Leukotriene receptor antagonists in the treatment of asthma: an update

Abstract

Leukotriene receptor antagonists (LTRAs), such as montelukast and zafirlukast, have been demonstrated in a number of studies to possess bronchodilating and anti-inflammatory properties, that make these drugs ideal candidates for the treatment of asthma. The last 1998-updating of the GINA Guidelines for the diagnosis and therapy of asthma recommends the use of LTRAs in the treatment of moderate and mild asthma. In patients with moderate asthma not completely controlled with moderate doses of inhaled corticosteroids, the addition of a LTRA is indicated in alternative to either the increase of the inhaled corticosteroid dose or the addition of an inhaled long-acting beta2-agonist. Both in vitro and in vivo evidences indicate that LTRAs possess an anti-inflammatory activity that is presumably complementary to that presented by corticosteroids. Moreover, clinical studies show that the addition of an LTRA, montelukast, is able to improve clinical and functional indexes in patients with asthma not controlled with inhaled corticosteroids, and to allow a reduction in corticosteroid dosage in patients with asthma well controlled by inhaled corticosteroids. In patients with mild persistent asthma monotherapy with an LTRA is indicated in alternative to a low-dose inhaled corticosteroid, an inhaled cromone, or an oral slow-release theophylline. Previous clinical studies in patients with mild to moderate asthma had demonstrated that monotherapy with LTRAs is able to improve airway function, asthma symptoms, use of as-needed medications, exacerbation rate, and quality of life, without evidence of tolerance with prolonged use. Recently, in a subgroup analysis of patients with mild persistent asthma, a 6-week treatment with oral montelukast or inhaled beclomethasone gave similar improvements in "rescue-free" days, days with well controlled asthma, FEV1, blood eosinophils, beta-agonist use, and nocturnal awakes due to asthma.

Lipoxygenase inhibitors: A comparative QSAR study review and evaluation of new QSARs

“…12a In particular, cysteinyl-LTs were demonstrated to be the chemical constituents of the slow reacting substance of anaphylaxis, already known since 1940 as a mixture of unidentified chemical mediators released in response to various stimuli, including anaphylactic reactions, and characterized by slow, but potent, long-acting contracting activity on smooth muscle cells. 15 Lipoxins (LX) and aspirin-triggered LX (ATL) evoke bioactions in a range of physiologic and pathophysiologic processes and serve as endogenous lipid/chemical mediators that stop neutrophilic infiltration and initiate resolution. LX carry their carbon-15 (C-15) hydroxyl group mainly in the 15S-configuration, which is inserted by LO-based mechanisms.…”

“…As we have already mentioned in our previous publication 31 Summers and co-workers 23,26 have synthesized, evaluated biologically a series of hydroxamic acids (Figs. [13][14][15][16] and studied them in terms of QSAR. Using their IC 50 values, on 5-LO taken from rat baseophilic leukemia cells RLB-1, we re-evaluated Equations (4)-(4d).…”

Optimisation, validation and application of a capillary electrophoretic method for the determination of zafirlukast in pharmaceutical formulations

“…Various aliquots of standard solutions were taken, the M added and then diluted to 1 mL with running buffer to give a final analyte concentration (2,5,10,20,30,40, 50, 60, 70 and 80 g mL −1 ). Standard solutions of ZAF were prepared daily by appropriate dilution of the stock solution with selected running buffer.…”

“…Leukotriene receptor antagonists, such as montelukast and zafirlukast, have been demonstrated in a number of studies to possess bronchodilating and anti-inflammatory properties, that make these drugs ideal candidates for the treatment of asthma [1,2].…”

Electrochemical characteristics of zafirlukast and its determination in pharmaceutical formulations by voltammetric methods

“…[4]. The drug is indicated for the prophylaxis and treatment of mild-to-moderate persistent and chronic asthma [5,6]. ZAF effectively improved symptoms and benefited lung function in asthmatic patients [3,7,8].…”