Mucolytics, Classification, MOA, Pk parameters, Therapeutic uses and ADRs

Mucolytics are agents that decrease the viscosity of sputum by altering the structure of mucus, making it easier to expel by coughing. They are particularly used in diseases involving thick, tenacious mucus (e.g., COPD, bronchiectasis, cystic fibrosis).
Thiol (Sulfhydryl) Derivatives:
- N-acetylcysteine (NAC)
Enzyme-Based Mucolytics:
- Dornase alfa
Surfactant-like Mucolytics:
- Bromhexine
Osmotic Mucolytics:
- Hypertonic Saline (3% or 7%)
Mucoregulators:
- Carbocisteine (S-carboxymethylcysteine)

1. MUCOLYTICS P. Harshitha Reddy

2. MUCOLYTICS Mucolytics are agents that decrease the viscosity of sputum by altering the structure of mucus, making it easier to expel by coughing. They are particularly used in diseases involving thick, tenacious mucus (e.g., COPD, bronchiectasis , cystic fibrosis).

3. Classification Thiol ( Sulfhydryl ) Derivatives: - N- acetylcysteine (NAC) Enzyme-Based Mucolytics : - Dornase alfa Surfactant-like Mucolytics : - Bromhexine Osmotic Mucolytics : - Hypertonic Saline (3% or 7%) Mucoregulators : - Carbocisteine (S- carboxymethylcysteine )

4. 1 . Thiol ( Sulfhydryl ) Derivatives Example: N- acetylcysteine (NAC) MOA: Breaks disulfide bonds in mucoproteins , reducing mucus viscosity. Also acts as a precursor to glutathione, offering antioxidant protection. PK Parameters: Route: Oral, IV, Inhalation Oral Bioavailability: ~10% (first-pass metabolism) Onset: ~1 hour (oral) Half-life: ~5.6 hours Metabolism: Hepatic (CYP450) Excretion: Renal

5. Example: N- acetylcysteine (NAC ) Therapeutic use: Acts as a mucolytic by breaking disulfide bonds in mucus, reducing its viscosity; used in chronic bronchitis, COPD, and cystic fibrosis. ADRs: Nausea , vomiting Bronchospasm (especially with inhaled form) Rash Hypersensitivity reactions Bad odor (rotten egg smell due to sulfur )

6. 2 . Enzyme-Based Mucolytics Example: Dornase alfa (recombinant human DNase I) MOA : Degrades extracellular DNA released by neutrophils in mucus (particularly in cystic fibrosis), reducing mucus viscosity. PK Parameters : Route: Inhalation Onset: Effects seen in 3–7 days Half-life: ~3–4 hours (localized in lungs) Metabolism: Proteolytic degradation in lungs Excretion: Not systemically absorbed

7. Example: Dornase alfa (recombinant human DNase I) Therapeutic use: Recombinant DNase that degrades DNA in thick mucus, making it less viscous; primarily used in cystic fibrosis. ADRs: Voice alteration ( dysphonia ) Pharyngitis , laryngitis Rash Conjunctivitis Chest pain

8. 3 . Surfactant-like Mucolytics Example: Bromhexine MOA : Enhances hydrolytic enzyme activity in lysosomes of secretory cells. Breaks down mucopolysaccharide fibers, thinning the mucus. PK Parameters : Route: Oral Bioavailability: ~20–30% (due to first-pass effect) Onset: 1–2 hours Half-life: ~12 hours Metabolism: Liver Excretion: Renal (as metabolites)

9. Example: Bromhexine Therapeutic use: Enhances mucus clearance by increasing serous mucus production and making phlegm less sticky; used in respiratory tract infections. ADRs: GI discomfort, nausea Allergic reactions Rhinorrhea , lacrimation Rare: bronchospasm

10. 4 . Osmotic Mucolytics Example: Hypertonic Saline (3% or 7%) MOA : Exerts osmotic pressure, drawing water into the airway surface layer. Hydrates mucus and improves ciliary clearance . PK Parameters : Route: Inhalation Onset: Immediate Duration: Short (minutes) Systemic absorption: Minimal

11. Example: Hypertonic Saline (3% or 7%) Therapeutic use: Draws water into the airways, thinning mucus and aiding in its clearance; commonly used in cystic fibrosis. ADRs: Bronchospasm Cough Sore throat Salt taste

12. 5 . Mucoregulators Example: Carbocisteine (S- carboxymethylcysteine ) MOA : Modulates mucus viscosity and elasticity by altering sialomucin / fucosomucin ratio. Also exhibits antioxidant and anti-inflammatory effects . PK Parameters : Route: Oral Bioavailability: ~10% Half-life: ~1.5–2 hours Metabolism: Minimal Excretion: Renal

13. Example: Carbocisteine (S- carboxymethylcysteine ) Therapeutic use: Regulates mucus production and reduces viscosity by modifying glycoprotein structure; used in chronic obstructive airway diseases. ADRs: GI upset (nausea, diarrhea) Skin rash Headache Rare: bleeding (in high doses)