LA CONSULTA SEMANAL

 

JULIO 2000

 

 

CONSULTA

Antileucotrienos en el tratamiento del asma bronquial

 

Drugs 2000 Apr;59(4):891-928 
Montelukast: a review of its therapeutic potential in persistent asthma. 
Jarvis B, Markham A 
Adis International Limited, Mairangi Bay, Auckland, New Zealand. demail@adis.co.nz 
Montelukast is a cysteinyl leukotriene receptor antagonist used to treat persistent asthma in patients aged > or = 6 years. The drug has a rapid onset of action. Improvements in lung function and reductions in as-needed beta2-agonist usage are apparent within 1 day of initiating montelukast treatment in adults and adolescents (aged > or = 15 years treated with 10 mg/day) or children (aged 6 to 14 years treated with 5 mg/day) with persistent asthma as shown in clinical trials. In two 12-week, multicentre, randomised, double-blind studies in adults and adolescents aged > or = 15 years with persistent asthma [forced expiratory volume in 1 second (FEV1) = 50 to 85% predicted] there was significantly (p < 0.05) greater improvement in FEV1, symptom scores, peak expiratory flow (PEF), as-needed beta2-agonist use, peripheral eosinophil counts and health-related quality of life (QOL) in patients treated with montelukast 10 mg/day than in recipients of placebo. Improvements were significantly greater in patients treated with inhaled beclomethasone 400 microg/day than in recipients of montelukast 10 mg/day in 1 of these studies. Nonetheless, 42% of montelukast recipients experienced > or = 11% improvement in FEV1, the median improvement in this parameter in beclomethasone-treated patients. In an 8-week multicentre, randomised, double-blind, study in children aged 6 to 14 years with persistent asthma (FEV1 50 to 85% predicted), montelukast 5 mg/day produced significantly greater improvements in FEV1, clinic PEF, as-needed beta2-agonist use, peripheral eosinophil counts, asthma exacerbations and QOL scores than placebo. The combination of montelukast 10 mg/day plus inhaled beclomethasone 200 microg twice daily provided significantly better asthma control than inhaled beclomethasone 200 microg twice daily in adults with poorly controlled asthma (mean FEV1 = 72% predicted) despite 4 weeks treatment with inhaled beclomethasone. Patients receiving the combination experienced significant improvements in FEV1 and morning PEF, significant reductions in daytime symptom scores, as-needed beta2 agonist usage and night-time awakenings with asthma, and had significantly lower peripheral blood eosinophil counts after 16 weeks in this multicentre, randomised, double-blind, placebo-controlled study. Among adults (FEV1 > or = 70%) treated with montelukast 10 mg/day for 12 weeks, inhaled corticosteroid dosages were titrated downward by 47% (vs 30% in placebo recipients), 40% of patients were tapered off of inhaled corticosteroids (vs 29%), and significantly fewer patients (16 vs 30%) experienced failed corticosteroid rescues in a multicentre, randomised, double-blind study. During clinical studies, the frequency of adverse events in montelukast-treated adults, adolescents and children was similar to that in placebo recipients. In 
conclusion, montelukast is well tolerated and effective in adults and children aged > or = 6 years with persistent asthma including those with exercise-induced bronchoconstriction and/or aspirin sensitivity. Furthermore, montelukast has glucocorticoid sparing properties. Hence, montelukast, as monotherapy in 
patients with mild persistent asthma, or as an adjunct to inhaled corticosteroids is useful across a broad spectrum of patients with persistent asthma. 

