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Protective effect of loop diuretics, piretanide and frusemide, against sodium metabisulphite-induced
C T Yeo1, B J O'Connor, M Chen-Worsdell
1Health Manpower Development Program of Singapore.
Abstract:
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.
Insights
Piretanide, like frusemide, inhibits sodium metabisulphite-induced bronchoconstriction in asthma patients. This protective effect, however, is short-lived, lasting less than 90 minutes.
Area of Science:
- Pulmonary Medicine
- Pharmacology
Background:
- Asthma is characterized by airway hyperresponsiveness.
- Sodium metabisulphite (MBS) is a common trigger for bronchoconstriction in asthmatic individuals.
- Loop diuretics, such as frusemide, have shown potential in mitigating such responses.
Purpose of the Study:
- To investigate the inhibitory effect of piretanide on MBS-induced bronchoconstriction in mild asthmatic subjects.
- To compare piretanide's action with that of frusemide.
- To determine the duration of action for piretanide's inhibitory effect.
Main Methods:
- Two studies were conducted involving 12 mild asthmatic subjects.
- Study 1: Inhaled placebo, piretanide (24 mg), or frusemide (40 mg) were administered. The provocative concentration of MBS causing a 20% fall in FEV1 (PC20MBS) was measured at various time points up to 24 hours.
- Study 2: PC20MBS was measured 90 minutes after inhalation of placebo, piretanide, or frusemide.
Main Results:
- Both piretanide and frusemide significantly increased PC20MBS compared to placebo, indicating inhibition of MBS-induced bronchoconstriction.
- Frusemide showed a greater increase in PC20MBS (3.8-fold) than piretanide (2.5-fold).
- The inhibitory effect of both diuretics was found to be short-lived, lasting less than 90 minutes, with no significant difference observed at this time point between the drugs.
Conclusions:
- Piretanide, similar to frusemide, effectively inhibits MBS-induced bronchoconstriction in asthmatic patients.
- The airway protective effect of these loop diuretics is transient, diminishing within 90 minutes.
- The precise mechanism underlying the action of loop diuretics in the airways remains to be elucidated.