Mucus-Controlling Drug Therapy

• These notes cover mucus-controlling drug therapy, mucoactive agents, airway clearance techniques, and related respiratory concepts.

Key Definitions

• Gel: A pseudoplastic material exhibiting both viscosity and elasticity due to its macromolecular structure.
• Mucokinetic agents: Medications that enhance the clearance of respiratory secretions by increasing cough effectiveness or ciliary action.
• Rheology: The study of how materials deform and flow under stress.
• Expectorants: Drugs intended to increase the volume or hydration of airway secretions, facilitating their removal.
• Mucin: The primary component of mucus.
• Viscosity: The resistance of a liquid to shear forces, indicating energy loss when stress is applied.
• Mucolytic Agents: Medications that break down polymers in secretions, reducing thickness.
• Mucus: A secretion from goblet cells and submucosal glands, consisting of water, proteins, and glycosylated mucins.
• Mucoactive agents: Any drug that affects mucus secretion.
• Sputum: Secretions expelled from the respiratory tract, containing oropharyngeal and nasopharyngeal material, bacteria, and inflammatory products like DNA and actin.
• Mucoregulatory agents: Drugs that reduce the volume of mucus secretion, particularly useful in hypersecretory conditions.
• Elasticity: A rheologic property characteristic of solids, indicating their ability to return to their original shape after deformation.
• Mucospissic agents: Medications that increase the viscosity of secretions, used for bronchorrhea therapy.
• Mucins: Proteins that determine mucus's physical and chemical properties like viscoelasticity.
• Sol: The periciliary layer in the airways.
• Oligosaccharide: A sugar unit that forms part of a glycoprotein.
• Phlegm: Purulent (pus-containing) material found in the airways.

Drug Control of Mucus

• Mucoactive therapy is considered after addressing infection and inflammation.
• Mucus serves multiple beneficial roles, including protection, lubrication, waterproofing, osmotic and inflammatory protection, and microorganism entrapment.

Mucoactive Agent Information

• N-acetylcysteine (NAC):
  • Brand Name: 10% Mucomyst, 20% Mucomyst
  • Use: Use not yet demonstrated.
  • Adult Dose: 3-5 mL via SVN.
• Dornase alfa:
  • Brand Name: Pulmozyme
  • Use: Cystic fibrosis only.
  • Adult Dose: 2.5 mg/ampule via SVN, one ampule daily.
• Aqueous water, saline (0.9%):
  • Use: Sputum induction
  • Adult Dose: 3-5 mL via SVN, as prescribed.
• Hyperosmolar saline 7%:
  • Brand Name: Hyper-Sal
  • Use: Airway clearance (mucokinetics) for CF therapy
  • Adult Dose: 4 mL via SVN.
• Dry powder mannitol:
  • Brand Name: Bronchitol.
  • Use: (7% saline and mannitol)
  • Adult Dose: 4mL SVN
• 3% hyperosmolar saline:
  • Use: Infantile bronchiolitis,
  • Adult Dose: 4 mL via SVN.

Physiology of the Mucociliary System

• The airway mucus layers consist of a gel layer (0.5 to 20 micrometers) propelled toward the larynx and a weak gel periciliary layer (height of fully extended cilium).
• Mucus lines the airway, while sputum is expectorated phlegm containing respiratory tract secretions.

Effects of Drugs on Mucociliary Clearance

• β-Adrenergic agents: Increase both ciliary beat and mucus production.
• Cholinergic agents: Increase both ciliary beat and mucus production.
• Methylxanthines: Increase both ciliary beat and mucus production.
• Corticosteroids: Have no noted effect on ciliary beat or mucus production.
• Anticholinergics: Have no effect on ciliary beat and may decrease mucus production in some cases.

Factors Slowing Mucociliary Transport

• COPD and CF
• Airway drying
• Narcotics
• Endotracheal suctioning, airway trauma, and tracheostomy
• Tobacco smoke and extracts
• Atmospheric pollutants
• Hyperoxia and hypoxia

Disease States Requiring Mucus-Controlling Drug Therapy

• Chronic Bronchitis: Submucosal glands produce excessive mucus.
• Asthma: Hypersecretion of viscous mucus leads to airway obstruction.
• Bronchorrhea: Large volumes of watery sputum are produced.
• Plastic Bronchitis: Formation of large, rigid airway casts.
• Cystic Fibrosis (CF): Airways filled with neutrophil-derived pus, requiring mucotherapy to decrease sputum viscosity and clear airways.
• CF secretions contain minimal intact mucin, largely composed of neutrophil degradation products.
• Adhesion reduces the ability to clear purulent sputum by airflow.

