Drugs that Affect the Respiratory System

The Influence of Health Policies and the Future of Health Care in the U.S
July 3, 2019
Explain the federal laws and regulations pertaining to employee workplace rights.
July 3, 2019

Short teaching presentation. Develop a patient teaching brochure for the management of asthma. One of your resources has to pharmacology for the primary care provider. I have included an example of a brochure

Drugs that Affect the Respiratory System:
Beta2 Agonists, Methylxanthines, Anticholinergics,
Mast Cell Stabilizers, Inhaled and Systemic Corticosteroids,
Leukotriene Modifiers, PDE4 Inhibitor, Cough and Cold Medications
Notes to Accompany
The Program
BY
Margaret Fitzgerald, DNP, FNP-BC, NP-C, FAANP, CSP, FAAN
President, Fitzgerald Health Education Associates, Inc.
North Andover, MA
Family Nurse Practitioner, Adjunct Faculty, Family Practice Residency
Greater Lawrence (MA) Family Health Center
Editorial Board Member
The Nurse Practitioner Journal, Prescriber’s Letter, American Nurse Today
© Fitzgerald Health Education Associates, Inc.
85 Flagship Drive, North Andover, MA 01845-6154
Phone 978.794.8366 | Fax: 978.794.2455 | Email: ce@fhea.com | www.fhea.com
All rights reserved
Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 1
STATEMENT OF LIABILITY
The information contained in this work whether written or oral
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available daily. Prudent practice dictates that the clinician consult
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Associates, Inc. disclaims any liability, loss, injury or damage incurred
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reserved. No part of this publication or the accompanying Program
may be reproduced or transmitted in any form or by any means,
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Requests for permission to make copies of or to incorporate any part
of the work into academic programs should be mailed to:
Permissions Department, FHEA, 85 Flagship Drive
North Andover, MA 01845-6154
ISBN 978-2-18514142-6 (08pconv4)
***
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978.794.8366 Fax 978.794.2455
Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 2
Instructions
The goals and objectives for this program are listed at the
bottom of this column. Please read the following material
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The goal of this educational program is:
To provide quality continuing education to advanced
practicing nurses to enhance their knowledge of drugs that
affect the respiratory system.
Objectives:
1. Describe the pathophysiology of asthma and
chronic obstructive pulmonary disease.
2. Develop a plan of pharmacologic intervention for
the person with an acute asthma flare or COPD
exacerbation, as well as long-term preventive
therapy using the NAEPP EPR-3 guidelines,
GOLDCOPD and ATS Guidelines based on the
mechanism of disease.
3. Describe the mechanism of action and potential
uses of commonly prescribed cough, cold and
allergic rhinitis therapies.
About the Author
Margaret A. Fitzgerald, DNP, FNP-BC, NP-C, FAANP,
CSP, FAAN, is the founder, president and principal
lecturer with Fitzgerald Health Education Associates,
Inc. (FHEA), an international provider of nurse
practitioner certification preparation and continuing
education for healthcare providers. More than 60,000
nurse practitioners have used the Fitzgerald review
course to successfully prepare for certification.
An internationally recognized presenter, Dr.
Fitzgerald has provided thousands of programs for
numerous professional organizations, universities,
national and state healthcare associations on a wide
variety of topics including clinical pharmacology,
assessment, laboratory diagnosis, healthcare and nurse
practitioner practice. For more than 20 years she has
provided graduate-level pharmacology courses for
nurse practitioner students at a number of universities
including Simmons College (Boston, MA), Husson
College (Bangor, ME), University of Massachusetts
Worcester, Pennsylvania State University, La Salle
University (Philadelphia, PA), and Samford University
(Birmingham, AL). In addition, she is a family nurse
practitioner at the Greater Lawrence Family Health
Center, Lawrence, MA, and adjunct faculty for the
Greater Lawrence Family Health Center Family Practice
Residency Program. She holds a Doctor of Nursing
Practice from Case Western Reserve University,
Cleveland, OH, where she received the Alumni
Association Award for Clinical Excellence.
Dr. Fitzgerald is the recipient of the National
Organization of Nurse Practitioner Faculties’ Lifetime
Achievement Award, given in recognition of vision and
accomplishments in successfully developing and
promoting the nurse practitioner role, the American
College of Nurse Practitioner’s Sharp Cutting Edge
Award and the Outstanding Nurse Award for Clinical
Practice by the Merrimack Valley Area Health Education
Council. She is also a Fellow of the American Academy
of Nursing and a charter fellow in the Fellows of the
American Academy of Nurse Practitioners. Dr.
Fitzgerald is a Professional Member of the National
Speakers Association and is the first nurse practitioner
to earn the Certified Speaking Professional (CSP)
designation in recognition of excellence and integrity as
a speaker.
Dr. Fitzgerald is an editorial board member for the
Nurse Practitioner Journal, Medscape Nurses, LexiComp,
Inc., American Nurse Today, and Prescriber’s
Letter. She is widely published with more than 100
articles, book chapters, monographs, and audio and
video programs to her credit. Her book, Nurse
Practitioner Certification Examination and Practice
Preparation (2nd edition) received the American Journal
of Nursing Book of the Year Award for Advanced
Practice Nursing and has been published in English and
Korean. She has provided consultation to nursing
organizations in the United States, Canada, the
Dominican Republic, Japan, South Korea, Hong Kong,
and the United Kingdom. Dr. Fitzgerald is an active
member of numerous professional organizations at
national and local levels.
Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 3
Drugs that Affect the Respiratory System:
Beta2 Agonists, Methylxanthines, Anticholinergics,
Mast Cell Stabilizers, Inhaled and Systemic
Corticosteroids, Leukotriene Modifiers, PDE4 Inhibitor,
Cough and Cold Medications
Margaret A. Fitzgerald,
DNP, FNP-BC, NP-C, FAANP, CSP, FAAN, DCC
President, Fitzgerald Health Education Associates, Inc., North Andover, MA
Family Nurse Practitioner, Adjunct Faculty, Family Practice Residency
Greater Lawrence (MA) Family Health Center
Editorial Board Member
The Nurse Practitioner Journal, Prescriber’s Letter, American Nurse Today
1
 Fitzgerald Health Education Associates, Inc.ã
Please note that significant portions
of this product are only available
on-line.
To access this essential material,
use Fitzgerald Health’s Learning
Management System,
NPexpert
Objectives
 Having completed the learning·
activities, the participant will be able
to:
– Recognize indications and therapeutic
actions of commonly used herb, mineral
and vitamin therapies.
 Fitzgerald Health Education Associates, Inc.ã
3
Objectives
 Having completed the learning·
activities, the participant will be able
to:
1. Describe the pathophysiology of
asthma and chronic obstructive
pulmonary disease.
 Fitzgerald Health Education Associates, Inc.ã
4
Objectives
(continued)
●Having completed the learning
activities…(cont.)
2. Develop a plan of pharmacologic
intervention for the person with an
acute asthma flare or COPD
exacerbation, as well as long-term
preventive therapy using the NAEPP
EPR-3 guidelines, GOLDCOPD and
ATS Guidelines based on the
 Fitzgerald Health Education Associates, Inc.ãmechanism of disease. 
5
Objectives
(continued)
●Having completed the learning
activities…(cont.)
3. Describe the mechanism of action
and potential uses of commonly
prescribed cough, cold and allergic
rhinitis therapies.
