Pharm Ch 9: Mucus Controlling Drug Therapy

Front 1

What does failure of the Mucociliary escalator result in?

Back 1

results in mechanical obstruction of the airway

Front 2

What are Causes of decreased mucus transport:

Back 2

changes in physical properties of mucus

decreased ciliary activity

Decreased hydration (more viscous sputum)

Front 3

What are the Properties of mucus?

Back 3

Protective

Lubricating

Waterproofing (helps humidify gases we breathe)

Entraps microorganisms

Front 4

What needs to be done before considering mucoactives?

Back 4

Mucoactives should only be considered after infection and inflammation have been treated.

Front 5

Define Mucolytic

Back 5

lysis = liquefying of thick mucus to a more watery state

Front 6

Focus of Mucoactive

Back 6

our focus is really aimed at (drugs that) changing the physical properties of mucus gel layer to improve mucociliary clearence

Front 7

Clinical Indication for Use

Back 7

To reduce accumulation of airway secretions, improve pulmonary function and gas exchange, prevention of repeated infection and airway damage / development of atelectasis

Front 8

Diseases to use mucolytics

Back 8

Cystic fibrosis (CF) **most common (CFTR gene dysfunctional, patient can't manage sodium chloride channels- very thick sputum- results in infectious processes)

Chronic bronchitis (increase chronic cough and sputum production)

Pneumonia

Pneumonia

Diffuse panbronchiolitis (DPB)- high vol of sputum production, larger AW bronchi

Primary ciliary dyskinesia

Asthma (usually later stages)

Bronchiectasis

Front 9

What to consider after

Back 9

Therapy to decrease infection/inflammation

Removal of irritants (including tobacco smoke)

Front 10

Mucoactive agent- effects what?

Back 10

mucus secretion

Front 11

What does a Mucokinetic agent do?

Back 11

increases cough or ciliary clearence

Drug ex: albuterol

Front 12

What does a Mucoregulatory agent do?

Back 12

– decrease volume of mucus

Front 13

What does Mucospissic agent do?

Back 13

increases viscosity of secretions

(Patient will have easier time coughing it out)

Front 14

What does Mucolytic agent do?

Back 14

degrades polymers of secretions

Front 15

Aqueous aerosols

Back 15

Water

Saline

Hyperosmolar saline 7%

Front 16

Mucoactive drugs

Back 16

Dornase alfa - Pulmozyme

N-Acetylcysteine (NAC) (mucomyst)

(Use with caution- harmful to lungs- bronchoconstriction, this is why we give bronchodilator first)

Aerosols

Front 17

Source of airway secretions

Back 17

Gel layer (0.5–20 μm)

Periciliary 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

Front 18

How many goblet cells do we have?

Where are they located?

Back 18

Surface epithelial cells

6000 goblet cells/mm2 of normal airway

Do not seem to be directly innervated in human lung

Submucosal glands

Provide airway surface mucin

Under parasympathetic control

Mucus & serous cells

Front 19

Ciliary system

Back 19

200 cilia per cell

Cilia are 7 μm in larger airways, 5 μm or less in smaller bronchioles

Effective (power) stroke

Recovery stroke

Functional surfactant layer separates periciliary fluid from mucus gel

Front 20

Factors that slow the mucociliary transport rate

Back 20

Chronic obstructive pulmonary disease (COPD)

CF

Airway drying (such as with use of dry gas for mechanical ventilation)

Dehydration

Narcotics

Endotracheal suctioning

Front 21

factors affecting mucociliary transport

Back 21

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

Front 22

Healthy person secretes how much mucus?

Back 22

100 mL/24 hours

Clear, viscoelastic, sticky

Front 23

Structure and composition of mucus

Two major classes of mucins

Back 23

1. Secreted mucins

2. Membrane-tethered mucins

Front 24

Epithelial Ion Transport under normal conditions

Back 24

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

Front 25

Chronic bronchitis is

Back 25

daily sputum production 3 months/year for 2 consecutive years

Front 26

Asthma and mucus

Back 26

hypersecretion during asthma episode, typically late phase

(80% have increased production)

Front 27

Bronchorrhea

Back 27

production of large volumes of watery sputum

Front 28

Plastic bronchitis

Back 28

rare disease, airway casting

Front 29

Cystic fibrosis

Back 29

hereditary, impaired function of CFTR protein.

