Assessment of Tachyphylaxis following Prolonged Therapy of Asthma with Inhaled Albuterol Aerosol

Repsher, Lawrence; Anderson, John A.; Bush, Robert K.; Falliers, Constantine J.; Kass, Irving; Kemp, James P.; Reed, Charles E.; Siegel, Sheldon C.; Webb, David

doi:10.1378/chest.85.1.34

Cited by 84 publications

(22 citation statements)

References 7 publications

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“…Some authors [7,[13][14][15][16][17] reported positive data for the occurrence of downregulation, whereas others obtained negative results in this regard [18][19][20][21][22], In our investigation, the administration of S by inhala tion for 2 weeks at the dose of 900 ug daily did not modify the acute bronchodilatation induced by intravenous ad ministration of S. Our results therefore demonstrate that at this dose the adrenergic agent does not induce desensi tization of airway [5-receptors. The absence of tachyphylaxis seems not to be due to the fact that desensitization by (5-stimulants was already present in basal conditions. In fact, all the subjects under went a 2-week pharmacological wash-out period which should have permitted restoration of receptor function [13].…”

Section: Discussionsupporting

confidence: 55%

Effects of Therapeutic Doses of Salbutamol Alone and Combined with Beclomethasone Dipropionate on Airway Responsiveness and Cyclic AMP Plasma Levels in Asthmatic Patients

Ferrari¹,

Testi²,

Romito³

et al. 1993

Respiration

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Twelve asthmatic patients received by inhalation for 2 weeks, in a double-blind, cross-over design, beclomethasone dipropionate (BDP; 600 μg/day) plus salbutamol (S; 900 μg/day), or S (900 μg/day) alone. Before and after each treatment course the subjects received intravenous cumulative doses of S up to 200 μg. In basal conditions and immediately before the next dose forced expiratory volume in 1 s (FEV₁) and plasma cyclic AMP (cAMP) were measured. BDP + S treatment increased FEV₁ basal values (p < 0.05) whereas inhaled S resulted in unsignificant improvement of ventilatory parameters. The slopes of the dose-response curves of FΕV₁ and plasma cAMP to intravenous S were unaffected by the two treatment courses. Our results suggest that DBP + S, differently from S alone, improves ventilatory function in asthmatic patients and that neither S nor S + BDP seem to affect adrenergic function.

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Section: Discussionsupporting

confidence: 55%

Effects of Therapeutic Doses of Salbutamol Alone and Combined with Beclomethasone Dipropionate on Airway Responsiveness and Cyclic AMP Plasma Levels in Asthmatic Patients

Ferrari¹,

Testi²,

Romito³

et al. 1993

Respiration

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“…Eight of this group were receiving corticosteroid therapy, and in this small sample this did appear to protect against the development of tolerance [12]. In contrast, several other studies assessing treatment with both oral and inhaled 02-adrenoceptor agonists by means of bronchodilator responses to single and cumulative doses of inhaled, intravenous, and subcutaneous I2-adrenoceptor agonists have failed to show evidence of tolerance [13][14][15].…”

mentioning

confidence: 92%

“…Repsher et al [11] found that tolerance to the duration, but not the peak bronchodilator response to a single dose of salbutamol (170 g,g) developed after 91 days treatment with salbutamol, 170 gg four times daily when compared with the response prior to treatment, but without placebo control. Weber and coworkers were able to demonstrate tolerance to both the peak and duration of the bronchodilator response to cumulative doses of terbutaline in a group of 13 asthmatics, following 12 weeks treatment with inhaled terbutaline, 500 kg four times daily.…”

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confidence: 99%

Tolerance with beta 2‐adrenoceptor agonists: time for reappraisal.

Grove

Lipworth

1995

Brit J Clinical Pharma

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“…However, although Harvey & Tattersfield (1982) showed subsensitivity in airways response after chronic dosing with inhaled salbutamol in normal subjects, this was not seen in asthmatics. Other studies have also failed to show tolerance to bronchial 3-adrenoceptor responses during long term treatment Repsher et al, 1981;Tomashefski, 1981).…”

Section: Discussionmentioning

confidence: 99%

Beta‐adrenoceptor responses to high doses of inhaled salbutamol in patients with bronchial asthma.

Lipworth

Clark

Dhillon

et al. 1988

Brit J Clinical Pharma

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1 Fourteen asthmatics (mean ± s.e. mean baseline FEV1 62 ± 6% of predicted) were given cumulative doubling doses of salbutamol by metered-dose inhaler as follows: 100 ,ug, 200 pg, 500 pg, 1000 pug, 2000 ,ug, 4000 ,ug. 2 Airways, tremor, haemodynamic and cyclic AMP responses were measured at each dose increment (made every 20 min). 3 There was a linear log dose-response relationship for each airways parameter (FEV1, VC, sGaw, FEF 50%). The plateau in the dose-response curve was not reached within our dose range. These changes were also mirrored in cyclic AMP responses. 4 There was a wide range in maximum airways response expressed in terms of absolute increase over baseline (95% confidence intervals: AFEV1 667-1483 ml; A VC 689-1695 ml; A sGaw 0.92-4.50 s-1 kPa-1; A FEF 50% 0.94-2.15 1 s-). Patients with a lower baseline showed a greater response in terms of percent increase in FEV1 (r = -0.83, P < 0.001). There was however, no correlation between baseline airway calibre and the dose required for maximum bronchodilatation.5 There were objective increases (mean ± s.e. mean) in both heart rate (maximum A HR of 14 ± 5 beats min-' at 4000 ,ug) and tremor power (maximum A Tr of 115 ± 44% at 2000 ,ug). These were not dose limiting side-effects as subjective symptoms were infrequent at higher doses. 6 Higher than conventional doses of salbutamol given by metered-dose inhaler may produce a distinct improvement in airways response without significant side-effects. There is a wide individual variation in airways response to inhaled salbutamol, although most patients required higher doses to achieve maximal bronchodilatation. The severity of asthma does not however predict the dose required for maximum airways response.

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Assessment of Tachyphylaxis following Prolonged Therapy of Asthma with Inhaled Albuterol Aerosol

Cited by 84 publications

References 7 publications

Effects of Therapeutic Doses of Salbutamol Alone and Combined with Beclomethasone Dipropionate on Airway Responsiveness and Cyclic AMP Plasma Levels in Asthmatic Patients

Effects of Therapeutic Doses of Salbutamol Alone and Combined with Beclomethasone Dipropionate on Airway Responsiveness and Cyclic AMP Plasma Levels in Asthmatic Patients

Tolerance with beta 2‐adrenoceptor agonists: time for reappraisal.

Beta‐adrenoceptor responses to high doses of inhaled salbutamol in patients with bronchial asthma.

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