Leukotriene Receptor Antagonist Zafirlukast Research Articles

Ferric Chloride Catalyzed 1,3‐Rearrangement of (Phenoxymethyl)heteroarenes to (Heteroarylmethyl)phenols

A highly useful and robust method to (heteroarylmethyl)phenols, derivatives of arylheteroarylmethanes, was developed based on iron(III)‐catalyzed 1,3‐rearrangement of (phenoxymethyl)heteroarenes. It features cheap catalyst, mild reaction conditions, short reaction time and broad substrate scope. The mechanism of reaction was supported by a crossover experiment. Its application was demonstrated by the synthesis of a key intermediate in the synthesis of an oral leukotriene receptor antagonist zafirlukast.

Successful management of refractory cough with the leukotriene receptor antagonist zafirlukast in a dog with chronic bronchitis: a case report

A 7-year-old spayed female Pomeranian dog was evaluated for a 6-month history of intractable coughing and dyspnoea. The cough was unresponsive to antibiotics and a bronchodilator medication prescribed by the previous animal hospital. No abnormalities were identified on the blood work, echocardiography and radiography. However, computed tomography revealed mild bronchiectasia. Based on the history, physical examination and non-specific diagnostic imaging findings, the dog was diagnosed with chronic bronchitis. The cough failed to resolve, despite an attempt to manage it with prednisolone, theophylline, codeine and N-acetylcysteine. With the owner’s consent, we stopped all previous medications and finally tried the leukotriene receptor antagonist zafirlukast. The cough progressively improved and had mostly resolved four weeks after starting the administration of zafirlukast. The dog remained in complete remission without recurrence for seven months. This case report is the first to describe the successful long-term management of chronic cough with zafirlukast in a dog.

Capsular Contracture after Breast Augmentation: An Update for Clinical Practice.

Capsular contracture is the most common complication following implant based breast surgery and is one of the most common reasons for reoperation. Therefore, it is important to try and understand why this happens, and what can be done to reduce its incidence. A literature search using the MEDLINE database was conducted including search terms 'capsular contracture breast augmentation', 'capsular contracture pathogenesis', 'capsular contracture incidence', and 'capsular contracture management', which yielded 82 results which met inclusion criteria. Capsular contracture is caused by an excessive fibrotic reaction to a foreign body (the implant) and has an overall incidence of 10.6%. Risk factors that were identified included the use of smooth (vs. textured) implants, a subglandular (vs. submuscular) placement, use of a silicone (vs. saline) filled implant and previous radiotherapy to the breast. The standard management of capsular contracture is surgical via a capsulectomy or capsulotomy. Medical treatment using the off-label leukotriene receptor antagonist Zafirlukast has been reported to reduce severity and help prevent capsular contracture from forming, as has the use of acellular dermal matrices, botox and neopocket formation. However, nearly all therapeutic approaches are associated with a significant rate of recurrence. Capsular contracture is a multifactorial fibrotic process the precise cause of which is still unknown. The incidence of contracture developing is lower with the use of textured implants, submuscular placement and the use of polyurethane coated implants. Symptomatic capsular contracture is usually managed surgically, however recent research has focussed on preventing capsular contracture from occurring, or treating it with autologous fat transfer.

Novel Therapies in Asthma

Asthma is one of the most common conditions seen in clinical practice and carries both a significant disease burden in terms of patient morbidity and a high economic burden in both direct and indirect costs. Despite this, it remains a comparatively poorly understood disease, with only modest advances in treatment over the past decade. Corticosteroids remain the cornerstone of therapy. Both patient compliance with medications and physician adherence to evidence-based guidelines are often poor, and a high percentage of patients continue to have inadequately controlled disease even with optimal therapy. Following a contextual overview of the current treatment guidelines, this review focuses on novel asthma therapies, beginning with the introduction of the leukotriene receptor antagonist zafirlukast in the 1990s, continuing through advanced endoscopic therapy and into cytokine-directed biologic agents currently in development. Along with clinically relevant biochemistry and pharmacology, the evidence supporting the place of these therapies in current guidelines will be highlighted along with data comparing these agents with more conventional treatment. A brief discussion of other drugs, such as those developed for unrelated conditions and subsequently examined as potential asthma therapies, is included.

