Advanced Pharmacology
Respiratory Pharmacology
Thomas W. Barkley, Jr., PhD, ACNP‐BC, FAANP
President, Barkley & Associates
www.NPcourses.com
and
Professor of Nursing
Director of Nurse Practitioner Programs
California State University, Los Angeles
Robert Fellin, PharmD, BCPS
Faculty, Barkley & Associates
Pharmacist, Cedars‐Sinai Medical Center
Los Angeles, CA
Unit 5
©2014 Barkley & Associates
Allergic Rhinitis
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Unit 5
Allergic rhinitis (hay fever) – resembles the
common cold:
 Tearing
 Sneezing
 Nasal congestion
 Postnasal drip
 Itchy throat
Due to antigen (allergen) exposure
 Pollen, mold spores, dust mites, certain foods,
animal dander
 Genetic predisposition
http://www.theage.com.au
©2014 Barkley & Associates
1
Allergic Rhinitis

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Seasonal vs. perennial allergic rhinitis
Pathophysiology: Inflammation of the mucous membranes in the
nose, throat and airways
Normal nasal mucosa has many mast cells and basophils (try to
recognize environmental agents as the enter the body)
 Allergic rhinitis patients have more mast cells
Histamine (chemical mediator of inflammation): responsible for
many of the symptoms of allergic rhinitis
H1-receptors: Responsible for allergic symptoms
Unit 5
©2014 Barkley & Associates
H1-receptor Antagonists/Antihistamines
FIRST
Generation
Agents:
brompheniramine (Dimetapp), chlorpheniramine (Chlor-Trimeton),
clemastine (Tavist), cyproheptadine (Periactin),
dexchlorpheniramine (Polaramine), dimenhydrinate (Dramamine),
diphenhydramine (Benadryl), hydroxyzine (Atarax, Vistaril),
promethazine (Phenergan)
Adverse Effects: sedation, dry mouth, headache, dizziness, urinary retention,
thickening of bronchial secretions, nausea, vomiting, hypotension,
tachycardia, QT prolongation
Comments:
Unit 5
All equally effective
Often combined with decongestant/antitussive
Most effective when taken prophylactically to prevent allergic
symptoms
Ability to reverse acute allergic symptoms is limited
Caution with alcohol and other CNS depressants
Some patients experience paradoxical excitation
©2014 Barkley & Associates
2
H1-receptor Antagonists/Antihistamines
SECOND
Generation
Agents:
azelastine (Astelin), cetirizine (Zyrtec), desloratadine (Clarinex),
fexofenadine (Allegra), levocetirizine (Xyzal), loratadine (Claritin),
olopatadine (Patanase, Patanol)
Adverse Effects: dry mouth, headache, dizziness, drowsiness, bitter taste
(olopatadine), nausea, hypotension, sedation (less than 1st
generation)
Comments:
Azelastine: intranasal formulation
Most effective when taken prophylactically to prevent allergic
symptoms
Ability to reverse acute allergic symptoms is limited
All equally effective
Caution with alcohol and other CNS depressants
Some patients experience CNS stimulation (nervousness,
insomnia, tremor, etc.)
