Mucoactive Agents: Mucus-Controlling Drug Therapy PDF

Mucoactive Agents or Mucolytics Mucus-Controlling Drug Therapy 1  Chapter 9 Mucus-Controlling Drug Therapy 2 3 4 Drug Control of Mucus: A Perspective Mucociliary escalator is the major defense system Failure...

Mucoactive Agents or Mucolytics Mucus-Controlling Drug Therapy 1  Chapter 9 Mucus-Controlling Drug Therapy 2 3 4 Drug Control of Mucus: A Perspective Mucociliary escalator is the major defense system Failure of this system may result in mechanical obstruction of the airway – mucus plugging Properties of mucus Protective Lubricating Waterproofing Entraps microorganisms 5 Clinical Indication for Use To reduce accumulation of airway secretions, improve pulmonary function and gas exchange, prevention of repeated infection and airway damage Diseases: Cystic fibrosis (CF) Chronic bronchitis Pneumonia Diffuse panbronchiolitis (DPB): a rare clinicopathologic syndrome characterized by bronchiolitis and chronic sinusitis Primary ciliary dyskinesia: a rare genetic lung disorder, also known as Immotile Cilia Syndrome and is associated with Kartagener's Syndrome. Asthma Bronchiectasis 6 Clinical Indication for Use (cont’d) Consider after: Therapy to decrease infection/inflammation Removal of irritants (including tobacco smoke) 7 Identification of Agents N-Acetylcysteine (NAC) - Mucomyst Dornase alfa - Pulmozyme Aqueous aerosols Water (sterile H2O or Hypotonic Saline) Saline (0.9% NaCl- or Isotonic Saline) Hyperosmolar saline (Hypertonic Saline 3%, 7%) 8 Mucus Statistics Normal person produces 100 mL of mucus per 24 hour period Most is reabsorbed back in the bronchial mucosa 10 mL reaches the glottis Most of this is swallowed 9  Mucociliary System Figure 9-1 Principal components and innervation of the mucociliary system in the respiratory tract. 10  Mucociliary System Figure 9-1 Principal components and innervation of the mucociliary system in the respiratory tract. 11 Terminology Mucoactive agent: Term connoting any medication or drug that has an effect on mucus secretion; may include mucolytic, expectorant, mucospissic, mucoregulatory, or mucokinetic agents. Most of these medications are thought to mobilize secretions by mechanisms other than direct thinning of mucus 12  Mucokinetic agent: Medication that increases cough or ciliary clearance of respiratory secretions. Mucoregulatory agent: Drug that reduces the volume of airway mucus secretion and appears to be especially effective in hypersecretory states, such as bronchorrhea, diffuse panbronchiolitis (DPB), CF, and some forms of asthma. 13  Mucospissic agent: Medication that increases viscosity of secretions and may be effective in the therapy of bronchorrhea. Mucolytic agent: Medication that degrades polymers in secretions. 14 15 Physiology of the Mucociliary System (cont’d) Ciliary system 200 cilia per cell Cilia are 7 μm in larger airways, 5 μm or less in smaller bronchioles 16  Physiology of the Mucociliary System (cont’d) Factors that slow the mucociliary transport rate Chronic obstructive pulmonary disease (COPD) Cystic Fibrosis (CF) Airway drying (such as with use of dry gas for mechanical ventilation) Narcotics Endotracheal suctioning 17 Physiology of the Mucociliary System (cont’d) More factors affecting mucociliary transport Airway trauma Tracheostomy Cigarette smoke Atmospheric pollutants (SO2, NO2, ozone) may transiently increase transport, especially at low concentration. At higher, toxic concentrations or with prolonged exposure these decrease transport rates Hyperoxia and hypoxia 18 Physiology of the Mucociliary System (cont’d) Food intake and mucus production No reported association between milk and dairy product intake and the upper or lower respiratory tract symptoms of congestion or nasal secretion weight 19 Respiratory Mucosa 20 Mucus in Disease States Chronic bronchitis Asthma Bronchorrhea Plastic bronchitis Cystic fibrosis 21 Viscosity and Elasticity Figure 9-7 Illustration of concepts of viscosity and elasticity. 