Can Fam Physician 2000 Apr;46(4):872-9 
Leukotriene-receptor antagonists. Role in asthma management. 
D'Urzo AD, Chapman KR 
Department of Family and Community Medicine University of Toronto. 
OBJECTIVE: To examine the role of leukotriene-receptor antagonists (LTRAs) in management of asthma. QUALITY OF EVIDENCE: Most data were derived from randomized, double-blind, controlled trials. MAIN MESSAGE: Leukotrienes appear to have an important role in the pathophysiology of asthma, including airway inflammation. Leukotriene-receptor antagonists are effective in improving asthma 
control end points, such as allergen, ASA, and exercise challenge, in clinical models of asthma. In chronic asthma, LTRA administration reduces asthma symptoms and rescue beta 2-agonist use, changes that are paralleled by improvements in lung function. Both zafirlukast and montelukast decrease circulating levels of eosinophils and could have other useful anti-inflammatory properties. Administration of LTRAs allows doses of inhaled corticosteroids to be reduced. Currently available LTRAs are free of serious side effects and are available as oral formulations. CONCLUSIONS: Leukotriene-receptor antagonists belong to a new class of asthma medication. While inhaled corticosteroids remain first-line therapy for managing chronic asthma, LTRAs should be considered for patients with ASA-sensitive asthma; as adjunct therapy when low to moderate doses of inhaled steroid alone provide incomplete control; or as adjunct therapy to allow reduction in doses of inhaled corticosteroids. 
Publication Types: 
Review 
Review, tutorial 

Drugs 2000;59 Suppl 1:35-42; discussion 43-5 
Tolerability of montelukast. 
Price D 

School of Health, Policy and Practice, University of East Anglia, Norwich, England. 
The tolerability of a medication, especially in children with asthma, is linked to a number of key factors. These include clinical effectiveness, adverse effects, frequency of drug regimen, ease and route of administration. and taste. Montelukast is unusual in that, in most countries, a licence for children aged > or =6 years was granted at the same time as the adult licence. This is related to a variety of evidence. which includes pharmacological and adult studies suggesting the specificity and safety of the drug at many times the licensed dose, and a tolerability profile similar to that with placebo or inhaled corticosteroids in both adult and paediatric studies. The most common adverse effects in paediatric studies were headache, asthma and upper respiratory tract infection at rates not statistically significantly different from those with 
placebo. Up to July 1999, more than 2 million patients worldwide have received montelukast, of whom nearly 220,000 have received the paediatric formulation. In the UK, one prescribing database suggests that, of children who commenced montelukast therapy, less than 25% discontinued the drug. This implies that montelukast is effective and well tolerated in most children. Adverse effect monitoring by regulatory bodies has revealed little that would not be expected on the basis of the results of clinical trials. Montelukast has been associated with Churg-Strauss syndrome in a very small number of adults. In most. the syndrome was associated with corticosteroid withdrawal, which may have unmasked the condition. Churg-Strauss syndrome has not been reported in children. Its clinical effectiveness, lack of major adverse effects, oral route of administration, palatability and the once-daily regimen combine to make montelukast a generally well tolerated medication in children. 
Publication Types: 
Review 
Review, tutorial 

Drugs 2000;59 Suppl 1:29-34; discussion 43-5 
Clinical evidence with montelukast in the management of chronic childhood asthma. 
Becker A 
Department of Pediatrics and Child Health, University of Manitoba, Winnipeg, Canada. 
OBJECTIVE: The aim of this article is to review data on the efficacy and safety of montelukast in the treatment of children with asthma. METHODOLOGY: Available published literature, including published abstracts, is reviewed. RESULTS: In patients aged 6 to 14 years with asthma (n = 27), montelukast 5mg demonstrated a significant decrease in exercise-induced bronchoconstriction 20 to 24 hours postdose after 2 days of treatment. For children with chronic asthma, only one study of the regular use of a leukotriene receptor antagonist has been published. The efficacy and safety of montelukast in children aged 6 to 14 years with asthma (n = 336) were studied during an 8-week, double-blind, placebocontrolled trial. There was a significantly greater improvement in forced expiratory volume in 1 second (FEV1) from baseline for the montelukast group (8.23%) compared with the placebo group (3.58%). There was a significant decrease in the use of a 3-agonist for symptom relief, as well as in the percentage of days and percentage of patients with asthma exacerbations. An asthma specific quality-of-life (QOL) questionnaire revealed a significant overall improvement in QOL and a significant improvement in the QOL domains for symptoms, activity and emotions in montelukast recipients. There was no significant difference between montelukast and placebo recipients in the frequency of adverse events, with the exception of allergic rhinitis, which was more prevalent in the placebo group. An open label follow-up of patients from the above study was undertaken. The effect of montelukast on FEV1 was consistent for up to 1.4 years, with the increase in FEV1 being not significantly different from that in a small control group treated with inhaled beclomethasone dipropionate. QOL remained significantly improved during the open treatment period. CONCLUSIONS: Montelukast appears effective and safe for the treatment of children with asthma. 
Publication Types: 
Review 
Review, tutorial 