Considered less effective than 1st generation agents
Unit 5
©2014 Barkley & Associates
Nasal Decongestants
Agents:
naphazoline (Privine), oxymetazoline (Afrin), phenylephrine (NeoSynephrine), pseudoephedrine (Sudafed)
MOA:
sympathomimetic, alpha-adrenergic activity
Adverse Effects:
Intranasal: transient nasal irritation, burning, sneezing, nasal dryness,
rebound congestion
All: headache, nervousness, insomnia, headache, dry mouth, CNS
excitation, tremors, dysrhythmias, tachycardia, difficulty in voiding
Comments:
Provide immediate relief for acute allergy symptoms
Intranasal: duration should not exceed 3 to 5 days as tolerance
develops
Tolerance: gradually switch to intranasal corticosteroids
Oral products do not produce rebound congestion
Prolonged use: hypersecretion of mucus, worsening nasal congestion
Onset of action: intranasal much faster than oral agents
Do not relive sneezing, tearing
Unit 5
©2014 Barkley & Associates
3
Intranasal Glucocorticoids
Agents:
MOA:
Adverse
Effects:
Comments:
Unit 5
beclomethasone (Beconase AQ), budesonide (Rhinocort
Aqua), ciclesonide (Omnaris), flunisolide (Nasalide),
fluticasone (Flonase), mometasone (Nasonex), triamcinolone
acetonide (Nasacort AQ)
reduce inflammation, edema; cause vasoconstriction
transient nasal irritation, burning, sneezing, nasal dryness,
epistaxis
DOC for allergic rhinitis
Minimal adverse effects
All administered by metered-spray device
All equally effective
May take 3-4 weeks to achieve peak response
Most effective when taken in advance of expected allergen
exposure
©2014 Barkley & Associates
Miscellaneous Agents
Agents:
cromolyn (NasalCrom), ipratropium (Atrovent), montelukast
(Singulair)
MOA:
mast cell stabilizer, anti-inflammatory (cromolyn)
anticholinergic agent (ipratropium)
leukotriene receptor antagonist (montelukast)
Adverse Effects: nasal burning, irritation (cromolyn)
nasal irritation, burning, sneezing, nasal dryness, cough, HA
(ipratropium)
HA, nausea, diarrhea (montelukast)
Comments:
Unit 5
Reserved for patients unresponsive to other therapies
May take 4 weeks to achieve peak response
Most effective when taken in advance of expected allergen
exposure
Limited effectiveness/less effective than other agents
Role of montelukast remains to be defined
©2014 Barkley & Associates
4
Antitussives: Opioids
Agents:
MOA:
Adverse
Effects:
Comments:
Unit 5
codeine, (Robitussin-AC), dextromethorphan (Benylin,
Delsym), hydrocodone (Hycodan)
suppress the cough reflex via CNS
lightheadedness, sedation, nausea, headache and
dizziness
Most effective agents available for cough suppression
Suppression of cough obtained at doses lower than those
needed for analgesia
Dextromethorphan max dose: 120 mg/day
Dextromethorphan: most frequently used antitussive (OTC
cough & cold products)
Use of codeine/hydrocodone has diminished
Codeine/hydrocodone: controlled substances
©2014 Barkley & Associates
Antitussives: Non-Opioids
Agents:
MOA:
Adverse
Effects:
Comments:
Unit 5
benzonatate (Tessalon Perles)
anesthetizes the stretch receptors in the lungs,
thus suppressing cough
nausea, dizziness, headache, sedated,
somnolence
Benzonatate requires prescription
Well tolerated with minimal adverse effects
Do not crush/chew benzonatate = numbing of the
mouth and pharynx
Chemically related to local anesthetics
©2014 Barkley & Associates
5
Expectorants
Agents:
MOA:
guaifenesin (Robitussin)
increases the volume and reduces the viscosity
of secretions in the trachea and bronchi
Adverse
Effects:
Comments:
nausea, vomiting
Most effective OTC expectorant (?)
