Antitussives and Expectorants

Cough Reflex & Targets - Hacking the Hack

• Cough Reflex Arc:
  • Afferent Limb: Irritant receptors (airways) → Vagus nerve.
  • Central Processor: Medulla oblongata.
  • Efferent Limb: Motor nerves → Respiratory muscles (diaphragm, intercostals, abdominal).
• Antitussive Drug Targets:
  • Central: Medullary cough center (e.g., opioids, dextromethorphan).
  • Peripheral: Afferent nerve endings in airways (e.g., demulcents, benzonatate).

⭐ Key Nerves: Afferent: Vagus nerve (from irritant receptors); Efferent: Recurrent laryngeal (larynx), phrenic (diaphragm), spinal motor nerves (expiratory muscles).

Antitussives - Shushing the Signals

• Mechanism: Suppress cough reflex by acting on the cough center in the medulla oblongata.
• Indications: Primarily for symptomatic relief of dry, non-productive cough.

⭐ Dextromethorphan, a non-analgesic d-isomer of levorphanol, acts centrally but has low addictive potential at therapeutic doses; high doses can cause hallucinations (NMDA receptor antagonism).

Expectorants & Mucolytics - Thinning the Thickness

These agents modify airway mucus, aiding its clearance.

These agents modify airway mucus, aiding its clearance.

in mucoproteins. Bromhexine/Ambroxol: ↓ Mucopolysaccharide viscosity; Ambroxol ↑ surfactant. | | Route | Oral | Acetylcysteine: Nebulized, PO, IV. Bromhexine/Ambroxol: PO; Ambroxol also Inhalation. | | Key Uses | Productive cough | Viscid mucus (COPD, CF). Acetylcysteine: Paracetamol poisoning (IV: 150 mg/kg loading). Ambroxol: Neonatal RDS. | | Key ADRs | GI upset, dizziness | Acetylcysteine: Bronchospasm (inhaled), N/V. Bromhexine/Ambroxol: Mild GI upset. |

⭐ N-acetylcysteine is the specific antidote for paracetamol (acetaminophen) poisoning, replenishing glutathione stores.

📌 Mnemonic: Acetylcysteine Snips Sulfide bonds.

Clinical Use & Combos - Cough Combat Guide

• Primary Goal: Symptomatic relief of cough; crucial to identify and treat the underlying pathology.
• Drug Selection Flow:

• Antitussives (for Dry, Hacking Cough):
  • Mechanism: Suppress cough reflex (central/peripheral).
  • Clinical Use: Non-productive cough causing distress or sleep disturbance.
  • Key Drugs: Codeine (opioid; potent, SE: constipation, sedation), Dextromethorphan (NMDA antagonist; less sedation, serotonin syndrome risk with MAOIs).
• Expectorants & Mucolytics (for Productive Cough with Tenacious Sputum):
  • Expectorants (Guaifenesin): ↑ volume & ↓ viscosity of secretions.
  • Mucolytics (Ambroxol, Bromhexine, Acetylcysteine): Directly break down mucopolysaccharides.
  • Clinical Use: Aid clearance in bronchitis, COPD, cystic fibrosis (Dornase alfa).
  • 📌 Acetylcysteine: "ACE" in parACEtamol poisoning.

⭐ Combining an antitussive with an expectorant is generally irrational, as suppressing cough while trying to expel mucus is counterproductive.

High‑Yield Points - ⚡ Biggest Takeaways

• Codeine & Dextromethorphan (DXM) are key centrally acting antitussives; DXM has lower abuse potential.
• Noscapine: A non-addictive, non-analgesic opioid derivative for cough suppression.
• Benzonatate: A peripherally acting antitussive that anesthetizes pulmonary stretch receptors.
• Guaifenesin: An expectorant that increases volume and reduces viscosity of respiratory secretions.
• Acetylcysteine: A potent mucolytic (breaks disulfide bonds); also the antidote for paracetamol poisoning.
• Ambroxol & Bromhexine: Mucolytics that depolymerize mucopolysaccharides and stimulate surfactant.