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哮喘患者在长期使用特布他林治疗期间支气管β肾上腺素能受体无抵抗现象。

Lack of bronchial beta adrenoceptor resistance in asthmatics during long-term treatment with terbutaline.

作者信息

Larsson S, Svedmyr N, Thiringer G

出版信息

J Allergy Clin Immunol. 1977 Feb;59(2):93-100. doi: 10.1016/0091-6749(77)90209-3.

Abstract

The increasing mortality in acute asthma noted during the sixties has been ascribed to resistance of the beta 2 receptors of the bronchi due to treatment with beta-stimulating drugs. This study questions that theory. Eight patients with reversible airways obstruction were studied. Treatment with oral terbutaline 5 mg 3 times a day was given for 1 yr. Thereafter, terbutaline as metered aerosol was added in the dose of 2 puffs (0.5 mg) 4 times a day for 4 days and 6 puffs (1.5 mg) 4 times a day for further 4 days. The responsiveness of the receptors of bronchi, heart, skeletal muscles, and peripheral vessels was tested before and after 1, 2, 3, 6, 9, and 12 mo of treatment with oral terbutaline and after the two 4-day periods with inhaled terbutaline. The receptors were tested by infusion of increasing doses of isoprenaline, so that dose-response curves for isoprenaline were recorded. No signs of resistance of the beta 2 receptors of the bronchi developed during the terbutaline treatment period. Thus no even spray in moderate overdose caused resistance. Within 1 mo of treatment with oral terbutaline, resistance developed to the tremorogenic effect of terbutaline. Six of the 8 patients showed no signs of development of resistance to the chronotropic effect of isoprenaline. No signs were found of resistance of the beta 2 receptors of peripheral blood vessels.

摘要

20世纪60年代观察到的急性哮喘死亡率上升被归因于使用β受体激动剂治疗导致支气管β2受体产生耐药性。本研究对该理论提出质疑。对8例可逆性气道阻塞患者进行了研究。给予口服特布他林5毫克,每日3次,持续1年。此后,添加特布他林定量气雾剂,剂量为每日4次,每次2喷(0.5毫克),共4天,之后每日4次,每次6喷(1.5毫克),再持续4天。在用口服特布他林治疗1、2、3、6、9和12个月后以及在吸入特布他林的两个4天疗程后,对支气管、心脏、骨骼肌和外周血管的受体反应性进行了检测。通过输注递增剂量的异丙肾上腺素来检测受体,从而记录异丙肾上腺素的剂量-反应曲线。在特布他林治疗期间,支气管β2受体未出现耐药迹象。因此,即使是适度过量的喷雾也不会导致耐药。在用口服特布他林治疗1个月内,对特布他林的致震颤作用产生了耐药性。8例患者中有6例对异丙肾上腺素的变时作用未表现出耐药迹象。未发现外周血管β2受体有耐药迹象。

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