Am J Respir Crit Care Med 2000 Feb;161(2 Pt 2):S147-53 
Antileukotriene therapy. Future directions. 
Holgate ST, Sampson AP 
University Medicine, Southampton General Hospital, Southampton, United Kingdom. 
Publication Types: 
Review 
Review, tutorial 

Am J Respir Crit Care Med 2000 Feb;161(2 Pt 2):S137-41 
Treatment of aspirin-intolerant asthma with antileukotrienes. 
Dahlen B 
Division of Respiratory Medicine, Department of Medicine, Karolinska Hospital, 
Karolinska Institutet, Stockholm, Sweden. barbro.dahlen@medks.ki.se 
Publication Types: 
Review 
Review, tutorial 

Am J Respir Crit Care Med 2000 Feb;161(2 Pt 2):S73-6 
Effects of antileukotrienes in the treatment of asthma. 
Barnes NC 
London Chest Hospital, London, United Kingdom. 
Publication Types: 
Review 
Review, tutorial 

Lancet 1999 Jan 2;353(9146):57-62 
Leukotriene-receptor antagonists. 
Lipworth BJ 
Department of Clinical Pharmacology & Therapeutics, Ninewells Hospital and Medical School, University of Dundee, UK. b.j.lipworth@dundee.uk 
Leukotriene-receptor antagonists are the first novel class of antiasthma drugs to become available over the past three decades. They have an unique profile in that they are a hybrid of an anti-inflammatory and bronchodilator drug, and they can be taken as a tablet once or twice daily. The published data with leukotriene-receptor antagonists such as montelukast or zafirlukast show good 
antiasthmatic activity over a wide spectrum of asthma severity either as monotherapy or with inhaled steroids. Another potential spin-off of leukotriene-receptor antagonists is that they also seem to be effective in treating allergic rhinitis, which commonly coexists in patients with asthma. Here I overview the clinical pharmacology of leukotriene antagonists and appraise the published data from clinical trials, and look at the appropriate position of these agents in asthma management guidelines. 

Publication Types: 
Review 
Review, tutorial 

CMAJ 1999 Jan 26;160(2):217-23 [Texto completo] 
Antileukotriene agents in asthma: the dart that kills the elephant? 
Renzi PM 
Research Centre, Centre hospitalier de I'Universite de Montreal Hospitals, Universite de Montreal, Que. renzip@alize.ere.umontreal.ca 
THE PERSISTENCE OF AIRWAY INFLAMMATION is believed to cause the mechanical changes and symptoms of asthma. After decades of research, a new class of medication has emerged that focuses on leukotrienes, mediators of inflammation. These substances are potent inducers of bronchoconstriction, increased vascular permeability and mucus production, and they potentiate the influx of inflammatory cells in the airways of patients with asthma. In this article the author reviews the development, mechanism of action, and clinical and toxic effects of the leukotriene synthesis inhibitors and receptor antagonists that are entering the North American market. These agents can decrease airway response to antigen, airway hyperresponsiveness and exercise-induced asthma. They are also effective inhibitors of ASA-induced symptoms. Although few published studies are available, the antileukotrienes seem almost as effective in the management of chronic asthma as low-dose inhaled corticosteroids, and their use permits a decrease in the frequency of use or dose of corticosteroids. Further evaluation and clinical experience will determine the position of targeted inhibition of the leukotriene pathway in the treatment of asthma. 
Publication Types: 
Review 
Review, tutorial 
Comments: 
Comment in: CMAJ 1999 Jan 26;160(2):209-10 

