Mucus-Controlling Drug Therapy PDF

Chapter 9 Mucus-Controlling Drug Therapy Copyright © 2016, Elsevier Inc. All rights reserved. 1 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  Properties of mucu...

Chapter 9 Mucus-Controlling Drug Therapy Copyright © 2016, Elsevier Inc. All rights reserved. 1 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  Properties of mucus  Protective  Lubricating  Waterproofing  Entraps microorganisms Copyright © 2016, Elsevier Inc. All rights reserved. 2 Clinical Indication for Use  To reduce accumulation of airway secretions, improve pulmonary function and gas exchange, prevent repeated infection and airway damage  Diseases:  Cystic fibrosis (CF)  Chronic bronchitis  Pneumonia  Primary ciliary dyskinesia  Asthma  Bronchiectasis Copyright © 2016, Elsevier Inc. All rights reserved. 3  Clinical Indication for Use (Cont.)  Consider only after:  Therapy to decrease infection/inflammation  Removal of irritants (including tobacco smoke) Copyright © 2016, Elsevier Inc. All rights reserved. 4 Identification of Agents N-Acetylcysteine (NAC) Dornase alfa Aqueous aerosols Water Saline Hyperosmolar saline (Hypertonic Saline) Copyright © 2016, Elsevier Inc. All rights reserved. 5 Physiology of the Mucociliary System  Source of airway secretions  Gel layer (0.5–20 μm)  Periciliary layer (sol layer) (7 μm)  Surface epithelial cells  Pseudostratified, columnar, ciliated epithelial cells  Surface goblet cells  Clara cells in the distal airway  Submucosal glands  With serous and mucous cells Copyright © 2016, Elsevier Inc. All rights reserved. 6  Surface-Active Phospholipids  Thin surfactant layer between the periciliary fluid and mucus gel  Prevents airway dehydration  Permits mucus spreading on extrusion from glands  Allows efficient ciliary coupling with mucus  More importantly, allows ciliary release from mucus once kinetic energy is transmitted  Surfactant therapy has been shown to be effective in treating chronic bronchitis and CF Copyright © 2016, Elsevier Inc. All rights reserved. 7 Terminology  Terminology  Mucoactive agent  Mucokinetic agent  Mucoregulatory agent  Mucospissic agent  Mucolytic agent  Most of these medications are thought to mobilize secretions by mechanisms other than direct thinning of mucus Copyright © 2016, Elsevier Inc. All rights reserved. 8  Physiology of the Mucociliary System Factors that slow the mucociliary transport rate  Chronic obstructive pulmonary disease (COPD)  CF  Airway drying (such as with use of dry gas for mechanical ventilation)  Narcotics  Endotracheal suctioning Copyright © 2016, Elsevier Inc. All rights reserved. 9 Physiology of the Mucociliary System (Cont.)  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 Copyright © 2016, Elsevier Inc. All rights reserved. 10 Physiology of the Mucociliary System (Cont.) 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  Normal hydration is necessary to maintain normal properties of mucus and is the assumption Copyright © 2016, Elsevier Inc. All rights reserved. 11  Nature of Mucus Secretion Healthy person secretes 100 mL/24 hours  Clear, viscoelastic, sticky Structure and composition of mucus  Two major classes of mucins 1. Secreted mucins 2. Membrane-tethered mucins Copyright © 2016, Elsevier Inc. All rights reserved. 12 Epithelial Ion Transport  Under normal conditions:  Healthy airway epithelia can absorb salt and water driven by an active sodium transport  Normal epithelia can also secrete liquid into periciliary fluid driven by active chloride transport through ion channels and passively through aquaporins or water channels 13 Copyright © 2016, Elsevier Inc. All rights reserved. 13  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 ◼ Mucolytics ◼ Expectorants Copyright © 2016, Elsevier Inc. All rights reserved. 14  N-Acetyl-L-cysteine (NAC)  Indications for use  Treatment of conditions associated with viscous secretions  Despite in vitro mucolytic activity and long history of use, no data demonstrate oral or aerosolized NAC is effective for any lung disease  Acetaminophen overdose ◼ Mode of action ◼ NAC disrupts the structure of the mucus polymer by substituting free thiol (sulfhydryl) groups for disulfide bonds connecting mucin proteins Copyright © 2016, Elsevier Inc. All rights reserved. 15 N-Acetyl-L-cysteine (NAC) Cont..  Hazards Bronchospasm  Less common with 10% solution Mechanical obstruction of airway Incompatibility with antibiotics in mixture 16 Copyright © 2016, Elsevier Inc. All rights reserved. 16  Dornase Alfa (Pulmozyme)  Indications and use in CF  For clearance of purulent secretions  To reduce frequency of respiratory infections requiring parenteral antibiotics  To improve or preserve pulmonary function in these subjects ◼ 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 Copyright © 2016, Elsevier Inc. All rights reserved. 17  Mucoactive Agents ◼ Hyperosmolar saline (7%) (HTS: Hypertonic Saline) ◼ May increase FEV1 in patients ◼ Alternate effect is an acute decrease in FEV1 ◼ Unpleasant taste; coughing may make it unsuitable for long-term use Copyright © 2016, Elsevier Inc. All rights reserved. 18 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 Copyright © 2016, Elsevier Inc. All rights reserved. 19 Mucoregulatory Medications Decrease mucus hypersecretion  Steroids  Anticholinergics  Atropine  Ipratropium bromide  Tiotropium  Macrolide antibiotics Copyright © 2016, Elsevier Inc. All rights reserved. 20  Mucoactive Therapy  Gravity  Not primary mechanism for normal mucociliary transport  Postural drainage may show benefit when incorporated into conventional chest physiotherapy (CPT) ◼ Insufflation-Exsufflation ◼ Inflates lungs with positive pressure followed by negative pressure to simulate cough ◼ Cycle begins with inspiratory pressure 25–35 cm H2O for 1–2 seconds, followed by expiratory pressure of -30–-40 cm H2O for 1–2 seconds ◼ Primary application in patients with neurological muscular weakness Copyright © 2016, Elsevier Inc. All rights reserved. 21  Mucoactive Therapy Cont. Autogenic drainage  Aims to “optimize” airflow in various generations of bronchi to move secretions  Active cycle of breathing (ACB) and forced expiratory technique (FET) maneuver  Combination of:  Breathing control (relaxed diaphragmatic breathing)  Thoracic expansion control (deep breaths)  Forced expiration technique from progressively increasing lung volumes  No documented studies showing benefit 22 Copyright © 2016, Elsevier Inc. All rights reserved. 22  Mucoactive Therapy (Cont.)  Chest wall compression  The Vest®  Reported to be effective for secretion clearance in patients with CF  Conjecture is that this device has a role in lung expansion for patients other than those with cystic fibrosis in acute care settings Copyright © 2016, Elsevier Inc. All rights reserved. 23 Mucoactive Therapy Cont.. Positive airway pressure techniques  Can be effective alternatives to chest physical therapy in expanding lungs and mobilizing secretions  Cough  FET  Pursed-lipped breathing 24 Copyright © 2016, Elsevier Inc. All rights reserved. 24 Mucoactive Therapy (Cont.) ◼ Oscillation of airway ◼ The FLUTTER® ◼ The Percussionator®  Exercise  Causes increased sputum production compared with rest  Appears to augment bronchial hygiene Copyright © 2016, Elsevier Inc. All rights reserved. 25