Hansel Trevor T, Neighbour Helen, Erin Edward M, Tan Andrew J, Tennant Rachel C, Maus Joachim G, Barnes Peter J
Clinical Studies Unit, National Heart and Lung Institute, Imperial College, Royal Brompton Hospital, Fulham Rd, London SW3 6HP, UK.
Chest. 2005 Oct;128(4):1974-9. doi: 10.1378/chest.128.4.1974.
Inhaled anticholinergic drugs are effective bronchodilators in the treatment of COPD, and tiotropium bromide has recently been introduced as a once-daily bronchodilator for use as a maintenance treatment. Racemic glycopyrrolate is an anticholinergic drug that has been used orally to control gastric acidity, parenterally as an antisialogogue and to reverse neuromuscular blockade, and has been studied by inhalation for asthma and COPD.
We investigated the duration of protection against the constrictor effects of inhaled methacholine of a single dose of inhaled nebulized racemic glycopyrrolate (0.5, 1.0, and 2.0 mg) compared with ipratropium bromide (0.5 mg) and placebo in 10 atopic asthmatic volunteers in a double-blind, five-way, crossover study.
Protection against methacholine-induced bronchospasm after administering glycopyrrolate was maintained to 30 h, the last time point measured. Both bronchodilatation and bronchoprotection were significantly longer with glycopyrrolate than after ipratropium bromide, and bronchoprotection was significant at all time points from 2 to 30 h compared to placebo. Dryness of the mouth and nose was described in 18% of patients after the highest dose of glycopyrrolate.
The prolonged bronchodilator response and the protection against methacholine-induced bronchospasm demonstrated in asthma suggests that inhaled racemic glycopyrrolate would be superior to ipratropium bromide for treatment of stable COPD.
吸入性抗胆碱能药物是治疗慢性阻塞性肺疾病(COPD)的有效支气管扩张剂,噻托溴铵最近已作为一种每日一次的支气管扩张剂用于维持治疗。消旋甘罗溴铵是一种抗胆碱能药物,已用于口服控制胃酸,胃肠外给药作为抗唾液分泌剂和用于逆转神经肌肉阻滞,并且已对其吸入治疗哮喘和COPD进行了研究。
在一项双盲、五路交叉研究中,我们比较了单剂量吸入雾化消旋甘罗溴铵(0.5、1.0和2.0毫克)与异丙托溴铵(0.5毫克)及安慰剂对10名特应性哮喘志愿者吸入乙酰甲胆碱所致收缩效应的保护持续时间。
给予甘罗溴铵后对乙酰甲胆碱诱导的支气管痉挛的保护作用持续至测量的最后一个时间点30小时。甘罗溴铵的支气管扩张和支气管保护作用均明显长于异丙托溴铵,并且与安慰剂相比,在2至30小时的所有时间点支气管保护作用均显著。在给予最高剂量的甘罗溴铵后,18%的患者出现口干和鼻干。
哮喘中显示的延长的支气管扩张反应和对乙酰甲胆碱诱导的支气管痉挛的保护作用表明,吸入消旋甘罗溴铵在治疗稳定期COPD方面优于异丙托溴铵。