Chapter 16: Asthma in pregnancy

The course of asthma during pregnancy may be affected by maternal physiological changes and triggers of asthma such as viral infections, exposure to allergens, and nonadherence with therapy. If asthma is uncontrolled, there are recognized harmful effects not only to the mother but also to the fetus. However, with effective asthma control, most women have outcomes, at or near that of the general population. Many medications are considered appropriate for use in pregnancy including inhaled corticosteroids (ICSs) such as budesonide, beclomethasone dipropionate, and fluticasone and the leukotriene receptor antagonists montelukast and zafirlukast. When ICSs or ICS/long-acting beta(2)-adrenergic agonist combinations are not effective during exacerbations of asthma, short courses of oral corticosteroids should be administered earlier rather than later. Spirometry and flow volume loop tracings are useful measures of pulmonary function for gravidas. Results may be compared with nonpregnant reference values. Vocal cord dysfunction may be suspected when the inspiratory loop is truncated. The gravida does not reject the fetus because of lack of vascular continuity, a trophoblast layer causing separation, and suppressive mechanisms at the placental interface. The secretion of IL-10 increases in pregnancy and is lower in women with recurrent spontaneous abortions. Only immunoglobulin G (IgG) subclasses are transported across the placenta, especially IgG1, IgG3, and IgG4. Fetal B cells can produce endogenous IgE by 20 weeks of gestation.

Efficacy of Montelukast as Added Therapy in Patients with Chronic Idiopathic Urticaria

Chronic idiopathic urticaria is a common skin disorder characterized by recurrent appearance of wheals and/or angioedema for more than 6 weeks without an identifiable cause. Consensus guidelines suggest use of leukotriene receptor antagonists (montelukast or zafirlukast) in patients whose urticaria is resistant to antihistamines. Our objectives were (1) document the efficacy of montelukast in our patients, and (2) evaluate whether any clinical features or available laboratory investigations were associated with a response to montelukast. Patients who received montelukast between the years 2008-2011 (4-year period) were retrospectively identified from clinic letters. Clinical features and laboratory investigations were collected and analyzed. The primary end point was adequate control of disease without the need for systemic steroid therapy. 25 patients (10 males and 15 females; median age, 33 years; age range, 13-66 years) with an average duration of urticaria at 3.8 years received montelukast 10mg daily. 12 patients (48%) were better on montelukast with combined anti-H1 and anti-H2 therapy, with no statistical significance between median age and duration of urticaria between males and females. In 11 patients, montelukast had no effect and in 2 patients the urticaria worsened after montelukast was started. 15 patients had peripheral blood basopenia of which 5 patients responded to montelukast. Two patients had positive antinuclear antibody, 3 thyroid peroxidase antibodies and 4 with positive basophil histamine release. All 20 patients who had complement C3 and C4 levels done were within normal limits. Four of 6 patients (67%) with positive specific IgE responded to montelukast and combined anti-H1/H2 therapy. Almost half of our patients with chronic urticaria responded to montelukast and combined anti-H1 and anti-H2 therapy. We were unable to identify any clinical features or laboratory markers that were associated with a response to montelukast. Further studies are required to understand the failure of response of leukotriene inhibition in urticaria.

The effect of the leukotriene receptor antagonist zafirlukast on neurokinin A-induced bronchoconstriction in patients with asthma—A comparison with leukotriene D 4 induced broncoconstriction

