Beta-2 Agonists
Beta-2 agonists provide selective relaxation of airway smooth muscle, widening the bronchial lumen. With prolonged uncontrolled use, receptors become desensitized to the drugs, so monitoring the inhalation regimen is essential.
Drugs are divided into two categories:
- Short-acting beta-2 agonists (SABAs) are emergency relief medications. Onset of action is in 3–5 minutes, peaking at 60–90 minutes post-inhalation. The frequency of SABA use serves as a marker of asthma control: the more often a patient uses the inhaler, the worse the disease control.
- Long-acting beta-2 agonists (LABAs) are included in maintenance therapy in combination with inhaled corticosteroids. They are not used as monotherapy because they do not suppress inflammation. Nor are they used as rescue medications due to the delayed peak of action. The exception is formoterol, which begins to act within 3–5 minutes and has a prolonged effect.
Anticholinergic Drugs
Mechanism of action: blockade of bronchoconstrictor reflexes through competition with acetylcholine at M-cholinergic receptors.
- Short-acting anticholinergics (ipratropium bromide) were previously used to relieve attacks, but they are inferior in efficacy to beta-2 agonists and are no longer used for this purpose.
- Long-acting anticholinergics (tiotropium bromide) are used primarily in COPD. In bronchial asthma, this is a second-line drug in combination with LABAs and ICS, as well as for the “asthma-COPD overlap” phenotype.
Inhaled glucocorticosteroids
Inhaled corticosteroids (ICS) possess potent anti-inflammatory action, partly by reducing immunoglobulin E production. Unlike oral corticosteroids, ICS lack most systemic side effects when used correctly, which is important to explain to patients.
ICS monotherapy is used at step 1 of therapy. At subsequent steps, ICS are used in fixed-dose combinations with LABAs. There are also triple fixed combinations: ICS + LABA + long-acting anticholinergic.
Of particular importance is the single-inhaler regimen (SMART therapy) — for example, the budesonide + formoterol combination: the patient uses the drug as maintenance therapy (morning and evening) and uses the same inhaler to relieve symptoms as they occur during the day.
Leukotriene Receptor Antagonists
The group includes montelukast and zafirlukast. The bronchodilator effect is achieved through an influence on arachidonic acid metabolism, but the effect is relatively weak — inferior even to low-dose ICS monotherapy.
Drugs are indicated for mild disease and have advantages in specific clinical situations:
- aspirin-exacerbated respiratory disease;
- exercise-induced asthma;
- cold-induced asthma.
Phosphodiesterase Inhibitors
Theophylline drugs were previously widely used in bronchial asthma and COPD. Currently, their use is sharply limited due to a narrow therapeutic index: the number and severity of side effects often outweigh the expected benefit. Nevertheless, the drug remains in recommendations for cases of difficult-to-control asthma: adding it to a fixed combination can improve disease control.
Targeted (Genetically Engineered) Therapy
Biologics are used exclusively for severe uncontrolled asthma that responds poorly to standard therapy. Limitations are related to high cost and the relative novelty of the agents.
There are two main directions:
- Anti-IgE therapy — omalizumab (used since 2003), binds free immunoglobulin E and reduces inflammation.
- Anti-interleukin therapy — drugs targeting key inflammatory cytokines (IL-5, IL-4, IL-13).
The range of genetically engineered drugs is expanding annually, improving the prognosis and quality of life for patients with severe asthma.
Key points
- SABAs are rescue medications; the frequency of their use reflects the level of asthma control.
- LABAs are not used as monotherapy or as rapid relief agents for acute attacks.
- ICS are the cornerstone of maintenance anti-inflammatory therapy; in modern regimens, they are used primarily in fixed combinations.
- The single-inhaler regimen (budesonide + formoterol) combines maintenance and rescue therapy.
- Leukotriene receptor antagonists are especially useful in aspirin-induced asthma, exercise-induced asthma, and cold-induced asthma.
- Tiotropium bromide is a second-line drug in severe asthma and the asthma-COPD overlap phenotype.
- Theophylline use is limited due to a narrow therapeutic window.
- Targeted therapy (omalizumab, anti-IL drugs) is a reserve for severe uncontrolled asthma.