Therapeutic Efficacy of Sulfasalazine and Its Metabolites in Patients with Ulcerative Colitis and Crohn's Disease

Klotz, Ulrich; Maier, Karlernst; Fischer, Christine; Heinkel, K

doi:10.1056/nejm198012253032602

Cited by 315 publications

(81 citation statements)

References 25 publications

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“…They do this by reducing synthesis of inflammatory cytokines and have been used for many years. 61 They are medications that can cause a host of side effects from common ones including nausea, vomiting and GI upset. 62 However, three are of particular importance and interest to dentists.…”

Section: -Asasmentioning

confidence: 99%

Inflammatory bowel disease and oral health

Chandan

Thomas

2017

BDJ Team

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Risk factors involved in IBDIBD is thought to result from inappropriate and ongoing activation of the mucosal immune system facilitated by defects in both the intestinal epithelium and mucosal immune system. 5 There are both genetic and environmental factors implicated in the aetiology of IBD. 6 Although traditionally associated with the developed world, recent epidemiological studies suggest an increasing incidence in rapidly developing countries, especially in South-East Asia. 7 In addition, the increased risk of IBD in the immigrant populations in the West suggests environment has a role in the development of IBD. 8 Genetic Detailed genetic mapping has identified specific genetic changes on chromosome 16 carried in families which appear linked to CD, however no significant changes have been mapped as of yet to UC. 9,10 Specifically, variants of the NOD2 gene provide the strongest association with susceptibility to CD. NOD2 plays a key role in regulating the gut mucosal barrier involving, specifically, the microbiota, as well as the related response by the innate and adaptive immune system. The IBDchip European Project showed NOD2 has been implicated in ileal location colitis with stenosing and penetrating disease behaviour. 11 A genome wide association study has also identified a strong link between the IL23R gene and CD. 12 The gene in particular codes for interleukin 23 that plays a role in regulating innate immunity within the intestine. 13 Cigarette smoking Unusually, cigarette smoking is associated with decreased rates of incidence of UC and has been associated with protective features to prevent further flare-ups of the condition 14-19 such as relapses, 20 ©SEBASTIAN KAULITZKI/Science Photo Library/Getty J. S. Chandan 1 and T. Thomas 1 summarise the treatments for inflammatory bowel disease (IBD) and how anti-inflammatory medications can have side effects that affect the oral cavity.

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Section: -Asasmentioning

confidence: 99%

Inflammatory bowel disease and oral health

Chandan

Thomas

2017

BDJ Team

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“…Pharmacokinetic studies have demonstrated that su lphasalaz ine passes through the upper gastrointestinal trace unmodified until it reaches the colon, where it is metabolized by e ndogenous bacteria to yield 5-aminosalicylic ac id (5-ASA) and sulfapyridine. Several clinical studies have demonstrated that 5-ASA is the pharmacologically active moiety of sulphasalazine (2)(3)(4) .…”

Section: U Lcerative Colitis Is a Recur-mentioning

confidence: 99%

Antioxidant Properties of 5-ASA: Potential Mechanism for Its Anti-Inflammatory Activity

Yamada¹,

Volkmer²,

Grisham³

1990

Canadian Journal of Gastroenterology

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There is a growing body of experimental data to rnggest chat the inflamed intestine and/or colon may be subjected to considerable oxidative stress. The most probable source of these oxidants are the phagocytic leukocytes, since these cells are present in large numbers in the inflamed mucosa and are known to produce significant amounts of potentially injurious reactive oxygen species in response to inflammatory stimuli. The authors' laboratory and others have demonstrated that 5-aminosalicylic acid (5-ASA) possesses potent antioxidant activity, including free radical scavenging properties and the ability to decompose neutrophilic oxidants (eg, hypochlorous acid) and detoxify he,noprotein-associated oxidizing agents. 5-ASA has the additional property of being able to chelate iron and render it poorly redox active. Therefore, it is proposed that much of the anti-inflammatory activity of 5-ASA may be due to its numerous antioxidant properties. CanJ Gastroenterol 1990;4(7):295-302 Key Words: Etiology , Intestinal injury , Neutrophils, Oxidants Les proprietes antioxydantes de l'acide 5-aminosalicylique: Mecanisme possible de son activite anti-inflammatoire RESUME: Des donnees experimentales de plus en plus nombreuses suggerent que l'intestin ou le colon irrite est peuc-ecre assujetti a un stress oxy

