Rectal bismuth subsalicylate as therapy for ulcerative colitis

Ryder, Stephen; Walker, Robin; Jones, H W; Rhodes, Jonathan M.

doi:10.1111/j.1365-2036.1990.tb00480.x

Cited by 39 publications

(10 citation statements)

References 17 publications

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“…Some metal ions act as non-specific enzyme inhibitors. Bismuth salts act this way [35,58] and have shown promise when used as enemas [59]. It is also likely that the therapeutic effect of topical arsenic, still sometimes used in suppositories for treatment of resistant proctitis, works via this mechanism.…”

Section: Development Of Therapies That Target the Mucosal Barriermentioning

confidence: 99%

Mucosal Barrier, Bacteria and Inflammatory Bowel Disease: Possibilities for Therapy

Merga

Campbell

Rhodes

2014

Dig Dis

157

113

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The mucosal barrier has three major components, the mucus layer, the epithelial glycocalyx and the surface epithelium itself, whose integrity largely depends on tight junction function. In health, there is relatively little direct interaction between the luminal microbiota and the epithelium - the continuous mucus layer in the colon keeps the surface epithelium out of contact with bacteria and the ileo-caecal valve ensures that the distal small intestine is relatively microbe free. Most interaction takes place at the Peyer's patches in the distal ileum and their smaller colonic equivalents, the lymphoid follicles. Peyer's patches are overlain by a ‘dome' epithelium, 5% of whose cells are specialised M (microfold) epithelial cells, which act as the major portal of entry for bacteria. There are no goblet cells in the dome epithelium and M cells have a very sparse glycocalyx allowing easy microbial interaction. It is intriguing that the typical age range for the onset of Crohn's disease (CD) is similar to the age at which the number of Peyer's patches is greatest. Peyer's patches are commonly the sites of the initial lesions in CD and the ‘anti-pancreatic' antibody associated with CD has been shown to have as its epitope the glycoprotein 2 that is the receptor for type-1 bacterial fimbrial protein (fimH) on M cells. There are many reasons to believe that the mucosal barrier is critically important in the pathogenesis of inflammatory bowel disease (IBD). These include (i) associations between both CD and ulcerative colitis (UC) with genes that are relevant to the mucosal barrier; (ii) increased intestinal permeability in unaffected relatives of CD patients; (iii) increased immune reactivity against bacterial antigens, and (iv) animal models in which altered mucosal barrier, e.g. denudation of the mucus layer associated with oral dextran sulphate in rodents, induces colitis. Whilst some IBD patients may have genetic factors leading to weakening of the mucosal barrier, it is likely that environmental factors may be even more important. Some may be subtle and indirect, e.g. the effects of stress on the mucosa barrier, whilst others may be more obvious, e.g. the effect of pathogen-related gastroenteritis, known often to act as trigger for IBD relapse. We have also been very interested in the potentially harmful effects of ingested detergents - either by contamination of cutlery by inadequate rinsing or via ingestion of processed foods containing permitted emulsifiers. In vitro and ex vivo studies show that even very small trace amounts of these surfactants can greatly increase bacterial translocation. Implications for therapy are not yet so obvious. We advise our IBD patients to avoid processed foods containing emulsifiers and to rinse their dishes well - whilst accepting that there is no direct evidence yet to support this. Therapies that aim to enhance the mucosal barrier have yet to come to market, but trials of enteric-delivered phosphatidylcholine in UC are promising. The faecal concentration of mucus-degrading bact...

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Section: Development Of Therapies That Target the Mucosal Barriermentioning

confidence: 99%

Mucosal Barrier, Bacteria and Inflammatory Bowel Disease: Possibilities for Therapy

Merga

Campbell

Rhodes

2014

Dig Dis

157

113

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“…The current view is that treatment strategies based on understanding of the factors that initiate or exacerbate IBD (targeted therapy) should be more effective and have fewer side effects (5,26). Accordingly, local application of medicine in the form of topically released drops or rectal enemas has been considered superior to systemic regimens (7)(8)(9)(10)(11)(12)(13)(14)(15)27). Further, given that inflammation of the mucosa, ulcers, and loss of the mucosal tissue are major complications of active UC, agents that have anti-inflammatory effects and promote tissue regeneration should represent ideal therapeutic options.…”

