Transcript Mucolytics - Macomb

Mucolytics
Module E
Mucolysis
• Mucolysis is the breakdown of mucus.
• Mucolysis is needed in diseases in which
there is increased mucus production:
•
•
•
•
Cystic Fibrosis
COPD
Bronchiectasis
Respiratory Infections
• Turberculosis
Mucolysis
• These diseases result in a marked slowing
of mucus transport
• Changes in properties of the mucus
• Decreased ciliary activity
• Both
Mucolytics
• acetylcysteine
• sodium bicarbonate (NaHCO3)
• dornase alfa
• Pulmozyme
Airway Anatomy
Mucus Layer
• Gel (1 to 2 mm): Gelatinous and sticky (flypaper)
• Sol (4 to 8 mm): Watery, Cilia in this layer
• Total layer thickness: 5 to 10 mm thick
• Surface Epithelial Cells
•
•
•
•
Pseudostratified ciliated columnar
Surface goblet cells (6,800/mm2)
Serous cells – Sol layer
Clara cells – Unknown function (enzymes?)
• Submucosal Gland
• Bronchial Gland
Mucus Layer
• Bronchial Gland
•
•
•
•
•
Found in submucosa
Found down to terminal bronchioles
Parasympathetic control (Vagus nerve)
Provide the majority of mucus secretion
Total volume 40 times greater than goblet cells
Mucus vs. Sputum
• Mucus is the total secretion from mucous
membranes including the surface goblet
cell and the bronchial glands.
• Sputum is the expectorated secretions that
contains mucus, as well as oropharyngeal
and nasopharyngeal secretions (saliva).
Mucociliary Escalator
• Mucosal Blanket
• Sol layer
• Gel layer
• Cilia
•
•
•
•
•
200 per cell
6 mm in length
Beat 1000/min
Move mucus 2 cm/min
Paralyzed by cigarette smoke
Viscosity and Elasticity
• Rheology
• Viscosity: Property of a liquid that measures the
resistance to movement when a force is applied.
• Increased viscosity, increased resistance to flow
• Olive oil vs. Water
• Elasticity: Property of solid whereby a solid
changes shape (deforms) when a force is
applied.
• Ideally, a solid is totally elastic, and returns to its
original shape when force is released.
• The mucus layer is ideally very elastic and has a
very low viscosity.
Function of Mucociliary
Escalator
• Protective function
• Remove trapped or inhaled particles and dead
or aging cells.
• Antimicrobial (enzymes in sol/gel)
• Humidification
• Insulation (prevents heat and moisture loss)
• NOTE: No cilia or mucus in lower airways
(respiratory bronchioles on down)
• Mucus also protects the epithelium from
toxic materials.
Structure and Composition of
Mucus
• Composition
• 95% water
• Need for water intake to replenish
• Mucus doesn’t easily absorb water once created
• 3% protein and carbohydrates
• 1% lipids
• Less than 0.3% DNA
Structure and Composition of
Mucus
• Glycoprotein
• Large (macro)molecules
• Strands of polypeptides (protein) that make up
the backbone of the molecule
• String of amino acids
• Carbohydrate side chains
• Chemical bonds “hold” mucus together
• Intramolecular: Dipeptide links
• Connect amino acids
• Intermolecular: Disulfide and Hydrogen bonds
• Connect adjacent macromolecules
Mucus Production
• 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
• Mucus production increases with lung
disease
Increased Mucus Production
•
•
•
•
•
•
Smoking
Environmental irritants
Allergy
Infections
Genetic predisposition
Foreign bodies
Increased Mucus Production






Viscosity of mucus
Ciliary effectiveness
Mucus plugs
Airway Resistance
Infections
Obstructed bronchioles leads to
atelectasis
Diseases that Increase Mucus
Production
•
•
•
•
•
Chronic Bronchitis
Asthma
Cystic Fibrosis
Acute Bronchitis
Pneumonia
• Also some drugs (anticholinergics,
antimuscarinics)
Factors that Impair Ciliary
Activity
•
•
•
•
•
•
•
Endotracheal tubes
Temperature extremes
High FiO2 levels
Dust, Fumes, Smoke
Dehydration
Thick Mucus
Infections
Facilitation of Mucus
Clearance
• Provide adequate hydration
• Increase fluid intake orally or IV
• Remove causative factors
• Smoking, pollution, allergens
• Optimize tracheobronchial clearance
• Use Mucolytics
• Reduce Inflammation
Dairy Intake
• No evidence to support the common belief
that drinking milk increases the production
of mucus or phlegm and congestion in the
respiratory tract
• There is a loose cough associated with
milk intake
Secretion Management
• Increase the depth of the sol layer
• Water
• Saline
• Expectorants
• Alter the consistency of the gel layer
• Mucolytics
• Improve ciliary activity
• Sympathomimetic bronchodilators
• Corticosteroids
Bland Aerosols
• “Dilutes” mucus molecule
• Also known as wetting agents
• Function may be more of an irritant than a wetter
• Types
• Sterile & Distilled Water
• Humectant
• Dense aerosols and asthmatics
• Normal (isotonic) Saline
• Hypertonic Saline
• Increase mucus production
• Hypotonic Saline
Expectorants
• Iodides
• Unclear function
• SSKI (Saturated Solution of Potassium Iodide)
• Guifenesin
• At high doses, stimulates bronchial gland
secretion
• Robitussin
Cough Suppressants
• Vagal stimulation causes a cough.
