Mechanism of Action and Pharmacodynamics
The primary goal of stabilizers is to prevent sensitized mast cells from rupturing (degranulating) upon contact with an allergen. If the cell membrane remains intact, inflammatory and allergic mediators—such as histamine, leukotrienes, prostaglandins, and platelet-activating factor (PAF)—are not released.
In pharmacology, there are two main views on this process:
- Classical theory: The drugs inhibit the transmembrane influx of calcium ions into the cell. Reducing intracellular calcium concentration prevents degranulation.
- Modern data: The effect is based on the blockade of chloride channels, leading to hyperpolarization of the cell membrane and its stable stabilization.
In addition to their direct action on mast cells, cromones exhibit supplementary pharmacodynamic effects. They suppress the chemotaxis of immune cells to the site of inflammation, reduce cytokine release from eosinophils and T-lymphocytes, and inhibit the cough reflex. The latter property is particularly valuable in exercise-induced bronchospasm or bronchospasm triggered by inhaling cold air.
Cromoglicic Acid and Nedocromil
These are typical representatives of the group, designed primarily for topical administration.
Cromoglicic acid has a bis-chromone structure featuring two carboxyl groups that impart acidic properties.
- Pharmacokinetics: Due to low solubility, the drug is poorly absorbed from the bronchial mucosa (only 5–15% of the dose enters the systemic circulation). The half-life is 1–1.5 hours, and a single dose lasts approximately 5 hours.
- Administration: For asthma, it is administered via inhalation 4–6 times daily. A nebulizer (from Latin nebula — mist) is often used to create a fine aerosol mist. The acid is also widely used in ENT practice (nasal sprays and drops for allergic rhinitis) and ophthalmology (eye drops for conjunctivitis).
- Safety: Pronounced systemic side effects are absent. Only local reactions related to airway irritation may occur, such as throat irritation and burning, coughing, and occasionally transient reflex bronchospasm.
Nedocromil sodium differs significantly in chemical structure, but works pharmacologically in a similar manner. About 8–17% is absorbed into the bloodstream, and the maximum prophylactic effect develops faster—by the end of the first week of regular use. It is prescribed 4 times daily.
Ketotifen: A Drug with Mixed Action
Ketotifen stands out markedly from inhaled cromones. It is a tricyclic compound (containing nitrogen and sulfur atoms in the central ring) with a dual mechanism of action:
- Stabilizes mast cell membranes.
- Blocks type 1 histamine receptors (similar to classical antihistamines).
It is important to remember that despite its antihistamine activity, ketotifen does not cause bronchodilation and is not suitable for relieving acute attacks.
- Pharmacokinetics: Taken orally with meals twice daily. It is almost completely absorbed from the gastrointestinal tract, but due to the first-pass effect in the liver, its bioavailability drops to about 50%. The half-life is 3–5 hours.
- Indications: Prophylaxis of bronchial asthma, atopic dermatitis, food allergies, and hay fever.
- Side effects: Because the drug acts systemically, it affects the central nervous system, causing sedation, drowsiness, and slowed psychomotor reactions. Other adverse events include dry mouth, nausea, dizziness, thrombocytopenia, and weight gain.