Pathophysiology of Cough
Cough is a vital protective reflex that serves to clear the airways of irritants, mucus, and foreign particles. It involves a complex interaction between sensory receptors, neural pathways, and effector muscles. The cough reflex can be divided into three main components:
- Afferent Limb:
- Sensory receptors in the respiratory tract (larynx, trachea, bronchi) detect mechanical or chemical stimuli such as dust, smoke, or inflammation.
- These receptors include rapidly adapting stretch receptors (RARs), slowly adapting stretch receptors (SARs), and C-fiber receptors.
- Signals from these receptors are transmitted via the vagus nerve to the brainstem’s cough center.
- Central Processing:
- The brainstem houses the “cough center,” primarily located in the medulla oblongata.
- This center integrates sensory input and coordinates motor output for coughing.
- Efferent Limb:
- Motor signals are sent from the brainstem to respiratory muscles (diaphragm, intercostal muscles) and laryngeal muscles via nerves like the phrenic nerve.
- This results in a forceful expulsion of air to clear irritants from the airway.
The cough reflex can be triggered by various conditions such as infections (e.g., upper respiratory infections), chronic diseases (e.g., asthma, COPD), or environmental irritants.
Sites of Action of Anti-Tussives with Examples
Anti-tussive agents work by targeting different components of the cough reflex pathway. They are classified based on their site of action:
1. Peripheral Acting Anti-Tussives:
- These drugs act on sensory nerve endings in the respiratory tract to reduce their excitability.
- Example: Levodropropizine reduces cough by inhibiting C-fiber activation without sedative effects.
- Another example is Moguisteine, which suppresses peripheral afferent activity.
2. Central Acting Anti-Tussives:
- These drugs suppress cough by acting on the brainstem’s cough center.
- Examples include:
- Codeine: An opioid that binds to μ-opioid receptors in the CNS to inhibit cough reflex but may cause sedation and dependence.
- Dextromethorphan: A non-opioid central anti-tussive that acts on NMDA receptors in the brainstem without causing significant sedation.
3. Mixed Mechanism Drugs:
- Some drugs have both central and peripheral actions.
- Example: Certain antihistamines like first-generation H1 blockers (e.g., diphenhydramine) reduce cough by acting centrally while also drying up secretions peripherally.
Mechanism of Action of Mucolytic Agents with Examples
Mucolytic agents are designed to break down mucus structure, making it less viscous and easier to expel through coughing. They target thickened mucus often seen in chronic lung conditions like cystic fibrosis or bronchiectasis.
Mechanisms of Action:
- Breaking Disulfide Bonds in Mucus Glycoproteins:
- Mucus contains glycoproteins held together by disulfide bonds; mucolytics cleave these bonds to reduce viscosity.
- Example: Acetylcysteine (NAC) breaks disulfide bonds and also has antioxidant properties.
- Enzymatic Degradation of DNA or Proteins in Mucus:
- In conditions like cystic fibrosis, DNA released from neutrophils contributes to mucus thickness.
- Example: Dornase alfa, a recombinant DNase enzyme, degrades extracellular DNA in mucus.
- Hydration of Mucus:
- Hypertonic saline solutions draw water into mucus layers via osmosis, thinning them for easier clearance.
- Example: Hypertonic saline nebulization is used for patients with cystic fibrosis.
- Reduction of Mucus Production or Secretion Regulation:
- Some mucolytics regulate secretion production or improve ciliary function for better clearance.
These agents improve airway clearance but do not directly suppress coughing itself; instead, they make coughing more productive.