 Fitzgerald Health Education Associates, Inc.ã
6
Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 4
Report of the Expert Panel: Guidelines
for the Diagnosis and Management of
Asthma (EPR-3)
www.nhlbi.nih.gov
 Fitzgerald Health Education Associates, Inc. 7ã
Asthma Defined
 “A common chronic disorder of the·
airways that is complex and
characterized by variable and
recurring symptoms, airflow
obstruction, bronchial
hyperresponsiveness, and
underlying inflammation.”
– Source- NHLBI, 2007
8
 Fitzgerald Health Education Associates, Inc.ã
The Interplay Between Airway
Inflammation, Clinical Symptoms &
Pathophysiology
(EPR-3)
9
 Fitzgerald Health Education Associates, Inc.ã
Goal of Asthma Therapy:
Achieve Control
 Reduce impairment·
– Prevent chronic and troublesome symptoms
– Require infrequent use of inhaled SABA (≤2
days/week)
– Maintain (near) “normal” pulmonary
function
– Maintain normal activity levels
– Meet patient’s expectations of, and
satisfaction with, asthma care
10
 Fitzgerald Health Education Associates, Inc.ã
Goal of Asthma Therapy:
Achieve Control
(continued)
 Reduce risk·
– Prevent recurrent exacerbations
– Minimize need for emergency
department visits or hospitalizations
– Prevent progressive loss of lung
function
– Provide optimal pharmacotherapy,
with minimal or no adverse effects 11
 Fitzgerald Health Education Associates, Inc.ã
Classification of Asthma Severity
(Youths≥12 Years of Age and Adults)
Classifying severity for patients who are
not currently taking long-term control medications
Components of Severity Persistent
Impairment
Normal
FEV1/FVC:
8-19 yr 85%
20-39 yr 80%
40-59 yr 75%
60-80 yr 70%
Symptoms
Intermittent Mild Moderate Severe
≤2 days/week >2 days/week
but not daily Daily Throughout the day
Nighttime
awakenings ≤2x/month 3-4x/month >1x/week but
not nightly Often 7x/week
Short-acting beta2-
agonist use for
symptom control
(not prevention of
EIB)
≤2 days/week
>2 days/week
but not
>1x/day
Daily Several times per day
Interference with
normal activity None Minor limitation Some limitation Extremely limited
Lung function
Normal FEV1
between
exacerbations
FEV1>80%
predicted
FEV1>80%
predicted
FEV1>60% but
5%
Risk
Exacerbations
requiring oral
systemic
corticosteroids
0-1/year (see note) ≥2/year (see note)
Consider severity and interval since last exacerbation. Frequency and severity
may fluctuate over time for patients in any severity category.
Relative annual risk of exacerbations may be related to FEV1
 Fitzgerald Health Education Associates, Inc. 12ã
Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 5
Classification of Asthma Control
12 Years of Age and Adults)³(Youths 
Components of Control
Impairment
Symptoms Well-controlled Not Wellcontrolled
Very Poorly
Controlled
≤2 days/week >2 days/week Throughout the day
Nighttime awakenings ≤2 x/month 1-3x/week ≥4x/week
Interference with normal
activity None Some limitation Extremely limited
Short-acting beta2-agonist
use for symptom control
(not prevention of EIB)
≤2 days/week >2 days/week Several times per day
FEV1 or peak flow >80% predicted/personal
best
60-80%
predicted/personal
best
< 47=”” y/o=””>· Fitzgerald Health Education Associates, Inc. Linda ã Fitzgerald Health Education Associates, Inc. Your patient is a 17 yo with asthma who uses fluticasone with salmeterol BID and albuterol PRN. He asks for a note to be excused from gym. What is the most appropriate response to this request? 15 ã60% predicted/personal best Validated Questionnaires ATAQ ACQ ACT 0 ≤0.75* ≥20 1-2 ≥1.5 16-19 3-4 N/A ≤15 Exacerbations 0-1/year ≥2/year (see note) Consider severity and interval since last exacerbation Risk Progressive loss of lung function Evaluation requires long-term follow-up care Treatment-related adverse effects Medication side effects can vary in intensity from none to very troublesome and worrisome. The level of intensity does not correlate to specific levels of control but should be considered in the overall assessment of risk. *ACQ values of 0.76-1.4 are indeterminate regarding well-controlled asthma. Key: EIB, exercise-induced bronchospasm; FEV1, forced expiratory volume in 1 second. See figure 3-8 for full name and source of ATAQ, ACQ, ACT. 13 Monitoring Control in Clinical Practice: Asthma Control Test™ for Patients Aged≥12 Years http://www.asthma.com/resources/asthma-control-test.html, accessed 2.7.12. Level of Control Based on Composite Score ≥20 = Controlled 16-19 = Not Well Controlled ≤15 = Very Poorly Controlled Regardless of patient’s selfassessment of control in Question 5 14  >20 y-hx of asthma
 Current asthma medications·
– Fluticasone 44 µg/puff, 1 puff BID
– Albuterol via MDI 2 puffs QID PRN
– Albuterol 2.5 mg via nebulizer q 4h
PRN during flares
16
 Fitzgerald Health Education Associates, Inc.ã
Linda
(continued)
 Concomitant health problems·
– HTN, dyslipidemia, allergic rhinitis
 Medications for these problems·
– Atenolol 100 mg QD
– Lisinopril 40 mg QD
– Simvastatin 20 mg QD
– Loratadine PRN, uses about 2-3 times
per week when “pollen in the air”
17
 Fitzgerald Health Education Associates, Inc.ã
Linda
(continued)
 Does she have increased risk of·
ACEI-induced cough?
 What is the mechanism of ACEIinduced·
cough?
 Other issue(s) with HTN therapy?·
18
 Fitzgerald Health Education Associates, Inc.ã
Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 6
Renin-angiotensin Cascade:
What Works Where?
Angiotensinogen
 Angiotensin IÝ
 Angiotensin IIÝ
AT1
AT2 ATn
Bradykinin
Inactive
peptides
Non-renin
(e.g. tPA)
Non-ACE
(e.g. chymase) ACE
Renin
19
©Fitzgerald Health Education Associates, Inc.
ACEI-induced Cough
 The mechanism of ACE inhibitor-induced·
cough remains unresolved, but likely involves
the protussive mediators bradykinin and
substance P, agents that are degraded by
ACE and therefore accumulate in the upper
respiratory tract or lung when the enzyme is
inhibited, and prostaglandins, the production
of which may be stimulated by bradykinin.
– http://chestjournal.chestpubs.org/content/129/1_suppl/169S.full,
accessed 2.6.12.
 Fitzgerald Health Education Associates, Inc.ã
20
Linda
(continued)
 Does not check PEF at home·
– “Not sure this makes a difference.”
 No asthma action plan·
 No allergic rhinitis control plan·
21
 Fitzgerald Health Education Associates, Inc.ã
Patient Report of
Asthma Pattern
 “I wake up 1-2 times per week·
coughing.”
 “I usually have 3-4 times a year·
when my asthma acts up. I need to
go to the emergency room.”
 “I usually use about a canister of·
albuterol every month and my
nebulizer practically every day.”
