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. 2000 Dec;76(902):767–773. doi: 10.1136/pmj.76.902.767

Leukotriene receptor antagonist therapy

O Dempsey 1
PMCID: PMC1741850  PMID: 11085767

Abstract

Leukotriene receptor antagonists (LTRA) are a new class of drugs for asthma treatment, available in tablet form. Their unique mechanism of action results in a combination of both bronchodilator and anti-inflammatory effects. While their optimal place in asthma management is still under review, LTRA represent an important advance in asthma pharmacotherapy.


Keywords: leukotriene receptor antagonist; asthma; montelukast; zafirlukast

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Selected References

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  1. Altman L. C., Munk Z., Seltzer J., Noonan N., Shingo S., Zhang J., Reiss T. F. A placebo-controlled, dose-ranging study of montelukast, a cysteinyl leukotriene-receptor antagonist. Montelukast Asthma Study Group. J Allergy Clin Immunol. 1998 Jul;102(1):50–56. doi: 10.1016/s0091-6749(98)70054-5. [DOI] [PubMed] [Google Scholar]
  2. BROCKLEHURST W. E. The release of histamine and formation of a slow-reacting substance (SRS-A) during anaphylactic shock. J Physiol. 1960 Jun;151:416–435. doi: 10.1113/jphysiol.1960.sp006449. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Bronsky E. A., Kemp J. P., Zhang J., Guerreiro D., Reiss T. F. Dose-related protection of exercise bronchoconstriction by montelukast, a cysteinyl leukotriene-receptor antagonist, at the end of a once-daily dosing interval. Clin Pharmacol Ther. 1997 Nov;62(5):556–561. doi: 10.1016/S0009-9236(97)90051-5. [DOI] [PubMed] [Google Scholar]
  4. Busse W., Nelson H., Wolfe J., Kalberg C., Yancey S. W., Rickard K. A. Comparison of inhaled salmeterol and oral zafirlukast in patients with asthma. J Allergy Clin Immunol. 1999 Jun;103(6):1075–1080. doi: 10.1016/s0091-6749(99)70182-x. [DOI] [PubMed] [Google Scholar]
  5. Busse WW. Leukotrienes and inflammation . Am J Respir Crit Care Med. 1998 Jun;157(6 Pt 1):S210–S213. [PubMed] [Google Scholar]
  6. Carucci J. A., Washenik K., Weinstein A., Shupack J., Cohen D. E. The leukotriene antagonist zafirlukast as a therapeutic agent for atopic dermatitis. Arch Dermatol. 1998 Jul;134(7):785–786. doi: 10.1001/archderm.134.7.785. [DOI] [PubMed] [Google Scholar]
  7. Cowburn A. S., Sladek K., Soja J., Adamek L., Nizankowska E., Szczeklik A., Lam B. K., Penrose J. F., Austen F. K., Holgate S. T. Overexpression of leukotriene C4 synthase in bronchial biopsies from patients with aspirin-intolerant asthma. J Clin Invest. 1998 Feb 15;101(4):834–846. doi: 10.1172/JCI620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. D'Cruz D. P., Barnes N. C., Lockwood C. M. Difficult asthma or Churg-Strauss syndrome? BMJ. 1999 Feb 20;318(7182):475–476. doi: 10.1136/bmj.318.7182.475. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Dahlén S. E., Hedqvist P., Hammarström S., Samuelsson B. Leukotrienes are potent constrictors of human bronchi. Nature. 1980 Dec 4;288(5790):484–486. doi: 10.1038/288484a0. [DOI] [PubMed] [Google Scholar]
  10. Dempsey O. J., Wilson A. M., Sims E. J., Mistry C., Lipworth B. J. Additive bronchoprotective and bronchodilator effects with single doses of salmeterol and montelukast in asthmatic patients receiving inhaled corticosteroids. Chest. 2000 Apr;117(4):950–953. doi: 10.1378/chest.117.4.950. [DOI] [PubMed] [Google Scholar]
