Leukotrienes are substances produced in white blood cells, also known as leukocytes, when fatty acid is broken down. Even in small amounts, they register a high effect as mediators in allergic reactions and inflammation.
What are leukotrienes?
The medical name leukotriene already refers to white blood cells. In the Greek language, “leukós” means “white.” Leukotrienes were first discovered in white blood cells. The chemical derivation goes back to arachidonic acid and other polyunsaturated C20 fatty acids. Leukotrienes are highly active biological substances. Biosynthesis is dependent on the enzyme 5′-lipoxygenase. Arachidonic acid reacts in two steps with 15′-lipoxygenase and 5′-lipoxygenase.
Function, action, and roles
Leukotrienes are derived from arachidonic acid. They are active tissue hormones. They act as mediator substances that respond to inflammatory and allergic reactions by attracting neutrophilic leukocytes. They increase vascular permeability and trigger asthma attacks by means of bronchoconstriction. Leukotrienes have three conjugated triene compounds (double compound). They belong to the substance group of eicosanoids. Leukotrienes and prostaglandins go back to arachidonic acid, which forms the initial substance. This acid is derived from phospholipids in cell membranes. Inflammatory cells such as mast cells, monocytes, endothelial cells, and neutrophilic, eosinophilic, and basophilic leukocytes are capable of producing leukotrienes. Synthesis of prostaglandins occurs via cyclooxigenase. Leukotrienes are formed via lipoxigenase. Inhibition of prostaglandins releases more arachidonic acid to form leukotrienes. ASA-induced asthma results from this process. Leukotrienes play an important role in inflammatory and allergic reactions in the human body. They are also called inflammatory mediators and are significant in the course of lung diseases. Leukotriene “D4” constricts the airway muscles and increases the production of mucus in the upper airway organs. The bronchi are also affected by this process. There are different leukotrienes with designations such as B, C, and D. The cysteinyl leukotrienes “LTC4-LTE4 have bronchoconstrictor and secretory effects. They are capable of causing anaphylactic or allergic reactions within the lungs. These incidents lead to constricted airways and consequent asthma attacks. A chemical stimulus (chemotaxis) causes leukocytes to adhere (adhere) to the blood vessel wall. Inflammation is promoted and tissue may be destroyed by superoxide radicals during this process. Leukotrienes interact with interferons and interleukins. At this stage of the disease process, leukotriene antagonists, for example montelukast, become active to eliminate the undesirable effects on the lungs, airways and bronchi. They block the receptors of the original messenger. These unwanted messenger substances occur in the form of irritants such as house dust, pollen or cold air, which particularly affects asthma patients. Leukotriene antagonists dilate the bronchial tubes, combat inflammation in the lungs and counteract constriction of the airway muscles. Symptoms such as coughing, a constant feeling of tightness, and decreased oxygenation due to breathing problems are reduced and lung function is improved. Leukotriene receptors, which act as antagonists, are used to suppress asthmatic, allergic and inflammatory processes in the human body. The first drug of choice is Montelukast Singulair. This drug relaxes tense bronchial muscles and reduces mucus production in hay fever (allergic rhinitis) and bronchial asthma (bronchial asthma). Young children with intermittent asthma are treated with montelukast during short periods of therapy at the beginning of an asthma episode. Most asthma patients can live well with their disease while taking this medication. Side effects usually turn out to be less than the treatment success.
Formation, occurrence, properties, and optimal levels
Leukotriene antagonists are used to treat asthma and allergic rhinitis. In the treatment of asthma, they belong to the range of controllers. Controllers are long-term medications; they are taken permanently.Leukotriene antagonists compete with glucocorticoid therapy, which is more effective but has more side effects and a greater treatment risk. Montelukast may be used as an alternative to glucocorticoid therapy in children up to fourteen years of age when appropriate treatment is indicated. As monotherapy, montelukast is not approved in Germany in people 15 years of age and older. In accordance with international guidelines, it may only be used if the treating physician is opposed to glucocorticoid therapy, for example if patients show side effects in which the harm is to be classified as higher than the expected treatment success. Patients who are unable to inhale glucocorticoids are also entitled to the alternative treatment with montelukast. Leukotriene antagonists can also be used in combination glucocorticoids and beta-2 sympathomimetics (e.g., ambroxol, clenbuterol, bambuterol) to achieve reduced dosing. However, patients must be adults. Montelukast acts as a so-called “add on” in this therapy. It is not suitable for treating an acute asthma attack. However, it is possible to prevent an exertional asthma attack. Here, the preparation acts as a supplement to the basic medication of inhaled glucocorticoids and beta-adrenergic substances (adrenoceptors). These are phylogenetic coupled receptors (GPCR) related to the G protein. They are initiated by the hormone epinephrine.
Diseases and disorders
Leukotriene antagonists are given orally in tablet form. They are also available as chewable tablets or granules. These drugs exert their maximum effect about two hours after ingestion. Despite the possible side effects, montelukast is generally well tolerated. The side effects depend on the individual situation of the patient. They include mental disturbances, skin rash, upper respiratory tract infections, gastrointestinal symptoms, muscle and joint pain, Churg-Strauss syndrome (lung and asthma disease), and increased bleeding tendency.