Hypokalaemia and other non-bronchial effects of inhaled fenoterol and salbutamol: a placebo-controlled dose-response study in healthy volunteers.
1. The hypokalaemia-inducing effects of two widely used inhaled antiasthmatic beta 2-adrenoceptor agonists, fenoterol and salbutamol, were compared in six healthy male volunteers. 2. Each drug was administered in three different doses, 400, 600 and 800 micrograms, which were repeated three times with 30 min intervals (total doses 1200, 1800 and 2400 micrograms in 1 h). The treatments were given at 1 week intervals in random order in a single-blind fashion. 3. The concentration of potassium in plasma was dose-dependently reduced by both drugs with peak effects 75-90 min after the first inhalations. The hypokalaemic effect of fenoterol was significantly greater than that of equal doses of salbutamol (average +/- s.d. reductions of 1.13 +/- 0.32 and 0.67 +/- 0.25 mEq l-1, respectively, after the highest doses, P less than 0.05). Concomitantly, decreases were noted in the amplitude of the T-wave on the ECG. 4. The concentration of cyclic AMP in plasma was measured and used as an indicator of systemic beta 2-adrenoceptor agonistic effects of the drugs. Increases in cAMP were a close mirror image of the drugs' effects on potassium in plasma. 5. Plasma renin activity, noradrenaline in plasma and heart rate were also dose-dependently increased by the treatments, whereas blood pressure remained unaltered. 6. While the clinical significance of hypokalaemia induced by inhaled beta 2-adrenoceptor sympathomimetics still is a matter of debate, our results point to possible differences between therapeutically equipotent doses of fenoterol and salbutamol in their propensity to cause hypokalaemia and other acute non-bronchial effects.
Scheinin
M
M
Department of Clinical Pharmacology, University of Turku, Finland.
Koulu
M
M
Laurikainen
E
E
Allonen
H
H
D000280:Administration, Inhalation; D000328:Adult; D000420:Albuterol / Q000008:administration & dosage / Q000009:adverse effects*; D000242:Cyclic AMP / Q000097:blood; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D005280:Fenoterol / Q000008:administration & dosage / Q000009:adverse effects*; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007008:Hypokalemia / Q000139:chemically induced*; D008297:Male; D009638:Norepinephrine / Q000097:blood; D011188:Potassium / Q000097:blood; D012083:Renin / Q000097:blood; D014202:Tremor / Q000139:chemically induced
D005280:Fenoterol; D000242:Cyclic AMP; D012083:Renin; D000420:Albuterol; D011188:Potassium; D009638:Norepinephrine