Holland E G, Taylor A T
University of Georgia College of Pharmacy, Athens.
J Fam Pract. 1991 May;32(5):512-9.
The many unique features of glucocorticoids makes therapy with these steroids challenging. The anti-inflammatory potency, relative mineralocorticoid activity, plasma half-life, and route of administration of the synthetic cortisol preparations are compared. Because they produce profound anti-inflammatory and immunosuppressive effects, exogenously administered glucocorticoids are effective therapy for a variety of diseases and conditions. The appropriate dosing regimen is an adequate dose administered for a sufficient period to precipitate an acceptable response. It is impossible to predict the regimen that will suppress the hypothalamic-pituitary-adrenocortical (HPA) axis and thereby increase the risk of developing adrenal insufficiency during periods of stress. Until recovery of the axis is complete, patients require daily physiologic replacement doses; high-dose supplemental therapy may be required during a major illness or surgery. Once there are signs of improvement, the dosing regimen should be adjusted to a single morning dose, then to an alternate-day regimen, and, as soon as possible, the steroid should be discontinued. This tapering process maintains disease suppression while minimizing toxicity; however, it is often complicated by exacerbation of the disease and withdrawal symptoms. Potential complications associated with glucocorticoid therapy are numerous, involve all organ systems, and are potentially more devastating than the HPA axis suppression.
糖皮质激素的诸多独特特性使得使用这些类固醇进行治疗颇具挑战性。本文比较了合成皮质醇制剂的抗炎效力、相对盐皮质激素活性、血浆半衰期及给药途径。由于外源性给予的糖皮质激素可产生显著的抗炎和免疫抑制作用,因而对多种疾病和病症均为有效的治疗手段。合适的给药方案是给予足够剂量并持续足够时间以引发可接受的反应。无法预测何种方案会抑制下丘脑 - 垂体 - 肾上腺皮质(HPA)轴,进而增加应激期间发生肾上腺功能不全的风险。在该轴恢复完全之前,患者需要每日给予生理替代剂量;在重大疾病或手术期间可能需要高剂量补充治疗。一旦有改善迹象,给药方案应调整为单日早晨剂量,然后改为隔日方案,并且应尽快停用类固醇。这种逐渐减量过程可维持对疾病的抑制,同时将毒性降至最低;然而,其常因疾病加重和撤药症状而变得复杂。与糖皮质激素治疗相关的潜在并发症众多,累及所有器官系统,且可能比HPA轴抑制更具破坏性。