  11. Dessanges J. F., Préfaut C., Taytard A., Matran R., Naya I., Compagnon A., Dinh-Xuan A. T. The effect of zafirlukast on repetitive exercise-induced bronchoconstriction: the possible role of leukotrienes in exercise-induced refractoriness. J Allergy Clin Immunol. 1999 Dec;104(6):1155–1161. doi: 10.1016/s0091-6749(99)70007-2. [DOI] [PubMed] [Google Scholar]
  12. Donnelly A. L., Glass M., Minkwitz M. C., Casale T. B. The leukotriene D4-receptor antagonist, ICI 204,219, relieves symptoms of acute seasonal allergic rhinitis. Am J Respir Crit Care Med. 1995 Jun;151(6):1734–1739. doi: 10.1164/ajrccm.151.6.7767514. [DOI] [PubMed] [Google Scholar]
  13. Drazen J. M., Israel E., O'Byrne P. M. Treatment of asthma with drugs modifying the leukotriene pathway. N Engl J Med. 1999 Jan 21;340(3):197–206. doi: 10.1056/NEJM199901213400306. [DOI] [PubMed] [Google Scholar]
  14. Drazen J. M., Yandava C. N., Dubé L., Szczerback N., Hippensteel R., Pillari A., Israel E., Schork N., Silverman E. S., Katz D. A. Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment. Nat Genet. 1999 Jun;22(2):168–170. doi: 10.1038/9680. [DOI] [PubMed] [Google Scholar]
  15. Dworski R., Fitzgerald G. A., Oates J. A., Sheller J. R. Effect of oral prednisone on airway inflammatory mediators in atopic asthma. Am J Respir Crit Care Med. 1994 Apr;149(4 Pt 1):953–959. doi: 10.1164/ajrccm.149.4.8143061. [DOI] [PubMed] [Google Scholar]
  16. Edelman J. M., Turpin J. A., Bronsky E. A., Grossman J., Kemp J. P., Ghannam A. F., DeLucca P. T., Gormley G. J., Pearlman D. S. Oral montelukast compared with inhaled salmeterol to prevent exercise-induced bronchoconstriction. A randomized, double-blind trial. Exercise Study Group. Ann Intern Med. 2000 Jan 18;132(2):97–104. doi: 10.7326/0003-4819-132-2-200001180-00002. [DOI] [PubMed] [Google Scholar]
  17. Enrique E., García-Ortega P., Gaig P., San Miguel M. M. Failure of montelukast to prevent anaphylaxis to diclofenac. Allergy. 1999 May;54(5):529–530. doi: 10.1034/j.1398-9995.1999.00148.x. [DOI] [PubMed] [Google Scholar]
  18. Finnerty J. P., Wood-Baker R., Thomson H., Holgate S. T. Role of leukotrienes in exercise-induced asthma. Inhibitory effect of ICI 204219, a potent leukotriene D4 receptor antagonist. Am Rev Respir Dis. 1992 Apr;145(4 Pt 1):746–749. doi: 10.1164/ajrccm/145.4_Pt_1.746. [DOI] [PubMed] [Google Scholar]
  19. Fish J. E., Kemp J. P., Lockey R. F., Glass M., Hanby L. A., Bonuccelli C. M. Zafirlukast for symptomatic mild-to-moderate asthma: a 13-week multicenter study. The Zafirlukast Trialists Group. Clin Ther. 1997 Jul-Aug;19(4):675–690. doi: 10.1016/s0149-2918(97)80092-6. [DOI] [PubMed] [Google Scholar]
  20. Gibbs C. J., Coutts I. I., Lock R., Finnegan O. C., White R. J. Premenstrual exacerbation of asthma. Thorax. 1984 Nov;39(11):833–836. doi: 10.1136/thx.39.11.833. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Hansen-Flaschen J., Schotland H. New treatments for exercise-induced asthma. N Engl J Med. 1998 Jul 16;339(3):192–193. doi: 10.1056/NEJM199807163390309. [DOI] [PubMed] [Google Scholar]
  22. Howarth P. H. Leukotrienes in rhinitis. Am J Respir Crit Care Med. 2000 Feb;161(2 Pt 2):S133–S136. doi: 10.1164/ajrccm.161.supplement_1.ltta-26. [DOI] [PubMed] [Google Scholar]
