title: Rebound hyperresponsiveness to muscarinic stimulation after chronic therapy with an inhaled muscarinic antagonist.
abstract: In 9 young subjects with mild asthma, we investigated the possibility that chronic daily administration of an inhaled muscarinic antagonist (ipratropium bromide) might increase the response of muscarinic receptors in airway smooth muscle to agonist stimulation caused by receptor upregulation. Subjects inhaled 60 micrograms of ipratropium 4 times daily for 3 wk. Methacholine bronchoprovocation (with or without acute pretreatment with ipratropium) was performed before (control period) and during 3 wk of daily ipratropium therapy (medication period). At the end of the medication period, subjects returned at 12, 24, 48, and 72 h after the last dose of ipratropium (withdrawal period) to determine the provocative concentration of methacholine producing a 20% decrease in FEV1 (PC20). During the medication period, there was no significant diminution of the acute bronchodilator response to ipratropium or of the protective effect of ipratropium against methacholine-induced bronchospasm when compared with the control period. During the withdrawal period, mean in PC20 was significantly less (increased airway responsiveness) at 24 h than during the control period (p less than 0.01) and returned to the control period value within 48 to 72 h. We conclude that daily administration of ipratropium to mildly asthmatic subjects for 3 wk does not produce tolerance to either the bronchodilator effect of ipratropium or to its inhibition of methacholine-induced bronchospasm but does induce transient supersensitivity of airway cholinergic receptors to muscarinic stimulation.
authors.forename: R
authors.initials: R
authors.lastname: Newcomb
authors.forename: D P
authors.initials: DP
authors.lastname: Tashkin
authors.forename: K K
authors.initials: KK
authors.lastname: Hui
authors.forename: M E
authors.initials: ME
authors.lastname: Conolly
authors.forename: E
authors.initials: E
authors.lastname: Lee
authors.forename: B
authors.initials: B
authors.lastname: Dauphinee
mesh_terms: D000328:Adult; D001249:Asthma / Q000188:drug therapy / Q000503:physiopathology*; D001980:Bronchi / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D005260:Female; D005541:Forced Expiratory Volume; D006801:Humans; D009241:Ipratropium / Q000627:therapeutic use; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds; D009130:Muscle, Smooth / Q000503:physiopathology; D011976:Receptors, Muscarinic / Q000502:physiology*; D014797:Vital Capacity
chemical_list: D008688:Methacholine Compounds; D011976:Receptors, Muscarinic; D016210:Methacholine Chloride; D009241:Ipratropium