Antileukotrienes in Upper Airway Inflammatory Diseases

Abstract

Leukotrienes (LTs) are a family of inflammatory mediators including LTA4, LTB4, LTC4, LTD4, and LTE4. By competitive binding to the cysteinyl LT1 (CysLT1) receptor, LT receptor antagonist drugs, such as montelukast, zafirlukast, and pranlukast, block the effects of CysLTs, improving the symptoms of some chronic respiratory diseases, particularly bronchial asthma and allergic rhinitis. We reviewed the efficacy of antileukotrienes in upper airway inflammatory diseases. An update on the use of antileukotrienes in upper airway diseases in children and adults is presented with a detailed literature survey. Data on LTs, antileukotrienes, and antileukotrienes in chronic rhinosinusitis and nasal polyps, asthma, and allergic rhinitis are presented. Antileukotriene drugs are classified into two groups: CysLT receptor antagonists (zafirlukast, pranlukast, and montelukast) and LT synthesis inhibitors (5-lipoxygenase inhibitors such as zileuton, ZD2138, Bay X 1005, and MK-0591). CysLTs have important proinflammatory and profibrotic effects that contribute to the extensive hyperplastic rhinosinusitis and nasal polyposis (NP) that characterise these disorders. Patients who receive zafirlukast or zileuton tend to show objective improvements in, or at least stabilisation of, NP. Montelukast treatment may lead to clinical subjective improvement in NP. Montelukast treatment after sinus surgery can lead to a significant reduction in eosinophilic cationic protein levels in serum, with a beneficial effect on nasal and pulmonary symptoms and less impact in NP. Combined inhaled corticosteroids and long-acting β-agonists treatments are most effective for preventing exacerbations among paediatric asthma patients. Treatments with medium- or high-dose inhaled corticosteroids, combined inhaled corticosteroids and LT receptor antagonists, and low-dose inhaled corticosteroids have been reported to be equally effective. Antileukotrienes have also been reported to be effective for allergic rhinitis.

Biliverdin Reductase inhibitors did not improve severe unconjugated hyperbilirubinemia in vivo

“…Montelukast is a cysteinyl leukotriene receptor type 1 antagonist which is clinically used as add-on therapy to inhaled corticosteroids for asthma patients 35 . By blocking the leukotriene pathway it improves symptoms of asthma and reduces inflammation 36 .…”

“…By blocking the leukotriene pathway it improves symptoms of asthma and reduces inflammation 36 . Montelukast is generally well tolerated in both pediatric and adult patients, with few adverse reactions reported 35 . This lipophilic compound with high protein binding affinity 37 could possibly displace UCB from albumin by competitive binding, although literature to support this assumption lacks.…”

Pain and Inflammation. Part 2. The Analgesic Potential of Anti-Inflammatory Drugs

“…Так, блокаторы рецеп-торов цистеин-содержащих ЛТЕ (ЛТЕС 4 , ЛТЕD 4 , ЛТЕЕ 4 ) -cysLT 1 , такие как зилеутон, зафирлукаст и мон-телукаст, применяются для лечения бронхиальной астмы [82,83]. Икатибант (блокатор В2-рецепторов брадикини-на) зарегистрирован как средство для лечения наследст-венного ангионевротического отека [84].…”

Eicosanoids and Inflammation

“…Речь идет о блокато-рах рецепторов цистеин-содержащих ЛТЕ (ЛТЕС4, ЛТЕD4, ЛТЕЕ4) -cysLT1, таких как зилеутон, зафирлукаст и монте-лукаст, которые применяются для лечения бронхиальной астмы. Однако эти лекарства пока не опробованы в качест-ве собственно противовоспалительного средства при других заболеваниях и патологических состояниях [107,108].…”