Mechanism of Action
Glucocorticoids possess the broadest spectrum of anti-inflammatory activity. Their effects are primarily mediated through genomic mechanisms (regulation of gene expression).
- Blockade of inflammatory mediators: Drugs stimulate the synthesis of lipocortin, which inhibits the enzyme phospholipase A2. This halts the release of arachidonic acid from cell membranes and blocks the synthesis of leukotrienes and prostaglandins. Additionally, glucocorticoids suppress the gene responsible for COX-2 synthesis.
- Immunosuppression: The function of macrophages, T cells, and B cells is inhibited. The production of pro-inflammatory cytokines (IL-1, IL-2, IL-4) and immunoglobulin E (IgE) is reduced.
- Effect on mast cells: The number of IgE receptors decreases, and cell membranes are stabilized, preventing degranulation and histamine release. Drugs also inhibit the proliferation of mast cell clones.
- Inhibition of cell migration: The synthesis of intercellular adhesion molecules is suppressed, preventing leukocytes and monocytes from infiltrating bronchial tissues.
- Permissive action: Glucocorticoids increase the sensitivity of bronchial $\beta_2$-adrenergic receptors to circulating epinephrine, enhancing its bronchodilatory effect.
Pharmacokinetic Features
Inhaled formulations are designed to act directly within the bronchi (topical action).
The main pharmacokinetic advantage of this group is high presystemic (first-pass) elimination. The fraction of the drug that is inevitably swallowed with saliva and absorbed into the systemic circulation is rapidly degraded during its first pass through the liver. This minimizes the risk of severe systemic side effects characteristic of oral steroids. Nevertheless, prolonged administration carries a risk of suppressing endogenous glucocorticoid production via negative feedback.
Key Representatives
These medications are intended for systematic (controller) treatment. Efficacy is achieved only with regular use.
- Beclometasone: The prototype of the group. It is a halogenated steroid (contains a chlorine atom that enhances activity). Maximum therapeutic effect occurs on days 5–7. Administered 2–4 times daily.
- Budesonide: A non-halogenated drug. It features an acetal group that increases lipophilicity and receptor affinity. It has a longer duration of action (administered 1–2 times daily), but the onset is slower (1–2 weeks). Specific adverse effects include central nervous system effects (nervousness, excitability, depression). Systemic absorption is about 28%.
- Flunisolide: Similar to beclometasone, but with pronounced presystemic metabolism, resulting in a bioavailability not exceeding 40%.
- Fluticasone: Kinetics are similar to budesonide; systemic absorption is approximately 20%.
"Soft" Glucocorticoids
This is a modern direction in pharmacology aimed at developing drugs with an improved safety profile. A prominent representative in pulmonology is ciclesonide.
Chemically, it is a non-halogenated esterified steroid that acts as a prodrug. In case of accidental ingestion, its bioavailability is negligible (0.5–1%). Upon reaching the pulmonary tissue, local esterases convert it into the active metabolite desisobutyryl-ciclesonide (des-ciclesonide), which possesses potent anti-inflammatory activity.
Advantages of ciclesonide: administered only once daily, excellent tolerability, and significantly lower suppression of endogenous cortisol production compared to classical agents (e.g., fluticasone).