The bronchoconstriction caused by inhaled neurokinin A (NKA) in patients with asthma is indirect. The mediators involved in NKA-induced bronchoconstriction are unknown. Studies with various H 1 receptor antagonists were negative, making an important contribution of histamine unlikely. To study the role of cysteinyl leukotrienes in neurokinin A-induced bronchoconstriction, we performed a randomised, double-blind, cross-over, placebo controlled trial in 12 patients with mild to moderate asthma. Zafirlukast and matching placebo were given orally, 40 mg the evening before and 40 mg the morning of assessment. In one period NKA was administered, in the other period leukotriene D 4 (LTD 4). Increasing concentrations of NKA and LTD 4 were inhaled from a 30 L bag, after nebulization via a Mallinckrodt nebuliser. The difference between log 10PC 20LTD 4 after treatment with placebo or zafirlukast was highly significant ( p<0.0001). A trend was observed towards a difference between log 10PC 20 neurokinin A after treatment with placebo or zafirlukast ( p=0.0741). The dose ratio for the neurokinin A provocation was 4.4 and for the LTD4 provocation 67.7. In conclusion, zafirlukast had a large inhibitory effect on LTD 4-induced bronchoconstriction, but offered only limited protective effect against neurokinin A-induced bronchoconstriction. We suggest that leukotrienes play a limited role in the bronchoconstrictor effect of neurokinin A in patients with asthma.

Responsabilité des antileucotriènes dans la survenue d'un syndrome de Churg et Strauss

Churg-Strauss syndrome is a systemic necrotizing vasculitis involving small and medium-sized vessels. Classic features include asthma and hypereosinophilia. Antineutrophil cytoplasm antibodies (ANCA) are detected in about 40% of patients. Churg-Strauss syndrome has been reported in patients receiving leukotriene modifiers for asthma, in particular, leukotriene receptor antagonists (LTRA) (montelukast, zafirlukast or pranlukast). Clinical manifestations cases do not differ in these cases from those in Churg-Strauss syndrome without antileukotriene exposure. It is increasingly less likely that LTRA is the direct cause of this syndrome in those patients, although this hypothesis has not been completely ruled out. In many patients, LTRA treatment is prescribed because of worsening asthma, which is an early sign of Churg-Strauss syndrome. LTRA for asthma patients should be prescribed with great care, especially in cases of atypical or rapidly aggravated asthma. The onset of Churg-Strauss syndrome in patients treated with LTRA usually requires that they stop this treatment. Prescription of LTRA In patients with Churg-Strauss syndrome should be discussed with specialists.

Montelukast and zafirlukast do not affect the pharmacokinetics of the CYP2C8 substrate pioglitazone

Pioglitazone, a thiazolidinedione antidiabetic drug, is metabolised mainly by the cytochrome P450 (CYP) 2C8 enzyme. The leukotriene receptor antagonists montelukast and zafirlukast have potently inhibited CYP2C8 activity and the metabolism of pioglitazone in vitro. Our objective was to determine whether montelukast and zafirlukast increase the plasma concentrations of pioglitazone in humans. In a randomised, double-blind crossover study with three phases and a washout period of 3 weeks, 12 healthy volunteers took either 10 mg montelukast once daily and placebo once daily, or 20 mg zafirlukast twice daily, or placebo twice daily, for 6 days. On day 3, they received a single oral dose of 15 mg pioglitazone. The plasma concentrations of pioglitazone and its metabolites M-IV, M-III, M-V and M-XI were measured for 96 h. The total area under the plasma concentration-time curve of pioglitazone during the montelukast and zafirlukast phases was 101% (range 71-143%) and 103% (range 78-146%), respectively, of that during the placebo phase. Also, the peak plasma concentration and elimination half-life of pioglitazone remained unaffected by montelukast and zafirlukast. There were no statistically significant differences in the pharmacokinetics of any of the metabolites of pioglitazone between the phases. Montelukast and zafirlukast do not increase the plasma concentrations of pioglitazone, indicating that their inhibitory effect on CYP2C8 is negligible in vivo, despite their strong inhibitory effect on CYP2C8 in vitro. The results highlight the importance of in vivo interaction studies and of the incorporation of relevant pharmacokinetic properties of drugs, including plasma protein binding data, to in vitro-in vivo interaction predictions.