CMAJ 1999 Jan 26;160(2):209-10 [Texto completo] 
Antileukotrienes, asthma pathogenesis and the pharmaceutical industry. 
O'Byrne PM 
Publication Types: 
Comment 
Editorial 
Review 
Review, tutorial 
Comments: 
Comment on: CMAJ 1999 Jan 26;160(2):217-23 

BMJ 1999 Feb 6;318(7180):380-4 [Texto completo] 
Fortnightly review: modern drug treatment of chronic asthma. 
Lipworth BJ 
Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and 
Medical School, University of Dundee, Dundee DD1 9SY. b.j.lipworth@dundee.ac.uk 
Publication Types: 
Review 
Review literature 

N Engl J Med 1999 Jan 21;340(3):197-206 
Published errata appear in N Engl J Med 1999 Feb 25;340(8):663 and 1999 Nov 18;341(21):1632 
Treatment of asthma with drugs modifying the leukotriene pathway. 
Drazen JM, Israel E, O'Byrne PM 
Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, 
Boston, MA 02115, USA. 
Publication Types: 
Review 
Review, tutorial 

Postgrad Med 1998 Sep;104(3):127-36, 139 
Anti-inflammatory drugs for controlling asthma. 
Volcheck GW, O'Connell EJ 
Division of Allergy and Outpatient Infectious Disease and Internal Medicine, Mayo Clinic, Rochester, MN 55905, USA. 
Anti-inflammatory agents are the first-line treatment for controlling mild persistent, moderate persistent, and severe persistent asthma. The choice of drug and dosage must be individualized to the patient. In general, the glucocorticoids are widely accepted as the most potent and preferred asthma treatment in most adults and some children. Cromolyn, because of its safety and availability in a nebulized form, is the first-line treatment in most young children. The leukotriene inhibitors appear to be effective in mild asthma, but further clinical studies are needed to determine their role more precisely. As the mechanisms of inflammation in asthma are further defined, new pharmaceutical products will be developed to aid in arresting this process. 
Publication Types: 
Review 
Review, tutorial 

Drugs 1998 Aug;56(2):251-6; discussion 257 
Montelukast. 
Markham A, Faulds D 
Adis International Limited, Auckland, New Zealand. demail@adis.co.nz 
Montelukast is a selective antagonist of the leukotriene D4 (LTD4) receptor. In patients with asthma, montelukast 5 to 250 mg/day attenuated LTD4-induced bronchoconstriction and, at a dosage of 10 mg, significantly reduced early and late airway response to allergen (dust mite extract) relative to placebo. In 
studies evaluating the effects of various dosages of montelukast on exercise-induced bronchoconstriction the optimal dose of the drug was found to be 10 mg. Montelukast 10 mg/day controlled asthma significantly more effectively than placebo in a 3-month randomised double-blind study. In a 9-month open extension of this trial, during which patients were randomised to treatment with montelukast 10 mg/day or beclomethasone (approximately 400 micrograms/day), daytime symptom score and beta-agonist use decreased to a similar extent in each group. In a further study, treatment with montelukast 10 mg/day permitted clinically significant tapering of corticosteroid dosage in patients with stable asthma. Montelukast (5 mg/day) has also demonstrated efficacy in childhood asthma. The tolerability profile of montelukast was similar to that of placebo in placebo-controlled clinical trials in adults and children; the most common adverse event was headache. 
Publication Types: 
Clinical trial 
Randomized controlled trial 
Review 
Review, tutorial 

