Baker E H
Clinical Pharmacology and Therapeutics Section, Institute of Medical and Biomedical Education, St George's University Hospitals NHS Foundation Trust, London, UK.
Institute for Infection and Immunity, St George's, University of London, St George's University Hospitals NHS Foundation Trust, London, UK.
Br J Clin Pharmacol. 2020 Dec 1. doi: 10.1111/bcp.14679.
Glucocorticoids are highly effective medicines in the treatment of inflammatory disorders. However they cause severe adverse reactions, particularly where taken at high doses systemically for prolonged periods. Systemic glucocorticoids are therefore given at dosage sufficient to control the disease, then withdrawn as fast as is possible to minimise dose- and time-related adverse drug reactions without losing disease control. Adverse withdrawal reactions present a major challenge in the withdrawal of long term glucocorticoids. Suppression of the hypothalamic-pituitary-adrenal (HPA) axis causes adrenal insufficiency, which is potentially life threatening and can become symptomatic as treatment is withdrawn. Adrenal insufficiency can be extremely difficult to differentiate from 'glucocorticoid withdrawal syndrome', where patients experience symptoms despite adequate adrenal function, and from psychological dependence. Long term systemic glucocorticoids should therefore be withdrawn slowly. The rate at which the dose is tapered should initially be determined by treatment requirements of the underlying disease. Once 'physiological' doses are reached, the rate of reduction is determined by rate of HPA recovery and need for exogenous glucocorticoid cover while endogenous secretion recovers. If symptoms prevent treatment withdrawal, HPA testing should be used to look for adrenal insufficiency. Patients with adrenal insufficiency require 'physiological' doses of glucocorticoids for adrenal replacement, which may be lifelong if the HPA axis fails to recover.
糖皮质激素是治疗炎症性疾病的高效药物。然而,它们会引起严重的不良反应,尤其是在大剂量全身长期使用时。因此,全身性糖皮质激素的给药剂量要足以控制疾病,然后尽快停药,以尽量减少与剂量和时间相关的药物不良反应,同时又不失去对疾病的控制。撤药不良反应是长期糖皮质激素撤药过程中的一个重大挑战。下丘脑-垂体-肾上腺(HPA)轴的抑制会导致肾上腺功能不全,这可能危及生命,并且在撤药治疗时可能会出现症状。肾上腺功能不全极难与“糖皮质激素撤药综合征”区分开来,后者是指患者尽管肾上腺功能正常但仍出现症状,也难以与心理依赖区分开来。因此,长期全身性糖皮质激素应缓慢撤药。剂量递减的速率最初应由基础疾病的治疗需求决定。一旦达到“生理”剂量,减量速率则由HPA恢复的速率以及内源性分泌恢复时对外源性糖皮质激素覆盖的需求决定。如果症状妨碍撤药治疗,应进行HPA检测以查找肾上腺功能不全。肾上腺功能不全的患者需要“生理”剂量的糖皮质激素进行肾上腺替代治疗,如果HPA轴未能恢复,可能需要终身治疗。