Managing Asthma in Expectant Mothers

Pregnancy does not appear to have a consistent effect on the frequency or severity of asthma. The most common cause of worsening asthma in pregnancy is likely to be noncompliance with medication. Emphasizing to the patient in advance that fetal well-being is dependent on maternal well-being may help prevent this.In general, well controlled asthma is not associated with a higher risk of adverse pregnancy outcomes. Essential to successful asthma management is patient education that helps to ensure effective medication use, avoidance of triggers, and prompt treatment. This education should include measurement of peak expiratory flow rate and a written asthma action plan. Most of the medications that are used to control asthma in the general population can be safely used in pregnant women. Inhaled beta-adrenoceptor agonists (beta-agonists), cromolyn sodium (sodium cromoglycate), and inhaled and systemic corticosteroids all appear to be very well tolerated by the fetus. Budesonide and beclomethasone should be considered as the preferred inhaled corticosteroids for the treatment of asthma in pregnancy. Use of the leukotriene receptor antagonists zafirlukast and montelukast in pregnancy is probably safe but should be limited to special circumstances, where they are viewed essential for asthma control. Zileuton should not be used in pregnancy.Acute asthma exacerbations in pregnant women should be treated in a similar manner to that in non-pregnant patients. Maternal blood glucose levels should be monitored periodically in pregnant women receiving systemic corticosteroids because of the deleterious effects of hyperglycemia upon embryos and fetuses. During pregnancy, maternal arterial oxygen saturations should be kept above 95% if possible for fetal well-being. Ambulatory oxygenation should be checked prior to discharge to ensure that women do not desaturate with their daily activities.Acute exacerbations of asthma during labor and delivery are rare. Dinoprost, ergometrine, and other ergot derivatives can cause severe bronchospasm, especially when used in combination with general anesthesia, and should be avoided in asthmatic patients. Pregnant women who have been treated with corticosteroids in the past year may require stress-dose corticosteroids during labor and delivery. Most asthma medications, including oral prednisone, are considered compatible with breast-feeding.

The effect of leukotriene receptor antagonist zafirlukast on exercise-induced asthma in children

目的 探讨扎鲁司特对儿童运动性哮喘的治疗作用。方法 选取40例运动性哮喘患儿，随机分为两组，治疗组予扎鲁司特口服。对两组分别进行运动激发试验．并监测FEV1变化。结果 运动激发后，两组患儿FEV1均有明显下降，但对照组降低幅度较治疗组显著，且运动激发后FEV1恢复时间较长。结论 扎鲁司特对儿童运动性哮喘有较好的治疗作用。

Zafirlukast for severe recurrent vulvovaginal candidiasis: an open label pilot study

Background: Recurrent vulvovaginal candidiasis (VVC) has been linked to allergic disease, particularly allergic rhinitis. Objective: A pilot study to assess the possible use of the leukotriene receptor antagonist zafirlukast as...

Effects of zafirlukast on bronchial asthma and allergic rhinitis

Asthma and allergic rhinitis are common conditions, occurring with increasing prevalence and frequently coexist. In both conditions histamine and cysteinil leukotrienes are important pathogenic inflammatory mediators. We evaluated the effects of the leukotriene receptor antagonist zafirlukast, 20 mg administered twice daily for 2 weeks, in patients with allergic rhinitis and bronchial asthma during the grass pollen season. Patients underwent skin prick testing, spirometry, rhinomanometry, mucus transport test with saccharine, nasal epithelial brushing to study ciliary beat and, finally, nasal lavage. Thirty-five subjects completed the study. At the end of the study period, zafirlukast significantly reduced asthma and rhinitis symptoms ( P≤0.05); FEV 1 values were unchanged ( P=0.10), whereas nasal resistances showed a decrease following treatment ( P=0.01). Ciliary beat frequency (CBF) also improved ( P=0.00), although mucociliary transport showed no improvement ( P=0.87). The number of eosinophils in nasal lavage fluid decreased ( P=0.00) while that of neutrophils was unchanged ( P=0.09). These positive effects suggest that zafirlukast may be usefully employed in the treatment of both bronchial asthma, as previously demonstrated, and allergic rhinitis.

