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Yuan Zhang - One of the best experts on this subject based on the ideXlab platform.

  • Fenoterol inhibits lps induced ampk activation and inflammatory cytokine production through β arrestin 2 in thp 1 cell line
    Biochemical and Biophysical Research Communications, 2015
    Co-Authors: Wei Wang, Yuan Zhang
    Abstract:

    The AMP-activated protein kinase (AMPK) pathway is involved in regulating inflammation in several cell lines. We reported that Fenoterol, a β2-adrenergic receptor (β2-AR) agonist, had anti-inflammatory effects in THP-1 cells, a monocytic cell line. Whether the Fenoterol anti-inflammatory effect involves the AMPK pathway is unknown. In this study, we explored the mechanism of β2-AR stimulation with Fenoterol in a lipopolysaccharide (LPS)-induced inflammatory cytokine secretion in THP-1 cells. We studied whether Fenoterol and β-arrestin-2 or AMPKα1 subunit knockdown could affect LPS-induced AMPK activation, nuclear factor-kappa B (NF-κB) activation and inflammatory cytokine secretion. LPS-induced AMPK activation and interleukin 1β (IL-1β) release were reduced with Fenoterol pretreatment of THP-1 cells. SiRNA knockdown of β-arrestin-2 abolished the Fenoterol inhibition of LPS-induced AMPK activation and interleukin 1β (IL-1β) release, thus β-arrestin-2 mediated the anti-inflammatory effects of Fenoterol on LPS-treated THP-1 cells. In addition, siRNA knockdown of AMPKα1 significantly attenuated the LPS-induced NF-κB activation and IL-1β release, so AMPKα1 was a key signaling molecule involved in LPS-induced inflammatory cytokine production. These results suggested the β2-AR agonist Fenoterol inhibited LPS-induced AMPK activation and IL-1β release via β-arrestin-2 in THP-1 cells. The exploration of these mechanisms may help optimize therapeutic agents targeting these pathways in inflammatory diseases.

Richard Beasley - One of the best experts on this subject based on the ideXlab platform.

  • partial vs full β receptor agonism a clinical study of inhaled albuterol and Fenoterol
    Chest, 1996
    Co-Authors: P. Bremner, Richard Beasley, Julian Crane, Robert Siebers, C Burgess
    Abstract:

    Study objective To compare the maximal extrapulmonary effects of the β-agonists albuterol and Fenoterol in eight healthy volunteers. Subjects and methods In this double-blind study, we have examined the maximum cardiac effects (electromechanical systole [QS 2 I]— a measure of inotropy, heart rate, BP) and metabolic effects (plasma K+ and cyclic adenosine monophosphate [cAMP]) of repeated inhalation of albuterol and Fenoterol. In eight healthy volunteers, 400 µg of each drug was administered every 10 min until QS 2 I and plasma K+ had reached a plateau (±0.1 mmol/L for K+, and ±10 ms for QS 2 I). The maximum response (Emax) and the dose of albuterol required to produce 50% of the maximum response to Fenoterol (ED 50F ) were calculated. Results The Emax for Fenoterol was significantly greater than albuterol for plasma K+ (-1.4 vs −1.03 mmol/L; p 2 I (-71.8 vs −57.5 ms; p=0.047), and cAMP (33.8 vs 18.1 nmol/L; p 50F was significantly greater for albuterol than for Fenoterol with potency ratios of 1.75, 1.61, and 2.26 for plasma K+, QS 2 I, and cAMP, respectively. There were no significant differences between Fenoterol and albuterol with respect to heart rate (Emax, 44.9 vs 32.5 beats/min; p=0.19; potency ratio, 1.98; p=0.052). Conclusions These findings suggest that albuterol behaves as a partial agonist at β-receptors when compared with Fenoterol, and that when inhaled in doses currently recommended for severe asthma, albuterol will result in lesser maximum cardiac and metabolic effects than Fenoterol. These findings are consistent with the hypothesis that the property of full receptor agonism may contribute to the increased risk of death associated with Fenoterol.

