edit

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 Edit

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

Cost Edit

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 Edit

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

References Edit

  1. ^ "Sulfasalazine Use During Pregnancy". Drugs.com. 9 November 2018. Retrieved 24 January 2020.
  2. ^ a b c d "Sulfasalazine 250mg/5ml Oral Suspension - Summary of Product Characteristics (SmPC)". electronic medicines compendium (emc). 13 September 2019. Retrieved 4 December 2019.
  3. ^ a b c d e f "Salazopyrin Tablets - Summary of Product Characteristics". electronic medicines compendium (emc). February 2014. from the original on 16 April 2017.
  4. ^ a b c d Vallerand AH, Sanoski CA, Deglin JH (5 June 2014). Davis's drug guide for nurses (Fourteenth ed.). Philadelphia. ISBN 978-0-8036-4085-6. OCLC 881473728.{{cite book}}: CS1 maint: location missing publisher (link)
  5. ^ a b c d e f g h i j k "Sulfasalazine". The American Society of Health-System Pharmacists. from the original on 21 December 2016. Retrieved 8 December 2016.
  6. ^ a b c d World Health Organization (2009). Stuart MC, Kouimtzi M, Hill SR (eds.). WHO Model Formulary 2008. World Health Organization. pp. 41, 45. hdl:10665/44053. ISBN 9789241547659.
  7. ^ Hamilton R (2015). Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab-Coat Edition. Jones & Bartlett Learning. p. 464. ISBN 9781284057560.
  8. ^ World Health Organization (2019). World Health Organization model list of essential medicines: 21st list 2019. Geneva: World Health Organization. hdl:10665/325771. WHO/MVP/EMP/IAU/2019.06. License: CC BY-NC-SA 3.0 IGO.
  9. ^ "The Top 300 of 2020". ClinCalc. Retrieved 7 October 2022.
  10. ^ "Sulfasalazine - Drug Usage Statistics". ClinCalc. Retrieved 7 October 2022.
  11. ^ a b "Azulfidine- sulfasalazine tablet". DailyMed. 8 May 2019. from the original on 29 October 2015. Retrieved 24 January 2020.
  12. ^ Cantarini L, Tinazzi I, Biasi D, Fioravanti A, Galeazzi M (June 2007). "Sulfasalazine-induced immune thrombocytopenia". Postgraduate Medical Journal. 83 (980): e1. doi:10.1136/pgmj.2006.055194. PMC 2600053. 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". from the original on 21 October 2011. Retrieved 8 March 2012.
  15. ^ Hernández-Díaz S, Werler MM, Walker AM, Mitchell AA (November 2000). "Folic acid antagonists during pregnancy and the risk of birth defects". The New England Journal of Medicine. 343 (22): 1608–1614. doi:10.1056/NEJM200011303432204. PMID 11096168.
  16. ^ Dixon SJ, Patel DN, Welsch M, Skouta R, Lee ED, Hayano M, et al. (May 2014). "Pharmacological inhibition of cystine-glutamate exchange induces endoplasmic reticulum stress and ferroptosis". eLife. 3: e02523. doi:10.7554/eLife.02523. PMC 4054777. PMID 24844246.
  17. ^ . Merck & Co., Inc. January 2012. Archived from the original on 29 August 2011. Retrieved 28 July 2012.{{cite web}}: CS1 maint: unfit URL (link)
  18. ^ De Koninck AS, Groen LA, Maes H, Verstraete AG, Stove V, Delanghe JR (2016). "An Unusual Type of Kidney Stone". Clinical Laboratory. 62 (1–2): 235–239. doi:10.7754/Clin.Lab.2015.150605. hdl:1854/LU-6847821. PMID 27012055.
  19. ^ "Sulfasalazine". WebMD. from the original on 26 January 2016.
  20. ^ Bridges RJ, Natale NR, Patel SA (January 2012). "System xc⁻ cystine/glutamate antiporter: an update on molecular pharmacology and roles within the CNS". British Journal of Pharmacology. 165 (1): 20–34. doi:10.1111/j.1476-5381.2011.01480.x. PMC 3252963. PMID 21564084.
  21. ^ Costigan M, Latremoliere A, Woolf CJ (February 2012). "Analgesia by inhibiting tetrahydrobiopterin synthesis". Current Opinion in Pharmacology. 12 (1): 92–99. doi:10.1016/j.coph.2011.10.019. PMC 3288148. PMID 22178186.
  22. ^ Benucci M, Saviola G, Manfredi M, Sarzi-Puttini P, Atzeni F (2011). "Cost effectiveness analysis of disease-modifying antirheumatic drugs in rheumatoid arthritis. A systematic review literature". International Journal of Rheumatology. 2011: 845496. doi:10.1155/2011/845496. PMC 3228304. PMID 22162693.
  23. ^ Baumgart DC (2017). Crohn's Disease and Ulcerative Colitis: From Epidemiology and Immunobiology to a Rational Diagnostic and Therapeutic Approach. Springer. p. 395. ISBN 978-3-319-33703-6.
  24. ^ Oakley F, Meso M, Iredale JP, Green K, Marek CJ, Zhou X, et al. (January 2005). "Inhibition of inhibitor of kappaB kinases stimulates hepatic stellate cell apoptosis and accelerated recovery from rat liver fibrosis". Gastroenterology. 128 (1): 108–120. doi:10.1053/j.gastro.2004.10.003. PMID 15633128.
  25. ^ Gupta AK, Ellis CN, Siegel MT, Duell EA, Griffiths CE, Hamilton TA, et al. (April 1990). "Sulfasalazine improves psoriasis. A double-blind analysis". Archives of Dermatology. 126 (4): 487–493. doi:10.1001/archderm.1990.01670280071013. PMID 1690970.
  26. ^ McGirt LY, Vasagar K, Gober LM, Saini SS, Beck LA (October 2006). "Successful treatment of recalcitrant chronic idiopathic urticaria with sulfasalazine". Archives of Dermatology. 142 (10): 1337–1342. doi:10.1001/archderm.142.10.1337. PMID 17043190.
  27. ^ Brumshtein B, Esswein SR, Salwinski L, Phillips ML, Ly AT, Cascio D, et al. (November 2015). "Inhibition by small-molecule ligands of formation of amyloid fibrils of an immunoglobulin light chain variable domain". eLife. 4: e10935. doi:10.7554/eLife.10935. PMC 4758944. PMID 26576950.

