SSZ MOA

 Q:  How Sulfasalazine (SSZ) works to be used in the management of two different diseases? 

Answer: SSZ is a unique drug that is used in two very different diseases via its route of elimination. It goes through a very interesting roller coaster ride after its oral ingestion. SSZ is a combination (inactive prodrug) of two compounds - 5-aminosalicylic acid (5-ASA) and sulfapyridine. 5-ASA helps in inflammatory bowel disease and sulfapyridine is used as a disease-modifying antirheumatic drug (DMARD). 

About one-third of SSZ absorbed by the small bowel and returned back intact via enterohepatic circulation into the bile. And from here most of the SSZ reaches the large intestine. SSZ needs coliform bacteria in the colon to be effective. Azoreductase is the enzyme that comes from the bacteria and breaks SSZ into its two compounds 5-ASA and sulfapyridine. 

5-ASA gets excreted in the feces making it very useful in the treatment of inflammatory bowel disease. Sulfapyridine is a DMARD. Sulfapyridine gets metabolized in the liver.

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References:

1. Box SA, Pullar T. Sulphasalazine in the treatment of rheumatoid arthritis. Br J Rheumatol 1997; 36:382.

2. Smedegård G, Björk J. Sulphasalazine: mechanism of action in rheumatoid arthritis. Br J Rheumatol 1995; 34 Suppl 2:7.

3. Das KM. Sulfasalazine therapy in inflammatory bowel disease. Gastroenterol Clin North Am. 1989 Mar;18(1):1-20. PMID: 2563989.