22
 Fitzgerald Health Education Associates, Inc.ã
Classification of Asthma Control
12 Years of Age and Adults)³(Youths 
Components of Control
Impairment
Symptoms
Wellcontrolled
Not Wellcontrolled
Very Poorly
Controlled
≤2 days/week >2 days/week Throughout the day
Nighttime awakenings ≤2 x/month 1-3x/week ≥4x/week
Interference with
normal activity None Some limitation Extremely limited
Short-acting beta2-
agonist use for
symptom control (not
prevention of EIB)
≤2 days/week >2 days/week Several times per day
FEV1 or peak flow
>80%
predicted/personal
best
60-80%
predicted/personal
best
< fitzgerald=”” health=”” education=”” associates,=”” inc.=”” estimated=”” comparative=”” daily=”” dosages=”” for=”” ics=”” in=”” patients=”” aged≥12=”” years=”” soiurce-=”” http://www.nhlbi.nih.gov/guidelines/asthma/asthsumm.pdf.,=”” accessed=”” 2.7.12.=”” low=”” daily=”” dose=”” medium=”” daily=”” dose=”” high=”” daily=”” dose=”” beclomethasone=”” hfa=”” 40=”” or=”” 80=”” µg/puff=”” budesonide=”” dpi=”” 200=”” µg/inhalation=”” flunisolide=”” 250=”” µg/puff=”” flunisolide=”” hfa=”” 80=”” µg/puff=”” fluticasone=”” hfa=”” mdi=”” 44,=”” 110,=”” or=”” 220=”” µg/puff=”” fluticasone=”” dpi=”” 50,=”” 100,=”” or=”” 250=”” µg/puff=”” mometasone=”” dpi=”” 200=”” µg/puff=”” 80-240=”” µg=”” 200-600=”” µg=”” 500-1000=”” µg=”” 320=”” µg=”” 88-264=”” µg=”” 100-300=”” µg=”” 200=””>ã Fitzgerald Health Education Associates, Inc. 30 Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 8 What dose of inhaled corticosteroid is Linda currently using? 31 ã First to market – Inhaled beclomethasone, at dose of 4 puffs per day, with 42 ug per puff (164 ug per total daily dose) – Low potency, marginal clinical effect, inconvenient dosing regimens limited acceptance of this therapy initially. · Introduced in mid-1970s · Fitzgerald Health Education Associates, Inc. Inhaled Corticosteroids ã Inhibit production of inflammatory agents – Cytokines, an effect which reduces eosinophil infiltration, inhibits macrophage and eosinophil function – Decreases epithelium mediator cells, reduces vascular permeability, reduces the production of leukotrienes 29 · Normally endogenously by adrenal cortex · Fitzgerald Health Education Associates, Inc. Mechanism of Action Corticosteroids ã Asmanex ® 28 · Mometasone · Beclovent ® · Beclomethasone · Flovent ® · Fluticasone · Pulmicort® · Budesonide · Fitzgerald Health Education Associates, Inc. 27 Controller Drugs to Prevent Inflammation Inhaled Corticosteroids (ICS) ã12 Years: NAEPP EPR-3 Guidelines Step 1 Preferred: SABA PRN Step 2 Preferred: Low-dose inhaled corticosteroid (ICS) Alternative: Mast cell stabilizer (Cromolyn nedocromil), leukotriene receptor antagonist (LTRA), or theophylline Step 3 Preferred: Medium-dose ICS or Low-dose ICS + LABA Alternative: Low-dose ICS and either LTRA, theophylline, or zileuton Step 5 Preferred: High-dose ICS + LABA and omalizumab (Xolair) use can be considered for patients who have allergies. Step 4 Preferred: Medium-dose ICS + LABA Alternative: Medium-dose ICS and either LTRA, theophylline, or zileuton Step 6 Preferred: High-dose ICS + LABA + oral corticosteroid and consider omalizumab for patients who have allergies Severe Persistent Moderate Mild Persistent Persistent Intermittent ³ Fitzgerald Health Education Associates, Inc. Stepwise Approach for Managing Asthma in Patients Agedã Fitzgerald Health Education Associates, Inc. Adapted from Bousquet et al. Am J Respir Crit Care Med. 2000;161:1720-1745. Airway inflammation • I • Mucosal edema • Inflammatory cell infiltration, activation • Cellular proliferation • Epithelial damage • Basement membrane thickening • Bronchoconstriction • Bronchial hyperreactivity • Hyperplasia/Hypertrophy • Inflammatory mediator release Symptoms/Exacerbations Smooth muscle dysfunction 26 ã Physical exam – Decreased breath sounds – Expiratory wheezing 25 · PEF=225 ml with fair to good effort · SaO2=92% on room air · Congested cough w/small amount green sputum production · T= 99.5⁰F (37.5⁰C), BP=140/88, HR 110 BPM, RR 26 BPM · Fitzgerald Health Education Associates, Inc. Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 7 Physical Exam ã 72 h history – URI symptoms including clear nasal discharge, sore throat, feeling feverish, green sputum production X 24 h – Worsening asthma symptoms with decreased response to albuterol 24 · Presents today for emergency care ·60% predicted/personal best Validated Questionnaires ATAQ ACQ ACT 0 ≤0.75* ≥20 1-2 ≥1.5 16-19 3-4 N/A ≤15 Exacerbations 0-1/year ≥2/year (see note) Consider severity and interval since last exacerbation Risk Progressive loss of lung function Evaluation requires long-term follow-up care Treatment-related adverse effects Medication side effects can vary in intensity from none to very troublesome and worrisome. The level of intensity does not correlate to specific levels of control but should be considered in the overall assessment of risk. *ACQ values of 0.76-1.4 are indeterminate regarding well-controlled asthma. Key: EIB, exercise-induced bronchospasm; FEV1, forced expiratory volume in 1 second. See figure 3-8 for full name and source of ATAQ, ACQ, ACT. 23 Linda (continued)  >240-480 µg
>600-1200 µg
1000-2000 µg
320-640 µg
264-440 µg
300-500 µg
400 µg
>480 µg
>1200 µg
>2000 µg
>640 µg
>440 µg
>500 µg
>400 µg
32
Inhaled Corticosteroids:
True or false?
 Most PCPs are well versed in the·
relatively potency of the inhaled
corticosteroids and prescribe an
appropriate dose for the patient’s
clinical presentation.
 Approximately 80% of the ICS corticosteroid·
dose is systemically absorbed.
33
 Fitzgerald Health Education Associates, Inc.ã
Controller Drugs to
Prevent Inflammation
 Leukotriene receptor antagonists,·
 LTRA, LTM·also known as leukotriene modifiers 
– Montelukast (Singulair®)
– Zafirlukast (Accolate®)
– Zileuton (Zyflo®)
34
 Fitzgerald Health Education Associates, Inc.ã
Mechanism of Action
LTRA, LTM
 Selective and competitive·
antagonists of the cysteinyl
leukotriene (Cys LT1) receptor
– Cysteinyl leukotriene (LTC4, LTD4 and
LTE4) production and receptor
occupation, including airway edema,
smooth muscle constriction, and
altered cellular activity associated with
inflammatory process 35
 Fitzgerald Health Education Associates, Inc.ã
Asthma Care:
True or false?
 The LTRM and ICS are·
interchangeable clinically since both
groups of medications have
equivalent antiinflammatory effect.
36
 Fitzgerald Health Education Associates, Inc.ã
Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 9
Controller Drugs to
Prevent Inflammation
 Mast cell stabilizers·
– Cromolyn (Intal®)
– Nedocromil (Tilade®)
37
 Fitzgerald Health Education Associates, Inc.ã
Mast Cell Stabilizers:
True or false?
 Nedocromil (Tilade®) is no longer·
available on the US market.
 This product was removed from·
the market due to safety
considerations.
38
 Fitzgerald Health Education Associates, Inc.ã
Mechanism of Action
Mast Cell Stabilizers
 Prevent release of type I mediators·
for allergic reactions
– Include histamine and slow-reacting
substance of anaphylaxis, from
sensitized mast cells
– Specific mechanism(s) of action of the
drug on mast cells unclear
39
 Fitzgerald Health Education Associates, Inc.ã
Mast Cell Stabilizers:
True or false?
