Leukotriene Antagonists

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Chapter: Essential pharmacology : Drugs for Cough and Bronchial Asthma

Since it was realized that cystenyl leukotrienes (LTC4/D4) are important mediators of bronchial asthma, efforts were made to develop their antagonists and synthesis inhibitors. Two cysLT1 receptor antagonists montelukast and zafirlukast are available.


LEUKOTRIENE ANTAGONISTS

 

Since it was realized that cystenyl leukotrienes (LTC4/D4) are important mediators of bronchial asthma, efforts were made to develop their antagonists and synthesis inhibitors. Two cysLT1 receptor antagonists montelukast and zafirlukast are available.

 

Montelukast and Zafirlukast

 

Both have similar actions and clinical utility. They competitively antagonize cysLT1 receptor mediated bronchoconstriction, increased vascular permeability and recruitment of eosinophils. Bronchodilatation, reduced sputum eosinophil count, suppression of bronchial inflammation and hyperreactivity are noted in asthma patients. Parameters of lung function show variable but definite improvement. Some studies have found that certain patients are ‘responders’ while others are ‘non-responders’ to anti-LT therapy.

 

Montelukast and zafirlukast are indicated for prophylactic therapy of mild to moderate asthma as alternatives to inhaled glucocorticoids. Though overall efficacy is lower than inhaled steroids, they may obviate need for the latter, and may be more acceptable in children. In severe asthma, they may permit reduction in steroid dose and need for rescue β2 agonist inhalations. However, they are not to be used for terminating asthma episodes. cysLT1 antagonists are effective in aspirin induced asthma.

 

Both montelukast and zafirlukast are very safe drugs; produce few side effects like headache and rashes. Eosinophilia and neuropathy are infrequent. Few cases of Churg-Strauss syndrome (vasculitis with eosinophilia) have been reported.

 

They are well absorbed orally, highly plasma protein bound and metabolized by CYP2C9 (montelukast also by CYP3A4). The plasma t½ of montelukast is 3–6 hours, while that of zafirlukast is 8–12 hours.

 

Montelukast: 10 mg OD; children 2–5 yr mg OD, 6–14 yr 5 mg OD;

 

EMLUKAST, MONTAIR, VENTAIR 4 mg, 5 mg, 10 mg tabs Zafirlukast: 20 mg BD; children 5–11 yr 10 mg BD; ZUVAIR 10 mg, 20 mg tabs.

 

Zileuton

 

It is a 5LOX inhibitor, blocks LTC4/D4 as well as LTB4 synthesis. It therefore has the potential to prevent all LT induced responses including those exerted by activation of cysLT1 receptor. However, clinical efficacy in asthma is similar to montelukast. The duration of action of zileuton is short and it has hepatotoxic potential. These limitations have restricted its use.

 

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