Disodium Cromoglycate and Sodium Nedocromil

Mechanism

Mechanism of action

Disodiumcromoglycate acts topically on the surface of the bronchial epithelium by modulating cellular ion channels:

1. Blockade of calcium-sensitive chloride channels (ClC₃): By binding to the membrane of inflammatory mast cells, it prevents the flow of chloride necessary for depolarization and the subsequent opening of voltage-gated calcium channels. This prevents the massive influx of extracellular calcium, stopping the fusion of secretory granules with the cell membrane and the consequent release of histamine, leukotrienes, eosinophil chemotactic factor (ECF-A) and cytokines.
2. Inhibition of the activation of afferent neuronal cells (C-fibers): Blocks local bronconstrictor reflexes induced by chemical irritants or temperature changes, reflexively relieving cough and bronchial hyperreactivity.
3. Inhibition of eosinophil recruitment in the respiratory mucosa.

Pharmacokinetics

Pharmacokinetics

• Absorption: Pulmonary absorption of the inhaled fraction of approximately 8% - 10%. The swallowed portion is eliminated completely without being absorbed in the feces.
• Distribution: Short tissue retention in plasma. It does not accumulate in organs.
• Metabolism: Inert molecule that does not undergo any biotransformation.
• Excretion: Rapid unaltered mixed excretion via bile/fecal (50%) and renal-urinary (50%) routes. Half-life of 1.5 hours.

Indicators and dose

Clinical indications

• Prevention and prophylaxis of mild persistent bronchial asthma of allergic (extrinsic) type in children and adults.
• Prevention of bronchospasm induced by exercise, cold air or known inhaled allergens (administration 15-30 minutes prior).
• Allergic rhinitis and ophthalmic instillation in seasonal allergic conjunctivitis.

Dosage

• Disodium Cromoglycate pMDI (5 mg/puff): 2 inhalations four times a day (high frequency that limits its use).
• Solution for nebulization (20 mg/ampoule): 1 ampoule inhaled every 6 to 8 hours using an appropriate nebulization system. The full therapeutic effect takes 2 to 4 weeks to manifest itself stably.

Security

Exceptional Safety in Pediatrics

Since sodiumcromoglycate has extremely low systemic absorption (< 1%) and completely lacks activity on systemic hormonal or metabolic receptors, its overall toxicity profile is comparable to that of placebo. This historically positions it as an extremely safe alternative for the control of mild persistent asthma in the pediatric and childhood population, although it requires multiple daily doses that make adherence difficult.

Adverse effects (ADRs)

Sodiumcromoglycate is extraordinarily well tolerated by inhalation. Reported side effects are mild and transient:

• Throat irritation and reflex post-inhalation cough: (Due to mechanical impaction of the powder or solution in the oropharynx). It is prevented by drinking water immediately after administration.
• Transient paradoxical bronchospasm: Rare; It is associated with the use of dry powders and rapid inhalation.
• Mild nasal congestion and local conjunctival irritation.