Protective effect of loop diuretics, piretanide and frusemide, against sodium metabisulphite-induced bronchoconstriction in asthma.
We determined whether the loop diuretic, piretanide, had a similar inhibitory action against sodium metabisulphite (MBS)-induced bronchoconstriction in asthmatic subjects as frusemide and, if so, its duration of action. In the first study, we compared the effect of inhaled placebo, piretanide (24 mg), or frusemide (40 mg), on the provocative concentration of MBS needed to cause a 20% fall in baseline forced expiratory volume in one second (FEV1) (PC20MBS) in 12 mild asthmatic subjects before, immediately after, and at 1.5, 3, 6, and 24 h, after inhalation. Both piretanide and frusemide induced a significant diuresis lasting at least 24 h. Frusemide caused a mean 3.8 fold (95% confidence interval: 2.3-6.3 fold), piretanide a 2.5 fold (1.8-3.4 fold) and placebo a 1.7 fold (1.5-1.9 fold) increase in PC20MBS. The effects of frusemide and piretanide were significantly greater than that of placebo. At later time points, tachyphylaxis to the bronchoconstrictor effects of MBS was observed during the placebo limb. In the second study, we measured PC20MBS at 90 min after inhalation of either placebo, piretanide (24 mg), or frusemide (40 mg). No significant difference in PC20MBS was observed. We conclude that piretanide in addition to frusemide significantly inhibits MBS-induced bronchoconstriction and that this action is short-lived over less than 90 min. Frusemide was more potent in inhibiting MBS-induced bronchoconstriction despite causing a smaller diuretic effect than piretanide. The basic mechanism of action of the loop diuretics in the airways remains unclear.
Yeo
C T
CT
Health Manpower Development Program of Singapore.
O'Connor
B J
BJ
Chen-Worsdell
M
M
Barnes
P J
PJ
Chung
K F
KF
D000280:Administration, Inhalation; D000328:Adult; D001249:Asthma / Q000503:physiopathology*; D001985:Bronchial Provocation Tests / Q000379:methods; D016084:Bronchoconstriction / Q000187:drug effects*; D004232:Diuretics / Q000494:pharmacology*; D004311:Double-Blind Method; D005260:Female; D005665:Furosemide / Q000494:pharmacology*; D006801:Humans; D008297:Male; D013447:Sulfites / Q000037:antagonists & inhibitors; D013449:Sulfonamides / Q000494:pharmacology*; D013997:Time Factors
D004232:Diuretics; D013447:Sulfites; D013449:Sulfonamides; C005200:sodium metabisulfite; D005665:Furosemide; C015451:piretanide