  23. In K. H., Asano K., Beier D., Grobholz J., Finn P. W., Silverman E. K., Silverman E. S., Collins T., Fischer A. R., Keith T. P. Naturally occurring mutations in the human 5-lipoxygenase gene promoter that modify transcription factor binding and reporter gene transcription. J Clin Invest. 1997 Mar 1;99(5):1130–1137. doi: 10.1172/JCI119241. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Kemp J. P., Dockhorn R. J., Shapiro G. G., Nguyen H. H., Reiss T. F., Seidenberg B. C., Knorr B. Montelukast once daily inhibits exercise-induced bronchoconstriction in 6- to 14-year-old children with asthma. J Pediatr. 1998 Sep;133(3):424–428. doi: 10.1016/s0022-3476(98)70281-1. [DOI] [PubMed] [Google Scholar]
  25. Kemp J. P., Minkwitz M. C., Bonuccelli C. M., Warren M. S. Therapeutic effect of zafirlukast as monotherapy in steroid-naive patients with severe persistent asthma. Chest. 1999 Feb;115(2):336–342. doi: 10.1378/chest.115.2.336. [DOI] [PubMed] [Google Scholar]
  26. Knorr B., Matz J., Bernstein J. A., Nguyen H., Seidenberg B. C., Reiss T. F., Becker A. Montelukast for chronic asthma in 6- to 14-year-old children: a randomized, double-blind trial. Pediatric Montelukast Study Group. JAMA. 1998 Apr 15;279(15):1181–1186. doi: 10.1001/jama.279.15.1181. [DOI] [PubMed] [Google Scholar]
  27. Laviolette M., Malmstrom K., Lu S., Chervinsky P., Pujet J. C., Peszek I., Zhang J., Reiss T. F. Montelukast added to inhaled beclomethasone in treatment of asthma. Montelukast/Beclomethasone Additivity Group. Am J Respir Crit Care Med. 1999 Dec;160(6):1862–1868. doi: 10.1164/ajrccm.160.6.9803042. [DOI] [PubMed] [Google Scholar]
  28. Leff J. A., Busse W. W., Pearlman D., Bronsky E. A., Kemp J., Hendeles L., Dockhorn R., Kundu S., Zhang J., Seidenberg B. C. Montelukast, a leukotriene-receptor antagonist, for the treatment of mild asthma and exercise-induced bronchoconstriction. N Engl J Med. 1998 Jul 16;339(3):147–152. doi: 10.1056/NEJM199807163390302. [DOI] [PubMed] [Google Scholar]
  29. Lipworth B. J. Leukotriene-receptor antagonists. Lancet. 1999 Jan 2;353(9146):57–62. doi: 10.1016/S0140-6736(98)09019-9. [DOI] [PubMed] [Google Scholar]
  30. Lynch K. R., O'Neill G. P., Liu Q., Im D. S., Sawyer N., Metters K. M., Coulombe N., Abramovitz M., Figueroa D. J., Zeng Z. Characterization of the human cysteinyl leukotriene CysLT1 receptor. Nature. 1999 Jun 24;399(6738):789–793. doi: 10.1038/21658. [DOI] [PubMed] [Google Scholar]
  31. Löfdahl C. G., Reiss T. F., Leff J. A., Israel E., Noonan M. J., Finn A. F., Seidenberg B. C., Capizzi T., Kundu S., Godard P. Randomised, placebo controlled trial of effect of a leukotriene receptor antagonist, montelukast, on tapering inhaled corticosteroids in asthmatic patients. BMJ. 1999 Jul 10;319(7202):87–90. doi: 10.1136/bmj.319.7202.87. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Malmstrom K., Rodriguez-Gomez G., Guerra J., Villaran C., Piñeiro A., Wei L. X., Seidenberg B. C., Reiss T. F. Oral montelukast, inhaled beclomethasone, and placebo for chronic asthma. A randomized, controlled trial. Montelukast/Beclomethasone Study Group. Ann Intern Med. 1999 Mar 16;130(6):487–495. doi: 10.7326/0003-4819-130-6-199903160-00005. [DOI] [PubMed] [Google Scholar]