 Little systemic absorption of these·
medications occurs with inhaled or
intranasal use.
 The medications need to be used,·
in general, 3+ times per day for
approximately 3 weeks prior to
seeing significant clinical effect.
40
 Fitzgerald Health Education Associates, Inc.ã
Medications to Treat or
Prevent Bronchospasm
 Rescue drugs for·
bronchospasm
– Albuterol
(Proventil®)
– Pirbuterol (Maxair®)
– Levalbuterol
(Xopenex®)
 Long-acting beta2-·
agonists (LABA) to
prevent
bronchospasm
– Salmeterol
(Serevent®)
– Formoterol
(Foradil®)
– Arformoterol
(Brovana®)
41
 Fitzgerald Health Education Associates, Inc.ã
PK Comparisons: SABA vs LABA
Is there a PD difference?
 SABA (albute·rol)
– Time to clinical
effect=½ h
– T ½=4 h
 LABA (salmeterol)·
– Time to clinical
effect=1-2 h
– T ½=8 h
42
 Fitzgerald Health Education Associates, Inc.ã
Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 10
Mechanism of Action
Beta2 Adrenergic Agonists
 Stimulate intracellular adenyl·
cyclase
– Enzyme that catalyzes conversion of
adenosine triphosphate to cyclic-3′, 5′-
adenosine monophosphate (cAMP)
– Increased cAMP levels cause
relaxation of bronchial smooth muscle
43
 Fitzgerald Health Education Associates, Inc.ã
Albuterol:
Nebulizer vs. MDI
 Typical nebulized albuterol·
dose=2.5 mg with 12%
deposition=300 mcg
 Typical MDI albuterol dose=180·
mcg with 20% deposition=36 mcg
Source- Optimizing Deposition of Aerosolized Drug in the Lung, available at
http://www.medscape.com/viewarticle/717395 , accessed 2.7.12.
44
 Fitzgerald Health Education Associates, Inc.ã
The use of >2 canisters per month of
inhaled short-acting beta2-agonist is an
asthma death risk factor per EPR-3.
How much albuterol is Linda
currently using?
45
 Fitzgerald Health Education Associates, Inc.ã
“Boxed,” formerly known as
“Black Box,” Warnings
FDA mandate to warn that studies
indicate that the drug carries a
significant risk of serious or even
life-threatening adverse effects.
 Fitzgerald Health Education Associates, Inc.ã46 
“Boxed” Warning:
LABA Patient Information
 “The information in FDA’s mandated·
changes to the product labels explains
that, even though long-acting beta2-
agonist (LABA, salmeterol, formoterol)
decrease the number of asthma
episodes, these medicines may increase
the chances of a severe asthma episode
when they do occur.”
47
 Fitzgerald Health Education Associates, Inc.ã
“Boxed” Warning:
LABA Patient Information
(continued)
 “In one asthma medicine study, an·
increased number of people taking a
long-acting beta2-agonist (LABA,
salmeterol, formoterol) in addition to
their usual asthma care died from their
asthma compared to people taking a
placebo in addition to their usual asthma
care, although the number of asthma
deaths in the study was small.” 48
 Fitzgerald Health Education Associates, Inc.ã
Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 11
“Boxed” Warning:
LABA Patient Information
(continued)
 LABAs should not be the first·
medicine used to treat asthma and
should be added to the asthma
treatment plan only if other
medicines do not control asthma,
including the use of low-or-medium
dose corticosteroids.
 Do not use your LABA to treat·
wheezing that is getting worse.
49
 Fitzgerald Health Education Associates, Inc.ã
“Boxed” Warning:
LABA Patient Information
(continued)
 Call your healthcare professional·
right away if wheezing worsens
while using a LABA.
 LABAs do not relieve sudden·
wheezing. Always have a short
acting bronchodilator medicine with
you to treat sudden wheezing.
 Fitzgerald Health Education Associates, Inc.ã
50
Inhaled Corticosteroids with LABA
 Advair Diskus®=1 puff BID·
– Fluticasone (Flovent®) with salmeterol
 100 mcg/50 mcg·
 250 mcg/50 mcg·
– Recommended COPD dose
 500 mcg/50 mcg·
 Advair HFA®=2 puff BID·
– Fluticasone (Flovent®) with salmeterol
 45 mcg/21 mcg·
 115 mcg/21 mcg·
 Fitzgerald Health Education Associates, Inc.ã 230 mcg/21 mcg ·
51
Inhaled Corticosteroids with LABA
(continued)
 Symbicort®=2 puff BID·
– Budesonide (Pulmicort®) with
formoterol
 80 mcg/4.5 mcg·
 160 mcg/4.5 mcg·
– Recommended dose for COPD
 Fitzgerald Health Education Associates, Inc.ã
52
Inhaled Corticosteroids with LABA
(continued)
 Dulera®=2 puff BID·
– Mometasone with formoterol
 100 mcg/5 mcg·
 200 mcg/5 mcg·
– FDA approved for asthma but not
COPD therapy
 Fitzgerald Health Education Associates, Inc.ã
53
Theophylline
 Usually characterized as a mild to·
moderate bronchodilator
– Inexpensive but requires periodic
monitoring of theophylline levels,
which drives up cost and
inconvenience in its use
– See EPR-3 for full details on its use
 Fitzgerald Health Education Associates, Inc.ã
54
Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 12
Theophylline
(continued)
 Drug class-Methylxanthine·
– Other drugs in this class include
caffeine, theobromine
 MW=180.17 d·
– Clinical significance?
 Fitzgerald Health Education Associates, Inc.ã
55
Theophylline:
Mechanism of Action
 Increases levels in cyclic adenosine·
monophosphate (cAMP)
 Anticipated effect of increased cAMP·
levels
– Stimulation of cardiac function
– Relaxation of smooth muscle
– Reduction in immune/inflammatory
 Fitzgerald Health Education Associates, Inc.ãactivity from select cells 
56
Theophylline:
Anticipated Therapeutic Effect
 Increases force of contraction of·
diaphragmatic muscles
 Increase cardiac function·
 Mild anti·inflammatory effect
 Smooth muscle relaxation·
– Anticipated potential adverse effect
with use of smooth muscle relaxers?
 Fitzgerald Health Education Associates, Inc.ã
57
Theophylline: What keeps this
from being a more helpful drug?
 NTI·
– ED50:LD50=>2
 PK influence·
– Dosing interval, rate of theophylline
absorption and clearance in individual
patient, with marked differences
person to person
 Fitzgerald Health Education Associates, Inc.ã
58
How significant are PK differences?
 Dosing range to reach a therapeutic·
concentration in 10-20 mcg/mL range
– 400-1600 mg/day in adults< dose=”” example=”” –=”” 900=”” mg/d=”” in=””>· Fitzgerald Health Education Associates, Inc. 59 Example ã No single theophylline dose that will provide both safe and effective serum concentrations for all patients ·60 years old – 10-36 mg/kg/day in children 1-9 years old < steady-state=”” peak=”” serum=”” concentration=”” at=”” this=”” dose=””>·60 years, 22 mg/kg/d in children 1-9 years  · At therapeutic levels – Usually transient caffeine-like adverse effects such as nausea, vomiting, headache, insomnia · Fitzgerald Health Education Associates, Inc. 61 Theophylline Adverse Effects: Similar to Caffeine in Excess ã With theophylline – Distributes poorly into body fat – As result, mg/kg dose should be calculated on the IBW basis. · What influences this? – What is drug’s affinity to fat? · Fitzgerald Health Education Associates, Inc. 60 Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 13 Base dose on actual or ideal body weight (IBW)? ã10 mcg/mL in ~30%, 10-20 mcg/mL in ~50%, 20-30 mcg/mL in ~20% – Source- Uniphyl PI  >20 mcg/mL
– Vomiting, cardiac dysrhythmias,
seizures, potentially lethal
 Fitzgerald Health Education Associates, Inc.ã
62
What influences theophylline’s PK?
