New generation anti-leukotriene drugs: a list of the best

2024 Author: Curtis Blomfield | [email protected]. Last modified: 2024-01-02 05:35

Antileukotriene drugs are a new class of drugs that reduce inflammation that have an infectious or allergic etiology.

In order to understand the principle of action of such drugs, it is worth understanding what leukotrienes are.

Leukotrienes

Are mediators of inflammatory processes. According to their chemical structure, they are fatty acids, which are formed by arachidonic acid.

Leukotrienes are involved in the development of bronchial asthma. As well as histamine, they are a mediator of allergic reactions of the immediate type. Histamine can cause a rapid but short-term bronchospasm, while leukotrienes cause a delayed and longer spasm.

How are antileukotriene drugs classified?

The following leukotrienes are currently classified: A₄, B₄, C₄, D 4_{, E}4_.

The synthesis of leukotrienes comes from arachidonic acid. It is converted to leukotriene by 5-lipoxygenase. A₄. After that, a cascade reaction occurs, resulting in the formation of the following leukotrienes B₄-C₄-D₄-E 4_{. The end product of such a reaction is LTE}4_.

It has been established that LTE₄, D₄, E_{4 can cause a bronchoconstrictor effect, increase secretion of mucus, may contribute to the development of edema, inhibit mucociliary clearance.}

B₄, D₄, E_{4 have chemotactic activity, that is, they can attract neutrophils and eosinophils in the area of the inflammatory process.}

Scientists have proven that leukotrienes are produced by macrophages, mast cells, eosinophils, neutrophils, T-lymphocytes, which are directly involved in the inflammatory response. Anti-leukotriene drugs are often used in bronchial asthma.

After the cells come into contact with the allergen and the airways cool down or after exercise, the synthesis of LT is activated. That is, synthesis begins when the osmolarity of bronchial contents increases.

Four groups of drugs

Currently, only four groups of antileukotriene drugs are known:

1. "Zileuton", which is a direct inhibitor of 5-lipoxygenase.
2. Preparations that are FLAP inhibitors, preventing the process of binding this protein to arachidonic acid.
3. Zafirlukast, Pobilukast, Montelukast, Pranlukast, Verlukast, which are sulfidopeptide receptor antagonistsleukotrienes.
4. Leukotriene B receptor antagonists_4.

Antileukotriene drugs of the first group and agents of the third group are the most studied. Let's take a closer look at the representatives of these groups.

Zileuton

Zileuton is a reversible inhibitor of 5-lipoxygenase. It is able to inhibit the formation of sulfidopeptide LT and LT B_{4. The drug can have a bronchodilatory effect lasting up to five hours. It is also able to prevent the occurrence of bronchial spasm, which is a consequence of exposure to cold air or "Aspirin".}

Multiple studies prove that Zileuton, prescribed to patients suffering from bronchial asthma for one to six months, can reduce the patient's need for inhaled β2-agonists and glucocorticoids. A single dose of Zileuton prevents sneezing and nasal obstruction in those patients who suffer from allergic rhinitis after a nasal allergen injection.

Six-week therapy with the use of Zileuton in patients with atopic asthma showed significant results. Doctors note a qualitative decrease in the level of eosinophils and neutrophils. The tumor necrosis factor in the bronchoalveolar type lavage fluid also decreased after the allergen test. What is unique about antileukotriene drugs,the mechanism of action is based on this.

"Zileuton" is characterized by a fairly short period during which its half-life occurs. This suggests that the drug should be taken often enough, up to four times a day. In addition, "Zileuton" is able to lower the clearance of theophylline. This must be taken into account if theophylline and Zileuton are supposed to be taken in parallel. That is, the dose of the first should be reduced. If "Zileuton" is prescribed for a long time, then the level of liver enzymes should be monitored.

But there are new generation antileukotriene drugs, a list of them is presented below.

Means that are antagonists of sulfidopeptide leukotrienes are highly selective competitors and reversible blockers of LT receptors D_{4. These drugs include Pranlukast, Zafirlukast, Montelukast.}

Akolat (Zafirlukast)

"Zafirlukast", aka "Acolat", is the most studied drug of this group of antileukotriene substances. It also has bronchodilator activity. The effect lasts quite a long time, up to five hours. "Zafirlukast" is able to prevent the development of an asthmatic reaction in case of inhalation with an allergen. Its effectiveness has also been proven in the prevention of bronchospasm, which is provoked by cold air, aspirin, physical activity, and pollutants. This drug and Montelukast canenhance the bronchodilator activity of β2-agonists.

"Acolat" ("Zafirlukast") has good absorption, the peak of its concentration in the blood is reached after three hours after its administration. Its half-life is slightly longer than that of Zileuton, and is 10 hours. In addition, it does not affect the clearance of theophylline. This drug should be taken either one hour before a meal or two hours after it, as food significantly reduces its absorption capacity. The agent is well tolerated by patients.

Conclusion

Antileukotriene drugs for allergies can be used for children, but not before they reach the age of two. With the help of these medicines, children are treated with recurrent bronchitis, allergic rhinitis, mild bronchial asthma.