Mediator Antagonists and Anti-Allergic Drugs

Abstract

Many inflammatory mediators have been implicated in the pathogenesis of asthma, and this has led the pharmaceutical industry to develop specific mediator antagonists and non-steroidal anti-allergy drugs as potential therapeutic agents for asthma. The role of these drugs in the treatment of chronic obstructive pulmonary disease (COPD) is largely untested. The leukotriene-receptor antagonists and the 5-lipoxygenase inhibitors have been shown to have a mild bronchodilator effect in asthmatic patients with airflow obstruction and to attenuate bronchoconstriction induced by exercise, allergen and aspirin. There is also some evidence to indicate that they have anti-inflammatory actions. Several therapeutic studies in mild to moderate asthma have shown evidence of efficacy. In clinical trials, the leukotriene-receptor antagonists zafirlukast and montelukast and the 5-lipoxygenase inhibitor zileuton have been well tolerated. The clinical effectiveness of the 5-lipoxygenase inhibitors and the leukotrienereceptor antagonists appears to be quite variable between individuals. The place of the leukotriene-receptor antagonists and 5-lipoxygenase inhibitors in asthma management has not been fully established. Current published evidence suggests a role as an alternative, but less effective first-line prophylactic agent to inhaled corticosteroids and as an alternative second-line add-on drug to long-acting β ₂-agonists for patients with persistent symptoms despite low-dose inhaled corticosteroid therapy. H₁-receptor antagonists have been shown to be mild bronchodilators and to attenuate bronchoconstriction induced by exercise and allergen. Current evidence would suggest that the antihistamines do not have a place in the treatment of chronic persistent asthma. The cromones, sodium cromoglycate and nedocromil sodium, have a limited role in the management of chronic asthma and are less effective anti-inflammatory agents than inhaled corticosteroids.