Common ingredient in many OTC cough and
cold preparations
Maximum dose: 2400 mg/24 hours
Unit 5
©2014 Barkley & Associates
FDA Statements: OTC Cold Products
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Unit 5
Not appropriate to take data from adults
and apply it to children under 12 years of
age
Products containing decongestants,
antihistamines and antitussives are NOT
effective in children < 6 years of age – and
may cause serious side effects
FDA: strongly recommend NOT using such
OTC products in children < 2 years of age
More studies about how these medicines
affect children are needed
www.sharp.com
©2014 Barkley & Associates
6
Mucolytics
Unit 5
©2014 Barkley & Associates
N-Acetylcysteine (Mucomyst)
Indications:
Adjuvant therapy in patients with abnormal or viscid
mucous secretions in acute and chronic bronchopulmonary disease
MOA:
exerts mucolytic action through its free sulfhydryl group
which opens up the disulfide bonds in the mucoproteins
thus lowering mucous viscosity
Dose:
1 mL of 20% solution or 2 mL of 10% solution via
nebulizer 4 times/day
Adverse
Effects:
Comments:
Nausea, vomiting, bronchospasm
Unit 5
Patients should receive a bronchodilator prior to
administration
©2014 Barkley & Associates
7
Dornase Alfa (Pulmozyme)
Indications:
Adjunct management of CF to reduce the frequency
of respiratory infections, and to improve pulmonary
function
MOA:
recombinant Human Deoxyribonuclease (rHDNase);
selectively cleaves DNA of neutrophils thereby
decreasing mucous viscosity
Dose:
2.5mg nebulized inhalation daily
Adverse
Effects:
chest pain, pharyngitis, cough dyspnea, hemoptysis,
wheezing, rash, conjunctivitis
Comments:
Should not be used routinely as a mucolytic outside
cystic fibrosis patients
Unit 5
©2014 Barkley & Associates
Drugs for Lower
Pulmonary Disorders
Unit 5
©2014 Barkley & Associates
8
Pulmonary Drugs via Inhalation
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
Aerosol – suspension of minute liquid droplets or fine sold
particles suspended in gas
Major Advantage: Delivers drugs to the immediate site of
action (reducing systemic effects)
 An oral drug would have to be given in a higher dose to
have an equivalent therapeutic dose
 All inhalation agents have the potential to produce
systemic effects (e.g., anesthetics, paint thinners, etc.)
Unit 5
©2014 Barkley & Associates
Devices for Inhalation
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Unit 5
Metered Dose Inhalers (MDIs) – use a propellant to deliver
a measured dose of drug to the lungs during each breath of
drug emitted from the MDI
Dry Powder Inhalers (DPIs) – small device that is activated
by inhalation to deliver a fine powder directly to the
bronchial tree
Nebulizers – small machines that vaporize a liquid
medication into a fine mist that can be inhaled, using a face
mask of handheld device
©2014 Barkley & Associates
9
Methods of Aerosol Delivery
Population
Optimal technique
Therapeutic issues
MDI
Age > 5 years
old
Actuation during slow deep
inhalation followed by 10
second breath holding
Open mouth technique
Close mouth technique
Deposition of 50~80% of
actuated dose in oralpharynx
Spacer and
Valve holding
chamber
Age > 4 years old
Actuation during slow deep
inhalation followed by 10
second breath holding
Bulky to carry
Decrease oral-pharyngeal
deposition & decrease risk
of thrush
Nebulizer
For patient who
cannot use MDI or a
face mask
Slow tidal breathing with
occasional deep breaths
Using a “blow-by”
technique is not
appropriate
Output is dependent on
device and operating
parameters
Use of face mask
decreases delivery to lungs
by 50%
Expert Panel Report: NHLBI Guidelines for the Diagnosis and Management of Asthma - Summary Report 2007
http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm
Unit 5
©2014 Barkley & Associates
Disadvantages of Aerosols
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Precise dose received by the patient is difficult to measure
 Optimally, only 10-50% actually reaches the lower
respiratory tract
Swallowing medication may cause systemic SE
 Rinse mouth thoroughly after use
http://www.myrespiratorysupply.com
Unit 5
http://www.aafa.org
www.parknicollet.com
©2014 Barkley & Associates
10
Which Method of Drug Delivery is Superior?
Metered-Dose
Inhaler
Unit 5
Nebulizer
Dry Powder
Inhaler
Pharmacology for Nurses: A Pathophysiologic Approach (4th Edition)
©2014 Barkley & Associates
Asthma
“Chronic inflammatory disorder of the airways… causing
recurrent episodes of wheezing, breathlessness, chest
tightness and coughing…that is reversible either
spontaneously or with treatment.”