Class effect or individual product?
 CYP1A2 inhibitors·
– Ciprofloxacin
– Cimetidine
 CYP1A2 inducer·
– Omeprazole
– Tobacco use – Sourcehttp://medicine.iupui.edu/clinpharm/DDIs/ClinicalTable.aspx
,
accessed 2.7.12.
 Fitzgerald Health Education Associates, Inc.ã
63
You see a patient with COPD
who is taking theophylline…
 He is a 54 year-old man, BMI=34,·
who smokes 1.5 PPD and states he
wants to quit. He inquires about
using varenicline (Chantix®).
 Fitzgerald Health Education Associates, Inc.ã
64
Varenicline (Chantix®)
 “In vitro studies demonstrated that·
varenicline does not inhibit the
following cytochrome P450 enzymes:
1A2, 2A6, 2B6, 2C8, 2C9, 2C19, 2D6,
2E1, and 3A4/5. Also, in human
hepatocytes in vitro, varenicline does
not induce the cytochrome P450
enzymes 1A2 and 3A4.” – Source- Varenicline PI
 Fitzgerald Health Education Associates, Inc.ã
65
What about smoking cessation
and theophylline use?
 “A stepwise daily dose reduction of·
approximately 10% until the fourth
day after smoking cessation
accompanied by therapeutic drug
monitoring has been proposed.”
– Source- http://www.healthanddna.com/healthcareprofessional/p450-1a2-genotyping.html,
accessed 2.11.12.
 Fitzgerald Health Education Associates, Inc.ã
66
Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 14
Theophylline vs. Caffeine:
Commonalities and Differences
Theophylline
 Substrate·
– CYP 1A2
– Levels influenced by
amount of tobacco use
 Pharmacogenomics·
implications
– Documented
influences dependent
on amount, activity of
CYP 1A2
Caffeine
 Substrate·
– CYP 1A2
– Levels influenced by
amount of tobacco use
 Pharmacogenomics·
implications
– Documented
influences dependent
on amount, activity of
 Fitzgerald Health Education Associates, Inc.ãCYP 1A2 
67
Is Linda’s current asthma
management plan adequate?
 Fitzgerald Health Education Associates, Inc. 68ã
69
 Fitzgerald Health Education Associates, Inc.ã
70
Stepwise Approach for Managing Asthma
12 Years:³in Patients Aged
NAEPP EPR-3 Guidelines
Step 1
Preferred:
SABA PRN
Step 2
Preferred:
Low-dose inhaled
corticosteroid (ICS)
Alternative:
Mast cell stabilizer
(Cromolyn
nedocromil),
leukotriene
receptor antagonist
(LTRA),
or
theophylline
Step 3
Preferred:
Medium-dose
ICS
or
Low-dose ICS +
LABA
Alternative:
Low-dose ICS
and either
LTRA,
theophylline,
or zileuton
Step 5
Preferred:
High-dose ICS +
LABA
and
omalizumab use
can be
considered for
patients who
have allergies.
Step 4
Preferred:
Medium-dose
ICS + LABA
Alternative:
Medium-dose
ICS
and either
LTRA,
theophylline,
or zileuton
Step 6
Preferred:
High-dose ICS +
LABA + oral
corticosteroid
and
consider
omalizumab for
patients who
have allergies
Severe Persistent
Moderate
Mild Persistent
Persistent Intermittent
 Fitzgerald Health Education Associates, Inc.ã
Acute Asthma
Flare Management
 Aggressive treatment of·
inflammation with corticosteroid
– Example- Prednisone 40-60 mg qd X
3-10 d (average 5-7 d)
 Increased use of rescue drug·
71
 Fitzgerald Health Education Associates, Inc.ã
Are systemic
corticosteroids equipotent?
72
 Fitzgerald Health Education Associates, Inc.ã
Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 15
Corticosteroids
(Equipotent Doses)
 Higher potency corticosteroids·
– Betamethasone 0.6 to 0.75 mg
– Dexamethasone 0.75 mg
 T ½=36-54 hours·
73
 Fitzgerald Health Education Associates, Inc.ã
Corticosteroids
(Equipotent Doses)
(continued)
 Medium potency corticosteroids·
– Methylprednisolone 4 mg
– Triamcinolone 4 mg
– Prednisolone 5 mg
– Prednisone 5 mg
 T ½=18-36 hours·
74
 Fitzgerald Health Education Associates, Inc.ã
Corticosteroids
(Equipotent Doses)
(continued)
 Lower potency·
– Hydrocortisone 20 mg
– Cortisone 25 mg
 T ½=8-12 hours·
75
 Fitzgerald Health Education Associates, Inc.ã
Dosages Used for Asthma Exacerbations:
Prednisone, Methylprednisolone, Prednisolone
Child Adult
ED 1 mg/kg divided bid
(max 60 mg/day)
until PEF 70%
predicted/personal
best
40-80 mg/day in
1-2 divided doses until
PEF 70% predicted or
personal best
Outpatient 1-2 mg/kg/day
(max 60 mg/day)
for 3-10 days
40-60 mg/day in 1-2
divided doses
for 5-10 days
76
 Fitzgerald Health Education Associates, Inc.ã
True or false?
In general, =>2 weeks of higher
dose systemic corticosteroid
therapy needs to be taken prior to
developing drug-induced or
secondary adrenal suppression.
77
 Fitzgerald Health Education Associates, Inc.ã
True or false?
With protracted (i.e. months) of
higher dose systemic corticosteroid
therapy, the adrenal-pituitary axis
might need as long as 2-12
months to fully recover.
78
 Fitzgerald Health Education Associates, Inc.ã
Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 16
Risk Factors for
Death From Asthma
 Past history·
– Sudden severe exacerbations
– Intubation or admission to ICU for
asthma
 In the past year·
– =>2 hospitalizations for asthma
– =>3 ED visits for asthma – NAEPP 3 2007
79
 Fitzgerald Health Education Associates, Inc.ã
Risk Factors for
Death From Asthma
(continued)
 Hospitalization or an ED visit for asthma·
in the past month
 Current use of systemic corticosteroids·
or recent withdrawal from systemic
corticosteroids
 Use of· >2 canisters per month of
inhaled short-acting beta2-agonist – NAEPP 3 2007
80
 Fitzgerald Health Education Associates, Inc.ã
Risk Factors for
Death From Asthma
(continued)
 Difficulty perceiving airflow obstruction·
or its severity
 Comorbidity, as from cardiovascular·
diseases or chronic obstructive
pulmonary disease
 Serious psychiatric disease or·
psychosocial problems – NAEPP 3 2007 81
 Fitzgerald Health Education Associates, Inc.ã
Risk Factors for
Death From Asthma
(continued)
 Low socioeconomic status·
 Urban residence·
 Illicit drug use·
 Sensitivity to Alternaria·
– Common fungus causing potato blight,
tomato canker, other infections – NAEPP 3 2007
82
 Fitzgerald Health Education Associates, Inc.ã
Beta2-Agonists
Potential Adverse Effects
 Common·
– Tachycardia
– Muscle tremor
– Headache
 More often w/·
frequent, HD use
– Lactic acidemia
– Hypokalemia
– Hyperglycemia
– Worsening CV
status
83
 Fitzgerald Health Education Associates, Inc.ã
Levalbuterol and (S)-Albuterol
 Levalbuterol·
– Responsible for the bronchodilation
demonstrated with racemic albuterol
– B-receptor stimulation, increase cAMP
in bronchial muscle tissue yields
bronchodilatation
 (S)-albuterol·
-agonistb– Not a 
– Pharmacology distinct from
levalbuterol 84
 Fitzgerald Health Education Associates, Inc.ã
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Clearance of Albuterol Isomers:
(S)-Albuterol is Cleared Slowly
 Fitzgerald Health Education Associates, Inc. 85ã
Improved Bronchodilation in Severe*
Patients (First Dose)
 Fitzgerald Health Education Associates, Inc. 86ã
Linda has a congested, productive
cough with small amounts of green
sputum. Does she need an antibiotic?
