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Gastrointestinal diseases and pregnancy
Published in Hung N. Winn, Frank A. Chervenak, Roberto Romero, Clinical Maternal-Fetal Medicine Online, 2021
Murtaza Arif, Anjana Sathyamurthy, Jessica Winn, Jamal A. Ibdah
Aminosalicylates are one of the cornerstones of medical therapy of IBD and are considered low risk for use in pregnancy. Most are pregnancy category B (sulfasalazine, mesalamine, and balsalazide) with the exception of olsalazine, which is category C. Sulfasalazine contains a sulfapyridine residue linked to 5-aminosalicylic acid (5-ASA), the active moiety. Its mechanism of action is unknown, but it has been shown to inhibit production of leukotriene B4, an important mediator of inflammation, block prostaglandin production, and inhibit immunoglobulin secretion by mononuclear cells. Sulfasalazine crosses the placenta (85) and is found in breast milk, although in low concentrations. Serum levels of sulfasalazine in newborns are the same as in the mother (86). This drug is thought to be safe during pregnancy (87). There are a few case reports of congenital defects in infants of treated patients; however, a population-based study did not find a significant increase in congenital abnormalities in children of women treated with sulfasalazine (88). Its efficacy in maintaining remission in UC makes its continuation during pregnancy an important consideration. Patients are usually tapered to the lowest dose that is effective in suppressing disease activity. Sulfasalazine has anti-folate effects, and it is recommended that women take folate supplementation of at least 2mg daily during the prenatal period and pregnancy.
Gastrointestinal Tract Development and Its Importance in Toxicology
Published in Shayne C. Gad, Toxicology of the Gastrointestinal Tract, 2018
Alma M. Feldpausch, Joseph V. Rodricks, Rosalind A. Schoof, Brittany A. Weldon
Metabolism of pharmaceuticals and other xenobiotics by the gut microbiome include reduction by azoreductases and nitroreductases, and hydrolysis by sulfatases, beta-glucuronidases, beta-lyases, and beta-flucuronidases (Claus et al., 2016; Spanogiannopoulos et al., 2016). Tralau et al. (2015) list pharmaceuticals metabolized in the gut, noting reactions with both positive and negative effects of the gut microbiome on drug efficacy as well as resulting side effects. In many cases, potential side effects associated with microbiome metabolism are unknown or not documented. In other cases, side effects are adverse to the host, as is the case with microbial-mediated azoreduction of sulfasalazine used in treatment of ulcerative colitis which has a positive influence on drug efficacy while also potentially contributing to microbe-induced anorexia, nausea, and skin rash.
Management of Psoriatic Arthritis
Published in Siba P. Raychaudhuri, Smriti K. Raychaudhuri, Debasis Bagchi, Psoriasis and Psoriatic Arthritis, 2017
Siba P. Raychaudhuri, Reason Wilken, Debashis Sarkar, Emanual Maverakis, Smriti K. Raychaudhuri
Sulfasalazine has been assessed in six RCTs in PsA [65–69]. Sulfasalazine is a sulfa drug that is prepared by combining salicylate and sulfapyridine through an azo bond. Its mechanism of action is not very clear; there are suggestions that sulfasalazine may work by inhibiting the 5-lipoxygenase pathway [70]. Clegg and colleagues, in a large sulfasalazine study that included 221 patients, randomized 2 g/day of sulfasalazine against a placebo [71]. The study showed that about 55% of patients in the treatment arm compared with 45% patients in the placebo arm achieved response based on PsARC. The other RCTs with sulfasalazine had fewer patients; only pain scores were considered an outcome measure; also, these studies do not have any results on radiologic progression [68,69]. Sulfasalazine can cause gastrointestinal intolerance, arthralgia, and reversible oligospermia, as well as some severe outcomes, such as leukopenia and agranulocytosis [71,72].
Regulation of BCRP expression and sulfasalazine pharmacokinetics by the nuclear receptor REV-ERBα
Published in Xenobiotica, 2023
Chunhong Wu, Yifei Xiao, Caimei Wu, Dihao Xie, Meixue Luo, Dingyi Yao, Min Chen, Danyi Lu
In addition, sulfasalazine is an anti-inflammatory drug wildly used to manage ulcerative colitis and rheumatoid arthritis (Sutherland et al. 1993; Plosker and Croom 2005). We and other groups have revealed that REV-ERBα is a crucial regulator of immune functions and inflammation responses, and small molecular agonists of REV-ERBα (e.g. SR9009 and berberine) exert satisfactory efficacy against many types of inflammatory diseases including ulcerative colitis and rheumatoid arthritis (Wang et al. 2018; Liu et al. 2020; Zhou et al. 2020). Accordingly, it is likely that the pharmacokinetics, efficacy and/or toxicity of sulfasalazine might be altered when REV-ERBα activity is modulated with these ligands. Also, it is reasonable to propose that combination therapy with REV-ERBα ligand may be a potent strategy for the enhancement of sulfasalazine efficacy in treating inflammatory diseases.
Effect of capsaicin on breast cancer resistance protein (BCRP/Abcg2) and pharmacokinetics of probe substrates in rats
Published in Xenobiotica, 2022
Fen Chen, Liu Wang, Xuejia Zhai, Nanxi Wang, Yanjie Qin, Chaoran Zhu, Sanlan Wu, Yongning Lu
Figure 1 shows the plasma concentration–time curves of sulfasalazine after an oral administration at the dose of 20 mg/kg. In the positive control group, AUC0–∞ and t1/2 of sulfasalazine were increased by 1.6- and 3.1-folds compared with the control group. Meanwhile, CL/F and Cmax of sulfasalazine in the positive control group were decreased by 32% and 28%. AUC0–∞ and CL/F in the group pre-treated with 3 mg/kg/d CAP were increased by 1.5-folds and decreased by 33% (p < 0.05). Respectively, in the group pre-treated with 8 mg/kg/d CAP, AUC0–∞ and CL/F were increased by 1.6-folds and were decreased by 38% (p < 0.05). Those were increased by 1.7-folds (p < 0.05) and were decreased by 42% (p < 0.01) in the group pre-treated with 25 mg/kg/d CAP (Table 4). The differences in Tmax, t1/2 and Cmax were not statistically significant among CAP groups.
The risk factors and incidence of major infectious diseases in patients with ankylosing spondylitis receiving tumor necrosis factor inhibitors
Published in Modern Rheumatology, 2021
Bon San Koo, Yu-Cheol Lim, Min-Young Lee, Ja-Young Jeon, Hyun-Jeong Yoo, In-Sun Oh, Ju-Young Shin, Tae-Hwan Kim
The overall incidence rate of serious infection in our study was 46.65 per 1,000 person-years, which was higher than that noted in previous studies. There was no statistically significant difference in the risk of a serious infection among the TNFis. However, older age, corticosteroid therapy, and previous history of serious infection were associated with serious infection during TNFi therapy, which is similar to the results of a study by Moura et al. [18]. Sulfasalazine showed a significantly high risk in crude HR, but not in adjusted HR. However, it has been reported that sulfasalazine has a protective effect against pneumocystis infection and tuberculosis in patients with RA [19,20]. Well-designed clinical studies are needed to determine the role of sulfasalazine in preventing or exacerbating infections.