  • Withdrawal of Fenoterol and the End of the New Zealand Asthma Mortality Epidemic
    International archives of allergy and immunology, 1995
    Co-Authors: Richard Beasley, Neil Pearce, Julian Crane, Carl Burgess
    Abstract:

    In response to the evidence that Fenoterol was a major cause for the second epidemic of asthma deaths in New Zealand, the Department of Health severely restricted its availability, thereby allowing an ‘experiment in prevention’ to be undertaken. These regulatory actions, which effectively removed Fenoterol from the market in New Zealand, were associated with a sudden and marked reduction in asthma mortality, providing further evidence for a causative role of Fenoterol in the epidemic of asthma deaths in New Zealand.

  • Confounding by severity does not explain the association between Fenoterol and asthma death
    Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 1994
    Co-Authors: Richard Beasley, Carl Burgess, Neil Pearce, K Woodman, Julian Crane
    Abstract:

    Summary. Three recent case-control studies from New Zealand, and one from Saskatchewan, Canada, have found that Fenoterol increases the risk of death in patients with severe asthma. It has been suggested that these findings may be due to confounding by severity, if Fenoterol was selectively prescribed to more severe asthmatics. This ‘confounding by severity’ hypothesis has now been investigated in further analyses of data from the New Zealand case-control studies. This analysis found that among patients whose asthma was severe enough to require hospital admission (the population in whom the case-control studies were conducted), Fenoterol was not preferentially prescribed to the more severe asthmatics. There was greater co-prescribing of other drugs with Fenoterol (compared with salbutamol) during the later years of the epidemic, but these differences did not explain the excess risk associated with Fenoterol, and there was little evidence of greater co-prescribing during the earlier years of the New Zealand epidemic of asthma deaths. There was no association between the prescription of Fenoterol and markers of acute asthma severity or psychosocial problems. Patients were not selectively changed to Fenoterol as a result of a severe attack resulting in a hospital admission. Most importantly, in the case-control studies of asthma deaths, the inhaled Fenoterol relative risk increased when the analysis was restricted to sub-groups defined by markers of chronic asthma severity; whereas the relative risk would have decreased towards 1.0 in these sub-group analyses if the overall elevated risk for Fenoterol was due to confounding by severity. We conclude that in patients whose asthma is severe enough to require hospital admission, there is little evidence that Fenoterol was selectively prescribed to the more severe patients and that the findings in the most severe sub-groups effectively exclude the ‘confounding by severity’ hypothesis as an explanation for the recent case-control findings.

  • A comparison of the cardiovascular and metabolic effects of formoterol, salbutamol and Fenoterol
    The European respiratory journal, 1993
    Co-Authors: P. Bremner, Carl Burgess, Neil Pearce, K Woodman, Julian Crane, Gordon Purdie, Richard Beasley
    Abstract:

    The cardiovascular and metabolic effects of the long-acting beta 2-agonist formoterol were compared with those of salbutamol, Fenoterol and placebo in 12 healthy volunteers, using a randomised, double-blind, cross-over design. On the study days, the subjects inhaled either formoterol (24 micrograms), salbutamol (400 micrograms), Fenoterol (400 micrograms) or placebo, at 30 min intervals for five doses. Heart rate (HR) total electromechanical systole (Q-S2I) (a measure of inotropy), the corrected QT interval (QTc), systolic and diastolic blood pressure, plasma glucose and plasma potassium (K+) were measured prior to drug administration, 10 min after each inhalation and at 30 min intervals for 3 h after the last inhalation. All of the active agents significantly increased HR, QTc and plasma glucose, and decreased Q-S2I, diastolic blood pressure and plasma K+ compared to placebo. Fenoterol had a significantly greater maximum effect on HR, QTc and Q-S2I than either salbutamol or formoterol. Formoterol and Fenoterol caused a similar maximum reduction in plasma K+, greater than that due to salbutamol. We conclude that formoterol is a more selective beta 2-agonist than Fenoterol, and has similar cardiovascular effects to salbutamol when inhaled repeatedly by normal volunteers.