87
 Fitzgerald Health Education Associates, Inc.ã
Antibiotics per NAEPP EPR-3
 “Evidence from clinical trials suggest no·
benefit from antibiotic therapy for asthma
exacerbation whether administered
routinely or when suspicion of bacterial
infection is low…except as needed for
comorbid conditions- e.g. for those
patients with fever and purulent sputum,
evidence of pneumonia or suspected
bacterial sinusitis.”
88
 Fitzgerald Health Education Associates, Inc.ã
Omalizumab (Xolair®)
 Recombinant DNA-derived humanized·
IgG1 monoclonal antibody that
selectively binds to human IgE
– Inhibits binding of IgE to high-affinity IgE
receptor (Fc RI) on the surface of mast
cells and basophils.
– Reduction in surface-bound IgE on Fc RIbearing
cells limits the degree of release of
mediators of the allergic response.
89
 Fitzgerald Health Education Associates, Inc.ã
90
Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 18
Omalizumab (Xolair®)
(continued)
 Indication·
– Patients with moderate to severe
allergy-related asthma who are
currently inadequately controlled with
high-dose inhaled corticosteroids,
typically with LABA
 Mechanism of administration·
– SC injection only
91
 Fitzgerald Health Education Associates, Inc.ã
Omalizumab (Xolair®)
Special Evaluation Needed Prior to Use
 Evidence of allergic contribution to asthma·
– Recent evidence of elevated total IgE level &
specific allergy testing results conducted within
past 2 years to allergens
 IgE levels=·>30-700 IU/mL (=>300-7000 IU/L) (for
adults)
– Positive skin test or in vitro testing (i.e., a
blood test for allergen-specific IgE antibodies
such as the radioallergosorbent test {RAST})
for one or more perennial aeroallergens.
 Fitzgerald Health Education Associates, Inc.ã
92
Omalizumab (Xolair®)
Special Evaluation Needed Prior to Use
(continued)
 Recent pulmonary function testing·
demonstrating inadequate disease
control with optimized therapy
 Fitzgerald Health Education Associates, Inc.ã
93
Omalizumab (Xolair®)
(continued)
 Insurance issues·
– Typically will approve reimbursement for
medication only if ordered by specialist
such as pulmonologist, immunologist,
allergist
 Dosing, frequency, duration of use·
– Weight and IgE results dependent
 Caution·
– “Boxed” warning about anaphylactic risk
post injection (see patient information HO)
94
 Fitzgerald Health Education Associates, Inc.ã
Monoclonal Antibodies
 All drugs with –mab suffix·
– Animal source of product
 Letter prior to –mab·
 MAB source·
– -umab=human
– -omab=mouse
– -ximab=chimera
 Lab animal with cells from =·>2 species
95
 Fitzgerald Health Education Associates, Inc.ã
Disease or
Target Subclass
 -vir- viral·
 -bac- bacteria·
 -lim- immune/immuno modular·
96
 Fitzgerald Health Education Associates, Inc.ã
Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 19
Examples of Monoclonal
Antibody Medications
 Rituximab (Rituxan®)·
– Non Hodgkin lymphoma
 Daclizumab (Zenapax®)·
– Transplant immunosuppression
 Palivizumab (Synagis®)·
– Anti RSV medication
 Infliximab (Remicade®)·
– Rheumatoid arthritis, others 97
 Fitzgerald Health Education Associates, Inc.ã
In order…
 …to create a unique name, a·
distinct, compatible syllable
should be selected as the starting
prefix…”
 Prescriber’s Letter (2001) Naming·
monoclonal antibodies, available at
www.prescribersletter.com
98
 Fitzgerald Health Education Associates, Inc.ã
Global Initiative for Chronic
Obstructive Lung Disease
National Heart, Lung, and Blood
Institute
NIH
World Health Organization
www.goldcopd.org
99
 Fitzgerald Health Education Associates, Inc.ã
Definition of COPD
 COPD is a preventable and treatable·
disease with some significant
extrapulmonary effects that may
contribute to the severity in
individual patients.
 Fitzgerald Health Education Associates, Inc.ã
100
Definition of COPD
(continued)
 Its pulmonary component is·
characterized by airflow limitation
that is not fully reversible.
 The airflow limitation is usually·
progressive and associated with an
abnormal inflammatory response of
the lung to noxious particles or
gases.
 Fitzgerald Health Education Associates, Inc.ã
101
102
Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 20
Small Airway Narrowing
Small airways narrow, resulting in
partially reversible airflow limitation
Source- www.goldcopd.org
Normal Small Airway Mucus Hypersecretion
103
 Fitzgerald Health Education Associates, Inc.ã
Histopathologic
Features of COPD
Normal Obstructive Bronchiolitis Emphysema
Barnes PJ. Chronic obstructive pulmonary disease. N Engl J Med. 2000;343:269-280.
Used with permission. 104
 Fitzgerald Health Education Associates, Inc.ã
Sutherland E and Cherniack R. N Engl J Med 2004;350:2689-2697
Pulmonary Hyperinflation
in Patients with COPD
105
 Fitzgerald Health Education Associates, Inc.ã
106
Low, Flattened Diaphragm Increased A-P Diameter
Air Trapping
CXR in COPD
I: Mild II: Moderate III: Severe IV: Very Severe
Figure 9-3: Therapy at Each Stage of COPD
•FEV1/FVC<>§70%  >80%
predicted
FEV1/FVC<>§70% <><=””>
exacerbations in 3 years
Add long term oxygen if
chronic respiratory failure.
Consider surgical treatments
Active reduction of risk factor(s); influenza vaccination
Add short-acting bronchodilator such as albuterol (salbutamol) (when needed)
COPD Therapy: True or false?
 Since use of the existing·
medications for COPD therapy have
not been shown to modify the longterm
decline in lung function,
pharmacotherapy for COPD is used
to decrease symptoms and/or
complications.
 Fitzgerald Health Education Associates, Inc.ã
108
Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 21
Antimuscarinics/
Anticholinergics
 Examples·
– Ipratropium bromide (Atrovent® with
albuterol-Combivent®)
 Combivent® contains CFC, will no longer·
be available as of December 2013
 Ipratropium via HFA MDI will remain·
available.