  33. Menendez R., Venzor J., Ortiz G. Failure of zafirlukast to prevent ibuprofen-induced anaphylaxis. Ann Allergy Asthma Immunol. 1998 Mar;80(3):225–226. doi: 10.1016/S1081-1206(10)62961-4. [DOI] [PubMed] [Google Scholar]
  34. Murphy R. C., Hammarström S., Samuelsson B. Leukotriene C: a slow-reacting substance from murine mastocytoma cells. Proc Natl Acad Sci U S A. 1979 Sep;76(9):4275–4279. doi: 10.1073/pnas.76.9.4275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Nakasato H., Ohrui T., Sekizawa K., Matsui T., Yamaya M., Tamura G., Sasaki H. Prevention of severe premenstrual asthma attacks by leukotriene receptor antagonist. J Allergy Clin Immunol. 1999 Sep;104(3 Pt 1):585–588. doi: 10.1016/s0091-6749(99)70327-1. [DOI] [PubMed] [Google Scholar]
  36. Nathan R. A., Bernstein J. A., Bielory L., Bonuccelli C. M., Calhoun W. J., Galant S. P., Hanby L. A., Kemp J. P., Kylstra J. W., Nayak A. S. Zafirlukast improves asthma symptoms and quality of life in patients with moderate reversible airflow obstruction. J Allergy Clin Immunol. 1998 Dec;102(6 Pt 1):935–942. doi: 10.1016/s0091-6749(98)70331-8. [DOI] [PubMed] [Google Scholar]
  37. Nathan R. A., Minkwitz M. C., Bonuccelli C. M. Two first-line therapies in the treatment of mild asthma: use of peak flow variability as a predictor of effectiveness. Ann Allergy Asthma Immunol. 1999 May;82(5):497–503. doi: 10.1016/S1081-1206(10)62728-7. [DOI] [PubMed] [Google Scholar]
  38. Nelson J. A., Strauss L., Skowronski M., Ciufo R., Novak R., McFadden E. R., Jr Effect of long-term salmeterol treatment on exercise-induced asthma. N Engl J Med. 1998 Jul 16;339(3):141–146. doi: 10.1056/NEJM199807163390301. [DOI] [PubMed] [Google Scholar]
  39. Neustrom M. R., Friesen C. Treatment of eosinophilic gastroenteritis with montelukast. J Allergy Clin Immunol. 1999 Aug;104(2 Pt 1):506–506. doi: 10.1016/s0091-6749(99)70404-5. [DOI] [PubMed] [Google Scholar]
  40. Noonan M. J., Chervinsky P., Brandon M., Zhang J., Kundu S., McBurney J., Reiss T. F. Montelukast, a potent leukotriene receptor antagonist, causes dose-related improvements in chronic asthma. Montelukast Asthma Study Group. Eur Respir J. 1998 Jun;11(6):1232–1239. doi: 10.1183/09031936.98.11061232. [DOI] [PubMed] [Google Scholar]
  41. Pearlman D. S., Ostrom N. K., Bronsky E. A., Bonuccelli C. M., Hanby L. A. The leukotriene D4-receptor antagonist zafirlukast attenuates exercise-induced bronchoconstriction in children. J Pediatr. 1999 Mar;134(3):273–279. doi: 10.1016/s0022-3476(99)70449-x. [DOI] [PubMed] [Google Scholar]
  42. Pullerits T., Praks L., Skoogh B. E., Ani R., Lötvall J. Randomized placebo-controlled study comparing a leukotriene receptor antagonist and a nasal glucocorticoid in seasonal allergic rhinitis. Am J Respir Crit Care Med. 1999 Jun;159(6):1814–1818. doi: 10.1164/ajrccm.159.6.9810016. [DOI] [PubMed] [Google Scholar]
  43. Reiss T. F., Chervinsky P., Dockhorn R. J., Shingo S., Seidenberg B., Edwards T. B. Montelukast, a once-daily leukotriene receptor antagonist, in the treatment of chronic asthma: a multicenter, randomized, double-blind trial. Montelukast Clinical Research Study Group. Arch Intern Med. 1998 Jun 8;158(11):1213–1220. doi: 10.1001/archinte.158.11.1213. [DOI] [PubMed] [Google Scholar]