 22.9 million people in the US have asthma
 One of the most common chronic diseases of childhood
 Variability in response to medications requires
individualization of therapy
Unit 5
©2014 Barkley & Associates
11
Asthma
 Increased
responsiveness of the trachea and bronchi to stimuli
 Narrowing of airways
http://www.lincoln.ne.gov/city/health/environ/pollu/dirtair.htm
Unit 5
©2014 Barkley & Associates
Asthma: Pathophysiological Characteristics
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Hypertrophy of smooth muscle
Mucosal edema and hyperemia
Thickening of epithelial
basement membrane
Hypertrophy of mucus gland
Acute inflammation
Plugging of airways by thick,
viscous mucus
http://www.asthmainschools.com/index.php?option=com_content&view=article&id=59&Itemid=51
Unit 5
©2014 Barkley & Associates
12
Asthma
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Most important allergens are encountered indoors!
 Dust, pets, roaches, molds, cigarette smoke, exercise, etc.
Labs/Diagnostics
 Signs and symptoms (intermittent dyspnea, cough &
wheezing)
 Physical exam & Patient history
 PFT values (spirometry)
 Chest x-ray findings: hyperinflation
2007 Asthma Guidelines: National Heart, Lung and Blood
Institute
Unit 5
©2014 Barkley & Associates
Classification of Asthma Severity
Asthma Severity
Components of
Severity
Intermittent
Mild
Moderate
Severe
Symptoms
< 2 days/week
>2 days/week
Daily
Throughout the day
Nighttime awakening
< 2 x/month
3-4 x/month
> 1 x/week, not nightly
Often 7 x/week
Short acting β agonist for symptom
control
< 2 day/week
> 2 days/week
Daily
Several times a day
Interference with normal activities
none
Minor
Some
Extreme
FEV1
> 80%
> 80 %
60-80 %
< 60%
FEV1/ FVC
normal
normal
Reduced < 5%
Reduced > 5%
Lung function
Risk
Exacerbation requiring oral
systemic corticosteroids
Recommended Step for
Initiating therapy
Unit 5
Persistent
0-1 / year
> 2 / year
Step 3
Step 1
Step 2
Step 4 or 5
Consider short course of oral
systemic corticosteroids
Expert Panel Report: NHLBI Guidelines for the Diagnosis and Management of Asthma - Summary Report 2007
http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm
©2014 Barkley & Associates
13
Management of Asthma
Unit 5
Expert Panel Report: NHLBI Guidelines for the Diagnosis and Management of Asthma - Summary Report 2007
http://www.nhlbi.nih.gov/guidelines/asthma/asthgdln.htm
©2014 Barkley & Associates
Beta-Agonists/Sympathomimetics
Indications:
Agents:
MOA:
Adverse
Effects:
Comments:
Unit 5
DOC for acute bronchoconstriction;
Intermittent symptoms;
Exercise-Induced Bronchospasm (EIB)
Short acting agents (SABA’s):
albuterol (Proventil), levalbuterol (Xopenex), metaproterenol
(Alupent), pirbuterol (Maxair), terbutaline (oral; Brethine)
cause bronchial smooth muscle relaxation
dose-related tachycardia, tremor, palpitations, nausea,
headache, hypokalemia
Scheduled daily use not recommended
Quick onset of action
Duration of action: 5-6 hours
Levalbuterol is NOT superior to other agents
DPI’s not indicated for acute severe exacerbations
©2014 Barkley & Associates
14
Inhaled Corticosteroids (ICS)
Indications:
Agents:
Preferred therapy for long-term control of persistent
asthma in all patients
beclomethasone (Beclovent), budesonide (Pulmicort),
ciclesonide (Alvesco), flunisolide (Aerospan),
fluticasone (Flovent), mometasone (Asmanex)
MOA:
anti-inflammatory; inhibits inflammatory cells and
release of inflammatory mediators
Adverse Effects: headache, pharyngitis, dysphonia, oral candidiasis
Comments:
Administer on scheduled basis, not “prn”
NOT used to treat an acute asthma attack
Rinse mouth thoroughly after inhalation
Budesonide is preferred in pregnancy
Systemic adverse effects can occur with any ICS
Unit 5
©2014 Barkley & Associates
Beta-Agonists/Sympathomimetics
Indications:
Treatment and prevention of bronchospasm only as
concomitant therapy inhaled corticosteroid;
Exercise-Induced Bronchospasm (EIB)
Agents:
Long acting (LABA’s): arformoterol (Brovana)*,
formoterol (Foradil), indacaterol (Arcapta)*, salmeterol
(Serevent)
MOA:
cause bronchial smooth muscle relaxation
Adverse Effects: tachycardia, tremor, palpitations, nausea, headache,
hypokalemia
Comments:
DO NOT act quickly
NOT for acute symptom management
Duration of action: 12 hours
Should not be used as monotherapy
*FDA labeled only for COPD
Unit 5
©2014 Barkley & Associates
15
Methylxanthines
Indications: Alternative, not preferred, therapy for mild persistent
asthma or as adjunct therapy with ICS
Agents:
aminophylline (IV),
theophylline (oral; Theo-Dur)
MOA:
bronchodilation through smooth muscle relaxation
Adverse
Effects:
nausea, vomiting, headache, insomnia, tremor,
irritability, restlessness, tachycardia, seizures
Comments: Clinical utility limited by low therapeutic index
Many drug-drug interactions
Metabolism/clearance is age dependent
Monitor dug levels
Unit 5
©2014 Barkley & Associates
Mast Cell Stabilizers
Indications:
Agents:
MOA:
Adverse
Effects:
Comments:
Unit 5
Alternative, but not preferred for mild persistent
asthma; Exercise induced bronchospasm (EIB)
cromolyn (Intal)
anti-inflammatory; prevents bronchoconstriction;
blocks the release of histamine
Relatively non-toxic; taste disturbances, cough
Not a substitute for ICS
Not as effective as beta-agonist for EIB
As effective as theophylline or leukotriene antagonists
May take up to 4 weeks to achieve benefit
©2014 Barkley & Associates
16
Leukotriene Modifiers
Indications:
Alternative, but not preferred for mild persistent asthma;
Exercise induced bronchospasm (EIB)
Agents:
montelukast (Singulair), zafirlukast (Accolate), zileuton
(Zyflo)
MOA:
inhibit bronchoconstriction; may prevent airway edema
and smooth muscle contraction
Adverse Effects: abdominal pain, dizziness, rash, dyspepsia,
hepatotoxicity
Comments:
Not all patients report a benefit with treatment
Difficult to predict who will respond
Several drug interactions
Zileuton: hepatotoxicity; monitor LFT’s
Less effective than low dose ICS
Not as effective as LABA’s when added to ICS
Unit 5
©2014 Barkley & Associates
Anticholinergics
Indications:
Adjunct therapy in acute asthma exacerbation not
completely responsive to beta agonist
Agents:
ipratropium bromide (Atrovent)
MOA:
blocks acetylcholine at parasympathetic sites in
bronchial smooth muscle causing bronchodilation
Adverse Effects: Rare: mydriasis, dry mouth, taste disturbances
Comments:
Unit 5
ipratropium + beta agonists = greater and
prolonged bronchodilation than using either agent
separately
Additional long-term studies are needed to
determine its role in asthma
*Not FDA labeled for asthma
©2014 Barkley & Associates
17
Systemic Corticosteroids
Indications:
Acute severe exacerbations not responding completely to
initial inhaled beta-agonist therapy
Agents:
prednisone (Deltasone), methylprednisolone (SoluMedrol), prednisolone (Millipred)
MOA:
anti-inflammatory; inhibits inflammatory cells and release
of inflammatory mediators
Adverse Effects: nausea, hyperglycemia, psychosis, weight gain,
osteoporosis
Comments:
