Nicorandil and Idiopathic Anal Ulceration

Abstract

Failure to recognize nicorandil as an etiologic factor in the development of anal ulceration, when other potential underlying well-recognized inflammatory or neoplastic processes have been excluded, may lead to unnecessary surgical intervention in a group of high-risk patients. One of our patients had a potentially avoidable abdominoperineal resection. Pharmaceutical manipulation with alternative antiangina medication may induce healing. Pharmacologic manipulation should be coordinated with a physician to minimize precipitation of unstable angina.

Nicorandil, Gastrointestinal Adverse Drug Reactions and Ulcerations: A Systematic Review

“…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. Patel et al [153] argued that nicorandil, in a dose-dependent manner, dephosphorylates myosin and so hinders the actin filament contraction that is necessary for cell migration, as would be required to repair mucosal microtrauma and surgical wounds.…”

“…within the MHRA database. While no anal ulceration was formally mentioned in the IONA, it has been suggested that the overall incidence might be around 0.07% [18]. A higher rate was estimated by Colvin et al (0.37%) [19] in their retrospective cohort study, where the number of exposed was calculated from prescriptions in general practices.…”

“…The occurrence of gastrointestinal ADR in the form of ulcerative and fistulating disease, is underestimated [17][18][19][20][21] and the awareness of the problem is still suboptimal among physicians. No systematic review has ever been conducted, published or registered and such a study would assess the extent of the problem from a broader perspective.…”

“…In analogy with oral ulcerations, there is a tendency for the histology to be aspecific, with simple features of inflammation; a condition of vaginal leukoplakia with intra-epithelial neoplasia in the context of perianal, vaginal and perineal ulceration has been described [18], as well as elastophagocytosis with foreign body giant cells [109] and perianal actinomycosis [110]. Perianal fistulating disease whilst taking nicorandil appears more rare, constituting 1.9% and 1.2% of the MHRA and WHO gastrointestinal reaction reports, respectively.…”

“…Perianal fistulating disease whilst taking nicorandil appears more rare, constituting 1.9% and 1.2% of the MHRA and WHO gastrointestinal reaction reports, respectively. Data from the literature regarding 165 patients with ulcerations of the distal gastrointestinal tract [18][19][20]93,96,101,102, is presented in table 3.…”