令舒-糖皮质激素的药理学基础-程能能--无有效期.ppt

Slide 9 我们来看一看普米克与其它吸入激素相比的主要特点。1，普米克水溶性明显高于其它激素，因此普米克能较好的溶解于气道粘液中，更易与气道上皮细胞接触。2，普米克全身清除率高于氟替卡松，说明普米克从全身排出快，显示普米克全身副作用可能比氟替卡松小3，氟替卡松表观分布容积远大于普米克818比183，而血浆半衰期明显长于普米克14.4比2.8小时，显示氟替卡松在全身组织中广泛蓄积，血液中存留时间长，全身副作用肯定大于普米克。4，从吸入的肺生物利用度来看，普米克28％，氟替卡松只有16％，普米克有更好的局部作用。 英国著名呼吸药理专家Lipworth教授总结22个有关不同吸入激素对肾上腺皮质功能影响的剂量－效应关系实验，对他们进行了荟萃分析后1998年发表文章在美国呼吸急救医学杂志，我们来看一下结果。由图可以看出氟替卡松对人肾上腺皮质功能的影响明显大于普米克，二丙酸倍氯米松也大于普米克。因此可以说普米克是最安全的吸入激素。 Ref.: Lipworth B et al, Am J Respir Crit Care Med 1998;19:625-46 * * * * 可达到正常成年身高，对身高的影响非进展性，不累积（如图） 身高降低数据不同文献数据不同，kelly研究显示在治疗第一年平均身高布地奈德组低1.2cm，但两组都达到了成年后的正常平均身高，且治疗后期两组间生长速度相比无统计学差异。 需要在治疗过程中权衡的是：哮喘控制不良也严重影响患儿生长发育。 Kelly HW, 2012： Mean adult height was 1.2 cm lower (95% confidence interval [CI], ?1.9 to ?0.5) in the budesonide group than in the placebo group (P = 0.001) and was 0.2 cm lower (95% CI, ?0.9 to 0.5) in the nedocromil group than in the placebo group (P = 0.61). A larger daily dose of inhaled glucocorticoid in the first 2 years was associated with a lower adult height (?0.1 cm for each microgram per kilogram of body weight) (P = 0.007). The reduction in adult height in the budesonide group as compared with the placebo group was similar to that seen after 2 years of treatment (?1.3 cm; 95% CI, ?1.7 to ?0.9). During the first 2 years, decreased growth velocity in the budesonide group occurred primarily in prepubertal participants. Agertoft L,et al.N Engl J Med. 2000 Oct 12;343(15):1064-9： The children in the budesonide group attained adult height after a mean of 9.2 years of budesonide treatment (range, 3 to 13) at a mean daily dose of 412 μg (range, 110 to 877). The mean cumulative dose of budesonide was 1.35 g (range, 0.41 to 3.99). The mean differences between the measured and target adult heights were +0.3 cm (95 percent confidence interval, –0.6 to +1.2) for the budesonide-treated children, –0.2 cm (95 percent confidence interval, –2.4 to +2.1) for the control children with asthma, and +0.9 cm (95 percent confidence