External links Edit

  • "Sulfasalazine". Drug Information Portal. U.S. National Library of Medicine.

September 02, 2023
sulfasalazine, sold, under, brand, name, azulfidine, among, others, medication, used, treat, rheumatoid, arthritis, ulcerative, colitis, crohn, disease, considered, some, first, line, treatment, rheumatoid, arthritis, taken, mouth, clinical, datatrade, namesaz. 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 5 SulfasalazineClinical dataTrade namesAzulfidine Salazopyrin Sulazine othersOther namesSulphasalazine SSZAHFS Drugs comMonographMedlinePlusa682204License dataUS DailyMed SulfasalazinePregnancycategoryAU A 1 Routes ofadministrationBy mouthDrug classSulfonamidesATC codeA07EC01 WHO Legal statusLegal statusUK POM Prescription only 2 3 US onlyPharmacokinetic dataBioavailability lt 15 Elimination half life5 10 hoursExcretiondrug metabolites are excreted in urine and feces 4 IdentifiersIUPAC name 2 hydroxy 5 E 2 4 pyridin 2 yl sulfamoyl phenyl diazen 1 yl benzoic acidCAS Number599 79 1 YPubChem CID5339DrugBankDB00795 YChemSpider10481900 YUNII3XC8GUZ6CBKEGGD00448 YC07316 YChEBICHEBI 9334ChEMBLChEMBL421 NCompTox Dashboard EPA DTXSID0021256ECHA InfoCard100 009 069Chemical and physical dataFormulaC 18H 14N 4O 5SMolar mass398 39 g mol 13D model JSmol Interactive imageMelting point240 to 245 C 464 to 473 F dec SMILES C1 CC NC C1 NS O O C2 CC C C C2 N NC3 CC C C C3 O C O OInChI InChI 1S C18H14N4O5S c23 16 9 6 13 11 15 16 18 24 25 21 20 12 4 7 14 8 5 12 28 26 27 22 17 3 1 2 10 19 17 h1 11 23H H 19 22 H 24 25 YKey NCEXYHBECQHGNR UHFFFAOYSA N Y N Y what is this verify 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 Contents 1 Medical uses 2 Side effects 3 Pharmacology 4 Chemistry 5 Cost 6 Research 7 References 8 External linksMedical uses EditSulfasalazine 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 EditUse 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 mg 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 EditAround 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 EditIt is a codrug which is a combination of sulfapyridine and 5 aminosalicylic acid coupled with an azo linkage Cost EditIn 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 EditSulfasalazine has been studied in cirrhosis 24 psoriasis 25 idiopathic urticaria 26 and amyloidosis 27 References Edit Sulfasalazine Use During Pregnancy Drugs com 9 November 2018 Retrieved 24 January 2020 a b c d Sulfasalazine 250mg 5ml Oral Suspension Summary of Product Characteristics SmPC electronic medicines compendium emc 13 September 2019 Retrieved 4 December 2019 a b c d e f Salazopyrin Tablets Summary of Product Characteristics electronic medicines compendium emc February 2014 Archived from the original on 16 April 2017 a b c d Vallerand AH Sanoski CA Deglin JH 5 June 2014 Davis s drug guide for nurses Fourteenth ed Philadelphia ISBN 978 0 8036 4085 6 OCLC 881473728 a href Template Cite book html title Template Cite book cite book a CS1 maint location missing publisher link a b c d e f g h i j k Sulfasalazine The American Society of Health System Pharmacists Archived from the original on 21 December 2016 Retrieved 8 December 2016 a b c d World Health Organization 2009 Stuart MC Kouimtzi M Hill SR eds WHO Model Formulary 2008 World Health Organization pp 41 45 hdl 10665 44053 ISBN 9789241547659 Hamilton R 2015 Tarascon Pocket Pharmacopoeia 2015 Deluxe Lab Coat Edition Jones amp Bartlett Learning p 464 ISBN 9781284057560 World Health Organization 2019 World Health Organization model list of essential medicines 21st list 2019 Geneva World Health Organization hdl 10665 325771 WHO MVP EMP IAU 2019 06 License CC BY NC SA 3 0 IGO The Top 300 of 2020 ClinCalc Retrieved 7 October 2022 Sulfasalazine Drug Usage Statistics ClinCalc Retrieved 7 October 2022 a b Azulfidine