Mechanism of action and pharmacodynamics
The primary objective of stabilizers is to prevent sensitized mast cells from breaking down (degranulating) upon contact with an allergen. If the cell maintains an intact membrane, inflammatory and allergic mediators—such as histamine, leukotrienes, prostaglandins, and platelet-activating factor (PAF)—are not released.
In pharmacology, there are two views on the mechanism of this process:
- Classical theory: the drugs inhibit transmembrane calcium ion influx into the cell. Reduced calcium concentration prevents degranulation.
- Modern data: the effect is based on the blockade of chloride channels, which leads to cell membrane hyperpolarization and its reliable stabilization.
In addition to their direct action on mast cells, cromones possess additional pharmacodynamic effects. They suppress the chemotaxis of immune cells into the focus of inflammation, reduce cytokine release by eosinophils and T lymphocytes, and inhibit the cough reflex. The latter property is particularly valuable in exercise-induced bronchospasm or bronchospasm caused by inhaling cold air.
Cromoglicic acid and Nedocromil
These are typical representatives of the group, intended primarily for topical use.
Cromoglicic acid has a bis-chromone structure with two carboxyl groups that impart acidic properties.
- Pharmacokinetics: Due to poor solubility, the drug is practically unabsorbed from the bronchial mucosa (only 5–15% of the dose reaches the systemic circulation). The half-life is 1–1.5 hours, and the duration of action of a single dose is about 5 hours.
- Application: For asthma, it is administered by inhalation 4–6 times a day. A nebulizer is often used for this purpose (from Lat. nebula — mist), creating a fine aerosol cloud. The acid is also widely used in ENT practice (nasal sprays and drops for allergic rhinitis) and ophthalmology (eye drops for conjunctivitis).
- Safety: There are no prominent systemic side effects. Only local reactions associated with respiratory tract irritation may occur: tickling and burning in the throat, coughing, and occasionally transient reflex bronchospasm.
Nedocromil sodium differs significantly in chemical structure, but works pharmacologically in a similar manner. It is absorbed into the bloodstream in the amount of 8–17%, and the maximum prophylactic effect develops faster—by the end of the first week of regular intake. It is prescribed 4 times a day.
Ketotifen: a drug with mixed action
Ketotifen stands out markedly against the background of inhaled cromones. It is a drug with a tricyclic structure (containing nitrogen and sulfur atoms in the central ring) that has a dual mechanism of action:
- Stabilizes mast cell membranes.
- Blocks type 1 histamine receptors (similar to classic 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 (by mouth) with meals 2 times a day. It is almost completely absorbed from the gastrointestinal tract, but due to the first-pass effect through the liver, its bioavailability drops to 50%. The half-life is 3–5 hours.
- Indications: Prophylaxis of bronchial asthma, atopic dermatitis, food allergy, hay fever.
- Side effects: Since the drug acts systemically, it affects the central nervous system, causing a sedative effect, drowsiness, and slowed psychomotor reactions. Other adverse events include dry mouth, nausea, dizziness, thrombocytopenia, and weight gain.
The main rule of using cromones can be remembered by association: "Cromones are like an umbrella: open them before the rain". They protect against an allergic reaction only when taken in advance and are completely useless if the "downpour" (acute bronchospasm) has already begun.
Class and exam questions
Why does cromoglicic acid cause almost no systemic side effects?
The drug has poor solubility and is practically unabsorbed from mucous membranes (only 5–15% of the dose enters the bloodstream). Therefore, its action remains predominantly local.
Can ketotifen be used to relieve an asthma attack?
No, ketotifen does not cause bronchodilation. Like other drugs in this group, it is used exclusively for the baseline prevention of attacks.
How quickly does the effect of cromoglicic acid inhalations develop?
The drug's effect builds up gradually. The maximum therapeutic effect is achieved only after 2–4 weeks of systematic use.
What else to study on this topic
- Chemical structure of bis-chromones and the influence of carboxyl groups on molecule properties
- Pharmacokinetic features of ketotifen: the first-pass effect through the liver
- The role of chloride channels in mast cell membrane hyperpolarization
- Trade names and dosage forms of cromones for ophthalmology and ENT practice
- The effect of membrane stabilizers on T lymphocytes, eosinophils, and chemotaxis
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