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. email@example.com
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
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.
Drugs 2000;59 Suppl 1:35-42; discussion 43-5
Tolerability of montelukast.
School of Health, Policy and Practice, University of East Anglia, Norwich,
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.
Drugs 2000;59 Suppl 1:29-34; discussion 43-5
Clinical evidence with montelukast in the management of chronic childhood
Department of Pediatrics and Child Health, University of Manitoba, Winnipeg,
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.
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.
Am J Respir Crit Care Med 2000 Feb;161(2 Pt 2):S137-41
Treatment of aspirin-intolerant asthma with antileukotrienes.
Division of Respiratory Medicine, Department of Medicine, Karolinska Hospital,
Karolinska Institutet, Stockholm, Sweden. firstname.lastname@example.org
Am J Respir Crit Care Med 2000 Feb;161(2 Pt 2):S73-6
Effects of antileukotrienes in the treatment of asthma.
London Chest Hospital, London, United Kingdom.
Lancet 1999 Jan 2;353(9146):57-62
Department of Clinical Pharmacology & Therapeutics, Ninewells Hospital and
Medical School, University of Dundee, UK. email@example.com
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.
CMAJ 1999 Jan 26;160(2):217-23 [Texto completo]
Antileukotriene agents in asthma: the dart that kills the elephant?
Research Centre, Centre hospitalier de I'Universite de Montreal Hospitals,
Universite de Montreal, Que. firstname.lastname@example.org
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.
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.
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.
Department of Clinical Pharmacology and Therapeutics, Ninewells Hospital and
Medical School, University of Dundee, Dundee DD1 9SY. email@example.com
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
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.
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.
Drugs 1998 Aug;56(2):251-6; discussion 257
Markham A, Faulds D
Adis International Limited, Auckland, New Zealand. firstname.lastname@example.org
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.
Randomized controlled trial
Am J Respir Crit Care Med 1998 Jun;157(6 Pt 2):S238-45; discussion S245-8
Summary of clinical trials with zafirlukast.
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.
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
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
Am J Respir Crit Care Med 1998 Jun;157(6 Pt 2):S214-8; discussion S218-9, S247-8
Pharmacology of leukotriene receptor antagonists.
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.
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
Am J Med 1998 Mar;104(3):287-300
New approaches to anti-inflammatory therapy for asthma.
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.
Hosp Pract (Off Ed) 1998 Feb 15;33(2):25-6, 31-3, 36-8
New directions in asthma drug therapy.
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.
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. email@example.com
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.
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.
Chest 1997 Feb;111(2 Suppl):35S-45S
Pharmacology of leukotriene receptor antagonists. More than inhibitors of
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.