  44. Reiss T. F., Hill J. B., Harman E., Zhang J., Tanaka W. K., Bronsky E., Guerreiro D., Hendeles L. Increased urinary excretion of LTE4 after exercise and attenuation of exercise-induced bronchospasm by montelukast, a cysteinyl leukotriene receptor antagonist. Thorax. 1997 Dec;52(12):1030–1035. doi: 10.1136/thx.52.12.1030. [DOI] [PMC free article] [PubMed] [Google Scholar]
  45. Sanak M., Simon H. U., Szczeklik A. Leukotriene C4 synthase promoter polymorphism and risk of aspirin-induced asthma. Lancet. 1997 Nov 29;350(9091):1599–1600. doi: 10.1016/s0140-6736(05)64015-9. [DOI] [PubMed] [Google Scholar]
  46. Sarau H. M., Ames R. S., Chambers J., Ellis C., Elshourbagy N., Foley J. J., Schmidt D. B., Muccitelli R. M., Jenkins O., Murdock P. R. Identification, molecular cloning, expression, and characterization of a cysteinyl leukotriene receptor. Mol Pharmacol. 1999 Sep;56(3):657–663. doi: 10.1124/mol.56.3.657. [DOI] [PubMed] [Google Scholar]
  47. Spector S. L., Smith L. J., Glass M. Effects of 6 weeks of therapy with oral doses of ICI 204,219, a leukotriene D4 receptor antagonist, in subjects with bronchial asthma. ACCOLATE Asthma Trialists Group. Am J Respir Crit Care Med. 1994 Sep;150(3):618–623. doi: 10.1164/ajrccm.150.3.8087328. [DOI] [PubMed] [Google Scholar]
  48. Stirling R. G., Chung K. F. Leukotriene antagonists and Churg-Strauss syndrome: the smoking gun. Thorax. 1999 Oct;54(10):865–866. doi: 10.1136/thx.54.10.865. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Suissa S., Dennis R., Ernst P., Sheehy O., Wood-Dauphinee S. Effectiveness of the leukotriene receptor antagonist zafirlukast for mild-to-moderate asthma. A randomized, double-blind, placebo-controlled trial. Ann Intern Med. 1997 Feb 1;126(3):177–183. doi: 10.7326/0003-4819-126-3-199702010-00001. [DOI] [PubMed] [Google Scholar]
  50. Szczeklik A. Mechanism of aspirin-induced asthma. Allergy. 1997 Jun;52(6):613–619. doi: 10.1111/j.1398-9995.1997.tb01039.x. [DOI] [PubMed] [Google Scholar]
  51. Tamaoki J., Kondo M., Sakai N., Nakata J., Takemura H., Nagai A., Takizawa T., Konno K. Leukotriene antagonist prevents exacerbation of asthma during reduction of high-dose inhaled corticosteroid. The Tokyo Joshi-Idai Asthma Research Group. Am J Respir Crit Care Med. 1997 Apr;155(4):1235–1240. doi: 10.1164/ajrccm.155.4.9105060. [DOI] [PubMed] [Google Scholar]
  52. Tashkin D. P., Nathan R. A., Howland W. C., Minkwitz M. C., Simonson S. G., Bonuccelli C. M. An evaluation of zafirlukast in the treatment of asthma with exploratory subset analyses. J Allergy Clin Immunol. 1999 Feb;103(2 Pt 1):246–254. doi: 10.1016/s0091-6749(99)70498-7. [DOI] [PubMed] [Google Scholar]
  53. Villaran C., O'Neill S. J., Helbling A., van Noord J. A., Lee T. H., Chuchalin A. G., Langley S. J., Gunawardena K. A., Suskovic S., Laurenzi M. Montelukast versus salmeterol in patients with asthma and exercise-induced bronchoconstriction. Montelukast/Salmeterol Exercise Study Group. J Allergy Clin Immunol. 1999 Sep;104(3 Pt 1):547–553. doi: 10.1016/s0091-6749(99)70322-2. [DOI] [PubMed] [Google Scholar]
  54. Wardlaw A. J., Hay H., Cromwell O., Collins J. V., Kay A. B. Leukotrienes, LTC4 and LTB4, in bronchoalveolar lavage in bronchial asthma and other respiratory diseases. J Allergy Clin Immunol. 1989 Jul;84(1):19–26. doi: 10.1016/0091-6749(89)90173-5. [DOI] [PubMed] [Google Scholar]

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