Sulfonamides
M. Lindsay Grayson, Sara E. Cosgrove, Suzanne M. Crowe, M. Lindsay Grayson, William Hope, James S. McCarthy, John Mills, Johan W. Mouton, David L. Paterson in Kucers’ The Use of Antibiotics, 2017
The active moiety of sulfasalazine is 5-ASA, and the parent drug acts only as a vehicle for its delivery to distal disease sites in the bowel (Azad Khan et al. 1977; van Hees et al., 1978; Klotz et al., 1980). Additionally, Campieri et al. (1981) showed that treatment with 5-ASA, 4 g daily given by retention enema, was superior to similar treatment with hydrocortisone, 100 mg daily. Resin-coated tablets containing 5-ASA are now available commercially, which after oral administration remain intact until they reach the colon. The mechanism by which 5-ASA (generic name mesalazine) is beneficial in inflammatory bowel disease remains unclear (Peppercorn, 1984). It has been combined with carrier agents other than sulfapyridine, including the combination of two molecules of mesalazine together (olsalazine). All these preparations (e.g. olsalazine, ipsalazide, balsalazide) deliver 40–60% of available mesalazine to the feces and appear to have a similar therapeutic response but without the toxicity, including male infertility (Editorial, 1987; Raimundo et al., 1991).
Information on level of drugs into breastmilk
Wendy Jones in Breastfeeding and Medication, 2013
Mesalazine may cause headache and GI disturbances, such as nausea, diarrhoea and abdominal pain in mothers. However, 80% of patients who are unable to tolerate sulphasalazine are able to tolerate mesalazine. Tablets are enteric coated to delay absorption until after they have passed through the stomach. The drug is poorly absorbed from the GI tract. The concentrations of mesalazine in maternal plasma and breastmilk in a woman taking 500 mg three times daily, were 410 and 110 ng per ml respectively. The authors concluded that the amount of mesalazine distributed into breastmilk was small and that it was compatible with breastfeeding. Maternal use of mesalazine 500 mg suppositories twice daily has been associated with watery diarrhoea in one breastfed infant. It seems likely to have been an idiosyncratic response (Jenss et al. 1990; Klotz and Harings-Kaim 1993; Nelis 1989). Most products are not licensed for children below the age of 12 years. Relative infant dose quoted as 0.1 to 8.8% (Hale 2012 online access). The BNF states that diarrhoea in a breastfed infant has been reported but that negligible amounts can be detected in breastmilk; monitor infant for diarrhoea. Compatible with breastfeeding, measured levels low. Be alert for watery diarrhoea.
Information on level of drugs into breastmilk
Wendy Jones in Breastfeeding and Medication, 2018
Mesalazine may cause headache and GI disturbances, such as nausea, diarrhoea and abdominal pain in mothers. However, 80% of patients who are unable to tolerate sulphasalazine are able to tolerate mesalazine. Tablets are enteric coated to delay absorption until after they have passed through the stomach. The drug is poorly absorbed from the GI tract. The concentrations of mesalazine in maternal plasma and breastmilk in a woman taking 500 mg three times daily, were 410 and 110 ng per millilitre respectively. The authors (Nguyen 2016) concluded that the amount of mesalazine distributed into breastmilk was small and that it was compatible with breastfeeding. Maternal use of mesalazine 500 mg suppositories twice daily has been associated with watery diarrhoea in one breastfed infant. It seems likely to have been an idiosyncratic response (Jenss et al. 1990; Klotz and Harings-Kaim 1993; Nelis 1989).
Advancements of compounds targeting Wnt and Notch signalling pathways in the treatment of inflammatory bowel disease and colon cancer
Published in Journal of Drug Targeting, 2021
Zhuonan Pu, Fang Yang, Liang Wang, Yunpeng Diao, Dapeng Chen
Mesalazine and its derivatives are widely used in IBD patients for treatment of relapses and maintenance of remission. Mesalazine modulates multiple biological pathways. During treatment with mesalazine in the context of colon cancer, phosphorylated β-catenin accumulates and nuclear translocation of β-catenin is inhibited to suppress Wnt signalling [92–94]. The mechanism by which mesalazine promotes phosphorylation of β-catenin remains unclear, but this process is mediated by various factors, including protein phosphatase 2A and KLF4 [95,96]. Mesalazine prevents the occurrence of colon cancer via suppression of the Wnt pathway [97]. ETC-159 and G007-LK have similar activity, but specifically inhibit porcupine receptor and tankyrase, respectively, to suppress the Wnt pathway [98–100].
N-acetyltransferase: the practical consequences of polymorphic activity in man
Published in Xenobiotica, 2020
Stephen C. Mitchell
Sulfasalazine (salicylazosulfapyridine) is a large molecule consisting of sulfapyridine joined via an azo linkage to mesalazine (5-aminosalicylic acid) (Askelöf et al., 1946). Both of these components are pharmacologically active. Although a small portion of an oral dose is absorbed in the small intestine the majority (90%) of the drug reaches the colon where the azo bond is cleaved by the resident bacteria (Peppercorn & Goldman, 1972; Schröder & Campbell, 1972). The liberated sulfapyridine, a sulphonamide drug, is absorbed and is responsible for suppressing the inflammatory activity of rheumatoid arthritis and related rheumatic disorders. The mesalazine component remains mainly in the large intestinal lumen and has a local anti-inflammatory effect useful in the treatment of chronic bowel disorders.
Mesalazine Suppresses Proinflammatory Cytokines in Patients with Acute Anterior Uveitis Independently of HLA-B27
Published in Ocular Immunology and Inflammation, 2022
Nikola Smatlik, Nourhan Mortada, Martin Röcken, Amir S. Yazdi, Manfred Zierhut
Mesalazine (mesalamine, 5-ASA) without sulfasalazine has been also widely used in the treatment of inflammatory bowel disease and rheumatoid arthritis. Different mechanisms of mesalazine (5-ASA) action have been proposed, but the exact mechanism still remains poorly understood. Although its mode of action still remains cryptic, reactive oxygen intermediate (ROI) scavenging by neutrophils, monocytes, and macrophages are one supposed mechanism.13 ROIs are involved in the activation of nuclear factor kappa B (NFkB), with sulfasalazine being a potent inhibitor of NFkB.14,15 Later it was postulated that the anti-inflammatory effects of mesalazine (5-ASA) are mediated, at least in part, by peroxisome proliferator-activated receptor gamma (PPARγ).16 Some other possible mechanisms described include inhibition of the platelet-activating factor, and reduced ROS.17
Related Knowledge Centers
- Inflammatory Bowel Disease
- Ulcerative Colitis
- Crohn's Disease
- Rectal Administration
- Pericarditis
- Liver Disease
- Kidney Failure
- Pregnancy
- Breastfeeding
- Sulfonamide