sulfasalazine tablet DailyMed 8 May 2019 Archived from the original on 29 October 2015 Retrieved 24 January 2020 Cantarini L Tinazzi I Biasi D Fioravanti A Galeazzi M June 2007 Sulfasalazine induced immune thrombocytopenia Postgraduate Medical Journal 83 980 e1 doi 10 1136 pgmj 2006 055194 PMC 2600053 PMID 17551063 Inflammatory Bowel Disease workup at eMedicine Women With Autoimmune Diseases Medications During Pregnancy and Lactation Sulfasalazine Women with Autoimmune Diseases Medications During Pregnancy and Lactation Sulfasalazine Archived from the original on 21 October 2011 Retrieved 8 March 2012 Hernandez Diaz S Werler MM Walker AM Mitchell AA November 2000 Folic acid antagonists during pregnancy and the risk of birth defects The New England Journal of Medicine 343 22 1608 1614 doi 10 1056 NEJM200011303432204 PMID 11096168 Dixon SJ Patel DN Welsch M Skouta R Lee ED Hayano M et al May 2014 Pharmacological inhibition of cystine glutamate exchange induces endoplasmic reticulum stress and ferroptosis eLife 3 e02523 doi 10 7554 eLife 02523 PMC 4054777 PMID 24844246 SulfaSALAzine Drug Information Provided by Lexi Comp Merck amp Co Inc January 2012 Archived from the original on 29 August 2011 Retrieved 28 July 2012 a href Template Cite web html title Template Cite web cite web a CS1 maint unfit URL link De Koninck AS Groen LA Maes H Verstraete AG Stove V Delanghe JR 2016 An Unusual Type of Kidney Stone Clinical Laboratory 62 1 2 235 239 doi 10 7754 Clin Lab 2015 150605 hdl 1854 LU 6847821 PMID 27012055 Sulfasalazine WebMD Archived from the original on 26 January 2016 Bridges RJ Natale NR Patel SA January 2012 System xc cystine glutamate antiporter an update on molecular pharmacology and roles within the CNS British Journal of Pharmacology 165 1 20 34 doi 10 1111 j 1476 5381 2011 01480 x PMC 3252963 PMID 21564084 Costigan M Latremoliere A Woolf CJ February 2012 Analgesia by inhibiting tetrahydrobiopterin synthesis Current Opinion in Pharmacology 12 1 92 99 doi 10 1016 j coph 2011 10 019 PMC 3288148 PMID 22178186 Benucci M Saviola G Manfredi M Sarzi Puttini P Atzeni F 2011 Cost effectiveness analysis of disease modifying antirheumatic drugs in rheumatoid arthritis A systematic review literature International Journal of Rheumatology 2011 845496 doi 10 1155 2011 845496 PMC 3228304 PMID 22162693 Baumgart DC 2017 Crohn s Disease and Ulcerative Colitis From Epidemiology and Immunobiology to a Rational Diagnostic and Therapeutic Approach Springer p 395 ISBN 978 3 319 33703 6 Oakley F Meso M Iredale JP Green K Marek CJ Zhou X et al January 2005 Inhibition of inhibitor of kappaB kinases stimulates hepatic stellate cell apoptosis and accelerated recovery from rat liver fibrosis Gastroenterology 128 1 108 120 doi 10 1053 j gastro 2004 10 003 PMID 15633128 Gupta AK Ellis CN Siegel MT Duell EA Griffiths CE Hamilton TA et al April 1990 Sulfasalazine improves psoriasis A double blind analysis Archives of Dermatology 126 4 487 493 doi 10 1001 archderm 1990 01670280071013 PMID 1690970 McGirt LY Vasagar K Gober LM Saini SS Beck LA October 2006 Successful treatment of recalcitrant chronic idiopathic urticaria with sulfasalazine Archives of Dermatology 142 10 1337 1342 doi 10 1001 archderm 142 10 1337 PMID 17043190 Brumshtein B Esswein SR Salwinski L Phillips ML Ly AT Cascio D et al November 2015 Inhibition by small molecule ligands of formation of amyloid fibrils of an immunoglobulin light chain variable domain eLife 4 e10935 doi 10 7554 eLife 10935 PMC 4758944 PMID 26576950 External links Edit Sulfasalazine Drug Information Portal U S National Library of Medicine Portal nbsp Medicine Retrieved from https en wikipedia org w index php title Sulfasalazine amp oldid 1172162587, wikipedia, wiki, book, books, library,

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