Allergy 2013 May-16

 

Should antihistamines be re-considered as antiasthmatic drugs as adjuvants to anti-leukotrienes?

Eur J Pharmacol. 2013 Feb 15;701(1-3):181-4.

Bartho L, Benko R.

Department of Pharmacology and Pharmacotherapy, University Medical School of Pécs, Pécs, Hungary. Lorand.Bartho@aok.pte.hu

Abstract

In spite of histamine mimicking the symptoms of allergic bronchoconstriction and severe anaphylaxis, histamine antagonists most probably represent no effective treatment for these conditions. Anti-leukotrienes proved effective for preventing attacks of allergic asthma. In vitro evidence supports a supra-additive effect of histamine H1 receptor antagonists and anti-leukotrienes in vitro, in asthma models utilizing human bronchi. The same seems to hold true for human allergen provocation tests in vivo. We conclude that combinations of second-generation antihistamines and anti-leukotrienes deserve a large-scale clinical trial for preventing and/or treating attacks of allergic asthma. If useful, these drugs could provide a cost-effective alternative to some recent antiasthmatics. Given that redundant mechanisms may be included in asthma pathophysiology, other combinations (including thromboxane or platelet activating factor antagonists) could also be considered. Copyright © 2013 Elsevier B.V. All rights reserved.

PMID: 23353593

 

Supplement:

Allergic asthma is a frequent, potentially severe respiratory dysfunction characterized by difficulty in breathing, i.e., dyspnea (especially expiration becomes difficult). The immediate cause of this condition is bronchial constriction combined with inflammatory swelling of the airway mucosa. Many allergens can sensitize the susceptible patient, which leads to production of antibodies of the IgE type. IgE binds to Fc receptors of mast cells (and possibly other cell types). Subsequent exposure to the allergen results in the binding of allergen molecules to the fixed IgE, formation of cross-linkages berween such complexes and ultimately activation of the mast cell. Activation includes several cascades of signal transduction. As a results, mast cells release pre-formed mediators (stored in granules) such as histamine (serotonin only in some non-human animal species), heparin, proteases and others. Proteases can split several substrates, leading to formation of bronchoconstrictor and inflammatory mediators (and stimulation of the so-called protease-activated receptors, PARs) that may play a role in the pathogenesis of allergic asthma. Upon being activated, mast cells also release non-preformed, fresly-synthesized mediators of which arachidonic acid derivatives (eicosanoids), more particularly the 5-lipoxygenase product cysteinyl-leukotrienes seem especially important. Antagonists of their receptors (non-officially called „-lukasts”), as well as a 5-lipoxygenase inhibitor are able to reduce the severity and frequency of asthmatic attacks. Standard treatment of asthma also includes bronchodilator adrenergic beta-2 receptor agonists, as well as anti-inflammatory corticosteroids. To date, antihistamines (H1 receptor antagonists that have an established role in the treatment of allergic rhinoconjunctivitis, i.e. hay fever) are considered practically ineffective in allergic asthma. However, data of the literature (both in vitro on human isolated bronchi and in vivo, using allergen provocation tests) seem to indicate that antihistamines can potentiate the bronchodilator effect of anti-leukotrienes. We conclude that antihistamine−anti-leukotriene combinations may be a more effective treatment of allergic asthma than anti-leukotrienes alone and that this combination would deserve a large-scale clinical study.

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