Mucus Controlling Agents
Drug Control of Mucus
I.
One of the major defense mechanisms of the lung is the selfrenewing, self-cleansing mucociliary escalator
a. Mucus seems to serve protective purposes
i. Lubrication
ii. Waterproofing
iii. Protection against osmotic changes
iv. Protection against inflammatory changes
b. Failure of this system results in mechanical obstruction of the
airway, with thickened, adhesive secretions
II.
Historically, drug therapy for respiratory secretions has been aimed
at liquefying thick mucus to a watery state
III.
Diseases associated with abnormal mucociliary function
a. Bronchitis
i. ATS definition: daily, productive cough for 3 consecutive
months each year for 2 consecutive years
ii. Hypertrophy of submucosal glands
iii. Increased number of goblet cells
b. Bronchiectasis
i. dilation and distortion of bronchi leading to impaired
clearance
c. Cystic fibrosis
i. increased viscosity of secretions leading to impaired
clearance
ii. retention of secretions leads to chronic bacterial infection
d. Asthma
i. increased mucus production
1. during acute episode
2. may be a chronic feature of asthma
Clinical Indication for Use
I.
To reduce accumulation of airway secretions
a. improvement in pulmonary function
b. improvement in gas exchange
c. prevention of repeated infection
d. prevention of airway damage
Identification of Agents
Drug
Acetylcysteine 10%
Brand Name
Mucosil-10
Adult Dosage
SVN: 6-10 ml tid
or qid
Use
Secretion
mobilization
Acetylcysteine 20%
Mucomyst,
Mucosil-20
SVN: 3-5 ml of
20% solution tid
or qid
Direct Instillation:
1-2 ml
Secretion
mobilization
Dornase alfa
Pulmozyme
Cystic
fibrosis
Aqueous solutions:
Water, saline
(0.45%, 0.9%,
5-10%)
N/A
SVN: 2.5 mg
ampule, one
ampule qd
SVN: 3-5 ml
USN: 3-5 ml
Sputum
induction,
secretion
mobilization
Physiology of the Mucociliary System
I.
Components of the mucociliary system
a. Surface epithelial cells
b. Pseudostratified, columnar, ciliated epithelial cells
c. Surface goblet cells
d. Clara cells in the distal airways
e. Submucosal glands
i. Serous cells
ii. Mucous cells
II.
Mucociliary Escalator
a. Primary defense mechanism against mucus obstruction in the
airways
b. Lines the nasal cavity, oropharynx and the conducting airways
III.
Mucus Production
a. Submucosal glands
i. found in the cartilaginous airways
ii. produce the majority of the mucous blanket
iii. secretions from the mucous cells and serous granular cells
mix together and are secreted through a ciliated duct onto
the airway lumen
iv. under parasympathetic (vagal) control
1. respond to cholinergic stimulation
a. increased mucus production
v. also respond to sympathetic stimulation
vi. histology of the lining of the tracheobronchial tree
ep=surface epithelial cells
LP=lamina propria
d = ducts of submucosal glands
b. Goblet cells
i. Found in the cartilaginous airways
ii. interspersed among the ciliated columnar cells (5:1)
iii. Not directly innervated by the nervous system
1. respond to irritation
2. may respond to sympathomimetic agents
IV.
The Mucous Blanket
a. Terms
i. Mucus - total secretion from the mucous membranes
1. surface goblet cells
2. submucosal glands
ii. Sputum - mucus plus saliva
iii. Viscosity – resistance to flow
iv. Elasticity - property of deforming under force, then
resuming its previous state
b. Two layers
i. Gel
1. on top near airway lumen
2. behaves partially as a fluid
a. has viscosity
b. flows forward under applied force (cilia)
3. behaves partially as a solid
a. has elasticity
b. gel is stretched and elastic recovery moves it
forward
ii. Sol
1. adjacent to the epithelial lining
2. has some viscosity but no elasticity
3. watery airway surface fluid
V.
Ciliary System
a. Mucociliary transport results from the movement of the mucous
gel by the beating cilia
b. A ciliary beat is made up of an effective (power) stroke and a
recovery stroke
i. effective stroke
1. the cilia moves in an upright position to contact the
underside of the gel layer and move it forward
ii. recovery stroke
1. the cilia swing back around to the starting point
through the sol layer
c. Approximately 200 cilia per cell
d. Beat 660-1080 per minute
VI.
Factors Affecting Mucocilary Transport
a. COPD
b. Parasympatholytics (Atropine)
c. Narcotics
d. Endotracheal suctioning
e. Cigarette smoke
f. Atmospheric pollutants
g. Hyperoxia
h. Hypoxia
VII.
Nature of Mucus Secretion
a. Healthy individuals produce 100 ml/24 hours
b. Clear viscoelastic substance
c. Most reabsorbed in the bronchial mucosa
d. About 10 ml reaches the glottis
i. Swallowed or aspirated
e. Increased in disease states
f. Milk not found to increase mucous production
g. Functions to transport and remove trapped inhaled particles,
cellular debris, or dead and aging cells
VIII. Characteristics of Infected Mucus
a. The DNA from WBC debris changes mucus from clear to opaque
b. The enzyme myeloperoxidase (cellular breakdown) changes
mucus to yellow or green
IX.
