Leukotriene Receptor Antagonists

Marzena E. Krawiec, MD, Nizar J. Jarjour, MD


Semin Respir Crit Care Med. 2002;23(4) 

In This Article

Abstract and Introduction


In the past decade, heightened emphasis has been placed on the importance of inflammation in the pathogenesis of asthma. Although corticosteroids have remained the primary anti-inflammatory agents in the management of the persistent asthmatic, new classes of drugs have recently been added. The leukotriene receptor antagonists (LTRAs) are the first new approach in asthma therapy in the past 25 years and the first class of drugs to target specific components of the inflammatory process. These drugs reverse the primary biological effects of the cysteinyl leukotrienes in relation to the pathogenesis of asthma including bronchoconstriction, mucus hypersecretion, and airway inflammation. The LTRAs have demonstrated efficacy against exercise- and allergen-induced bronchoconstriction, aspirin-sensitive asthma, and additive benefit in symptomatic moderate asthmatics on maintenance inhaled corticosteroids, as well as potential steroid-sparing effects. Finally, although evidence for their role as first-line controller agents for the management of mild persistent asthma has grown stronger in recent years, this role continues to evolve.

Objectives: Upon completion of this article, the reader should be better able to: (1) discuss the role of leukotrienes in the pathophysiology of asthma; (2) identify the role of the LTRAs in the treatment of clinical asthma and their areas of efficacy based on asthma challenge models; (3) describe the potential use of the LTRAs as controller therapy in mild persistent asthma and as steroid-sparing agents; and (4) understand that the LTRAs are generally safe and well-tolerated agents that target a specific component of the asthmatic inflammatory cascade.
Accreditation: The University of Michigan is accredited by the Accreditation Council for Continuing Medical Education to sponsor continuing medical education for physicians.
Credits: The University of Michigan designates this educational activity for a maximum of 1.0 hour in category one credits toward the AMA Physicians Recognition Award.


Asthma is characterized by reversible airway obstruction, hyperresponsiveness, and inflammation. This inflammation is present in early or mild disease as demonstrated by Beasley and colleagues based on their description of increased activated eosinophils and monocytes, degranulated mast cells, epithelial cell shedding, and subepithelial fibrosis in the bronchial biopsies of eight patients with mild atopic asthma.[1] Numerous additional studies have supported these findings, which has led to the universal recommendation of therapies aimed at diminishing airway inflammation in asthma patients with persistent symptoms.

"Targeted" anti-inflammatory therapies for the treatment of asthma have been limited due to the heterogeneous nature of the disease. As demonstrated by these early biopsy studies, multiple inflammatory pathways involving a complex interplay of various cells and mediators have been identified, and it is likely that more remain. Despite such complexity, drugs aimed at reversing the action of specific lipid mediators, known as leukotrienes (LTs), have gained considerable attention in the past decade. Structurally elucidated in 1979, the term leukotriene is derived from early animal experiments showing the origins of these compounds from leukocytes and the presence of a common conjugated triene structure.[2] Early interest arose based primarily on studies demonstrating that the LTs were potent bronchoconstrictors[3,4,5,6] and could result in significant influxes of inflammatory cells into human airways.[7] These properties suggested that the LTs are important contributors to the classic pathophysiological features of asthma and led to the development of a new class of drugs known as leukotriene receptor antagonists (LTRAs).

Two approaches were initially pursued in the development of LT inhibiting drugs. The LTRAs are the first class of asthma drugs to uniquely target a specific component of the asthmatic inflammatory cascade. These drugs prevent LT binding and the subsequent activation of LT receptors, the LTRAs. The second approach was to inhibit LT synthesis using 5-lipoxygenase (5-LO) and 5-lipoxygenase activating protein (FLAP) inhibitors. This review focuses on the three currently available drugs that constitute the group known as the LTRAs.


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