Comparison of the effects of prolonged treatment with low and high doses of inhaled terbutaline on beta-adrenoceptor responsiveness in patients with chronic obstructive pulmonary disease.
Eleven patients with chronic obstructive pulmonary disease (age, 61 +/- 2 yr; FEV1, 1.36 +/- 0.24 L, 46 +/- 7% predicted) were given 4 wk of treatment with either a conventional low dose of inhaled terbutaline (LDT), 500 micrograms four times a day, or a high dose of inhaled terbutaline (HDT), 2,000 micrograms four times a day, delivered by a spacer. A randomized double-blind crossover design was used with 2-wk run-in and washout periods, when ipratropium bromide was substituted for inhaled beta-agonists. Dose response curves (DRC) to cumulative doubling doses of inhaled terbutaline (125 to 4,000 micrograms) were constructed after each treatment period, and baseline spirometry, finger tremor (Tr), plasma potassium (K), plasma cAMP, and ECG (HR and T wave) were measured at each dose step of the DRC. Daily PEFR measurements (A.M. and P.M.) and Holter ECG were performed during run-in and treatment periods. Baseline values for FEV1 were not significantly different during run-in, treatment, or washout periods. There were dose-related increases in FEV1 (p less than 0.0001) with no significant differences between DRC after treatment with HDT compared with those with LDT: delta FEV1 max, 0.46 +/- 0.14 L, 15.5 +/- 3.7% predicted (HDT); 0.50 +/- 0.11 L, 16.0 +/- 3.1% predicted (LDT). There were also no differences between DRC for delta FVC: 1.08 +/- 0.22 L, 31.1 +/- 5.4% predicted (HDT); 0.99 +/- 0.14 L, 28.5 +/- 3.8% predicted (LDT). There were no significant changes in K or HR in response to cumulative doses of terbutaline after either treatment.(ABSTRACT TRUNCATED AT 250 WORDS)
Lipworth
B J
BJ
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, Scotland.
Clark
R A
RA
Dhillon
D P
DP
McDevitt
D G
DG
D000280:Administration, Inhalation; D000242:Cyclic AMP / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004311:Double-Blind Method; D004562:Electrocardiography; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D008173:Lung Diseases, Obstructive / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D011188:Potassium / Q000097:blood; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D013726:Terbutaline / Q000008:administration & dosage* / Q000627:therapeutic use; D013997:Time Factors; D014202:Tremor / Q000139:chemically induced
D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D013726:Terbutaline; D011188:Potassium