每日给药噻托溴铵对哮喘患者甲胆碱所致支气管收缩的影响

IF 3.3 3区 医学 Q2 PHARMACOLOGY & PHARMACY
Beth E. Davis, Donald W. Cockcroft
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引用次数: 0

摘要

定期使用吸入β 2激动剂后,支气管对直接和间接作用刺激的保护作用丧失,在短效和长效制剂中都存在。相对而言,对于常规使用毒蕈碱受体拮抗剂后耐受性的发展知之甚少。两项短效毒蕈碱受体拮抗剂异丙托溴铵的研究报告称,定期使用吸入的甲胆碱后无耐受性。据我们所知,没有关于定期使用长效毒蕈碱受体拮抗剂后支气管保护丧失的数据。因此,我们观察了每日剂量噻托溴铵对轻度哮喘人群中甲胆碱诱导的支气管收缩的影响。方法采用随机、双盲、安慰剂对照的交叉研究,比较噻托品®5 μg与安慰剂在成人哮喘患者中的疗效。每个治疗组从基线甲胆碱挑战开始,随后立即给予治疗。1小时后进行治疗后乙酰胆碱激发。在接下来的六天里,参与者每天在家中服用(两次),并在第8天返回实验室,在服用甲胆碱前1小时进行最后一次治疗。结果单次给药噻托溴铵后,甲胆碱PD20平均增加3.9倍,安慰剂组平均增加0.93倍(p = 0.003)。常规使用后,甲胆碱PD20在噻托溴铵组进一步增加至6.4倍剂量,而安慰剂组则减少0.57倍剂量(p <0.001)。结论对于控制不良的哮喘患者,lama可作为单药治疗的辅助治疗或三联治疗。因此,我们可以放心地知道,经常使用这种药物不会像使用β - 2激动剂支气管扩张剂那样导致支气管保护功能的丧失。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Effect of daily dosing with tiotropium against methacholine induced bronchoconstriction in asthmatics

Introduction

Loss of bronchoprotection against direct and indirect acting stimuli following regular use of inhaled beta2-agonists occurs with both short and long-acting formulations. Comparatively little is known about the development of tolerance following regular use of inhaled muscarinic receptor antagonists. Two investigations with the short-acting muscarinic receptor antagonist ipratropium bromide have reported no tolerance after regular use against inhaled methacholine. To our knowledge, there are no data regarding loss of bronchoprotection following regular use of long-acting muscarinic receptor antagonist. We therefore looked at the effect of daily dosing with tiotropium on methacholine induced bronchoconstriction in a population of mild asthmatics.

Methods

We performed a randomized, double-blind, placebo-controlled cross-over study comparing tiotropium Respimat® 5 μg to placebo in adult asthmatics. Each treatment arm began with baseline methacholine challenge followed immediately by treatment administration. One hour later a post treatment methacholine challenge was performed. Participants dosed daily (two puffs) at home for the next six days and returned to the lab on Day 8 for a final dose of treatment 1 h prior to methacholine challenge.

Results

The average doubling dose increase in methacholine PD20 following a single dose of tiotropium was 3.9 doubling doses whereas that following placebo was 0.93 (p = 0.003). After regular use, methacholine PD20 was further increased to 6.4 doubling doses following tiotropium whereas that following placebo decreased by 0.57 doubling doses (p < 0.001).

Conclusion

LAMA are indicated for use as add-on monotherapy or in triple therapy combination for poorly controlled asthma. It may be reassuring to know therefore, that regular use does not result in loss of bronchoprotection like that which occurs with beta2-agonist bronchodilators.

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来源期刊
CiteScore
6.20
自引率
0.00%
发文量
41
审稿时长
42 days
期刊介绍: Pulmonary Pharmacology and Therapeutics (formerly Pulmonary Pharmacology) is concerned with lung pharmacology from molecular to clinical aspects. The subject matter encompasses the major diseases of the lung including asthma, cystic fibrosis, pulmonary circulation, ARDS, carcinoma, bronchitis, emphysema and drug delivery. Laboratory and clinical research on man and animals will be considered including studies related to chemotherapy of cancer, tuberculosis and infection. In addition to original research papers the journal will include review articles and book reviews. Research Areas Include: • All major diseases of the lung • Physiology • Pathology • Drug delivery • Metabolism • Pulmonary Toxicology.
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