Lacronique J
Service de Pneumologie (Pr Dusser), Hôpital Cochin, 27, rue du Faubourg-Saint-Jacques, 75014 Paris.
Rev Pneumol Clin. 2003 Jun;59(3):129-37.
The use of inhaled glucocorticosteroids for the treatment of asthma raises the important question of short- and long safety. Thus the assessment of the benefit-risk ratio is an essential part of the development of powerful agents with reinforced topical activity. Several factors determine the optimal profile for an inhaled glucocorticoid: topical activity, systemic bioavailability (influence of the first-pass liver metabolism, inhalation device, patient- and disease-related factors), and pharmacokionetic behavior, liposolubility being one of the determining elements. Taken together these different factors produce a therapeutic index expressing the topical and systemic effects of inhaled glucocorticosteroids and their variability under the particular conditions of each patient. Al high-dose inhaled glucocorticoids have an impact on the adrenal gland which is easy to demonstrate but with rather insignificant clinical relevance. In children for example, there is a transient inhibition of bone growth with no impact on final height in adulthood. In adults; the effect on bone metabolism raises the risk of osteoporosis which must be prevented and detected in patients at risk. More data must be acquired concerning the ocular risk. Overall, significant adverse systemic effects are not observed with administration of inhaled glucocorticoids, but there remains a certain degree of uncertainty concerning the effects of long-term administration of low effective doses.
吸入性糖皮质激素用于治疗哮喘引发了短期和长期安全性这一重要问题。因此,评估效益风险比是开发具有增强局部活性的强效药物的重要组成部分。有几个因素决定了吸入性糖皮质激素的最佳特性:局部活性、全身生物利用度(首过肝脏代谢、吸入装置、患者及疾病相关因素的影响)以及药代动力学行为,脂溶性是决定性因素之一。综合这些不同因素可得出一个治疗指数,该指数体现了吸入性糖皮质激素的局部和全身效应以及它们在每个患者特定条件下的变异性。所有高剂量吸入性糖皮质激素都会对肾上腺产生影响,这很容易证明,但临床相关性相当小。例如,在儿童中,会出现骨骼生长的短暂抑制,但对成年后的最终身高没有影响。在成年人中,对骨代谢的影响会增加骨质疏松的风险,必须对有风险的患者进行预防和检测。关于眼部风险还需要获取更多数据。总体而言,吸入性糖皮质激素给药未观察到明显的全身不良反应,但长期给予低有效剂量的影响仍存在一定程度的不确定性。