• Irritation of pharynx, larynx, and bronchi
lead to a reflex cough impulse.
• If the cough is dry and non-productive, it
may be desirable to suppress its activity.
• Cough suppressants depress the cough
center in medulla (?).
• Narcotic preparations (codeine)
• Non-Narcotic preparations (dextromethorphan)
• Caution in patients with thick secretions.
Function of Mucolytics
• Weakening of intermolecular forces binding
adjacent glycoprotein chains
• Disruption of Disulfide Bonds
• Alteration of pH to weaken sugar side
chains of glycoproteins
• Destruction of protein (Proteolysis)
contained in the glycoprotein core of
proteolytic enzymes
• Breaking down of DNA in mucus
Function of Mucolytics
• Disruption of Disulfide Bonds
• acetylcysteine breaks the bonds by substituting a
sulfhydril radical –HS
Function of Mucolytics
• Alteration of pH
• 2% NaHCO3 solutions are used to increase the
pH of mucus by weakening carbohydrate side
chains
• Can be injected directly into the trachea or
aerosolized (2-5 mL)
Function of Mucolytics
• Proteolysis
• Dornase alfa (Pulmozyme)
• Attacks the protein component of the mucus
Hazard of Mucolytics
• The problem with all three mucolytics is
that they destroy the elasticity of mucus
while reducing the viscosity.
• Elasticity is crucial for mucociliary
transport.
• The patient must be able to cough
adequately to remove the mucus.
acetylcysteine
• Indications
• Mucolytic by aerosol or direct instillation into
the ET tube.
• Given orally to reduce liver injury with
acetaminophen (Tylenol) overdose.
• Mix with cola or given by NG tube.
Dosage of acetylcysteine
• Concentration
• 10% or 20%
• Dosage
• 3-5 mL of a 20% solution TID or QID
• Maximum dose 10 mL
• 6-10 mL of a 10% solution TID or QID
• Maximum dose 20 mL
• 1-2 mL of a 10% or 20% for direct
instillation
Hazards of acetylcysteine
• Bronchospasm
• Asthma – may be a problem during an acute
asthma attack.
• Anecdotal; lack of evidence
• If used with asthma, use 10% and mix with a
bronchodilator (preferably a short-acting
agent).
• Increase mucus production
• Be prepared to suction a patient who cannot
cough or who is intubated.
Hazards of acetylcysteine
• Do not mix with antibiotics in the same
nebulizer (incompatible).
• Nausea & Vomiting
• Disagreeable odor (smells like rotten eggs)
due to the hydrogen sulfide.
• Open vials should be used within 96 hours
to prevent contamination.
sodium bicarbonate
• Weak base.
• Increasing the pH of mucus weakens the
polysaccharide chains.
• Available as 1.4%, 5%, and 7.5% solutions.
• Dosage: 2-5 mL of a 2.5% solution Q4-Q8.
• Mix 5% solution with equal volume of sterile
water.
• Can be irritating (especially the 5 & 7.5%
solutions).
dornase alfa
• Pulmozyme
• Clone of the natural human pancreatic
DNase enzyme which digests extracellular
DNA.
• Dornase alfa is a solution of recombinant
human deoxyribonuclease (rhDNase)
• Approved by FDA in 1994
dornase alfa – Pulmozyme
• Indications
• Reduce viscosity of secretions during an
infection by breaking down extracellular DNA.
• Used in cystic fibrosis, chronic bronchitis or
bronchiectasis.
• Maintenance therapy in CF
• Has no effect on non-infected sputum.
Infection
• Increased WBCs – neutrophils
• WBCs contain DNA
• WBCs release DNA when they die which
increases the viscosity of secretions
• Decreases the effectiveness of antibiotics
• Pancreas produces an enzyme called
deoxyribonuclease (DNase) which breaks
down the DNA
•
Function of rhDNase
Concentration and Dosage
•
•
•
•
Supplied in single dose vials (unit dose).
Concentration is 1 mg/mL (0.1% solution).
Each vial contains 2.5 mg /2.5 mL.
Administer one unit dose vial (2.5 mL)
daily.
• Some patients may benefit from BID
administration.
• Do not mix or dilute with other drugs.
• Nebulizer specific (per manufacturer).
Common Side Effect of
Pulmozyme
•
•
•
•
•
Voice Alteration
Pharyngitis/Laryngitis
Rash
Chest pain
Conjunctivitis
• Contraindicated in patients hypersensitive
to Chinese Hamster Ovary cell products.
amiloride
• Midamor
• Diuretic that can be given by aerosol for patients
with cystic fibrosis.
• It is a sodium channel blocker.
• In Cystic Fibrosis, Na+ is absorbed into the
epithelium along with H2O, leaving the mucus
thick and dehydrated.
• By blocking sodium absorption, dehydration of
the mucus is prevented.
• Drug is dissolved in 0.3% NaCl solution and
nebulized.
• Bronchial Asthma (?)
amiloride
denusfosol tetrasodium
• Experimental drug in CF research
• Phase II as of 8/07
• Enhances mucosal hydration and mucus
clearance by activating Cl- secretion and
inhibiting epithelial Na+ transport.
• 28 days of treatment