N-Acetylcysteine, Erdocysteine, Dornase Alfa and Poractant Alfa

Mechanism

Mechanism of action

The viscoelasticity of respiratory mucus depends on the density of chemical bonds in its polymer matrix:

• N-Acetylcysteine (NAC) and Erdocysteine (Sulfhydric mucolytics): They have free sulfhydryl (-SH) groups in their structure (or released after rapid hepatic metabolism in the case of erdocysteine). These sulfhydryl groups act directly by reducing the disulfide bridges (-S-S-) that covalently link the mucin glycoproteins of respiratory mucus. By breaking these chemical cross-links, they drastically reduce the viscosity of the mucus, facilitating its spontaneous expectoration.
• Dornase Alfa (Recombinant human deoxyribonuclease - rhDNase): In patients with cystic fibrosis, bronchial secretions are purulent and dense due to large amounts of extracellular polymerized DNA, which is released by degenerated neutrophils. Dornase alfa selectively cleaves this extracellular DNA by enzymatic hydrolysis, immediately liquefying the purulent sputum without altering the normal mucin of the epithelium.
• Poractant Alfa (natural porcine lung surfactant): Natural mixture of phospholipids (mainly dipalmitoylphosphatidylcholine - DPPC) and hydrophobic proteins (SP-B and SP-C). Reestablishes the endogenous alveolar surfactant film by reducing surface tension at the gastric alveolar air-liquid interface, preventing alveolar collapse during pulmonary expiration and improving compliance.

Indicators and dose

Approved clinical indications

• N-Acetylcysteine (Oral): Adjuvant in the treatment of chronic hypersecretory respiratory processes (chronic bronchitis, COPD).
• N-Acetylcysteine (Intravenous): Treatment of acute paracetamol (acetaminophen) poisoning to replenish depleted hepatic reserves of cellular glutathione.
• Dornase Alfa: Maintenance treatment in patients with cystic fibrosis (CF) with reduced forced vital capacity (FVC), to improve lung function and reduce the rate of recurrent lung infections.
• Poractant Alfa: Treatment and prophylaxis of neonatal respiratory distress syndrome (RDS) or hyaline membrane disease in low-weight premature infants.

Dosage and Clinical Adjustment

• N-Acetylcysteine (Oral Mucolytic): 600 mg once a day in effervescent tablets, or 200 mg every 8 hours.
• Dornase Alfa (Inhalation by Jet atomizer): 2.5 mg (one 2.5 mL ampoule) inhaled once a day using a specific atomizer to avoid physical denaturation of the recombinant enzyme.
• Poractant Alfa (Direct Endotracheal Instillation): Initial dose of 100 - 200 mg/kg body weight, administered through an endotracheal tube in the ventilated premature neonate.

Security

Risk of Bronchospasm with Inhaled N-Acetylcysteine

The administration of N-acetylcysteine by direct nebulization or intratracheal instillation can trigger severe and unpredictable paradoxical bronchospasm, mediated by irritation of the mucosal sensory endings and release of histamine. This is especially common in asthmatic patients with severe bronchial hyperreactivity. For this reason, its use by inhalation is strictly not recommended in patients with active asthma, preferentially recommending its use orally or in association with a previous SABA.