Nicorandil associated anal ulceration

Watson, Angus; Suttie, Stuart; Fraser, A.; O'Kelly, Terry; Loudon, Malcolm

doi:10.1111/j.1463-1318.2004.00599.x

Cited by 29 publications

(20 citation statements)

References 4 publications

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“…Nicorandil had a positive effect on colonic injury, lipid peroxidation, neutrophil infiltration, and associated inflammatory mediators. There are some reports of rare dose-related nicorandil-induced ulceration in some tissues that may appear months after starting nicorandil therapy [64][65][66]. These reports, however, are in contrast to the results presented here.…”

Section: Discussioncontrasting

confidence: 56%

Benefit of nicorandil using an immunologic murine model of experimental colitis

et al. 2009

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Inflammatoryboweldisease(IBD)isachronicinflammatoryconditionwithanunknownetiology.Nicorandil,apotassiumchannel opener, has been used for many years for the treatment of angina. Recently, it has been shown that nicorandil possesses some novel traits such as anti-apoptotic, gastroprotective, free radical scavenging, and anti-inflammatory properties. Therefore, we set out to examine the possible beneficial effect of nicorandil in a rat model of IBD. Colitis was induced by rectal administration of 2,4,6-trintrobenzene sulphonic acid (TNBS) into rats. Groups of animals used in this study were sham, control, and exposure to dexamethasone,nicorandil,glibenclamid(apureadenosinetriphosphatesensitivepotassiumchannel(KATP)blocker),ornicorandilplus glibenclamid.Drugswereadministeredbygavageandanimalsweresacrificedafter7days.Biochemicalmarkers,includingTNF-αand IL-1β,ferricreducing/antioxidantpower(FRAP),myeloperoxidase(MPO)activityandthiobarbitoricacid-reactivesubstance(TBARS), weremeasuredinthehomogenateofcolonictissue.Resultsindicatethatnicorandilsignificantlyreducesmacroscopicandhistological damageinducedbyTNBS.NicorandildiminishesMPOactivityandlevelsofTBARS,TNF-α,andIL-1βindamagedcolonictissuewith aconcomitantincreaseinFRAPvalue(P<0.01).Theseeffectswerenotreversedbycoadministrationofglibenclamide.Inconclusion, nicorandilisabletoameliorateexperimentalIBDwithadoseinwhichitdoesnotshowanyanti-hypertensiveeffect,andthemechanism ofwhichispartiallyortotallyindependentfromKATPchannels.Itishypothesizedthatnitricoxidedonationandfree-radicalscavenging propertiesofnicorandilupregulateendothelialnitricoxidesynthasemayberesponsibleforthisphenomenon.Thesefindingssuggest thatnicorandilcanbeusefulintreatmentofIBD,althoughfurtherinvestigationsareneededtoelucidatethemechanismsinvolved.

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Section: Discussioncontrasting

confidence: 56%

Benefit of nicorandil using an immunologic murine model of experimental colitis

et al. 2009

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“…While previous case series and reports describe anal ulcerations occurring mostly in patients taking 30mg of nicorandil twice daily, doses as low as 20mg per day have been associated with anal ulceration, 8 including two patients in our case series. The maximum duration of time reported from starting nicorandil to developing an anal ulcer is 66 months.…”

Section: Discussionmentioning

confidence: 76%

“…1 Since then, several other case series have confirmed this unusual complication of nicorandil. 2,3 Nicorandil associated anal ulceration is usually diagnosed when other causes of anal ulceration have been excluded by biopsy.…”

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confidence: 87%

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Nicorandil associated anal ulcers: an estimate of incidence

Colvin

Barakat

Moussa

et al. 2012

annals

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INTRODUCTION Nicorandil is a commonly prescribed antianginal medication that has been found to be associated with painful anal ulceration. The incidence of this complication is unknown. We have used the best data available to us to make an estimate of this figure in a health district with a remarkably stable population of approximately 200,000 people. METHODS Using an electronic search of all letters generated from colorectal and gastroenterology clinics as well as endoscopy reports from January 2004 to November 2010, patients with anal ulceration who were taking nicorandil were identified. Other causes of ulceration were excluded by biopsy in the majority of cases. The central hospital and community pharmacy database was interrogated to estimate the number of patients who were prescribed nicorandil over a six-year period (2004)(2005)(2006)(2007)(2008)(2009)(2010). RESULTS A total of 30 patients (24 men, 6 women) with a median age of 79.5 years were identified who fulfilled the criteria of: taking nicorandil; having no other identified cause for anal ulceration; and achieving eventual healing after withdrawal of nicorandil. In the six-year period an estimated mean of 1,379 patients were prescribed nicorandil each year. The mean annual incidence of anal ulcers among nicorandil users is therefore calculated to be in the region of 0.37%. CONCLUSIONS Anal ulceration appears to occur in approximately four in every thousand patients prescribed nicorandil each year. Prescribing physicians should explain the risk of this unpleasant complication to their patients.

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“…The vascular steal phenomenon has been cited as a possible explanation [108,146], however, animal studies demonstrate an anti-ulcer activity of nicorandil [91,92] and the presence of oral ulceration renders a hypothesis of ischemia in the well-vascularized oral cavity doubtful [10]. A direct local toxic action induced by electrolyte disturbance has been considered, secondary to nicorandil's activity on ATPsensitive potassium channels [150][151][152]; a hypersensitivity involving non-keratinizing squamous epithelium lining specific areas of the oral cavity and lower anal canal has been suggested [18]: this however would not explain the ulcerating and fistulating disease involving other segments of the gastrointestinal tract.…”

Section: Discussionmentioning

confidence: 99%