Structure of mucus molecule
a. Complex, high-molecular-weight macromolecule
i. Polypeptide backbone (protein) formed by a string of
amino acids
ii. Carbohydrate side chain
b. Forms a flexible strand cross-linked with disulfide bonds and
sometimes hydrogen bonds
c. Constituents of Mucus
i. 95% H2O
ii. 3% protein and carb
iii. 1% lipids
iv. <0.03% DNA
Mucus Controlling Agents
I.
Terms Associated With Drug Therapy of Respiratory Secretions
Term
Definition
Mucoactive
Any agent that has an effect on mucus secretion
Mucoregulatory
An agent that reduces mucus hypersecretion to
normal levels
Mucolytic
An agent that breaks down the structure of mucus,
usually reducing viscosity and elasticity
Mucokinetic
An effect of improving the mobilization and
clearance of mucus
Mucospissic
An effect of increasing the viscosity and elasticity of
mucus secretion
Expectorant
An agent improving expectoration of respiratory
secretions, usually by stimulation of bronchial
gland output
II.
Options for controlling mucous hypersecretion
a. Remove causative factors where possible
i. Treat infections
ii. Stop smoking
iii. Avoid pollution and allergens
b. Optimize tracheobronchial clearance
i. bronchodilators
ii. bronchial hygiene
1. hydration
2. DB&C
3. PD&P
iii. Improve airflow by exercise and nutrition rehabilitation
iv. Reduce inflammation
1. antibiotics
2. corticosteroids
v. Use mucoactive agents as indicated
1. mucolytics
2. expectorants
III.
Mucolytic Agents
a. Acetylcysteine
i. Brand Names
1. Mucomyst
2. Mucosil-10
3. Mucosit-20
ii. Indications
1. treat thick secretions (inhaled or instilled (topical)
2. treat acetaminophen overdose (oral)
a. to prevent hepatic injury
iii. Administration
1. SVN: 3-5 ml of 20% solution tid or qid
2. SVN: 6-10 ml of 10% solution tid or qid
3. Direct instillation: 1-2 ml of 10% or 20% solution
iv. Mode of Action
1. the sulfhydril group substitutes for the disulfide bond in
the mucoprotein complex to decrease viscosity and
elasticity
2. See text, page 179, Figure 9-9
v. Hazards
1. bronchospasm
a. More likely with 20% solution
b. Always administer with a fast-acting betaadrenergic agent
2. stomatitis – inflammation of the stoma
3. nausea – disagreeable odor from hydrogen sulfide
4. rhinorrhea – irritation
5. mechanical obstruction of the airway
vi. Handling
1. open vial should be refrigerated
a. discard after 96 hours
2. May change to light purple color due to the preservative
EDTA
a. Does not affect safety or efficacy
b. Dornase Alfa (Pulmozyme) (1994)
i. Viscolytic enzyme
1. Clone of human enzyme that digests extracellular DNA
ii. Indication
1. to preserve or improve lung function in cystic fibrosis
2. to decrease frequency and severity of respiratory
infections
iii. Mode of Action
1. breaks down DNA in infected secretions
a. infected secretions contain DNA (neutrophils)
which increases viscosity
2. retained secretions cause infection
iv. Administration
1. 2.5 mg (1 ampule) daily, 2.5 ml
v. Handling
1. protect from light
a. protective foil pouch
2. refrigerate
3. can not be mixed with other medications
vi. Common Adverse Effects
1. voice alteration
2. pharyngitis
3. laryngitis
4. rash
5. chest pain
6. conjunctivitis
IV.
Expectorants
a. Sodium Bicarbonate
i. Administration
1. 2% solution for inhalation or tracheal irrigation 2-5 ml
ii. Mode of Action
1. increases pH of bronchial secretions
2. weakens side chain bonding to decrease viscosity and
elasticity
iii. Caution
1. may cause local bronchial irritation pH>8.0
a. No systemic pH change
2. No clinical evidence for use
b. Aqueous Solutions
i. Sterile water
ii. Saline solutions
1. hypotonic (0.45%)
2. isotonic (0.9%)
3. hypertonic (5-10%)
iii. Administration
1. SVN: 3-5 ml as ordered
2. USN: 3-5 ml as ordered
iv. Use
1. sputum induction
a. cause vagally mediated irritation to increase
coughing and mucus production
2. no evidence that they decrease mucus viscosity by
topical hydration or mixing
a. gel surface is resistant to addition or removal of
H2O
b. short term 3-5 ml adds < 1 ml of liquid to lung
c. continuous treatment with USN can add large
amount of H2O to lung and cause watery
secretions
Goal of Future Research
Agents to restore mucus to normal viscosity and elasticity
FOR NOW: Best advice is probably GOOD SYSTEMIC HYDRATION