[The role of leukotrienes in inflammation and leukotriene inhibitors].
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.
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D000085:Acetates / Q000494:pharmacology / Q000627:therapeutic use*; D001094:Arachidonate 5-Lipoxygenase / Q000187:drug effects; D001249:Asthma / Q000378:metabolism*; D003521:Cyclopropanes; D006801:Humans; D006918:Hydroxyurea / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D007211:Indoles; D020024:Leukotriene Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D015289:Leukotrienes / Q000096:biosynthesis*; D048448:Phenylcarbamates; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use*; D013440:Sulfides; D013449:Sulfonamides; D014105:Tosyl Compounds / Q000494:pharmacology / Q000627:therapeutic use*
D000085:Acetates; D003521:Cyclopropanes; D007211:Indoles; D020024:Leukotriene Antagonists; D015289:Leukotrienes; D048448:Phenylcarbamates; D011804:Quinolines; D013440:Sulfides; D013449:Sulfonamides; D014105:Tosyl Compounds; D001094:Arachidonate 5-Lipoxygenase; C093875:montelukast; C063449:zileuton; D006918:Hydroxyurea; C062735:zafirlukast
Rola leukotrienów w zapaleniu i leki przeciwleukotrienowe.