  • Cardiovascular effects of Fenoterol under conditions of hypoxaemia.
    Thorax, 1992
    Co-Authors: P. Bremner, Carl Burgess, Neil Pearce, K Woodman, Julian Crane, D Mchaffie, D Galletly, Richard Beasley
    Abstract:

    BACKGROUND: The reason for the association of increased risk of death with Fenoterol in patients with asthma in New Zealand is unknown but may relate to its cardiovascular effects. Most deaths from asthma occur outside hospital, where hypoxaemia is likely to be a complicating factor. The cardiovascular effects of Fenoterol have been investigated therefore under conditions of normoxaemia and hypoxaemia. METHOD: Eight healthy men were studied on two occasions. Measurements of heart rate, blood pressure, total electromechanical systole (QS2I), electrocardiographic QTc interval, cardiac index, stroke volume, and ejection fraction were made under conditions of normoxaemia and hypoxaemia (arterial oxygen saturation 90%) before and after administration of 800 micrograms of Fenoterol by a metered dose inhaler. The order in which treatments were applied was according to a Latin square design. RESULTS: Before inhalation of Fenoterol hypoxaemia was associated with a significant increase in heart rate (8 beats/min) and QTc interval (15.6 ms). Under conditions of normoxaemia Fenoterol caused a significant increase in heart rate (14.3 beats/min), systolic blood pressure (7.7 mm Hg), stroke volume (27.7 ml), cardiac index (1.6 1/min/m2), ejection fraction (11.48), and QTc interval (32.9 ms) and a fall in QS2I (-23.2 ms) and diastolic blood pressure (-8.4 mm Hg). Under conditions of hypoxaemia the changes after inhalation of Fenoterol were similar to those recorded during normoxaemia; thus the effects of hypoxaemia and Fenoterol were additive (heart rate 21.9 beats/min, QTc 43.5 ms with Fenoterol and hypoxaemia). CONCLUSION: The chronotropic and electrophysiological effects of Fenoterol were enhanced by conditions of hypoxaemia.

Carl Burgess - One of the best experts on this subject based on the ideXlab platform.

  • Withdrawal of Fenoterol and the End of the New Zealand Asthma Mortality Epidemic
    International archives of allergy and immunology, 1995
    Co-Authors: Richard Beasley, Neil Pearce, Julian Crane, Carl Burgess
    Abstract:

    In response to the evidence that Fenoterol was a major cause for the second epidemic of asthma deaths in New Zealand, the Department of Health severely restricted its availability, thereby allowing an ‘experiment in prevention’ to be undertaken. These regulatory actions, which effectively removed Fenoterol from the market in New Zealand, were associated with a sudden and marked reduction in asthma mortality, providing further evidence for a causative role of Fenoterol in the epidemic of asthma deaths in New Zealand.

  • Confounding by severity does not explain the association between Fenoterol and asthma death
    Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology, 1994
    Co-Authors: Richard Beasley, Carl Burgess, Neil Pearce, K Woodman, Julian Crane
    Abstract:

    Summary. Three recent case-control studies from New Zealand, and one from Saskatchewan, Canada, have found that Fenoterol increases the risk of death in patients with severe asthma. It has been suggested that these findings may be due to confounding by severity, if Fenoterol was selectively prescribed to more severe asthmatics. This ‘confounding by severity’ hypothesis has now been investigated in further analyses of data from the New Zealand case-control studies. This analysis found that among patients whose asthma was severe enough to require hospital admission (the population in whom the case-control studies were conducted), Fenoterol was not preferentially prescribed to the more severe asthmatics. There was greater co-prescribing of other drugs with Fenoterol (compared with salbutamol) during the later years of the epidemic, but these differences did not explain the excess risk associated with Fenoterol, and there was little evidence of greater co-prescribing during the earlier years of the New Zealand epidemic of asthma deaths. There was no association between the prescription of Fenoterol and markers of acute asthma severity or psychosocial problems. Patients were not selectively changed to Fenoterol as a result of a severe attack resulting in a hospital admission. Most importantly, in the case-control studies of asthma deaths, the inhaled Fenoterol relative risk increased when the analysis was restricted to sub-groups defined by markers of chronic asthma severity; whereas the relative risk would have decreased towards 1.0 in these sub-group analyses if the overall elevated risk for Fenoterol was due to confounding by severity. We conclude that in patients whose asthma is severe enough to require hospital admission, there is little evidence that Fenoterol was selectively prescribed to the more severe patients and that the findings in the most severe sub-groups effectively exclude the ‘confounding by severity’ hypothesis as an explanation for the recent case-control findings.

