Bronchoconstriction of the asthmatic airway by inhaled and ingested propranolol.
Responsiveness to inhaled histamine and DL propranolol hydrochloride was measured in 31 adult asthmatics and compared with bronchoconstriction provoked by acute oral propranolol dosing (max 160 mg). Twelve asthmatics developed greater than or equal to 15% reduction in the forced expired volume in 1 s (FEV1), 2 h after less than or equal to 100 mg oral propranolol; cardiac beta-adrenoceptor blockade was confirmed by cycle exercise tests in the 19 without airway response. The provocative inhaled dose of each aerosol causing a 20% fall in FEV1 (PC20) was lower, histamine 0.43 mg.ml-1, propranolol 3.12 mg.ml-1, in the 12 with a positive oral test compared with the 19 with a negative test, PC20 histamine 1.65 mg.ml-1, PC20 propranolol 16.2 mg.ml-1 (P less than 0.001 for both aerosols). A correlation was demonstrated between the PC20 values for asthmatics with a negative oral test (r = 0.72, P less than 0.001, n = 19) but not for the remainder (r = 0.14, P greater than 0.05, n = 12). Plasma propranolol concentrations (CL, ng.ml-1) after the final oral dose did not correlate with the % delta FEV1 (26.3) (r = -0.28) when an airway response was provoked or with the reduction in exercise tachycardia (25.9%) (r = 0.31) when no bronchoconstriction occurred. CL exceeded the limit of detection after the final inhaled propranolol dose (7.5 ng.ml-1) and was weakly related to the PC20 propranolol value (r = 0.53, P = 0.01, n = 27). The prevalence of a positive oral challenge was low in this group (39%).(ABSTRACT TRUNCATED AT 250 WORDS)
Latimer
K M
KM
Department of Medicine, Flinders Medical Center, Bedford Park, South Australia.
Ruffin
R E
RE
D000280:Administration, Inhalation; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D001249:Asthma / Q000503:physiopathology*; D001985:Bronchial Provocation Tests; D016084:Bronchoconstriction / Q000187:drug effects*; D005260:Female; D005541:Forced Expiratory Volume / Q000187:drug effects; D006632:Histamine / Q000494:pharmacology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*
D006632:Histamine; D011433:Propranolol