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“…In practice, it is a reasonable rule of thumb to start oral steroids if diarrhoea fails to improve within 3 days of starting rectal steroids given as an enema or foam. A trial comparing the effects of oral prednisone in dosages of 20 mg, 40 mg and 60 mg per day showed that 40mg was more effective than 20mg but that there was no advantage in increasing the dosage further to 60 mg per day which caused more side-effects (14). Prednisolone, 40 mg given in one daily dose, is as effective as 10 mg four times per day (15) and is likely to cause less adrenal suppression (16).…”

Section: J M Rhodesmentioning

confidence: 99%

“…Sixty per cent of these patients with severe colitis will then go into remission if treated with an intensive regimen of intravenous feeding, intravenous prednisolone-2 1-phosphate, 60 mg per day, and intravenous tetracycline, 250 mg four times per day (19,20). Not all components of this regimen have been assessed separately.…”

Section: J M Rhodesmentioning

confidence: 99%

“…Most of the sulphapyridine is absorbed, acetylated and excreted in the urine, while very little of the 5-aminosalicylic acid is absorbed (56, 57). Sulphapyridine has no therapeutic effect whether given by suppository (%), enema (59) or orally (60), while 5-aminosalicylic acid given rectally is at least as effective as sulphasalazine (58, 59, 60, 61). 5-aminosalicylic acid taken by mouth is largely absorbed and gives very much lower drug levels in the colon than result from oral sulphasalazine.…”

Section: Maintenancementioning

confidence: 99%

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Therapeutic Progress—reviewix.

Rhodes

1983

J Clin Pharm Ther

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Ulcerative colitis is a disease of unknown aetiology in which colonic mucosal inflammation and ulceration result in rectal bleeding and diarrhoea. Most patients have relapses separated by long periods of disease inactivity, but a minority of patients have more chronic symptoms. The great majority of a t t x k s of ulcerative colitis settle with prompt medical management but in the few cases where this fails, colectomy is curative although generally leaves the patient with a permanent ileostomy. With good medical and surgical management, mortality from the disease should therefore approach zero. Acute atracksCorticosteroids are the only drugs which have been shown to have an important and unequivocal therapeutic effect in acute attacks of ulcerative colitis (1, 2,3,4). If the disease is confined to the rectum or distal colon, local steroid therapy is often sufficient to obtain a remission (2, 3, 5). It may be given in the form of suppositories, enemas or rectal foam. Suppositories are the simplest to use but are only likely to give adequate drug concentrations in the lower rectum and should therefore only be used in cases of localized distal proctitis. One might imagine that a liquid enema would reach further up the colon than rectal foam but abdominal scanning following rectal instillation of isotopically labelled steroid foam has shown convincingly that it usually passes up to the proximal sigmoid colon and sometimes well into the descending colon (6). In practice, hydrocortisone foam seems at least as effective as hydrocortisone enemas, similar in cost, and generally preferred by the patient (7). It has been shown that approximately half the steroid in enemas containing hydrocortisone or prednisolone-21-phosphate is absorbed (8, 9, 10, l l ) , although it is generally thought that some at least of the therapeutic effect results from the high levels obtained locally in the rectum (10, 11 , 12, 13). Prednisolone metasulphobenzoate sodium is probably as effective as prednisolone-2 1-phosphate when given rectally, but produces much lower free prednisolone levels in the blood (13) and would therefore be expected to cause less adrenal suppression. However, this probably is of little importance clinically if topical steroids are used for a fairly short course of a few weeks or less.

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Therapeutic Efficacy of Sulfasalazine and Its Metabolites in Patients with Ulcerative Colitis and Crohn's Disease

Cited by 315 publications

References 25 publications

Inflammatory bowel disease and oral health

Inflammatory bowel disease and oral health

Antioxidant Properties of 5-ASA: Potential Mechanism for Its Anti-Inflammatory Activity

Therapeutic Progress—reviewix.

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