Rebound Increase in Bronchial Responsiveness After Treatment With Inhaled Terbutaline

Vathenen, A.S.; Higgins, Bernard; Knox, Alan J.; Britton, John; Tattersfield, AE

doi:10.1016/s0140-6736(88)91352-9

Cited by 291 publications

(87 citation statements)

References 21 publications

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“…Acutely, this property of (± )salbuta mol is masked by the bronchodilator action of (-)salbuta mol, but following sustained infusion of (±)salbuta mol over several days, increased sensitivity of the airways can be demonstrated to antigen (9) and to airway spas mogens (10). Such findings are consistent with clinical reports of exacerbation of airway hyperreactivity follow ing regular administration of (±)fenoterol (11), (±)ter butaline (12)(13)(14) and (±)salbutamol (15); loss of protec tion against constrictor stimuli despite persisting bron chodilator responses, as reported for (±)salbutamol (16) and (±)salmeterol (17); and intensification of late-onset reactions to inhaled allergen, as following inhalation of (±)rimiterol (18).…”

supporting

confidence: 89%

Exacerbation of Airway Hyperreactivity by (±)Salbutamol in Sensitized Guinea Pigs

Hoshiko

Morley

1993

Japanese Journal of Pharmacology

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ABSTRACT-In guinea pigs passively sensitized to ovalbumin, sustained (6 days) subcutaneous infusion of (±)salbutamol (1 mg/kg/day) induced significant airway obstruction and heightened responsivity to airway spasmogens. Of these animals, a substantial proportion (78/235) were too responsive to injected spasmogens to permit infusion of ovalbumin or died following infusion of ovalbumin; yet there were few deaths (2/166) amongst the sensitized animals not exposed to (±)salbutamol.In comparison to the animals not exposed to (± )salbutamol, infusion of ovalbumin led to exaggerated responsivity of the airways to leukotriene C4, leukotriene E4, histamine, serotonin and acetylcholine, but not to prostaglandin F2a or bradykinin. The capacity of sustained exposure to high doses of (±)salbutamol to induce airway hyperreactivity to allergic mediators may account for an association between asthma death and regular, excessive use of sympathomimetics.

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confidence: 89%

Exacerbation of Airway Hyperreactivity by (±)Salbutamol in Sensitized Guinea Pigs

Hoshiko

Morley

1993

Japanese Journal of Pharmacology

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“…Regular use of short-acting β 2 -agonists has been associated with changes in airway responsiveness, including a rebound increase after cessation of therapy [23]. Tolerance to the protective effects of short-acting β 2 -agonists against methacholine-and allergen-induced bronchoconstriction has been shown after chronic use [24,25].…”

Section: Discussionmentioning

confidence: 99%

Effects of long-acting and short-acting beta-agonists on methacholine dose-response curves in asthmatics

Wong¹,

O'Shaughnessy²,

Walker³

et al. 1997

Eur Respir J

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Regular use of short-acting β-agonists may decrease control of asthma and increase airway responsiveness to bronchoconstrictor stimuli. The aim of this study was to determine the effects of regular treatment with the long-acting β-agonist, salmeterol, on the methacholine dose-response curve (DRC) in mild-tomoderate asthmatics.Changes in methacholine airway responsiveness were measured in 14 stable adult asthmatics, randomized in a double-blind, three-way cross-over design to receive salmeterol 50 µg, salbutamol 200 µg or placebo, each twice daily for 4 days. Two baseline methacholine DRC, were performed, one without premedication and one following a single dose of 200 µg salbutamol. Following 4 days of regular treatment, methacholine DRC to plateau were carried out commencing 15 min after the final dose of trial medication.There were no significant differences in mean baseline forced expiratory volume in one second (FEV1) between treatments. Four days treatment with salmeterol and salbutamol shifted the DRC to the right, but salmeterol provided less protection than salbutamol. The point of inflection of the curve from baseline moved 1.9 and 3.2 doubling doses, respectively, compared to placebo (p≤0.001), and the provocative concentration of methacholine required to produce a 20% fall in FEV1 (PC20) increased 1.6 and 3.1 doubling doses, respectively (p≤0.001). The slope of the DRC was increased slightly by both β-agonists compared to placebo (log slope 3.11, 3.06 and 2.77 for salmeterol, salbutamol and placebo, respectively). This effect of regular salmeterol on slope was more marked in subjects with lower baseline FEV1. Maximal response plateaus did not differ between the three treatments.These results suggest that regular use either of short-or long-acting β-agonists could increase the risk of a more precipitous asthma episode associated with "breakthrough" bronchoconstrictor responses, particularly in those with more severe initial airflow obstruction, if subjects are exposed to a sufficiently potent stimulus.

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“…Despite the ability of β-agonists to effect immediate reversal of airway obstruction, there has been continuing concern that regular use of these drugs may be associated with adverse outcomes. In some, but not all, studies, regularly scheduled use (e.g., multiple times per day, every day) of inhaled β-agonists has resulted in loss of asthma control, declines in morning peak flow, longer durations of asthma exacerbations, and rebound airway hyperresponsiveness (1)(2)(3)(4)(5)(6). These adverse effects appear to be particularly important with β-agonists of high intrinsic efficacy, like fenoterol, and in patients with certain β 2 AR genotypes.…”

Section: Commentariesmentioning

confidence: 99%

β-Agonists and asthma: too much of a good thing?

Shore

Drazen²

2003

J. Clin. Invest.

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Rebound Increase in Bronchial Responsiveness After Treatment With Inhaled Terbutaline

Cited by 291 publications

References 21 publications

Exacerbation of Airway Hyperreactivity by (±)Salbutamol in Sensitized Guinea Pigs

Exacerbation of Airway Hyperreactivity by (±)Salbutamol in Sensitized Guinea Pigs

Effects of long-acting and short-acting beta-agonists on methacholine dose-response curves in asthmatics

β-Agonists and asthma: too much of a good thing?

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