  • A comparison of the cardiovascular and metabolic effects of formoterol, salbutamol and Fenoterol
    The European respiratory journal, 1993
    Co-Authors: P. Bremner, Carl Burgess, Neil Pearce, K Woodman, Julian Crane, Gordon Purdie, Richard Beasley
    Abstract:

    The cardiovascular and metabolic effects of the long-acting beta 2-agonist formoterol were compared with those of salbutamol, Fenoterol and placebo in 12 healthy volunteers, using a randomised, double-blind, cross-over design. On the study days, the subjects inhaled either formoterol (24 micrograms), salbutamol (400 micrograms), Fenoterol (400 micrograms) or placebo, at 30 min intervals for five doses. Heart rate (HR) total electromechanical systole (Q-S2I) (a measure of inotropy), the corrected QT interval (QTc), systolic and diastolic blood pressure, plasma glucose and plasma potassium (K+) were measured prior to drug administration, 10 min after each inhalation and at 30 min intervals for 3 h after the last inhalation. All of the active agents significantly increased HR, QTc and plasma glucose, and decreased Q-S2I, diastolic blood pressure and plasma K+ compared to placebo. Fenoterol had a significantly greater maximum effect on HR, QTc and Q-S2I than either salbutamol or formoterol. Formoterol and Fenoterol caused a similar maximum reduction in plasma K+, greater than that due to salbutamol. We conclude that formoterol is a more selective beta 2-agonist than Fenoterol, and has similar cardiovascular effects to salbutamol when inhaled repeatedly by normal volunteers.

  • Cardiovascular effects of Fenoterol under conditions of hypoxaemia.
    Thorax, 1992
    Co-Authors: P. Bremner, Carl Burgess, Neil Pearce, K Woodman, Julian Crane, D Mchaffie, D Galletly, Richard Beasley
    Abstract:

    BACKGROUND: The reason for the association of increased risk of death with Fenoterol in patients with asthma in New Zealand is unknown but may relate to its cardiovascular effects. Most deaths from asthma occur outside hospital, where hypoxaemia is likely to be a complicating factor. The cardiovascular effects of Fenoterol have been investigated therefore under conditions of normoxaemia and hypoxaemia. METHOD: Eight healthy men were studied on two occasions. Measurements of heart rate, blood pressure, total electromechanical systole (QS2I), electrocardiographic QTc interval, cardiac index, stroke volume, and ejection fraction were made under conditions of normoxaemia and hypoxaemia (arterial oxygen saturation 90%) before and after administration of 800 micrograms of Fenoterol by a metered dose inhaler. The order in which treatments were applied was according to a Latin square design. RESULTS: Before inhalation of Fenoterol hypoxaemia was associated with a significant increase in heart rate (8 beats/min) and QTc interval (15.6 ms). Under conditions of normoxaemia Fenoterol caused a significant increase in heart rate (14.3 beats/min), systolic blood pressure (7.7 mm Hg), stroke volume (27.7 ml), cardiac index (1.6 1/min/m2), ejection fraction (11.48), and QTc interval (32.9 ms) and a fall in QS2I (-23.2 ms) and diastolic blood pressure (-8.4 mm Hg). Under conditions of hypoxaemia the changes after inhalation of Fenoterol were similar to those recorded during normoxaemia; thus the effects of hypoxaemia and Fenoterol were additive (heart rate 21.9 beats/min, QTc 43.5 ms with Fenoterol and hypoxaemia). CONCLUSION: The chronotropic and electrophysiological effects of Fenoterol were enhanced by conditions of hypoxaemia.

  • Fenoterol and Death from Asthma in New Zealand
    International Archives of Allergy and Immunology, 1992
    Co-Authors: Richard Beasley, Neil Pearce, Julian Crane, Carl Burgess
    Abstract:

    This article reviews the epidemiological evidence that the use of Fenoterol leads to an increased risk of death compared with other commonly used β-agonist drugs such as salbutamol, and that Fenoterol

Wei Wang - One of the best experts on this subject based on the ideXlab platform.

  • Fenoterol inhibits lps induced ampk activation and inflammatory cytokine production through β arrestin 2 in thp 1 cell line
    Biochemical and Biophysical Research Communications, 2015
    Co-Authors: Wei Wang, Yuan Zhang
    Abstract:

