Evolution of concepts regarding the mechanism of action
Classical pharmacology views cromoglicic acid as a drug that affects intracellular calcium metabolism. The drug inhibits the transmembrane influx of calcium ions ($Ca^{2+}$) into the mast cell. Decreasing the calcium concentration reliably stabilizes the membrane of the sensitized cell and prevents the degranulation process. As a result, the release of histamine, leukotrienes, prostaglandins, and platelet-activating factor—the main culprits of allergy and inflammation—is blocked.
Modern data complement this picture. It has been established that cromones are able to block chloride channels ($Cl^-$). This causes hyperpolarization of the cell membrane, rendering the mast cell unresponsive to stimuli.
In addition to its direct effect on mast cells, the drug exerts additional pharmacodynamic effects:
- Suppresses the release of cytokines by T-lymphocytes and eosinophils.
- Reduces the chemotaxis of immune cells into the inflammation site.
- Inhibits the cough reflex, which is critically important in bronchospasm induced by cold air or physical exertion.
Pharmacokinetics and routes of administration
The chemical structure of the drug is a "bis-chromone" (two chromone rings connected by a chain). The presence of two carboxyl groups imparts pronounced acidic properties to the molecule. Due to these features, cromolyn has extremely low solubility and is practically not absorbed from the gastrointestinal mucosa.
To deliver the active substance to target cells, local administration is used—either by inhalation using a nebulizer (from the Latin nebula — mist), which creates a fine dispersion cloud of the drug, or in the form of aerosols.
Key pharmacokinetic parameters:
- Absorption: only 5–15% of the administered dose enters the systemic circulation.
- Half-life ($t_{1/2}$): is 1–1.5 hours.
- Duration of action: the effect of a single dose lasts about 5 hours.
- Safety: due to predominantly local action and low systemic absorption, the drug does not cause pronounced systemic side effects.
Clinical application
The main rule of therapy with cromones: they are intended exclusively for the prevention (prophylaxis) of symptoms. In bronchial asthma, the drug is prescribed 4–6 times a day, and a stable therapeutic effect develops only after 2–4 weeks of regular use.
In addition to controlling bronchial asthma and preventing cold-induced bronchospasm, cromoglicic acid is widely used in ENT practice and ophthalmology:
- Allergic rhinitis: nasal drops or intranasal sprays are prescribed (trade names: Vividrin, Cromoglyn, Cromosol).
- Allergic conjunctivitis: eye drops are used (Vividrin, CromohexalHi-Crom, Lecrolyn).
Comparison with other drugs
There are other representatives in the mast cell stabilizer group that are important to be able to differentiate:
- Nedocromil sodium (Tilade). It differs significantly from cromoglicic acid in chemical structure, yet possesses an absolutely analogous mechanism of action and is used for the same indications.
- Ketotifen. This is a drug with a mixed mechanism of action. It has a tricyclic structure (contains sulfur and nitrogen atoms in the central ring) and is structurally close to antihistamines. Ketotifen combines the properties of a membrane stabilizer and an $H_1$-histamine receptor blocker. Unlike cromones, it can cause systemic side effects: pronounced sedation, dry mouth, nausea, dizziness, and weight gain. Like cromolyn, ketotifen does not cause bronchodilation and is not suitable for relieving acute attacks.
Briefly: answers to topical questions
What diseases are indications for the use of cromoglicic acid?
Cromoglicic acid is indicated for bronchial asthma, bronchospasm induced by cold or physical exertion, as well as for allergic rhinitis and allergic conjunctivitis.
- Bronchial asthma — exclusively prophylaxis (prevention), not for relieving attacks.
- Bronchospasm from cold or physical exertion.
- Allergic rhinitis — nasal drops and sprays.
- Allergic conjunctivitis — eye drops.
Used only for baseline (controller) therapy as an alternative drug in mild intermittent and persistent asthma, as well as a 1st-step agent for allergic rhinitis.
What local side effects does inhalation of cromolyn sodium cause?
Specific local side effects of inhaled cromolyn sodium are not described in the literature. It is indicated that the action is predominantly local, and pronounced systemic side effects are absent. The drug has poor solubility; 5–15% of the dose enters the systemic circulation after inhalation.
Cromolyn — COVers the Membrane. It acts like a protective dome covering the mast cell membrane, preventing calcium from entering and stopping mediators (histamine) from escaping outward.
Class and exam questions
Why is cromolyn sodium useless during an asthma attack?
The drug only prevents the release of new portions of mediators from mast cells, but does not cause bronchodilation. It has no effect on already released histamine and leukotrienes, and therefore is unable to relieve airway spasm.
Why administer the drug by inhalation if it is an acid?
Due to the features of its chemical structure (the presence of two carboxyl groups), the drug is practically not absorbed in the intestine. For it to act on mast cells in the bronchi, it must be delivered locally as a fine mist via a nebulizer.
How does cromoglicic acid differ from ketotifen?
Both drugs stabilize mast cell membranes, but ketotifen additionally blocks $H_1$-histamine receptors. Because of this mixed action, ketotifen more frequently causes systemic side effects such as drowsiness and weight gain.
What else to study on this topic
- $H_1$-histamine receptor blockers (1st and 2nd generation drugs)
- Leukotriene pathway inhibitors (montelukast, zafirlukast, zileuton)
- Anti-IgE therapy for bronchial asthma (omalizumab)
- Chemical structure and pharmacodynamics of ketotifen
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