Mucoactive Agents - Mucolytics

• Therapeutic options for controlling mucus hypersecretion include mucolytics and expectorants, in addition to mucoactive agents.
• NAC disrupts disulfide bonds, working more effectively in alkaline pH environments (7.0 to 9.0).
• Bronchospasm from aerosolized NAC can be reduced with pretreatment using a β-adrenergic bronchodilator.

Dornase Alfa

• Not recommended for bronchiectasis or COPD patients; studies show no efficacy in non-CF bronchiectasis. In COPD, it may decrease pulmonary function and increase mortality risk.

Indications for Dornase Alfa

• Cystic fibrosis maintenance to reduce infections
• Reducing viscosity and adhesivity of infected respiratory secretions
• Improving pulmonary function in CF patients
• Approved nebulizers and compressors include Hudson RCI UP-Draft II Opti-Neb, Acorn II nebulizer with a DeVilbiss Pulmonary-Aide compressor, and Pari LC Plus nebulizer with the PARI inhaler Boy compressor.
• Dornase alfa (Pulmozyme) requires a nebulizer system for suitable aerosol generation (particle size and quantity); the dose is 2.5 mg in 2.5 mL.
• Effectiveness of dornase alfa is evaluated by assessing expectorated sputum, IV antibiotic use, and lung function.

Expectorants

• Guaifenesin is FDA-approved as a bilayer extended-release tablet (Mucinex).

α Agonists

• Diseases with expiratory difficulties, such as COPD and asthma, benefit from increased expiratory airflow with α agonists.
• α Agonists are not recommended for patients with tracheomalacia or bronchomalacia due to potential airway collapse from muscle relaxation.

Mucoregulatory Medications

• Long-term use of mucoregulatory medications like ipratropium reduces mucus secretion volume in chronic bronchitis patients.

Antiproteases

• Helpful in diseases to restore the bacteria-killing capacity of neutrophils.

Hyperosmolar Saline

• Improves mucociliary transport.
• A 7% hypertonic saline solution administered twice daily (bid) requires a recommended delivery device.

Mucoactive Therapy

• A directed cough involves a conscious effort to cough effectively, while a huff cough is a forced expiratory technique to mobilize secretions.
• Conventional chest physical therapy (CPT) incorporating postural drainage results in significantly greater expectoration than no treatment in patients with CF (True).
• The insufflation-exsufflation device inflates the lungs with positive pressure followed by a negative pressure to simulate a cough (True).
• The active cycle of breathing techniques uses relaxed diaphragmatic breathing and does not include the insufflation-exsufflation device (False).
• Autogenic drainage incorporates staged breathing, starting with small tidal breaths from expiratory reserve volume (ERV), repeated until secretions “collect” in the central airways. It is recommended for patients more than 8 years of age (True).
• Exercise should not be substituted for other bronchial hygiene regimens (False).
• The intrapulmonary percussive ventilation delivers high-flow minibursts at rates exceeding 200 cycles/min.

Airway Clearance Devices

• Chest wall oscillation (The Vest) provides pressure pulses that fill a vest and vibrate the chest wall at variable frequencies.
• A 69-year-old patient with COPD uses pursed-lip breathing as an effective alternative to CPT in expanding the lungs and mobilizing secretions.
• A 32-year-old patient with CF uses a FLUTTER mucus clearance device when traveling, which combines positive expiratory pressure (PEP) with high-frequency oscillations at the airway opening.
• A 29-year-old CF patient uses autogenic drainage, incorporating staged breathing starting with small tidal breaths from ERV, and repeated until secretions “collect” in the central airways.
• An 18-year-old CF patient uses the Chest wall oscillation: The Vest which provides pressure pulses that fill a vest and vibrate the chest wall at variable frequencies.
• A 22-year-old man with CF uses intrapulmonary percussive ventilation, delivering breaths through a mouthpiece and delivers high-flow minibursts at rates exceeding 200 cycles/min.
• A 44-year-old woman with cerebral palsy uses an airway clearance device (not specified) that can generate high-frequency oscillations at the airway opening or on the chest wall.
• An 18-year-old with cerebral palsy and severe scoliosis uses an insufflation-exsufflation device, which inflates her lungs with positive pressure, followed by negative pressure to simulate a cough.
• A CF patient uses the active cycle of breathing technique, a combination of breathing control (relaxed diaphragmatic breathing), thoracic expansion control (deep breaths), and a forced expiration technique from progressively increasing lung volumes.

Explore mucus-controlling drug therapy, mucoactive agents, and airway clearance techniques. Understand key terms like 'gel', 'mucokinetic agents', and 'rheology'. Learn about expectorants, mucolytics, and the properties of mucus.