    The AMP-activated protein kinase (AMPK) pathway is involved in regulating inflammation in several cell lines. We reported that Fenoterol, a β2-adrenergic receptor (β2-AR) agonist, had anti-inflammatory effects in THP-1 cells, a monocytic cell line. Whether the Fenoterol anti-inflammatory effect involves the AMPK pathway is unknown. In this study, we explored the mechanism of β2-AR stimulation with Fenoterol in a lipopolysaccharide (LPS)-induced inflammatory cytokine secretion in THP-1 cells. We studied whether Fenoterol and β-arrestin-2 or AMPKα1 subunit knockdown could affect LPS-induced AMPK activation, nuclear factor-kappa B (NF-κB) activation and inflammatory cytokine secretion. LPS-induced AMPK activation and interleukin 1β (IL-1β) release were reduced with Fenoterol pretreatment of THP-1 cells. SiRNA knockdown of β-arrestin-2 abolished the Fenoterol inhibition of LPS-induced AMPK activation and interleukin 1β (IL-1β) release, thus β-arrestin-2 mediated the anti-inflammatory effects of Fenoterol on LPS-treated THP-1 cells. In addition, siRNA knockdown of AMPKα1 significantly attenuated the LPS-induced NF-κB activation and IL-1β release, so AMPKα1 was a key signaling molecule involved in LPS-induced inflammatory cytokine production. These results suggested the β2-AR agonist Fenoterol inhibited LPS-induced AMPK activation and IL-1β release via β-arrestin-2 in THP-1 cells. The exploration of these mechanisms may help optimize therapeutic agents targeting these pathways in inflammatory diseases.

Hossein Zia - One of the best experts on this subject based on the ideXlab platform.

  • In vitro transdermal permeation of Fenoterol hydrobromide
    Journal of Advanced Research, 2012
    Co-Authors: Ahmed H. Elshafeey, Yassin El-said Hamza, Soad Y. Amin, Hossein Zia
    Abstract:

    Abstract The aim of this study was to determine if transdermal penetration of Fenoterol, a β-agonist drug, could be enhanced and controlled by formulation modification and formulation of transdermal patches. Pre-formulation studies were performed to determine the feasibility of a transdermal dosage form of Fenoterol. Penetration of Fenoterol was determined using the hairless guinea pig skin with unjacketed Franz diffusion cell. Transdermal patches were formulated using drug in-adhesive technique. Several enhancers were investigated for Fenoterol skin penetration. Transcutol–oleic acid co-solvent gives the highest drug flux among all tested liquid formulations. Pretreatment of the skin with oleic acid 2 h before patch application significantly increases drug diffusion. Cis-oleic acid gives best results compared to oleic acid. Azone derivative (1-dodecyl-2-pyrrolidinone) gives the highest drug diffusion amongst all tested enhancers. Results of this study show the feasibility of using Fenoterol formulated in transdermal delivery system in the treatment of chronic asthma to improve patient compliance, bioavailability and reduce the inter-subject variability.

  • Enhanced Bioavailability of Fenoterol Transdermal Systems in Rabbits
    Journal of Bioequivalence & Bioavailability, 2011
    Co-Authors: Ahmed H. Elshafeey, Yassin El-said Hamza, S.y. Amin, Fatemeh Akhlaghi, Hossein Zia
    Abstract:

    The pharmacokinetic and bioavailability of Fenoterol, a B 2 adrenergic agonist were studied to determine the feasibility of enhanced transdermal delivery. Fenoterol has been widely used to treat asthmatic patients. Two Fenoterol formulations were studied; the first was a liquid formulation of Fenoterol in Transcutol: Oleic acid in a ratio 1:1(F1), while the second was a matrix system of Fenoterol in Duro-tak ® 87-2074 adhesive with 10% 1-dodecyl-2- pyrrolidinone as an enhancer (F2). For comparison, control matrix with Fenoterol without any enhancer (F3) was also tested. The tested formulations were applied to the shaved back skin of rabbits using HILL TOP CHAMBER ® in case of liquid formula. Blood samples were collected via auricle central vein for 24 hours and the plasma concentrations of Fenoterol were determined by LC-MS/MS method. Pharmacokinetic parameters were calculated using the WinNonlin computer program. The results showed a maximum concentration of Fenoterol in plasma of 514.8 ng/ml after application of the liquid formula while its AUC 0-∞ amounted to be 485972(ng*min/ml) with a dose of 3mg/kg. The transdermal matrix prepared with 10% 1-dodecyl-2-pyrollidinone had a C max of 219 ng/ml and AUC 0-∞ was 124636 (ng*min/ml) which is significantly higher than that obtained after application of the control patch without any enhancer. Therefore, the transdermal systems will offer an efficient drug delivery system for the treatment of bronchial asthma.