Differences between acute and long‐term metabolic and endocrine effects of oral beta‐adrenoceptor agonist therapy with pirbuterol for cardiac failure.

Abstract

1 The metabolic, hormonal and haemodynamic effects of oral pirbuterol, a new 132-adrenoceptor agonist, were studied acutely (n = 19) and after 3 months treatment (n = 11) in patients with severe heart failure receiving chronic frusemide therapy. 2 In the acute study fasted patients (n = 10) showed reductions in plasma K+ (P < 0.005) and cortisol (P < 0.01) and increases in plasma glucose (P < 0.005), insulin (P < 0.01), lactate (P < 0.005) and pyruvate (P < 0.0025). These acute changes were less in unfasted subjects (n = 9). 3 Maximal increase in stroke volume occurred at approximately half the plasma pirbuterol concentration required for maximal effect on plasma insulin. 4 Treatment with pirbuterol for 3 months was associated with sustained increases in stroke volume and fasting plasma glucose and insulin, but there was loss of all other acute metabolic effects. 5 Despite concurrent frusemide and digoxin therapy acute hypokalaemia caused no adverse effects. Hypokalaemia did not occur with chronic pirbuterol administration.

Pharmacology and Therapeutics of Bronchodilators

“…An increase in blood flow to the skeletal muscles through ␤ 2 -ARmediated vasodilation could also contribute to the increase in skeletal muscle K ϩ levels (Tesfamariam et al, 1998). Numerous studies have shown a dose-related fall in serum K ϩ level with increasing doses of ␤ 2 -AR agonist (Scheinin et al, 1987), although there is some evidence that this effect shows tolerance and that serum K ϩ levels after regular treatment are not reduced (Canepa-Anson et al, 1987). Such hypokalemia may precipitate arrhythmias; hence, the use of ␤ 2 -AR agonists is linked to an increased incidence of tachyarrhythmias (Du Plooy et al, 1994).…”

The use of ICS/LABA (extra-fine and non-extra-fine) in elderly asthmatics

“… 63 Several studies have shown a dose-related reduction in serum K + levels with increasing doses of β2-agonists, 64 although there is some evidence that tolerance develops after regular treatment. 65 By inducing hypokalemia, β2-agonists may precipitate arrhythmias, 66 and hypokalemia can be aggravated by concomitant treatments promoting potassium loss, such as diuretics, ICSs, and theophylline. Combining thiazide and loop diuretics with LABAs may enhance hypokalemia and, therefore, the risk of electrocardiogram modifications, especially with doses that are above the recommended range.…”