Am J Respir Crit Care Med 1998 Jun;157(6 Pt 2):S238-45; discussion S245-8 
Summary of clinical trials with zafirlukast. 
Calhoun WJ 
Division of Pulmonary, Allergy, and Critical Care Medicine, University of Pittsburgh, Pennsylvania 15261, USA. 
Zafirlukast is an orally active and selective cysteinyl leukotriene (cysLT) receptor antagonist. In humans, zafirlukast antagonized the effects of exogenously administered LTD4 and cysLTs released endogenously in response to physical and chemical stimuli. Zafirlukast antagonized LTD4-induced bronchoconstriction, with effects still evident 12 h after drug administration. In clinical models of asthma, zafirlukast inhibited bronchospasm after allergen or exercise challenge in patients with asthma. In multicenter trials in patients with chronic, stable asthma, zafirlukast reduced asthma symptoms, decreased as-needed beta-agonist use, and improved pulmonary function without increasing the number of adverse events. Zafirlukast also exhibited evidence of an anti-inflammatory effect in the lung in preliminary studies involving segmental antigen challenge. The results from these clinical trials demonstrate that zafirlukast is effective and safe for the prophylactic treatment of asthma. 
Publication Types: 
Review 
Review, tutorial 

Am J Respir Crit Care Med 1998 Jun;157(6 Pt 2):S233-7; discussion S247-8 
Clinical pharmacology of leukotriene receptor antagonists and 5-lipoxygenase inhibitors. 
Drazen J 
Brigham and Women's Hospital, Boston, Massachusetts 02115, USA. 
Blinded, randomized, and placebo-controlled clinical trials have established that cysteinyl leukotriene (cysLT) receptor antagonists and 5-lipoxygenase (5-LO) inhibitors are safe and effective asthma treatments. Trials of 13- to 26-wks' duration demonstrate that both the cysLT1 receptor antagonist, zafirlukast, and the 5-LO inhibitor, zileuton, improve pulmonary function and decrease daytime and nocturnal symptoms. Concomitant rescue beta-agonist inhaler use and the need for corticosteroid rescue are also reduced. Preliminary studies suggest that antileukotriene agents may also reduce indices of airway 
inflammation, including inflammatory cell counts and airway hyperresponsiveness. Both cysLT1 antagonists and 5-LO inhibitors offer a new approach to asthma management. 
Publication Types: 
Review 
Review, tutorial 

Am J Respir Crit Care Med 1998 Jun;157(6 Pt 2):S214-8; discussion S218-9, S247-8 
Pharmacology of leukotriene receptor antagonists. 
Aharony D 
Zeneca Pharmaceutical, Wilmington, Delaware 19897, USA. David.Aharony@phwilm.zeneca.com 
Preclinical pharmacological studies have demonstrated that cysLT, receptor antagonists, such as zafirlukast, montelukast, and pobilukast, are potent and selective antagonists of cysteinyl leukotriene (cysLT) activity. In vitro, these agents compete with [3H]LTD4 for binding to cysLT, receptors present on guinea pig and human lung cell membranes. Both zafirlukast and montelukast have affinities that are approximately two times greater than that of the natural ligand, LTD4. These agents block LTD4- and LTE4-induced contractions of isolated guinea pig trachea, but do not antagonize LTC4-induced contractions, which are putatively mediated by a different LT receptor, cysLT2. The cysLT2 receptor, however, has not yet been found in human airway smooth muscle. In animal models, these drugs inhibit LTD4-, LTE4-, and antigen-induced bronchoconstriction, reduce inflammatory markers in models of pulmonary inflammation, and inhibit antigen-induced late-phase bronchoconstriction. This preclinical profile suggests that cysLT, receptor antagonists may be useful in treating inflammatory conditions of the respiratory system, such as asthma and allergic rhinitis. 
Publication Types: 
Review 
Review, tutorial 

Am J Respir Crit Care Med 1998 May;157(5 Pt 1):1363-71 
The role of leukotriene modifiers in the treatment of asthma. 
Horwitz RJ, McGill KA, Busse WW 
Department of Medicine, University of Wisconsin Hospital and Clinics, Madison 53792, USA. 
Publication Types: 
Review 
Review, academic 

