Theophylline and its analogues have been used to treat bronchial asthma for more than 50 years. In the late 1960s, data on the increase in the incidence of deaths among patients with bronchial asthma began to be published. There have been attempts to explain this by the cardiotoxic effects of xanthines. But the suspicions were unfounded, but they stimulated the search for new drugs that affect the functional state of the bronchi. Special attention was drawn to studies on the use of the anhydrous form of theophylline. Gradually, a new approach to the development of long-acting theophylline drugs was formed. Currently, there are 2 main forms of theophylline: short-acting drugs and sustained-release forms of the active substance
The use of theophylline in reversible airway obstruction, ie in patients with bronchial asthma, has a clinical and experimental justification. The bronchodilator effect of theophylline directly correlates with its concentration in blood plasma. Its therapeutic level in the blood is from 10 to 20 μg / ml
Restoration of impaired ventilatory function of the lungs with the introduction of theophylline is due to excitation of the respiratory center, stimulation of the reticular activating system, increasing respiratory response to hypoxia, increasing the contractility of respiratory muscles and reducing their fatigue, relaxation of smooth muscles and dilation of large muscles. .
Studies show that improving the functional state of the airways and the general condition of the patient is associated with the anti-inflammatory effect of theophylline: it stabilizes the barrier properties of the epithelium of the airways and microvascular walls, prevents activation of polymorphonuclear leukocytes, reduces the release of airways, reduces the penetration of macromolecules through the lung epithelium
Theophylline has an immunomodulatory effect. In small doses (0.5-2 mg / kg) it is able to stimulate cellular immunity, without significantly affecting antibody production, and when increasing the dose - to suppress immunity
In addition to these effects, theophylline normalizes the gas composition of the blood in patients with bronchoobstructive diseases, increasing exercise tolerance. With the introduction of theophylline in patients with hypoxemia, there was a compensatory decrease in the affinity of hemoglobin for oxygen, which is aimed at improving tissue oxygenation.
The question of the therapeutic efficacy of theophylline in "irreversible" airway obstruction is unclear. The administration of theophylline in such patients is accompanied by a subjective improvement, although objective methods of research do not show this improvement. Thus, the appointment of theophylline in "irreversible" obstruction is acceptable, but should be done with caution to avoid toxic effects of the drug
A review of the place of theophylline in the treatment of bronchial asthma is currently being discussed. Some authors recommend adding theophylline drugs in the third stage of treatment as an additional bronchodilator in patients whose asthmatic symptoms are not adequately controlled by high doses of inhaled anti-inflammatory drugs. Others believe that theophylline should be introduced in the earlier stages of asthma treatment as an oral baseline therapy in combination with low-dose inhaled corticosteroids. In case of severe exacerbation or asthmatic status, intravenous drip administration of theophylline at an “increasing” dose of 5 μg / kg (if the patient has not previously taken slow-release theophylline) may be recommended, followed by switching to a maintenance dosing regimen (monitoring of serum concentrations is highly desirable).
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