IV therapy offers no therapeutic advantage over oral
administration
Duration of therapy: 5-10 days
High-dose regimens do not enhance outcomes and are
associated with higher rate of side effects
Should not be used as chronic maintenance therapy
Unit 5
©2014 Barkley & Associates
Recombinant Anti-IgE Antibody
Indications: Treatment of allergic asthma not well controlled on oral
corticosteroids or ICS
Agent:
omalizumab (Xolair)
MOA:
binds to the mast cells limiting the of release of mediators in
response to allergen exposure
Dose:
Based on baseline total serum IgE level & weight
Adverse
injection site reaction, headache, pharyngitis, sinusitis,
Effects:
thrombocytopenia, anaphylaxis
Comments: Do not abruptly stop systemic or ICS upon initiation of therapy
Subcutaneous injection
Cost of therapy is significant
Due to the potential for anaphylaxis, patients should be
observed for 2 hours after injection
Unit 5
©2014 Barkley & Associates
18
Asthma Action Plan
 Individualize
 Allows
for each patient
for self-management
 Teaches
patients to recognize
triggers/ early signs of
deterioration
 Allows
early institution of therapy
for acute exacerbations
 Improves
Unit 5
outcomes
http://www.pedipress.com/dap_using4zone_actionplan.html
©2014 Barkley & Associates
COPD
Chronic Bronchitis:
Excessive secretion of
bronchial mucus
– Present 3 months or more
in each of 2 consecutive
years
Emphysema:
Abnormal permanent
enlargement of air spaces
distal to the terminal
bronchiole
– Destruction of the alveoli
http://my.clevelandclinic.org/disorders/chronic_obstructive_pulmonary_disease/hic_understanding_copd.aspx
Unit 5
©2014 Barkley & Associates
19
COPD Diagnostics
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Symptoms (dyspnea at rest or on exertion, cough with or
without sputum production, progressive limitation of activity)
Spirometry showing airflow limitation that is incompletely
reversible with inhaled bronchodilator
 FEV1 and all other measurements of expiratory airflow
reduced
 TLC, FRC and RV may be increased
Absence of an alternative explanation for the symptoms and
airflow limitation
2014 GOLD Guidelines for COPD: Global Strategy for
Diagnosis, Management and Prevention of COPD
Unit 5
©2014 Barkley & Associates
Classification of COPD
Classification of Severity of Airflow Limitation in COPD
(Based on Post-Bronchodilator FEV1)
In patients with FEV1/FVC < 0.70:
GOLD 1:
Mild
FEV1 ≥ 80% predicted
GOLD 2:
Moderate
50% ≤ FEV1 < 80% predicted
GOLD 3:
Severe
30% ≤ FEV1 < 50% predicted
GOLD 4:
Very Severe
FEV1 < 30% predicted
Unit 5
http://www.goldcopd.org/uploads/users/files/GOLD_Report_2014_Jan23.pdf
©2014 Barkley & Associates
20
Global Strategy for Diagnosis, Management and Prevention of COPD
(C)
or > 1 leading
to hospital
admission
(D)
3
2
1 (not leading
to hospital
admission)
(B)
(A)
1
Risk
≥ 2
4
(Exacerbation history)
Risk (GOLD Classification of Airflow Limitation)
Combined Assessment of COPD
0
CAT < 10
CAT > 10
Symptoms
mMRC > 2
mMRC 0–1
Breathlessness
Unit 5
http://www.goldcopd.org/uploads/users/files/GOLD_Report_2014_Jan23.pdf
©2014 Barkley & Associates
Management of COPD
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Unit 5
Smoking cessation
Avoid irritants and allergens
Pulmonary rehabilitation
Immunizations
 Influenza vaccine
 Pneumococcal vaccine
Pharmacotherapy
 Bronchodilators
 Theophylline
 Corticosteroids
 Antibiotics
 Oxygen
©2014 Barkley & Associates
21
Beta-Agonists/Sympathomimetics
Indications: DOC for intermittent symptoms of COPD
Beta-agonist = anticholinergic
Agents:
