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Pharmaceuticals
Special Issues
Antiasthmatic Drugs
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Antiasthmatic Drugs

A special issue of Pharmaceuticals (ISSN 1424-8247).

Deadline for manuscript submissions: closed (31 December 2009) | Viewed by 178797

Special Issue Editors

Prof. Dr. Paolo Montuschi

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Guest Editor
Department of Pharmacology, Faculty of Medicine, Catholic University of the Sacred Heart, Largo Francesco Vito 1, 00168 Rome, Italy
Interests: asthma; chronic obstructive pulmonary disease (COPD); pharmacological therapy of asthma and COPD; allergy; non-invasive monitoring of lung inflammation; exhaled breath condensate; exhaled nitric oxide; electronic nose; metabolomics
Prof. Dr. Peter J. Barnes

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Guest Editor
National Heart and Lung Institute, Imperial College London, London SW3 6LY, UK
Interests: COPD; cellular senescence; oxidative stress; inflammation; airway epithelial cells

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Related Special Issue

Published Papers (4 papers)

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Review

20 pages, 368 KiB  
Review
Role of Leukotrienes and Leukotriene Modifiers in Asthma
by Paolo Montuschi
Pharmaceuticals 2010, 3(6), 1792-1811; https://doi.org/10.3390/ph3061792 - 2 Jun 2010
Cited by 46 | Viewed by 18526
Abstract
Leukotrienes (LTs), including cysteinyl LTs (CysLTs) and LTB4, are potent lipid mediators that are pivotal in the pathophysiology of asthma phenotypes. At least two receptor subtypes for CysLTs – CysLT1 and CysLT2 – have been identified. Most of the [...] Read more.
Leukotrienes (LTs), including cysteinyl LTs (CysLTs) and LTB4, are potent lipid mediators that are pivotal in the pathophysiology of asthma phenotypes. At least two receptor subtypes for CysLTs – CysLT1 and CysLT2 – have been identified. Most of the pathophysiological effects of CysLTs in asthma, including increased airway smooth muscle activity, microvascular permeability and airway mucus secretion, are mediated by the activation of the CysLT1 receptor. LTB4 may have a role in the development of airway hyperresponsiveness, severe asthma and asthma exacerbations. Although generally less effective than inhaled glucocorticoids, CysLT1 receptor antagonists can be given orally as monotherapy in patients with persistent mild asthma. In patients with more severe asthma, CysLT1 receptor antagonists can be combined with inhaled glucocorticoids. This therapeutic strategy improves asthma control and enables the dose of inhaled glucocorticoids to be reduced, while maintaining similar efficacy. The identification of subgroups of patients with asthma who respond to CysLT1 receptor antagonists is relevant for asthma management, as the response to these drugs is variable. The potential anti-remodeling effect of CysLT1 receptor antagonists might be important for preventing or reversing airway structural changes in patients with asthma. This review discusses the role of LTs in asthma and the therapeutic implications of the pharmacological modulation of the LT pathway for asthma. Full article
(This article belongs to the Special Issue Antiasthmatic Drugs)
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29 pages, 1162 KiB  
Review
Beta-Adrenergic Agonists
by Giovanni Barisione, Michele Baroffio, Emanuele Crimi and Vito Brusasco
Pharmaceuticals 2010, 3(4), 1016-1044; https://doi.org/10.3390/ph3041016 - 30 Mar 2010
Cited by 65 | Viewed by 36058
Abstract
Inhaled β2-adrenoceptor (β2-AR) agonists are considered essential bronchodilator drugs in the treatment of bronchial asthma, both as symptoms-relievers and, in combination with inhaled corticosteroids, as disease-controllers. In this article, we first review the basic mechanisms by which the β [...] Read more.
Inhaled β2-adrenoceptor (β2-AR) agonists are considered essential bronchodilator drugs in the treatment of bronchial asthma, both as symptoms-relievers and, in combination with inhaled corticosteroids, as disease-controllers. In this article, we first review the basic mechanisms by which the β2-adrenergic system contributes to the control of airway smooth muscle tone. Then, we go on describing the structural characteristics of β2-AR and the molecular basis of G-protein-coupled receptor signaling and mechanisms of its desensitization/ dysfunction. In particular, phosphorylation mediated by protein kinase A and β-adrenergic receptor kinase are examined in detail. Finally, we discuss the pivotal role of inhaled β2-AR agonists in the treatment of asthma and the concerns about their safety that have been recently raised. Full article
