ATTENUATION OF PROPRANOLOL-INDUCED BRONCHOCONSTRICTION BY FRUSEMIDE

Background - Inhaled propranolol causes bronchoconstriction in asthmat ic subjects by an indirect mechanism which remains unclear. Inhaled fr usemide has been shown to attenuate a number of indirectly acting bron choconstrictor challenges. The aim of this study was to investigate wh ether frusemide could protect against propranolol-induced bronchoconst riction in patients with stable mild asthma. Methods - Twelve asthmati c subjects were studied on three separate days. At the first visit sub jects inhaled increasing doubling concentrations of propranolol (0.25- 32 mg/ml), breathing tidally from a jet nebuliser. The provocative con centration of propranolol causing a 20% reduction in FEV1 (PC20FEV1 pr opranolol) was determined from the log concentration-response curve fo r each subject. At the following visits nebulised frusemide (4 ml x 10 mg/ml) or placebo (isotonic saline) was administered in a randomised, double blind, crossover fashion. FEV1 was measured immediately before and five minutes after drug administration. Individual PC20FEV1 propr anolol was then administered and FEV1 was recorded at five minute inte rvals for 15 minutes. Residual bronchoconstriction was reversed with n ebulised salbutamol. Results - Frusemide had no acute bronchodilator e ffect but significantly reduced the maximum fall in FEV1 due to propra nolol: mean fall 18.2% after placebo and 11.8% after frusemide. The me dian difference in maximum % fall in FEV1 within individuals between s tudy days was 3.6% (95% CI 1.2 to 11.7). Conclusions - Frusemide atten uates propranolol-induced bronchoconstriction, a property shared with sodium cromoglycate. Both drugs block other indirect challenges and th e present study lends further support to the suggestion that frusemide and cromoglycate share a similar mechanism of action in the airways.