22 Mucoactive Agents Mucolysis and mucociliary clearance Mucolytic agents decrease elasticity and viscosity of mucus because the gel structure is broken down Therapeutic options for controlling hypersecretion Remove causative factors Optimize tracheobronchial clearance Use mucoactive agents when indicated 23 Mucoactive Agents (cont’d) Mucolytics and expectorants Classic mucolytics reduce mucins by severing disulfide bonds 24 N-Acetyl-L-cysteine (NAC) Indications for use Treatment of conditions associated with viscous secretions Acetaminophen overdose 25 N-Acetyl-L-cysteine (cont’d) Mode of action NAC disrupts the structure of the mucus breaking disulfide bonds connecting mucin proteins 26 N-Acetyl-L-cysteine (cont’d) Hazards Bronchospasm Less common with 10% solution Mechanical obstruction of airway 27 N-Acetyl-L-cysteine (cont’d) Incompatibility with antibiotics in mixture Sodium ampicillin Amphotericin B Erythromycin lactobionate Tetracyclines (tetracycline, oxytetracycline) Aminoglycosides 28 Dornase Alfa (Pulmozyme) Indications and use in Cystic Fibrosis For clearance of purulent secretions To reduce frequency of respiratory infections requiring parenteral antibiotics To improve or preserve pulmonary function in these subjects 29 Dornase Alfa (Pulmozyme) (cont’d) Mode of action (when given by aerosol) Reduces viscosity and adhesivity by breaking down DNA Dose and administration Available as single-use ampule 2.5 mg of drug in 2.5 mL of clear, colorless solution Should be refrigerated and protected from light 30 Dornase Alfa (Pulmozyme) (cont’d) Dose and administration Usual dose is 2.5 mg daily Delivered by one of these tested and approved nebulizers: Hudson RCI UP-DRAFT II OPTI-NEB® Acorn II nebulizer® PARI LC PLUS nebulizer® 31 Dornase Alfa (Pulmozyme) (cont’d) Adverse effects Little difference between dornase alfa (3%) and placebo (2%) Common side effects: Voice alteration Pharyngitis Laryngitis Rash Chest pain Conjunctivitis 32 Expectorants Iodide-containing agents Iodide-containing agents (e.g., SSKI or supersaturated potassium iodide) are generally considered to be expectorants Thought to stimulate secretion of airway fluid 33 Expectorants (cont’d) Sodium bicarbonate Inflammation caused by bicarbonate is thought to draw water into secretions Has not been clinically demonstrated to improve airway mucus clearance Cannot recommend its use May be useful for Chlorine inhalation 34 Expectorants (cont’d) Guaifenesin Generally considered an expectorant Can be ciliotoxic when applied directly to respiratory epithelium Thought that expectorant action is mediated by stimulation of the GI tract 35 Mucokinetic Agents Increase cough clearance by increasing expiratory airflow or by reducing sputum adhesivity and tenacity Bronchodilators Increase ciliary beat, but this has little effect May increase mucus production 36 Mucoregulatory Medications Decrease mucus hypersecretion Steroids Anticholinergics Atropine Ipratropium bromide Tiotropium Macrolide antibiotics BIAXIN, ZITHROMAX 37 Other Mucoactive Agents Antiproteases α1-Antitrypsin (IV or inhalation) 38 Chest Physiotherapy 39 Using Mucoactive Therapy with Physiotherapy and Airway Clearance Devices (cont’d) Insufflation-Exsufflation (Cough Assist) Inflates lungs with positive pressure followed by negative pressure to simulate cough Cycle begins with positive inspiratory pressure followed by negative expiratory pressure Primary application in patients with neurological muscular weakness 40 Cough Assist 41 Using Mucoactive Therapy with Physiotherapy and Airway Clearance Devices (cont’d) High-frequency techniques High-frequency chest wall compression (HFCWC) has been shown to enhance secretion clearance Chest Vest 42 Chest Vest 43 Using Mucoactive Therapy with Physiotherapy and Airway Clearance Devices (cont’d) Flutter Valve P&PD PEP Therapy IPV EzPAP Meta Neb Chest Vest Exercise 44 45