scholarly journals Effect of pranlukast, an oral leukotriene receptor antagonist, on leukotriene D4 (LTD4) challenge in normal volunteers

Thorax ◽  
1997 ◽  
Vol 52 (6) ◽  
pp. 519-522 ◽  
Author(s):  
T. C. O'Shaughnessy ◽  
P. Georgiou ◽  
K. Howland ◽  
M. Dennis ◽  
C. H. Compton ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Leukotriene Receptor Antagonist ◽  
Leukotriene D4 ◽  
Normal Volunteers ◽  
Leukotriene Receptor

Zafirlukast: The First Leukotreene-Receptor Antagonist Approved for the Treatment of Asthma

1997 ◽  
Vol 31 (9) ◽  
pp. 1012-1021 ◽  
Author(s):  
Judy Shepard Kelloway
Keyword(s):  
Clinical Trials ◽  
Receptor Antagonist ◽  
Patient Adherence ◽  
Statistical Significance ◽  
Oral Dosage ◽  
Atopic Asthma ◽  
Leukotriene Receptor Antagonist ◽  
Leukotriene D4 ◽  
Safety And Efficacy ◽  
Leukotriene Receptor

Objective To review the pharmacology, pharmacokinetics, clinical efficacy, and adverse effects of zafirlukast. Therapeutic issues regarding the use of a leukotriene-receptor antagonist as prophylactic antiinflammatory therapy for asthma are also discussed. Data Sources A MEDLINE search was conducted to identify pertinent literature, including preclinical trials, clinical trials, and reviews. Pharmacokinetic and dosing information were abstracted from the product labeling. Study Selection All available published articles describing double-blind, placebo-controlled trials of both oral and aerosol zafirlukast in patients with asthma or rhinitis were reviewed. These included single-dose studies with zafirlukast against exercise, allergen, leukotriene D4 (LTD4), and platelet-activating factor (PAF) challenges, and 6- and 13-week trials in patients with asthma. Studies describing clinical trials with long-term use or comparisons with other asthma medications as reported in abstracts are also included. Data Extraction Information on the safety and efficacy of zafirlukast from single- and multiple-dose studies was evaluated on the basis of statistical significance relative to placebo treatment. Data Synthesis Zafirlukast, a potent and selective antagonist of the cysteinyl leukotriene receptor, blocks leukotriene-mediated pathologic events in both experimental animal and clinical disease models. Zafirlukast antagonizes LTD4-, PAF-, and exercise-induced bronchoconstriction, and blocks both early- and late-phase responses following allergen provocation in patients with atopic asthma. Greater efficacy is noted following oral administration than with aerosol dosing, presumably because of the enhanced delivery of drug when ingested rather than inhaled. Conclusions Zafirlukast is the first orally active leukotriene-receptor antagonist approved by the Food and Drug Administration for the prophylactic and chronic treatment of asthma. Since the leukotrienes play an important role in the underlying inflammatory processes of asthma, zafirlukast represents a new antiinflammatory option available in an oral dosage form. It is clear that this agent has therapeutic activity in patients with asthma, but its effectiveness relative to other antiasthma medications still needs confirmation. Data from clinical studies support the use of zafirlukast as first-line therapy in patients with mild-to-moderate asthma. Further research is needed to establish its role as an add-on agent for patients with severe asthma, aspirin-sensitive asthma, and both allergies and asthma. In addition to having a favorable safety and efficacy profile, zafirlukast has the advantage of being an oral agent with twice-daily dosing; these attributes offer the potential for greater patient adherence to pharmacotherapy and, thereby, improved control of asthma symptoms.

Regional differences in mechanism of action of oxygen on hamster arterioles

1993 ◽  
Vol 265 (2) ◽  
pp. H599-H603 ◽  
Author(s):  
W. F. Jackson
Keyword(s):  
Receptor Antagonist ◽  
Mechanism Of Action ◽  
Regional Differences ◽  
Cheek Pouch ◽  
Cremaster Muscle ◽  
Leukotriene Receptor Antagonist ◽  
Lipoxygenase Inhibitor ◽  
Hamster Cheek Pouch ◽  
Leukotriene D4 ◽  
Leukotriene Receptor

Leukotrienes have been implicated in the arteriolar constriction induced by elevated PO2 in the hamster cheek pouch. The role of leukotrienes in arteriolar O2 reactivity in other tissues has not been studied. To test the hypothesis that leukotrienes mediate O2 reactivity in all tissues, the effects of a leukotriene receptor antagonist, SKF-102922 (10 microM), a 5-lipoxygenase inhibitor, SC-43251 (30 microM), and a 5-lipoxygenase-activating protein antagonist, MK-886 (10 microM), on arteriolar O2 reactivity in hamster cheek pouch were compared with their effects on cremasteric arteriolar O2 reactivity. All three agents significantly decreased O2-induced arteriolar constriction in the cheek pouch, as reported previously. However, none of the antagonists inhibited O2-induced constriction of cremasteric arterioles. The efficacy of the leukotriene receptor antagonist, SKF-102922, was verified in the cremaster muscle: 10 microM SKF-102922 completely abolished constriction induced by topical application of leukotriene D4. These data support the hypothesis that leukotrienes mediate O2 reactivity in the cheek pouch. However, leukotrienes do not appear to mediate O2 reactivity in the cremaster muscle. These data suggest that there are significant regional differences in the mechanism of action of O2 on arterioles.

Montelukast, a Leukotriene-Receptor Antagonist, for the Treatment of Mild Asthma and Exercise-Induced Bronchoconstriction

1999 ◽  
Vol 43 (3) ◽  
pp. 185-186
Author(s):  
JONATHAN A. LEFF ◽  
WILLIAM W. BUSSE ◽  
DAVID PEARLMAN ◽  
EDWIN A. BRONSKY ◽  
JAMES KEMP ◽  
...  
Keyword(s):  
Receptor Antagonist ◽  
Mild Asthma ◽  
Leukotriene Receptor Antagonist ◽  
Leukotriene Receptor ◽  
Exercise Induced
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