A pilot study of zafirlukast as an anti-inflammatory agent in the treatment of adults with cystic fibrosis

Background: Persistent endobronchial inflammation is in part responsible for the attrition of lung function seen in cystic fibrosis. Leukotrienes act as pro-inflammatory mediators. The aim of this study was to assess the efficacy of the leukotriene receptor antagonist zafirlukast as a potential anti-inflammatory agent in the treatment of adult patients with cystic fibrosis. Methods: Clinically stable patients were enrolled in the study if they had no history or clinical evidence of asthma, bronchial hyper-reactivity, or aspergillosis. They were randomised to receive zafirlukast 20 mg twice daily with all routine treatment for four months or routine treatment alone in an open cross-over design. Primary endpoints were changes in respiratory function tests and a modified NIH clinical score. Results: Thirty patients were enrolled and 25 completed. There was a significant improvement in the modified NIH clinical score but no significant increase in respiratory function with zafirlukast. Conclusions: Patients receiving a leukotriene receptor antagonist in addition to routine treatments showed significant improvement in a clinical score which is a composite of clinical wellbeing, chest radiograph appearance, and physical examination. Respiratory function showed a non-significant trend towards improvement with treatment. Zafirlukast may benefit patients with CF. An adequately powered study is justified on the basis of these results.

Effects of Zafirlukast Upon Clinical, Physiologic, and Inflammatory Responses to Natural Cat Allergen Exposure

Purpose of the Study. Leukotriene receptor antagonists have been shown to attenuate physiologic changes in the upper and lower airways induced by inhaled allergen challenge. This study looks at the effects of the oral leukotriene receptor antagonist zafirlukast on natural exposure to cat in patients with cat allergy. This study examines clinical, physiologic and inflammatory responses of the upper and lower airways.Study Population. Eighteen asthmatic patients between the age of 12 and 65 participated. All patients had a positive prick skin test to cat allergen and a positive response to a screening cat room challenge. At the time of study entry, all subjects were free of upper and lower respiratory tract symptoms.Methods. This study used a randomized, double-blind, placebo-controlled cross-over design. Two weeks after the screening cat challenge, the patients were randomized to receive either zafirlukast 20 mg bid or placebo for 7 days before the first cat room challenge. All other allergic and asthmatic medications were held per standard protocol. Then, after a 14-day washout period, the patients were crossed-over to receive the alternate therapy for a week and then receive a second cat room challenge. Clinical symptoms, pulmonary function and sputum and nasal lavage fluid, cell and eosinophil cationic protein (ECP) measurements were performed before and after each natural cat challenge.Results. Fel d 1 concentrations were measured and were similar during both the placebo and the zafirlukast challenges. After cat challenge, zafirlukast significantly reduced scores for both wheezing (P = .0004) and chest tightness (P = .019) compared with placebo. Symptom scores for the upper airways (congestion, rhinorrhea, itching, sneezing) did not meet statistical significance between the 2 treatments. After 7 days of treatment, prechallenge FEV1 was significantly higher with zafirlukast vs. placebo (P = .001). After cat exposure, zafirlukast significantly attenuated the decrease in forced expiratory volume in 1 second (FEV1) compared with the placebo (-15.1% vs -25.1%; P = .019). The occurrence of late asthmatic responses during the study was low, with 1 placebo-treated patient and 3 zafirlukast-treated patients demonstrating changes in pulmonary function between 2 and 12 hours after cat challenge. Analysis of induced sputum demonstrated no statistically significant differences between zafirlukast and placebo in total cell counts, cell differential, or ECP before or after challenges. Analysis of nasal lavage fluid revealed significantly fewer total cells and absolute counts of lymphocytes, neutrophils, monocytes, and basophils for zafirlukast compared with placebo after challenge, but there were no statistically significant differences in absolute or percentage eosinophils or ECP.Conclusions. Zafirlukast 20 mg bid for 1 week demonstrated a significant protective effect on symptoms of asthma and alterations in pulmonary function induced by natural cat exposure. There were no effects noted on nasal symptoms, and no difference in the number of eosinophils or ECP in the upper or lower airway was seen with active treatment versus placebo.Reviewer’s Comments. A similar trial (J Allergy Clin Immunol. 2000;105:704–710) also demonstrated a significant improvement in FEV1 postchallenge at 15 and 30 minutes but not at 45 and 60 minutes. This study also showed improvement in both lower and upper respiratory symptoms and intranasal anatomy measured by acoustic rhinometry. Other studies have also shown that leukotriene receptor antagonists in Food and Drug Administration (FDA)-approved doses do not affect airway eosinophilia after a single allergen exposure. Only 1 study has been published to date looking at long-term use of montelukast in asthma showing attenuated sputum eosinophilia with chronic therapy.

