Systemic beta-adrenoceptor responses to salbutamol given by metered-dose inhaler alone and with pear shaped spacer attachment: comparison of electrocardiographic, hypokalaemic and haemodynamic effects.
1. Seven normal subjects were given cumulative doubling doses of inhaled salbutamol either by metered-dose inhaler (MDI) alone, or in conjunction with a pear shaped spacer attachment (PSS). Dose increments were made every 20 min from 100 micrograms to 2000 micrograms. 2. Plasma potassium (K), electrocardiographic (ECG) and haemodynamic (HR, SBP and DBP) responses were measured at each dose increment. 3. There were falls in K (as mean and 95% CI) in response to salbutamol (P less than 0.001): 3.70 mmol l-1 (3.46-3.95) to 3.20 mmol l-1 (2.91-3.49) MDI, 3.78 mmol l-1 (3.61-3.95) to 3.18 mmol l-1 (3.06-3.30) PSS. 4. Salbutamol produced marked ECG effects including T wave flattening (P less than 0.001): 0.46 mV (0.24-0.68) to 0.22 mV (0.07-0.37) MDI, 0.50 mV (0.23-0.77) to 0.24 mV (0.07-0.41) PSS; and Q-Tc interval prolongation (P less than 0.001): 0.382 s (0.372-0.392) to 0.409 s (0.397-0.421) MDI, 0.378 s (0.358-0.398) to 0.410 s (0.388-0.432) PSS. U waves occurred in five subjects with MDI and in four with PSS. S-T segment depression was present in two subjects with MDI and in three with PSS. These changes were not however associated with ventricular extrasystoles. There were also significant chronotropic effects (P less than 0.001): 63 beats min-1 (57-70) to 79 beats min-1 (69-89) MDI, 58 beats min-1 (53-63) to 75 beats min-1 (69-81) PSS. 5. Comparison of dose-response curves for MDI alone and with PSS showed no significant differences, for any of the variables measured.(ABSTRACT TRUNCATED AT 250 WORDS)
Lipworth
B J
BJ
Department of Clinical Pharmacology, Ninewells Hospital and Medical School, Dundee, Scotland.
McDevitt
D G
DG
Struthers
A D
AD
D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007008:Hypokalemia / Q000139:chemically induced*; D008297:Male; D009330:Nebulizers and Vaporizers; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D011943:Receptors, Adrenergic, beta; D000420:Albuterol