Short acting agents (SABA’s):
albuterol (Proventil), levalbuterol (Xopenex),
pirbuterol (Maxair)
MOA:
cause bronchial smooth muscle relaxation
dose-related tachycardia, tremor, palpitations, nausea,
Adverse
headache, hypokalemia
Effects:
Comments: Improve symptoms; do not slow decline of COPD
Scheduled daily use may be required
Quick onset of action
Levalbuterol is NOT superior to other agents
Frequently used in combination with anticholinergic
(Combivent)
Unit 5
©2014 Barkley & Associates
Anticholinergics
Indications:
DOC for COPD; use tiotropium for frequent and persistent
symptoms
NOT used as monotherapy for acute exacerbations
Agents:
Short acting: ipratropium bromide (Atrovent)
Long acting: tiotropium (Spiriva), aclidinium (Tudorza)
MOA:
blocks acetylcholine at parasympathetic sites in bronchial
smooth muscle causing bronchodilation
Adverse Effects: Rare: mydriasis, dry mouth, taste disturbances
Comments:
Unit 5
Improve symptoms; do not slow decline of COPD
Slower onset and more prolonged effect compared with
beta-agonist
Consider tiotropium when patients require short acting
agents on a scheduled basis
Frequently used in combination with beta-agonist
©2014 Barkley & Associates
22
Beta-Agonists/Sympathomimetics
Indications: Frequent and persistent symptoms of COPD; utilized when
patients require short acting agents on a scheduled basis
Agents:
Long acting (LABA’s): arformoterol (Brovana)*, formoterol
(Foradil), indacaterol (Arcapta)*, salmeterol (Serevent)
MOA:
Cause bronchial smooth muscle relaxation
Tachycardia, tremor, palpitations, nausea, headache,
Adverse
hypokalemia
Effects:
Comments: NOT for acute symptom management
More convenient: 12 hour duration
Useful for nocturnal symptoms
No dose titration; standard dosage for all agents
Improve symptoms and reduce exacerbations
*FDA labeled for COPD
Unit 5
©2014 Barkley & Associates
Methylxanthines
Indications:
Adjunct therapy for patients who have not achieved
optimal response to ipratropium/beta-agonist
Agents:
MOA:
theophylline (oral; Theo-Dur)
bronchodilation through smooth muscle relaxation;
respiratory stimulant; reduces diaphragmatic fatigue
Adverse
Effects:
nausea, vomiting, headache, insomnia, tremor, irritability,
restlessness, tachycardia, seizures
Clinical utility limited by low therapeutic index
Many drug-drug interactions
Monitor dug levels
Considered only for those who are intolerant or unable
to use an inhaled bronchodilator
Comments:
Unit 5
©2014 Barkley & Associates
23
Inhaled Corticosteroids (ICS)
Indications:
Agents:
MOA:
Adverse Effects:
Comments:
Symptomatic patients with a FEV1 < 50% & repeated
exacerbations (Stage III and IV)
beclomethasone (Beclovent), budesonide (Pulmicort),
ciclesonide (Alvesco), flunisolide (Aerospan), fluticasone
(Flovent), mometasone (Asmanex)
anti-inflammatory; inhibits inflammatory cells and release
of inflammatory mediators
headache, pharyngitis, dysphonia, oral candidiasis
Does not modify long-term decline of FEV1 in COPD
Reduces frequency of exacerbations
Combination therapy with LABA > either agent alone
Not all patients will benefit from ICS
Rinse mouth thoroughly after inhalation
Systemic adverse effects can occur with any ICS
Unit 5
©2014 Barkley & Associates
Systemic Corticosteroids
Indications:
Agents:
MOA:
Adverse
Effects:
Comments:
Unit 5
Acute exacerbation;
Chronic therapy should be avoided if possible
prednisone (Deltasone), methylprednisolone (SoluMedrol), prednisolone (Millipred)
anti-inflammatory; inhibits inflammatory cells and release