– Tiotropium bromide (Spiriva®)
109
 Fitzgerald Health Education Associates, Inc.ã
Antimuscarinics/Anticholinergics
(continued)
 Mechanism of action·
– Affinity to muscarinic receptors
– Inhibits M3-receptors at smooth
muscle leading to bronchodilation
 Fitzgerald Health Education Associates, Inc.ã
110
PK: Ipratropium vs Tiotropium
 Ipratropium·
– T ½=3-5 h
– Time to
Cmax=1-2 h
– Dosing interval
=Every 6
hours
 Tiotropium·
– T ½=14 h
– Time to
Cmax=1-3 h
– Dosing interval
=Once a day
111
 Fitzgerald Health Education Associates, Inc.ã
1.2
1.25
1.3
1.35
1.4
1.45
1.5
1.55
-1h -5min 30min 1h 2h 3h 4h 5h 6h
Time After Administration
FEV1 (Liter) 1.15
Day 1
Day 1
Day 8
Day 8 Day 364
Day 364
Tiotropium vs. Ipratropium
dose
Tio
Ib
112
 Fitzgerald Health Education Associates, Inc.ã
Anticholinergics: Safe or not?
 Fitzgerald Health Education Associates, Inc. 113ã
Safety Data from Pooled Analysis of
Tiotropium Trials and UPLIFT
Michele TM et al. N Engl J Med 2010;363:1097-1099.
114
 Fitzgerald Health Education Associates, Inc.ã
Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 22
Tiotropium versus Salmeterol for the
Prevention of Exacerbations of COPD
Claus Vogelmeier, M.D., Bettina Hederer, M.D.,
Thomas Glaab, M.D., Hendrik Schmidt, Ph.D.,
Maureen P.M.H. Rutten-van Mölken, Ph.D., Kai M.
Beeh, M.D., Klaus F. Rabe, M.D., Leonardo M.
Fabbri, M.D., for the POET-COPD Investigators
N Engl J Med
Volume 364(12):1093-1103
March 24, 2011
 Fitzgerald Health Education Associates, Inc. 115ã
Study Overview and Conclusion
● An important goal in the treatment of
COPD is the prevention of
exacerbations.
● In this trial, the investigators found
that treatment with tiotropium, as
compared with salmeterol, prolonged
the time to the first exacerbation of
COPD and decreased the number of
exacerbations.
 Fitzgerald Health Education Associates, Inc. 116ã
 These results show that, in patients·
with moderate-to-very-severe
COPD, tiotropium is more effective
than salmeterol in preventing
exacerbations.
 Fitzgerald Health Education Associates, Inc. 117ã
Study Overview and Conclusion
(continued)
Improvement in QoL with
LABAs vs Placebo
-8.0 -6.0 -4.0 -2.0 0 2.0 4.0
Adapted from Sin et al. JAMA. 2003;290:2301-2312.
-10.0 6.0 8.0 10.0
SGRQ
Reference
Wadbo et al., 2002
Chapman et al., 2002
Jones et al., 1997
Rossi et al., 2002
Dahl et al., 2001
Overall
Change in SGRQ
 Fitzgerald Health Education Associates, Inc.ã
118
Exacerbations in COPD Patients
Decreased by Tiotropium
Adapted from Barr et al. Cochrane Database of Systematic Reviews. 2005, Issue 2
Beeh et al. 2004
Brusasco et al. 2003
Calverley et al. 2003
Casaburi et al. 2002
Celli et al. 2003
Littner et al. 2000
Niewoeher et al. 2004
O’Donnell et al. 2004
Vincken et al. 2002
Overall
0.5 1.0 5.0 10.0
Odds Ratio
 Fitzgerald Health Education Associates, Inc.ã
119 Wilt T, Niewoehner DE, Kim C, et al.
AHRQ Report 05-E017-2, 2005 Relative risk (95% CI) of > 1 exacerbation
0.2 0.5 1 2 5
Burge
Calverley 1
Mahler
van der Valk
Paggiaro
Subtotal
Bourbeau
Calverley 2
Szafranski
Vestbo
Subtotal
Fluticasone
Budesonide
Weir
Subtotal
Total
Beclomethasone
0.83 (0.74 – 0.94)
Favors ICS Favors Placebo
Prevention of Exacerbations: ICS
120
Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 23
Peters SP et al. N Engl J Med 2010;363:1715-1726.
Anticholinergic Use in Asthma
 Fitzgerald Health Education Associates, Inc. 121ã
Currently FDA-Approved
for COPD Only
 Arformoterol (Brovana®)·
– Single isomer LABA
 Perforomist·
– Nebulized formoterol
 Fitzgerald Health Education Associates, Inc.ã122 
Currently FDA-Approved
for COPD Only
(continued)
 Indacaterol (Arcapta®)·
– Long-acting beta2-agonist
 Tiotropium bromide (Spiriva®)·
– Long-acting anticholinergic
 Fitzgerald Health Education Associates, Inc.ã
123
Arformoterol (Brovana®)
 Single isomer of formoterol·
– Formoterol is a racemic compound.
– With use of single isomer, possibly
better bronchodilatation with less
dose-dependent adverse effect
124
 Fitzgerald Health Education Associates, Inc.ã
Arformoterol (Brovana®)
(continued)
 Dosing·
– Inhalation solution 15 mcg
administered twice a day (morning
and evening) by nebulization
– No MDI formulation at present
125
 Fitzgerald Health Education Associates, Inc.ã
Arformoterol (Brovana®)
(continued)
 Likely user·
– Patient unable to use a non-nebulized
long-acting beta-agonist due to a
physical limitation
– Documented treatment failure with
non-nebulized long-acting betaagonists
(salmeterol [Serevent®]
formoterol [Foradil®])
 Fitzgerald Health Education Associates, Inc.ã
126
Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 24
Indacaterol (Arcapta®)
Neohaler
 Indication·
– Long-acting beta2-agonist indicated
for long-term, once-daily
maintenance bronchodilator in
patients with COPD
 Available·
– Capsule placed in special inhaler
 Fitzgerald Health Education Associates, Inc.ã
127
Indacaterol (Arcapta®)
Neohaler
(continued)
 Pharmacodynamics·
– Identical to others in class
 Warnings·
– Not indicated to treat acute deteriorations
of chronic obstructive pulmonary disease
– Not indicated to treat asthma
 Drug-class warning·
 Fitzgerald Health Education Associates, Inc.ã
128
Pharmacokinetics: Indacaterol
(Arcapta®) Neohaler
 Time to reach serum Cmax·
– ~15 minutes after single or repeated
inhaled
 Absolute bioavailability·
– 43-45%
 Fitzgerald Health Education Associates, Inc.ã
129
Pharmacokinetics: Indacaterol
(Arcapta®) Neohaler
(continued)
 Half-life (T ½)·
– 45-126 hours
 Time to steady-state·
– 12 to 15 days
– How many T ½ to reach steady state? – Sourcehttp://www.pharma.us.novartis.com/product/pi/pdf/arcapta.
pdf, accessed 2.27.12.
 Fitzgerald Health Education Associates, Inc.ã
130
Tachyphylaxis/Tolerance
No evidence of tachyphylaxis,
tolerance, reduced clinical effect
after 12-weeks of daily use
 Fitzgerald Health Education Associates, Inc. 131ã
Tachyphylaxis
 Defined·
– Acute decrease in the response to a
drug after its administration
– Usually caused by depletion or
marked reduction of amount of
neurotransmitter responsible for
creating drug’s effect, or by depletion
of target drug receptors
 Fitzgerald Health Education Associates, Inc.ã
132
Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 25
Tachyphylaxis
(continued)
 With beta2-agonist use·
– Likely genetically based
– Class effect – Sourcehttp://www.pharma.us.novartis.com/product/pi/pdf/arcapta.
pdf, accessed 2.27.12.
 Fitzgerald Health Education Associates, Inc.ã
133
With Long-acting
Bronchodilator Use
 If adding LABA·
– Advise patient to discontinue use of
timed SABA use.
 If adding tiotropium bromide·
– Advise patient to discontinue use of
ipratropium bromide.