(This article belongs to the Special Issue Antiasthmatic Drugs)
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23 pages, 363 KiB  
Review
Theophylline
by Peter J. Barnes
Pharmaceuticals 2010, 3(3), 725-747; https://doi.org/10.3390/ph3030725 - 18 Mar 2010
Cited by 104 | Viewed by 46648
Abstract
Theophylline (3-methyxanthine) has been used to treat airway diseases for over 70 years. It was originally used as a bronchodilator but the relatively high doses required are associated with frequent side effects, so its use declined as inhaled β2-agonists became more [...] Read more.
Theophylline (3-methyxanthine) has been used to treat airway diseases for over 70 years. It was originally used as a bronchodilator but the relatively high doses required are associated with frequent side effects, so its use declined as inhaled β2-agonists became more widely used. More recently it has been shown to have anti-inflammatory effects in asthma and COPD at lower concentrations. The molecular mechanism of bronchodilatation is inhibition of phosphodiesterase(PDE)3 and PDE4, but the anti-inflammatory effect may be due to histone deacetylase (HDAC) activation, resulting in switching off of activated inflammatory genes. Through this mechanism theophylline also reverses corticosteroid resistance and this may be of particular value in severe asthma and COPD where HDAC2 activity is markedly reduced. Theophylline is given systemically (orally as slow-release preparations for chronic treatment and intravenously for acute exacerbations of asthma) and blood concentrations are determined mainly by hepatic metabolism, which may be increased or decreased in several diseases and by concomitant drug therapy. Theophylline is now usually used as an add-on therapy in asthma patients not well controlled on inhaled corticosteroids and in COPD patients with severe disease not controlled by bronchodilator therapy. Side effects are related to plasma concentrations and include nausea, vomiting and headaches due to PDE inhibition and at higher concentrations to cardiac arrhythmias and seizures due to adenosine A1-receptor antagonism. Full article
(This article belongs to the Special Issue Antiasthmatic Drugs)
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27 pages, 1438 KiB  
Review
Inhaled Corticosteroids
by Peter J. Barnes
Pharmaceuticals 2010, 3(3), 514-540; https://doi.org/10.3390/ph3030514 - 8 Mar 2010
Cited by 202 | Viewed by 75089
Abstract
Inhaled corticosteroids (ICS) are the most effective controllers of asthma. They suppress inflammation mainly by switching off multiple activated inflammatory genes through reversing histone acetylation via the recruitment of histone deacetylase 2 (HDAC2). Through suppression of airway inflammation ICS reduce airway hyperresponsiveness and [...] Read more.
Inhaled corticosteroids (ICS) are the most effective controllers of asthma. They suppress inflammation mainly by switching off multiple activated inflammatory genes through reversing histone acetylation via the recruitment of histone deacetylase 2 (HDAC2). Through suppression of airway inflammation ICS reduce airway hyperresponsiveness and control asthma symptoms. ICS are now first-line therapy for all patients with persistent asthma, controlling asthma symptoms and preventing exacerbations. Inhaled long-acting β2-agonists added to ICS further improve asthma control and are commonly given as combination inhalers, which improve compliance and control asthma at lower doses of corticosteroids. By contrast, ICS provide much less clinical benefit in COPD and the inflammation is resistant to the action of corticosteroids. This appears to be due to a reduction in HDAC2 activity and expression as a result of oxidative stress. ICS are added to bronchodilators in patients with severe COPD to reduce exacerbations. ICS, which are absorbed from the lungs into the systemic circulation, have negligible systemic side effects at the doses most patients require, although the high doses used in COPD has some systemic side effects and increases the risk of developing pneumonia. Full article
(This article belongs to the Special Issue Antiasthmatic Drugs)
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