Mucus-Controlling Drug Therapy Flashcards

Drug Control of Mucus

• Mucociliary escalator is the major defense system.
• Failure of this system may result in mechanical obstruction of the airway.
• Mucus properties:
  • Protective
  • Lubricating
  • Waterproofing
  • Entraps microorganisms

Clinical Indications for Use

• Reduce accumulation of airway secretions, improve pulmonary function and gas exchange, prevent repeated infection and airway damage.
• Consider after therapy to decrease infection/inflammation and removal of irritants (including tobacco smoke).
• Diseases:
  • Cystic fibrosis (CF)
  • Chronic bronchitis
  • Pneumonia
  • Diffuse panbronchiolitis (DPB)
  • Primary ciliary dyskinesia
  • Asthma
  • Bronchiectasis

Agents

• N-Acetylcysteine (NAC)
• Dornase alfa
• Aqueous aerosols (Water, Saline, Hyperosmolar saline)

Source of Airway Secretions

• Mucus:
  • Gel layer (0.5–20 \mu m)
  • Weak gel periciliary layer
• Structures of the mucociliary system:
  • Surface epithelial cells (Pseudostratified, columnar, ciliated epithelial cells, Surface goblet cells, Clara cells in the distal airway)
  • Submucosal glands (With serous and mucous cells)

Terminology

• Mucus: Secretion from surface goblet cells and submucosal glands composed of water, proteins, and glycosylated mucins.
• Phlegm: Secretions in the airways.
• Sputum: Expectorated phlegm that contains respiratory tract, oropharyngeal, and nasopharyngeal secretions, bacteria, and products of inflammation, including polymeric DNA and actin.
• Mucoactive agent: Has an effect on mucus secretion.
• Mucokinetic agent: Increase cough or ciliary clearance of respiratory secretions.
• Mucoregulatory agent: Reduce the volume of airway mucus secretion.
• Mucospissic agent: Increase viscosity of secretions.
• Mucolytic agent: Degrades polymers in secretions.

Submucosal Glands

• Provide airway surface mucin
• Under parasympathetic control (responds to cholinergic stimulation by increasing mucus secreted).
• Two types of cells: Mucous and serous.

Ciliary System

• 200 cilia per cell.
• Cilia are 7 \mu m in larger airways, 5 \mu m or less in smaller bronchioles.
• Effective (power) stroke and Recovery stroke.
• Functional surfactant layer separates periciliary fluid from mucus gel.

Factors Affecting Mucociliary Transport Rate

• Chronic obstructive pulmonary disease (COPD)
• CF
• Airway drying
• Narcotics
• Endotracheal suctioning
• Airway trauma & Tracheostomy
• Cigarette smoke
• Atmospheric pollutants (SO2, NO2, ozone)
• Hyperoxia and hypoxia
• Food intake and mucus production: No reported association between milk/dairy and respiratory congestion.

Secretions in Disease States

• Mucus or mucociliary clearance abnormalities in:
  • Chronic bronchitis
  • Asthma
  • Cystic fibrosis

Mucoactive Agents

• Mucolytic agents decrease elasticity and viscosity of mucus.
• Therapeutic options:
  • Remove causative factors
  • Optimize tracheobronchial clearance
  • Use mucoactive agents when indicated
• Classic mucolytics reduce mucins by severing disulfide bonds or charge shielding.

N-Acetyl-L-Cysteine (NAC)

• Indications: Conditions associated with viscous secretions & Acetaminophen overdose
• Mode of action: Disrupts mucus structure by substituting free thiol groups for disulfide bonds.
• Hazards: Bronchospasm, Mechanical obstruction of airway.
• Incompatible with certain antibiotics (Sodium ampicillin, Amphotericin B, Erythromycin lactobionate, Tetracyclines, Aminoglycosides).
• Should not be used as a mucoactive medication.

Dornase Alfa (Pulmozyme)

• Indications: CF (clearance of purulent secretions, reduce respiratory infections, improve pulmonary function).
• Mode of action: Reduces viscosity and adhesivity by breaking down DNA.
• Dose: 2.5 mg in 2.5 mL daily via nebulizer.
• Adverse effects: Voice alteration, pharyngitis, laryngitis, rash, chest pain, conjunctivitis.

Mucokinetic Agents

• Increase cough clearance by increasing expiratory airflow or reducing sputum adhesivity and tenacity.
• Bronchodilators may increase ciliary beat and mucus production.

Surface-Active Phospholipids

• Thin surfactant layer between periciliary fluid and mucus gel prevents airway dehydration, permits mucus spreading, allows efficient ciliary coupling and release from mucus.
• Surfactant therapy effective in treating chronic bronchitis and CF.

Mucoregulatory Medications

• Decrease mucus hypersecretion.
  • Steroids
  • Anticholinergics (Atropine, Ipratropium bromide, Tiotropium)
  • Macrolide antibiotics

Other Mucoactive Agents

• Hyperosmolar saline (7%) and mannitol: May increase FEV1; may cause decrease in FEV1, unpleasant taste, coughing.

Mucoactive Therapy with Physiotherapy and Airway Clearance Devices

• Gravity: Postural drainage may benefit with CPT.
• Insufflation-Exsufflation: Inflates lungs with positive pressure followed by negative pressure to simulate cough.
  • Inspiratory pressure 25–35 cm H2O for 1–2 seconds, expiratory pressure of -30–-40 cm H2O for 1–2 seconds.
  • Primary application in patients with neurological muscular weakness.
• Active cycle of breathing (ACB) and forced expiratory technique (FET) maneuver: Breathing control, thoracic expansion control, forced expiration technique.
• Autogenic drainage: Aims to “optimize” airflow in bronchi to move secretions.
• Exercise: Causes increased sputum production.
• Positive airway pressure: Effective alternatives to chest physical therapy in expanding lungs and mobilizing secretions.
• Oscillatory PEP: The FLUTTER®, The Percussionator®
• Chest wall compression: The Vest® (effective for secretion clearance in CF patients).

Respiratory Care Assessment of Mucoactive Drug Therapy

• Before treatment: Level of consciousness (LOC), adequacy of cough.
• During treatment: Correct use of equipment, assess airflow changes, adverse effects.
• Long term: Number/severity of infections, ER visits, hospitalizations, need for antibiotics, pulmonary function testing.
• General contraindications:
  • Profound airflow compromise (FEV1 < 25% predicted).
  • Severely compromised VC & Expiratory flow
  • GERD
  • Inability to protect airway
  • Acute bronchitis or exacerbation of chronic disease.