Chronic inflammation and infection – bronchiectasis, progressive pulmonary decline

Front 30

Attractive forces between mucus and airway surface

Back 30

Adhesion- reduces secretion clearence

Abhesive agents- example surfactant Reduce adhesivity and/or

Agents that increase the power of airflow a

Front 31

Cohesive forces

Back 31

Attractive forces between like molecules

Spinnability

Rheology

Study of deformation and flow of matter

How it responds to applied force (stress)

Viscosity

Resistance of fluid to flow

Elasticity

Ability of deformed material to return to its original shape

Front 32

Spinnability (cohesivity) of mucus

Back 32

Ability of mucus to be drawn out into threads was initially identified for cervical mucus and was termed “spinability”

Gives information about internal cohesion forces of mucus

Increases with increased elasticity

Mixed findings with regards to effect on ciliary transport

Front 33

Tenacity

Back 33

Tenacity – “Tenacious”

Greater tenacity = decreased ability to clear via cough

Front 34

Mucolysis and mucociliary clearance

Back 34

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

Front 35

Mucolytics and expectorants

Back 35

Classic mucolytics reduce mucins by severing disulfide bonds or charge shielding

Front 36

N-Acetyl-L-cysteine (NAC) Indications

Back 36

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

Front 37

N-Acetyl-L-cysteine mode of action

Back 37

NAC disrupts the structure of the mucus polymer by substituting free thiol (sulfhydryl) groups for disulfide bonds connecting mucin proteins (decrease Elasticity)

Front 38

N-Acetyl-L-cysteine hazards

Back 38

Bronchospasm

Less common with 10% solution

BronchospasmLess common with 10% solutionMechanical obstruction of airway

Mechanical obstruction of airway

Front 39

N-Acetyl-L-cysteine hazards

Back 39

Bronchospasm

Less common with 10% solution

Mechanical obstruction of AW

Front 40

N-Acetyl-L-cysteine incompatable with

Back 40

Incompatibility with antibiotics in mixture

Sodium ampicillin

Amphotericin B

Erythromycin lactobionate

Tetracyclines (tetracycline, oxytetracycline)

Aminoglycosides

Front 41

Dornase Alfa (Pulmozyme) Indications

Back 41

**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

Front 42

Dornase Alfa (Pulmozyme) mode of action

Back 42

(when given by aerosol)

Reduces viscosity and adhesivity by breaking down DNA

Front 43

Dornase Alfa (Pulmozyme) dose and administration

Back 43

Available as single-use ampoule 2.5 mg of drug in 2.5 mL of clear, colorless solution

Should be refrigerated and protected from light

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®

Give Alone!! Usually has its own nebulizer: peri-neb (breath enhanced nebulizer)-wash/disinfect after each use

Front 44

Dornase Alfa (Pulmozyme) adverse effects

Back 44

Little difference between dornase alfa (3%) and placebo (2%)

Common side effects:

Voice alteration

Pharyngitis

Laryngitis

Rash

Chest pain

Conjunctivitis

Front 45

Dornase Alfa (Pulmozyme) clinical application

Back 45

Based not only on lung function, but also on:

Reduction in number and severity of infectious exacerbations

Need for antibiotics and hospitalization

Front 46

Mucokinetic Agents

Back 46

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

Front 47

Surface-Active Phospholipids

Back 47

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

Front 48

Mucoregulatory Medications

Back 48

Decrease mucus hypersecretion

Steroids

Anticholinergics

Atropine

Ipratropium bromide

Tiotropium

Macrolide antibiotics

Front 49

Hypeemolar saline

Mucoactive

Back 49

May increase fev1 or decrease

Unpleasant taste, coughing may make it Unsuitable for long time use

Front 50

Insufflation-Exsufflation

Back 50

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

Front 51

Autogenic drainage

Back 51

to "optimize" airflow in various generations of bronchi to move secretions

Incorporates staged breathing starting with small tidal breaths from expiratory reserve volume (ERV), repeated until secretions "collect" in central airways

Patients are instructed to suppress cough, and larger volume is taken for a series of 10–20 breaths, followed by a series of even larger (approaching vital capacity [VC]) breaths, and followed by several huff coughs

Front 52

Positive airway pressure techniques

Back 52

Can be effective alternatives to chest physical therapy in expanding lungs and mobilizing secretions

Cough

FET (Forced expiratory technique)Pursed-lipped breathing

Front 53

Oscillation of airway tools

Back 53

The FLUTTER®

The Percussionator (IPV)

Aerobika ®

Front 54

Chest wall compression

Back 54

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

Front 55

Future Mucus-Controlling Agents

Back 55

Thicker and denser strands of mucus would be moved more efficiently by ciliary contact and elastic recovery than would thin, low-viscosity solutions

Endotracheal aspiration of secretions using suction would be easier with low-viscosity mucus

Treatment of bronchial hypersecretion would be better aimed at normalizing the rheological properties of mucus to optimize transport

Mucospissic agents

Front 56

Before treatment assessment

Back 56

Level of consciousness (LOC)

Adequacy of cough (measure peak flow)

Need for adjunct bronchial hygiene

Front 57

During treatment and short term

Back 57

Correct use of equipment

Assess therapy

Airflow changes

Adverse effects

Mucus production

Respiratory rate and pattern

Subjective response

Adverse reactions

Front 58

Long term

Back 58

Number and severity of:

Infections

ER visits

Hospitalizations

Need for antibiotics

Pulmonary function testing

Front 59

Contraindications

Back 59

Profound airflow compromise

(FEV1 < 25% predicted) need to intubate

Severely compromised: decreased in lung functions

(VC , Expiratory flow)

Gastroesophageal reflux disease (GERD)

Inability to protect airway (need to be intubated)

Acute bronchitis or exacerbation of chronic disease may leave patient less responsive to treatment