Trechot Philippe, Jouzeau Jean-Yves, Brouillard Clotilde, Scala-Bertola Julien, Petitpain Nadine, Cuny Jean-François, Gauchotte Guillaume, Schmutz Jean-Luc, Barbaud Annick
Department of Clinical Pharmacology, University Hospital, Nancy, France.
Department of Toxicology, University Hospital, Nancy, France.
Int Wound J. 2015 Oct;12(5):527-30. doi: 10.1111/iwj.12147. Epub 2013 Sep 13.
Nicorandil, a nicotinamide ester, was first reported to be involved in the induction of oral ulcers in 1997. Since then, many reports of single or multiple nicorandil-induced ulcerations (NIUs) have been reported. We hypothesised that in the case of high-dosage nicorandil or after an increased dosage of nicorandil, nicotinic acid and nicotinamide (two main metabolites of nicorandil) cannot appropriately merge into the endogenous pool of nicotinamide adenine dinucleotide/phosphate, which leads to abnormal distribution of these metabolites in the body. In recent or maintained trauma, nicotinamide increases blood flow at the edge of the raw area, inducing epithelial proliferation, while nicotinic acid ulcerates this epithelial formation, ultimately flooding the entire scar. We demonstrate, by comparison to a control patient non-exposed to nicorandil, an abnormal amount of nicotinic acid (×38) and nicotinamide (×11) in the ulcerated area in a patient with NIUs. All practitioners, especially geriatricians, dermatologists and surgeons, must be aware of these serious and insidious side effects of nicorandil. It is critical to rapidly reassess the risk-benefit ratio of this drug for any patient, and not only for those with diverticular diseases.
尼可地尔，一种烟酰胺酯，于1997年首次被报道与口腔溃疡的诱发有关。从那时起，已有许多关于单发性或多发性尼可地尔诱发溃疡（NIU）的报道。我们推测，在高剂量使用尼可地尔或增加尼可地尔剂量后，烟酸和烟酰胺（尼可地尔的两种主要代谢产物）无法适当地融入烟酰胺腺嘌呤二核苷酸/磷酸的内源性池，这导致这些代谢产物在体内分布异常。在近期或持续的创伤中，烟酰胺会增加创面边缘的血流量，诱导上皮细胞增殖，而烟酸则会使这种上皮形成发生溃疡，最终使整个瘢痕破溃。与未接触尼可地尔的对照患者相比，我们证明了一名NIU患者溃疡区域中烟酸（×38）和烟酰胺（×11）的含量异常。所有从业者，尤其是老年病科医生、皮肤科医生和外科医生，必须意识到尼可地尔这些严重且隐匿的副作用。对于任何患者，而不仅仅是患有憩室病的患者，迅速重新评估这种药物的风险效益比至关重要。