Am J Med 1998 Mar;104(3):287-300 
New approaches to anti-inflammatory therapy for asthma. 
Wenzel SE 
National Jewish Medical and Research Center, Denver, Colorado 80206, USA. 
Currently, corticosteroids are the therapy of choice for the inflammatory component of asthma. This class of drug provides powerful anti-inflammatory effects in most patients; however, these effects are not specific and in some cases may result in serious side effects. Also, many patients have difficulty adhering to therapy with inhaled forms of these drugs, which are administered by metered-dose inhalers up to several times per day. There are several other therapies that provide potential anti-inflammatory effects, but they are of low efficacy, with little definitive anti-inflammatory effect. While efforts are currently under way to improve corticosteroid therapy, other directions include the development of targeted anti-inflammatory agents. For example, the leukotrienes, a family of inflammatory mediators that have been shown to enhance bronchoconstriction and airway mucus secretion, have been the focus of numerous investigations. Specific leukotriene receptor antagonists and synthesis inhibitors have been developed and are currently showing promise in clinical trials; one leukotriene receptor antagonist (zafirlukast) and one 5-lipoxygenase inhibitor (zileuton) were recently approved by the United States Food and Drug  Administration for the treatment of asthma. 
Publication Types: 
Review 
Review, tutorial 

Hosp Pract (Off Ed) 1998 Feb 15;33(2):25-6, 31-3, 36-8 
New directions in asthma drug therapy. 
Drazen JM 
Harvard Medical School, Boston, USA. 
A new generation of biologically informative treatments has altered our understanding of the disease--transforming what used to be viewed as a single entity into a family of airway disorders driven by different proinflammatory mediators. Although inhaled corticosteroids have been the treatment of choice for most patients, research is increasingly aimed at developing inhibitors targeted to specific effector systems. 
Publication Types: 
Review 
Review, tutorial 

Drugs 1998 Jan;55(1):121-44 
Zafirlukast. A review of its pharmacology and therapeutic potential in the management of asthma. 
Adkins JC, Brogden RN 
Adis International Limited, Auckland, New Zealand. demail@adis.co.nz 
Zafirlukast is a competitive and selective leukotriene receptor antagonist indicated for the prophylaxis and treatment of chronic asthma. The rationale for the development of leukotriene antagonists was based on in vitro and in vivo data demonstrating the extensive role of the cysteinyl leukotrienes C4 (LTC4), D4 (LTD4) and E4 (LTE4) in the pathogenesis of asthma. Initial data have demonstrated an improvement in pulmonary function and symptom control and a reduction in the use of short-acting inhaled beta 2-adrenoceptor agonist therapy in patients with mild to moderate asthma treated with oral zafirlukast at the recommended dosage of 20 mg twice daily. Available data also suggest that zafirlukast may significantly reduce the incidence of asthma exacerbations. Data on the comparative efficacy of zafirlukast and existing antiasthma medications are limited. Results from 2 double-blind randomised studies comparing zafirlukast 20 mg twice daily with sodium cromoglycate aerosol or dry powder inhalation reported similar efficacy for both drugs. In a comparison with inhaled beclomethasone dipropionate (0.2 to 0.25 mg twice daily), improvements in morning peak expiratory flow rate, forced expiratory volume in 1 second and daytime symptom score were significantly less with zafirlukast 20 mg twice daily for 6 weeks. However, available data suggest that patient compliance and patient preference may be greater with oral zafirlukast 20 mg twice daily than with twice-daily inhaled corticosteroid therapy. Confounding results from 2 studies preclude any clear conclusions regarding the potential steroid-sparing effect of zafirlukast at the recommended dosage of 20 mg twice daily. Furthermore, Churg-Strauss syndrome has been reported in 6 patients who were being withdrawn from oral corticosteroid therapy while receiving treatment with oral zafirlukast. It is, therefore, recommended that zafirlukast-treated patients who require a reduction in their oral corticosteroid therapy are closely monitored. Zafirlukast is generally well tolerated. Reports of elevated liver enzymes in patients receiving high dosages of zafirlukast (80 mg twice daily) preclude the use of dosages exceeding 40 mg twice daily. Careful monitoring is necessary in zafirlukast-treated patients receiving concomitant therapy with drugs such as warfarin, terfenadine and erythromycin because of the potential for drug interactions. Thus, zafirlukast is a potentially useful addition to current antiasthma therapies in patients with mild to moderate asthma. Because zafirlukast is administered orally, it may be particularly beneficial in patients poorly compliant with asthma therapy as a result of poor inhaler technique. Further investigation of the efficacy of zafirlukast is expected to more clearly define its position in the management of asthma. 
Publication Types: 
Review 
Review, tutorial 