Section: Discussionmentioning

confidence: 99%

“…To minimize these limitations, nonsteroidal drugs like high-dose 5-aminosalicylic acid (5-ASA), azathioprine, 6-mercaptoprine (2), and selective leukocytapheresis (4,6) are additional medications for increasing the response rate as well as maintaining remission. Further, for many years, the addition of topical or rectal enemas to combination therapy in patients with active UC has been an effective strategy to ensure maximum therapeutic benefit from conventional medications and to avoid side effects of systemic administration (7)(8)(9)(10)(11)(12)(13)(14)(15). Even with this additional strategy, an expected level of therapeutic benefit may be unachievable (16) and the search for more effective and safer medications continues.…”

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confidence: 99%

Efficacy of Rebamipide Enemas in Active Distal Ulcerative Colitis and Proctitis: A Prospective Study Report

2005

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Rebamipide has a broad spectrum of pharmacological actions that include suppression of neutrophil functions and stimulation of mucosal epithelial cell regeneration by increasing the expression of epithelial growth factor (EGF) and the EGF receptor. Sixteen patients with active ulcerative colitis (UC; mild in 1 patient, moderate in 11, and severe in 4) were recruited. Enemas containing 150 mg rebamipide per dosing were administered during the daytime after passage of stool, twice a day for 4 weeks. UC disease activity index (UC-DAI), endoscopic activity index (EAI), and Floren's grading (FG) of mucosal biopsy specimens were measured at entry and at 4 weeks. Five of 16 patients did not complete the study, and therefore, final efficacy assessment was done on 11 patients who completed the 4 weeks of treatment. Improvements were observed in UC-DAI (P = 0.0049), EAI (P = 0.0043), and FG (P = 0.0084). There was no serious rebamipide-related side effect in any of the 16 patients. In conclusion, rebamipide topical therapy appears to be effective for the treatment of mildly to moderately active distal UC. Further controlled studies are warranted for this promising drug.

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“…Two studies have reported the efficacy of bismuth enema treatment for distal ulcerative colitis. An open-labeled study with patients resistant to conventional treatment showed a 60% clinical response rate and 40% complete remission rate after 8 weeks of therapy 15. A second multicenter, double-blind, randomized, control trial that compared bismuth enema with 5-aminosalicylic acid enemas showed an equivalent therapeutic benefit with bismuth enemas for the treatment of left-sided ulcerative colitis 16…”

Section: Discussionmentioning

confidence: 99%

Oral bismuth for chronic intractable diarrheal conditions?

Thazhath

Haque²,

Florin

2013

CEG

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ObjectiveBismuth has antidiarrheal, antibacterial, and anti-inflammatory properties. We report our single-center experience with oral colloidal bismuth subcitrate (CBS) treatment for patients with chronic intractable diarrhea.MethodWe interrogated our web-based Inflammatory Bowel Disease Clinical and Research database to ascertain clinical details on all patients in our tertiary hospital gastroenterology service treated with CBS between 2000 and 2010. Treatment responses were based on prospective scoring of daily number of liquid stools. Responses were recorded prior to commencement of CBS and at follow-up visits over 12 months.ResultsThirty-one patients, mean age 47 years (range 17–79 years) and a mean duration of diarrhea of 22 weeks (range 6–104 weeks), were prescribed CBS at doses ranging from 120 mg to 480 mg/day for ≥1 month. Of these, 23 patients (74%) had an initial clinical response and 12 (39%) who continued with this treatment had a sustained clinical response at 1 year. Twelve patients with pouchitis and four patients with indeterminate colitis had initial responses of 92% and 75%, respectively, and sustained responses of 50% and 75%, respectively. Ulcerative colitis patients (n = 5) responded poorly with respect to both initial and sustained responses. Three patients with microscopic colitis showed encouraging initial response of 100% but did not have any sustained benefit. Three of four patients with diarrhea-predominant irritable bowel syndrome (dIBS) had an initial response and two (50%) had good sustained responses. There were no serious adverse events. One patient stopped therapy because of nausea.ConclusionThis is the largest report of oral bismuth treatment in chronic intractable diarrhea. CBS is cheap and appears to have the potential to be effective for ameliorating diarrheal symptoms in indeterminate colitis, pouchitis, and dIBS. An appropriately powered, blinded, randomized, controlled study appears warranted to establish the position of oral bismuth in routine practice.

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Rectal bismuth subsalicylate as therapy for ulcerative colitis

Cited by 39 publications

References 17 publications

Mucosal Barrier, Bacteria and Inflammatory Bowel Disease: Possibilities for Therapy

Mucosal Barrier, Bacteria and Inflammatory Bowel Disease: Possibilities for Therapy

Efficacy of Rebamipide Enemas in Active Distal Ulcerative Colitis and Proctitis: A Prospective Study Report

Oral bismuth for chronic intractable diarrheal conditions?

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