Participation of chemical mediators other than histamine in nasal allergy signs: a study using mice lacking histamine H 1 receptors

The purpose of this study was to investigate the involvement of chemical mediators other than histamine in nasal allergic signs using histamine H 1 receptor-deficient mice. In passively sensitized mice, antigen instillation into the nasal cavity induced significant increases in sneezing and nasal rubbing in wild-type mice, but no such increases were observed in histamine H 1 receptor-deficient mice. In actively sensitized mice, both sneezing and nasal rubbing were also significantly increased in a dose-dependent manner in both wild-type and histamine H 1 receptor-deficient mice. Histamine H 1 receptor antagonists such as cetirizine and epinastine significantly inhibited antigen-induced nasal allergic signs in wild-type mice, although the effects were incomplete. In addition, the thromboxane A 2 receptor antagonist ramatroban also inhibited these responses in wild-type mice. However, the leukotriene receptor antagonist zafirlukast showed no effects in wild-type mice. These results suggested that in the acute allergic model (passive sensitization), only histamine H 1 receptors are related to nasal signs induced by antigen, whereas in the chronic allergic model (active sensitization), both histamine H 1 receptors and thromboxane A 2 receptors were involved in the responses.

Antitussive Effect of the Leukotriene Receptor Antagonist Zafirlukast in Subjects with Cough-Variant Asthma*

Cough-variant asthma (CVA) occurs in a subgroup of asthmatics whose sole or predominant respiratory symptom is cough. Although bronchodilators are often sufficient to treat CVA, refractory cough may require therapy with inhaled or systemic corticosteroids. In a randomized, double-blind, placebo-controlled, crossover study, we examined the effect of a 14-day course of the leukotriene receptor antagonist zafirlukast on subjective cough score and cough-reflex sensitivity to inhaled capsaicin in eight subjects with CVA refractory to inhaled beta agonists, and in five subjects refractory to inhaled corticosteroids. Seven of eight subjects experienced significant subjective and objective improvement in cough after treatment with zafirlukast. Mean (± SEM) cough score improved from 7.75 ± 0.56 to 3.25 ± 0.84 (p = 0.0006). Cough sensitivity to capsaicin was suppressed by zafirlukast in all subjects. Patients with CVA may represent a distinct subgroup of asthmatics whose afferent cough receptors within the respiratory epithelium are hypersensitive relative to those of patients with the typical form of asthma. Zafirlukast appears to be particularly effective in treating CVA by inhibiting the sensitivity of these receptors. Leukotriene receptor antagonists may offer an alternative to corticosteroids for the treatment of CVA refractory to inhaled bronchodilators.

Effects of zafirlukast upon clinical, physiologic, and inflammatory responses to natural cat allergen exposure

Leukotriene receptor antagonists have been shown to attenuate physiologic changes in the upper and lower airways induced by allergen challenge. However, it is unknown whether these drugs modulate airway inflammation after exposure to allergen in a natural setting. To determine the effects of the oral leukotriene receptor antagonist zafirlukast upon symptoms, changes in pulmonary function, and indices of inflammation in the upper and lower airways induced by natural exposure to cats. Zafirlukast, 20 mg twice daily, or placebo was administered to 18 cat-allergic asthmatic patients in this randomized, double-blind, crossover study. Cat room challenges were performed after a 1-week period of each treatment. Upper and lower airway symptoms were measured and spirometry performed before and at regular intervals during each challenge. Nasal lavage and sputum induction were performed 24 hours before and after each challenge. Zafirlukast significantly improved the prechallenge baseline FEV1 (P = 0.001) and attenuated the decrease in FEV1 induced by cat challenge (P = 0.019). Zafirlukast also significantly reduced lower airway symptoms associated with cat challenge (P = 0.005) but had no effects on nasal symptoms. Although zafirlukast did not significantly differ from placebo in its effects on sputum inflammatory cells or eosinophil cationic protein, it significantly reduced the absolute counts of total white cells, lymphocytes, neutrophils, and basophils in nasal lavage fluid. Zafirlukast, 20 mg twice daily for 1 week, demonstrated a significant protective effect on symptoms of asthma and alterations in pulmonary function induced by natural cat exposure, whereas nasal symptoms and markers of sputum inflammation were not affected by the medication.