Ann Intern Med 1997 Sep 15;127(6):472-80 [Texto completo] 
Antileukotrienes in the treatment of asthma. 
O'Byrne PM, Israel E, Drazen JM 
Department of Medicine, McMaster University, Hamilton, Ontario, Canada. 
PURPOSE: To review the activity in clinical models, the efficacy, and the safety of antileukotrienes as a new class of antiasthma treatment. DATA SOURCES: English-language trials identified from the archival literature, including the MEDLINE database, through 1996; bibliographic references; and textbooks. STUDY SELECTION: Reports from placebo-controlled, double-blind, randomized trials were selected. DATA EXTRACTION: Study designs and results were extracted from the clinical trial reports. Statistical evaluation of combined results was not attempted. DATA SYNTHESIS: The various classes of antileukotrienes have shown activity in clinical models of asthma, including exercise-induced, cold air hyperventilation-induced, allergen-induced, and aspirin-induced bronchoconstriction. In addition, the antileukotrienes partially reverse spontaneous bronchoconstriction in asthmatic persons, an effect additive to that of inhaled beta 2-agonists. Clinical trials of the antileukotrienes have shown clinical benefit, as measured by reductions in asthma symptom scores, improvements in air flow obstruction, and reductions in the rescue use of inhaled beta 2-agonists. Some, but not all, of the antileukotrienes have been shown to cause liver microsomal activation with increases in hepatic aminotransferase levels. CONCLUSIONS: Antileukotrienes are an important new therapy for asthma. Inhibition of leukotriene synthesis or action has a beneficial effect in the treatment of both induced and spontaneous asthma. These results show that leukotrienes are important mediators of the asthmatic response. In addition, encouraging results have been obtained from clinical trials of antileukotrienes; however, these results do not yet provide guidelines for the optimal clinical use of antileukotrienes in asthma treatment. Such recommendations await the results of further studies. 
Publication Types: 
Review 
Review, academic 

Chest 1997 Feb;111(2 Suppl):35S-45S 
Pharmacology of leukotriene receptor antagonists. More than inhibitors of bronchoconstriction. 
Hay DW 
Department of Pulmonary Pharmacology, SmithKline Beecham Pharmaceuticals, King of Prussia, Pa 19406, USA. 
The cysteinyl leukotrienes (LTs) are chemical mediators that are thought to contribute to the pathophysiologic condition of asthma and other inflammatory diseases. The biological effects of the cysteinyl LTs in the lung are pleiotropic, including both bronchoconstrictor and a growing list of nonbronchoconstrictor activities that extend to inflammatory cell recruitment, vascular leakage, mucus production, neuronal dysfunction, and airways remodeling. This spectrum of effects of cysteinyl LTs is consistent with an expanded view of asthma that extends beyond simply bronchoconstriction and inflammation. Consequently, the clinical efficacy of cysteinyl LT receptor antagonists (LTRAs) in asthma may be related to antagonism of more than cysteinyl LT-induced bronchoconstriction. The relationship of antagonism of the multiple effects of cysteinyl LTs by cysteinyl LTRAs to their utility in the therapy of asthma is addressed, and the preclinical and clinical pharmacology of cysteinyl LTRAs is reviewed. 
Publication Types: 
Review 
Review, academic

 

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