Swiss Centre for Applied Human Toxicology and Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
Swiss Centre for Applied Human Toxicology and Division of Molecular and Systems Toxicology, Department of Pharmaceutical Sciences, University of Basel, Basel, Switzerland.
Mol Cell Endocrinol. 2021 Mar 15;524:111168. doi: 10.1016/j.mce.2021.111168. Epub 2021 Jan 21.
The syndromes of mineralocorticoid excess describe a heterogeneous group of clinical manifestations leading to endocrine hypertension, typically either through direct activation of mineralocorticoid receptors or indirectly by impaired pre-receptor enzymatic regulation or through disturbed renal sodium homeostasis. The phenotypes of these disorders can be caused by inherited gene variants and somatic mutations or may be acquired upon exposures to exogenous substances. Regarding the latter, the symptoms of an acquired mineralocorticoid excess have been reported during treatment with azole antifungal drugs. The current review describes the occurrence of mineralocorticoid excess particularly during the therapy with posaconazole and itraconazole, addresses the underlying mechanisms as well as inter- and intra-individual differences, and proposes a therapeutic drug monitoring strategy for these two azole antifungals. Moreover, other therapeutically used azole antifungals and ongoing efforts to avoid adverse mineralocorticoid effects of azole compounds are shortly discussed.
醛固酮增多症描述了一组异质性的临床表现，导致内分泌性高血压，通常通过直接激活醛固酮受体或间接通过受损的受体前酶调节或通过肾钠稳态紊乱来实现。这些疾病的表型可能由遗传基因突变和体细胞突变引起，也可能在外源性物质暴露后获得。关于后者，在使用唑类抗真菌药物治疗期间已报道了获得性醛固酮增多症的症状。本综述描述了在使用泊沙康唑和伊曲康唑治疗期间醛固酮增多症的发生情况，探讨了潜在的机制以及个体间和个体内的差异，并提出了这两种唑类抗真菌药物的治疗药物监测策略。此外，还简要讨论了其他治疗用唑类抗真菌药物和正在努力避免唑类化合物产生不良醛固酮作用的情况。
