Anticholinergic blockade of beta-blocker-induced bronchoconstriction.
The mechanism of propranolol-induced bronchoconstriction (PIB) remains unclear. Previous uncontrolled studies have suggested that atropine antagonizes PIB in asthma. We conducted a randomized, double-blind, placebo-controlled study of the effect of a new anticholinergic agent, oxitropium bromide, on bronchoconstriction induced by inhaled propranolol in seven subjects with mild asthma 24 to 39 yr of age. Inhaled propranolol induced long-lasting reduction in specific airway conductance (SGaw) in all subjects. This was associated with airway beta-adrenoceptor blockade as demonstrated by a shift in the isoproterenol dose-response curve. Propranolol was less potent than methacholine, with a geometric mean dose causing a 35% fall in SGaw of 4.7 mumol for propranolol compared with 0.48 mumol for methacholine. Pretreatment with oxitropium 200 micrograms completely inhibited the fall in SGaw in response to inhaled propranolol in all subjects. Oxitropium also revealed PIB. Cholinergic receptor blockade by oxitropium inhibits bronchoconstriction induced by inhaled propranolol, supporting involvement of cholinergic mechanisms in PIB.
Ind
P W
PW
Department of Medicine, Royal Postgraduate Medical School, London, United Kingdom.
Dixon
C M
CM
Fuller
R W
RW
Barnes
P J
PJ
D000328:Adult; D001249:Asthma / Q000503:physiopathology*; D001980:Bronchi / Q000187:drug effects* / Q000503:physiopathology; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D016210:Methacholine Chloride; D008688:Methacholine Compounds / Q000494:pharmacology; D010276:Parasympatholytics / Q000494:pharmacology*; D011433:Propranolol / Q000494:pharmacology*; D012123:Pulmonary Ventilation; D011897:Random Allocation; D012602:Scopolamine Derivatives / Q000494:pharmacology*
D008688:Methacholine Compounds; D010276:Parasympatholytics; D012602:Scopolamine Derivatives; D016210:Methacholine Chloride; C017590:oxitropium; D011433:Propranolol; D007545:Isoproterenol