Treating the Side Effects of Exogenous Glucocorticoids; Can We Separate the Good From the Bad?
Treating the Side Effects of Exogenous Glucocorticoids; Can We Separate the Good From the Bad?
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DOI：
10.1210/endrev/bnad016
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发表时间：
2023-11-09
影响因子：
20.3
通讯作者：
中科院分区：
文献类型：
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作者：
据估计，目前有2%至3%的人群接受全身或局部糖皮质激素治疗。糖皮质激素提供治疗益处的强效抗炎作用是毫无疑问的。然而，与它们的使用相关的副作用，包括中心体重增加、高血压、胰岛素抵抗、2型糖尿病（T2 D）和骨质疏松症，通常统称为医源性库欣综合征，与显著的健康和经济负担相关。支持糖皮质激素的差异作用以驱动期望的和不期望的效果的精确细胞机制仍然没有完全理解。面对限制糖皮质激素诱导的不良反应并确保保留抗炎作用的未满足的临床需求，人们采取了几种策略。现有的许可药物的共同处方治疗事件的不良反应可能是有效的，但数据检查不良反应的预防是有限的。已经设计了新的选择性糖皮质激素受体激动剂和选择性糖皮质激素受体调节剂，其目的是基于它们与糖皮质激素受体的相互作用特异性地和选择性地激活抗炎反应。这些化合物中有几种目前正在进行临床试验，以评估其疗效。最近，通过11β-羟基类固醇脱氢酶的同种型利用组织特异性糖皮质激素代谢的策略已经显示出早期潜力，尽管来自临床试验的数据有限。任何治疗的目的是最大限度地提高效益，同时最大限度地降低风险，在这篇综述中，我们定义了与糖皮质激素使用相关的不良反应概况，并评估了旨在限制副作用但保留理想疗效的当前和正在开发的策略。
It is estimated that 2% to 3% of the population are currently prescribed systemic or topical glucocorticoid treatment. The potent anti-inflammatory action of glucocorticoids to deliver therapeutic benefit is not in doubt. However, the side effects associated with their use, including central weight gain, hypertension, insulin resistance, type 2 diabetes (T2D), and osteoporosis, often collectively termed iatrogenic Cushing's syndrome, are associated with a significant health and economic burden. The precise cellular mechanisms underpinning the differential action of glucocorticoids to drive the desirable and undesirable effects are still not completely understood. Faced with the unmet clinical need to limit glucocorticoid-induced adverse effects alongside ensuring the preservation of anti-inflammatory actions, several strategies have been pursued. The coprescription of existing licensed drugs to treat incident adverse effects can be effective, but data examining the prevention of adverse effects are limited. Novel selective glucocorticoid receptor agonists and selective glucocorticoid receptor modulators have been designed that aim to specifically and selectively activate anti-inflammatory responses based upon their interaction with the glucocorticoid receptor. Several of these compounds are currently in clinical trials to evaluate their efficacy. More recently, strategies exploiting tissue-specific glucocorticoid metabolism through the isoforms of 11β-hydroxysteroid dehydrogenase has shown early potential, although data from clinical trials are limited. The aim of any treatment is to maximize benefit while minimizing risk, and within this review we define the adverse effect profile associated with glucocorticoid use and evaluate current and developing strategies that aim to limit side effects but preserve desirable therapeutic efficacy.
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DOI：
10.1210/clinem/dgac100
发表时间：
2022-06-16
期刊：
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影响因子：
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影响因子：
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影响因子：
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作者：
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通讯作者：
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影响因子：
2.1
作者：
ALLEBECK, P;RODVALL, Y;ALLANDER, E
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DOI：
10.14740/jocmr2153w
发表时间：
2015-06
期刊：
Journal of clinical medicine research
影响因子：
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作者：
Katsuyama H;Sako A;Adachi H;Hamasaki H;Yanai H
通讯作者：
Yanai H