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优化的糖皮质激素治疗:磨砺旧矛。

Optimised glucocorticoid therapy: the sharpening of an old spear.

作者信息

Buttgereit Frank, Burmester Gerd-Rüdiger, Lipworth Brian J

机构信息

Department of Rheumatology & Clinical Immunology, Charité University Hospital, Berlin, Germany.

出版信息

Lancet. 2005;365(9461):801-3. doi: 10.1016/S0140-6736(05)17989-6.

Abstract

CONTEXT

Glucocorticoids are frequently and successfully used drugs that mediate important immunosuppressive and anti-inflammatory effects. These drugs are also relatively inexpensive, but it is their broad range of adverse reactions that continuously stimulate efforts to optimise glucocorticoid treatment.

STARTING POINT

Last year, Mary Leonard and colleagues studied 60 children and adolescents with nephrotic syndrome intermittently treated with high-dose glucocorticoids (N Engl J Med 2004; 351: 868-75). The patients received an average of 23 g glucocorticoids and were significantly shorter, had a significantly greater body-mass index, and the prevalence of obesity was significantly higher than in controls. The expected deficits in the bone-mineral content of the spine or whole body were not seen, although this finding could be attributed to the highly increased body-mass index of many of the patients.

WHERE NEXT

Glucocorticoids are urgently needed to treat a wide range of diseases in children and adults. Therefore strategies such as preferred local application or fine-tuned dose regimens have been developed over the past five decades to improve the benefit-risk ratio. However, these efforts with conventional glucocorticoid drugs seem to have almost reached their limits. A further improvement needs qualitatively new drugs, which are currently in the development pipeline, with the most promising being the nitrosoglucocorticoids (nitrosteroids) and selective glucocorticoid-receptor agonists.

摘要

背景

糖皮质激素是常用且有效的药物,可介导重要的免疫抑制和抗炎作用。这些药物相对便宜,但正是其广泛的不良反应持续推动着优化糖皮质激素治疗的努力。

起点

去年,玛丽·伦纳德及其同事研究了60例间歇性接受大剂量糖皮质激素治疗的肾病综合征儿童和青少年(《新英格兰医学杂志》2004年;351: 868 - 75)。这些患者平均接受了23克糖皮质激素治疗,身高明显更矮,体重指数显著更高,肥胖患病率也显著高于对照组。虽然这一发现可能归因于许多患者体重指数的大幅增加,但未观察到预期的脊柱或全身骨矿物质含量不足。

下一步方向

儿童和成人的多种疾病迫切需要糖皮质激素治疗。因此,在过去五十年里开发了诸如优选局部应用或微调剂量方案等策略,以改善效益风险比。然而,这些针对传统糖皮质激素药物的努力似乎已几乎达到极限。进一步改进需要性质上全新的药物,目前这些药物正处于研发阶段,其中最有前景的是亚硝基糖皮质激素(硝基甾体)和选择性糖皮质激素受体激动剂

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