Evolution of the Mechanism of Action
Classical pharmacology views cromoglicic acid as an agent that affects intracellular calcium homeostasis. The drug inhibits the transmembrane influx of calcium ions ($Ca^{2+}$) into the mast cell. Decreasing the intracellular calcium concentration stabilizes the membrane of the sensitized cell and prevents degranulation. Consequently, this blocks the release of histamine, leukotrienes, prostaglandins, and platelet-activating factor—the primary drivers of allergy and inflammation.
Current data expand upon this mechanism. It has been established that cromones can also block chloride channels ($Cl^-$). This induces cell membrane hyperpolarization, rendering the mast cell refractory to external stimuli.
Beyond its direct effects on mast cells, the drug exhibits additional pharmacodynamic actions:
- Suppresses the release of cytokines from T-lymphocytes and eosinophils.
- Reduces the chemotaxis of immune cells toward the site of inflammation.
- Inhibits the cough reflex, which is critically important in cold air- or exercise-induced bronchospasm.
Pharmacokinetics and Routes of Administration
The chemical structure of the drug is a bis-chromone (two chromone rings linked by a chain). The presence of two carboxylic acid groups imparts marked acidic properties to the molecule. Due to these characteristics, sodium cromoglicate exhibits extremely poor solubility and is virtually unabsorbed from the gastrointestinal tract.
To deliver the active substance to target cells, topical administration is used: inhalation via a nebulizer (derived from the Latin nebula meaning mist), which creates a fine aerosol cloud, or via standard metered-dose inhalers.
Key Pharmacokinetic Parameters:
- Absorption: Only 5–15% of the administered dose reaches the systemic circulation.
- Half-life ($t_{1/2}$): Approximately 1–1.5 hours.
- Duration of Action: The effect of a single dose lasts about 5 hours.
- Safety Profile: Due to predominantly topical action and low systemic absorption, the drug lacks significant systemic adverse effects.
Clinical Application
The primary rule of cromone therapy is that they are intended strictly for prophylaxis (prevention) of symptoms. In bronchial asthma, the drug is administered 4–6 times daily, and a sustained therapeutic effect only develops after 2–4 weeks of regular use.
In addition to controlling asthma and preventing cold-induced bronchospasm, cromoglicic acid is widely used in otorhinolaryngology and ophthalmology:
- Allergic rhinitis: Administered as nasal drops or intranasal sprays.
- Allergic conjunctivitis: Administered as ophthalmic drops.
Comparison with Other Drugs
Within the mast cell stabilizer class, there are other agents that are clinically important to differentiate:
- Nedocromil sodium. Although it differs significantly from cromoglicic acid in chemical structure, it shares an identical mechanism of action and is used for the same clinical indications.
- Ketotifen. This is an agent with a mixed mechanism of action. It possesses a tricyclic structure (containing sulfur and nitrogen atoms in the central ring) and is structurally related to antihistamines. Ketotifen combines mast cell-stabilizing properties with $H_1$-antihistamine receptor blockade. Unlike cromones, it can cause systemic side effects, such as pronounced sedation, dry mouth, nausea, dizziness, and weight gain. Similar to cromolyn, ketotifen does not possess bronchodilatory properties and is not suitable for terminating acute attacks.