Pathophysiology of the cysteinyl leukotrienes and effects of leukotriene receptor antagonists in asthma

Cysteinyl leukotrienes, synthesized de novo from cell membrane phospholipids, are proinflammatory mediators that play an important role in the pathophysiology of asthma. These mediators are among the most potent of bronchoconstrictors and cause vasodilation, increased microvascular permeability, exudation of macromolecules and edema. The cysteinyl leukotrienes also have potent chemoattractant properties for eosinophils, causing an influx of eosinophils into the airway mucosa, which further fuels the inflammatory process. In addition, the cysteinyl leukotrienes are potent secretagogues and reduce ciliary motility, which may hinder mucociliary clearance. Asthmatic patients demonstrate increased production of cysteinyl leukotrienes during naturally occurring asthma and acute asthma attacks as well as after allergen and exercise challenge. The leukotriene receptor antagonists montelukast, zafirlukast and pranlukast inhibit bronchoconstriction in asthmatic patients undergoing allergen, exercise, cold air or aspirin challenge. They attenuate the hallmarks of asthmatic inflammation, including eosinophilia in the airway mucosa and peripheral blood. Moreover, exhaled nitric oxide concentrations, another correlate of airway inflammation, are decreased during montelukast treatment in children. Cysteinyl leukotriene synthesis is not blocked by corticosteroid therapy. This important observation suggests that the leukotriene receptor antagonists represent a novel therapeutic approach, one that may provide benefits that are additive with corticosteroid therapy. This supposition is supported by clinical observations that treatment with leukotriene receptor antagonists significantly improve asthma control when added to inhaled corticosteroid therapy. Moreover, the bronchodilator properties of the leukotriene receptor antagonists are additive with those of beta agonists. These data provide strong support for the use of leukotriene receptor antagonists for treating asthma.

Severe Liver Injury in Patients Taking the Asthma Medication Zafirlukast

Summaries for Patients19 December 2000Severe Liver Injury in Patients Taking the Asthma Medication ZafirlukastSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-133-12-200012190-00006 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail What is the problem and what is known about it so far?Zafirlukast is a relatively new asthma medication. In initial studies, up to 5% of patients who took this drug had abnormal results on liver tests, but no symptomatic liver problems occurred.Why did the researchers do this particular study?To describe three patients who developed severe liver injury while taking zafirlukast.Who was studied?The report describes three middle-aged women who developed liver problems while taking 20 mg of zafirlukast twice a day.How was the study done?The authors examined the patients and reviewed their medical records. ... Author, Article, and Disclosure InformationAffiliations: The summary below is from the full report titled, “Severe Liver Injury after Treatment with the Leukotriene Receptor Antagonist Zafirlukast.” It is in the 19 December 2000 issue of Annals of Internal Medicine (volume 133, pages 964-968). The authors are JF Reinus, S Persky, JS Burkiewicz, D Quan, NM Bass, and TJ Davern.Summaries for Patients are a service provided by Annals to help patients better understand the complicated and often mystifying language of modern medicine.Summaries for Patients are presented for informational purposes only. These summaries are not a substitute for advice from your own medical provider. If you have questions about this material, or need medical advice about your own health or situation, please contact your physician. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoSevere Liver Injury after Treatment with the Leukotriene Receptor Antagonist Zafirlukast John F. Reinus , Seth Persky , Jill S. Burkiewicz , David Quan , Nathan M. Bass , and Timothy J. Davern Metrics 19 December 2000Volume 133, Issue 12Page: I-63KeywordsAbdominal painAsthmaBiopsyDrugsLiverLiver diseasesRashesResearch laboratoriesSteroidsVomiting ePublished: 19 December 2000 Issue Published: 19 December 2000 Copyright & PermissionsCopyright © 2000 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...