Over recent years it has become widely accepted that
asthma is a chronic persistent inflammatory condition regulated by a variety of inflammatory cells and mediators such as
leukotrienes. It has been shown that there are increased levels of cysteinyl
leukotrienes in
biological fluids from patient with chronic
asthma and in acute
bronchospasm experimentally induced by
allergen or other stimuli. The evidence suggests that blocking the formation or action of cysteinyl
leukotrienes may be benefit in the treatment of chronic inflammatory diseases. In this article the
leukotriene pathway, the
biological role of these
lipid mediators and their antagonists are widely characterised. There are three groups of
leukotriene inhibitors: 5-lipooxygenase
inhibitors, FLAP (activating
protein) inhibitors and Cys-Lt1 receptor antagonists. On Polish market two representative drugs are currently:
montelukast and
zafirlukast, both
leukotriene receptor antagonists. They bind competitively and selectively to Cys-Lt1 receptors blocking the pro-inflammatory effects of the cysteinyl
leukotrienes. They offer protection against cold, dry air or exercise-induced bronchoconstriction significantly greater than placebo. These agents produce a modest improvement in lung function, symptom control and reduce the need for short acting inhaled beta2-agonist
therapy. Some guidelines suggest that they may be considered as an alternative treatment to low dose inhaled
corticosteroid therapy and cromones
therapy of mild persistent
asthma. It seems likely that
aspirin-sensitive asthmatic patients may be benefited by LTD4-antagonists. These drugs have the great advantage of efficacy by
oral administration and they do not appear any class-specific side effects. Also some basic information about zileuton--5-lipooxygenase inhibitor are given. Due to its induction of hepatic
enzyme activity
zileuton is not available in Poland, but it is important agent in evaluation of the
leukotriene inhibitors in some models of
inflammation. The introduction of
leukotriene antagonists is undoubtedly an important breakthrough in
asthma therapy.