of inflammatory mediators
nausea, hyperglycemia, psychosis, weight gain,
osteoporosis
Clinical benefit in chronic management not evident and
risk of toxicity is extensive
NOT considered as routine maintenance therapy
If required, use lowest effective dose
©2014 Barkley & Associates
24
Phosphodiesterase 4 Inhibitors
Indications:
Agents:
MOA:
Adverse
Effects:
Comments:
severe COPD associated with chronic bronchitis
roflumilast (Daliresp)
not well defined; increased levels of intracellular
cyclic AMP in lung cells, and reduced neutrophil
and eosinophil cell counts in the lungs
weight loss, decrease in appetite, diarrhea,
nausea, dizziness, headache, insomnia, anxiety,
depression, suicidal ideation, completed suicide
NOT for acute symptom management
Contraindicated in liver impairment
More studies are required to further define
roflumilast’s role in therapy
Unit 5
©2014 Barkley & Associates
Patient Group
Recommended First Choice
Alternative Choice
Other Possible Treatments**
A
Short-acting anticholinergic prn
or
Short-acting beta2-agonist prn
Long-acting anticholinergic
or
Long-acting beta2-agonist
or
Short-acting beta2-agonist and
short-acting anticholinergic
Theophylline
B
Long-acting anticholinergic
or
Long-acting beta2-agonist
Long-acting anticholinergic
and long-acting beta2 -agonist
Inhaled corticosteroid +
long-acting beta2-agonist
or
Long-acting anticholinergic
Long-acting anticholinergic
and long-acting beta2 -agonist
or
Long-acting anticholinergic
and phosphodiesterase-4 inhibitor
or
Long-acting beta2-agonist
and phosphodiesterase-4
Inhibitor
Inhaled corticosteroid +
long-acting beta2-agonist
and/or
Long-acting anticholinergic
Inhaled corticosteroid +
long-acting beta2-agonist and long-acting anticholinergic
or
Inhaled corticosteroid +
long-acting beta2-agonist and phosphodiesterase-4 inhibitor
or
Long-acting anticholinergic and
long-acting beta2-agonist
or
Long-acting anticholinergic and
phosphodiesterase-4 inhibitor
C
D
Short-acting beta2-agonist
and/or
Short-acting anticholinergic
Theophylline
Short-acting beta2-agonist
and/or
Short-acting anticholinergic
Theophylline
Carbocysteine
Short-acting beta2-agonist
and/or
Short-acting anticholinergic
Theophylline
*Medications in each box are mentioned in alphabetical order, and therefore not necessarily in order of preference
**Medications in this column can be used alone or in combination with other options in the Recommended First Choice and Alternative Choice columns
Unit 5
http://www.goldcopd.org/uploads/users/files/GOLD_Report_2014_Jan23.pdf
©2014 Barkley & Associates
25
Pneumonia
Unit 5
©2014 Barkley & Associates
Pneumonia: Signs/Symptoms






Fever
Shaking chills
Purulent sputum
Lung consolidation on physical exam
Malaise
Increased fremitus
www.med-ed.virginia.edu
Unit 5
©2014 Barkley & Associates
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Management of Pneumonia


Strep. pneumoniae: most common etiological agent for community
acquired pneumonia (CAP)
Outpatient Management of CAP:
 Healthy patients (< 60 years old with NO comorbidities)
 Macrolide (azithromycin, clarithromycin, erythromycin)
 Doxycycline
 Patients with other health problems (e.g., COPD, diabetes, heart
failure, cancer or > 65 years old)
 Respiratory fluoroquinolone (moxifloxacin, gemifloxacin or
levofloxacin
 Beta-lactam (amoxicillin-clavulanate, cefuroxime) plus a
macrolide or doxycycline
Unit 5
©2014 Barkley & Associates
The End
Unit 5
©2014 Barkley & Associates
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