 Fitzgerald Health Education Associates, Inc.ã
134
Roflumilast (Daliresp®):
A Member of a New Medication Class
for COPD Treatment
Sources
www.frx.com/pi/Daliresp_pi.pdf
www.daliresp.com/pdf/Daliresp_Medication_Guide.pdf
 Fitzgerald Health Education Associates, Inc.ã135 
Roflumilast (Daliresp®)
 Indications·
– Add-on therapy in severe COPD to
standard care (long-acting
bronchodilators, ICS) in order to
decrease exacerbation risk
 Not a bronchodilator·
– No role in treatment of acute
bronchospasm
 Fitzgerald Health Education Associates, Inc.ã
136
 Mechanism of action·
– Phosphodiesterase 4 (PDE4) inhibitor
 PDE4 present in inflammatory cells and is·
involved in promoting the pathogenesis of
COPD
 Fitzgerald Health Education Associates, Inc.ã
137
Roflumilast (Daliresp®)
(continued)
 Dosing recommendation·
– 500 mcg PO QD, approx same time
 Several weeks of consistent use needed·
prior to seeing clinical effect
– With or without food
 Fitzgerald Health Education Associates, Inc.ã
138
Roflumilast (Daliresp®)
(continued)
Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 26
Roflumilast (Daliresp®):
Special Considerations
 In elders·
– No dose adjustment
 With renal impairment·
– No dose adjustment
 Contraindicated·
– Moderate to severe hepatic impairment
(Child-Pugh Class B or C)
 Fitzgerald Health Education Associates, Inc.ã
139
 Adverse· effects
– Diarrhea=9.5%
– Weight decrease=7.5%
 Use with caution in hx, risk for weight loss·
– Nausea=4.7%
 Most common reason to discontinue·
– Headache=4.4%
– Insomnia=2.4%
 Fitzgerald Health Education Associates, Inc.ã
140
Roflumilast (Daliresp®)
Roflumilast (Daliresp®)
(continued)
 Per FDA direction·
– To be dispensed with medication guide
with potential risks of mental health
problems
 Changes in mood, thinking, behavior·
– Avoid use in patient with a history of
depression with suicidal thoughts or
behaviors.
 Fitzgerald Health Education Associates, Inc.ã
141
Roflumilast (Daliresp®):
Potential Drug Interaction
 Substrate·
– CYP3A4, CYP1A2, needed to convert to
active metabolite
 When given with CYP 3A4 inducer·
– Rifampicin, phenobarbital,
carbamazepine, phenytoin, likely St.
John’s wort, potential decrease
effectiveness
 Fitzgerald Health Education Associates, Inc.ã– Concomitant use should be avoided. 
142
Roflumilast (Daliresp®):
Potential Drug Interaction
(continued)
 With CYP3A4, 1A2 inhibitors·
– Examples- Erythromycin, clarithromycin,
ketoconazole, ciprofloxacin, cimetidine
 Concomitant use can result in·
increased exposure to roflumilast and
potential increased adverse reactions.
 Fitzgerald Health Education Associates, Inc.ã
143
Exacerbation:
Definition, Evaluation and Treatment
 An exacerbation of COPD is an·
event in the natural course of the
disease characterized by a change
in the patient’s baseline dyspnea,
cough and/or sputum beyond dayto-day
variability sufficient to
warrant a change in management.
 www.thoracic.org/COPD/13/definition.asp·
144
 Fitzgerald Health Education Associates, Inc.ã
Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 27
Susceptibility to Exacerbation
in Chronic Obstructive
Pulmonary Disease
NEJM, September 16, 2010
J.R. Hurst and Others
 Fitzgerald Health Education Associates, Inc. 145ã
Conclusion
 Exacerbations became more·
frequent (and more severe) as the
severity of COPD increased;
exacerbation rates in the first year
of follow-up were 0.85 per person
for patients with stage 2 COPD…
 Fitzgerald Health Education Associates, Inc.ã
146
Conclusion
(continued)
 …1.34 for patients with stage 3,·
and 2.00 for patients with stage 4.
Overall, 22% of patients with stage
2 disease, 33% with stage 3, and
47% with stage 4 had frequent
exacerbations (=>2 in the first year
of follow-up).
 Fitzgerald Health Education Associates, Inc.ã
147
Conclusion
(continued)
 The single best predictor of·
exacerbations, across all GOLD
stages, was a history of
exacerbations.
 Fitzgerald Health Education Associates, Inc.ã
148
Conclusion
(continued)
 In addition to its association with·
more severe disease and prior
exacerbations, the phenotype was
independently associated with a
history of gastroesophageal reflux
or heartburn, poorer quality of life,
and elevated white cell count.
 Fitzgerald Health Education Associates, Inc.ã
149
COPD Exacerbation:
Treatment
 Use of bronchodilators·
– Short-acting β2-agonist and/or
anticholinergic (ipratropium,
tiotropium bromide) as needed
– Consider adding long-acting
bronchodilator (salmeterol,
formoterol, tiotropium bromide) if
patient currently not using one
150
 Fitzgerald Health Education Associates, Inc.ã
Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 28
COPD Exacerbation:
Treatment
(continued)
 If baseline FEV1·< for=”” severe=”” paroxysms=”” of=”” post=”” infectious=”” cough,=”” consider=”” prescribing=”” 30=”” to=”” 40=”” mg=”” of=”” prednisone=”” per=”” day=”” for=”” a=”” short,=”” finite=”” period=”” of=”” time=”” when=”” other=”” common=”” causes=”” of=”” cough=”” including=”” rhinosinusitis,=”” asthma,=”” or=””>· Fitzgerald Health Education Associates, Inc. Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 30 ACCP Recommendations (continued) ã In patients with post infectious cough, when the cough adversely affects the patient’s quality of life and when cough persists despite use of inhaled ipratropium, consider the use of inhaled corticosteroids with the recognition that this product will take about 1 week of use prior to providing significant symptom relief. 162 · Fitzgerald Health Education Associates, Inc. ACCP Recommendations (continued) ã The use of inhaled ipratropium bromide (Atrovent®) can be helpful in attenuating the post infectious cough. 161 · Fitzgerald Health Education Associates, Inc. ACCP Recommendations (continued) ã Post infectious cough should be considered in the person who complains of cough that has been present for 3-8 weeks following symptoms of an acute respiratory infection. 160 · Fitzgerald Health Education Associates, Inc. ACCP Recommendations (continued) ã The newer generation of non-sedating antihistamines such as loratadine play no role in treating cough in this setting. 159 · Individuals with acute cough associated with the common cold can be treated with a first-generation antihistamine/ decongestant preparation such as brompheniramine and sustained-release pseudoephedrine (Trade name-Bromfed®). · Fitzgerald Health Education Associates, Inc. ACCP Recommendations ã Fitzgerald Health Education Associates, Inc. 156 Sanford Guide Recommendation for Antimicrobial Therapy Mild to moderate COPD exacerbation/ acute exacerbation of chronic bronchitis Antimicrobial therapy usually not indicated. If prescribed, consider using the following agents: –Amoxicillin –Cephalosporin –TMP-SMX –Doxycycline Source- Gilbert, D., Moellering R., Eliopoulos, G., Chambers, H., Saag, M. (2011) The Sanford Guide to Antimicrobial Therapy (41th ed.). Sperryville, VA: Antimicrobial Therapy, Inc. pp. 34. Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 29 157 Sanford Guide Recommendation for Antimicrobial Therapy More severe COPD exacerbation/ acute exacerbation of chronic bronchitis Use one of the following agents. –Amoxicillin-clavulanate –Cephalosporin –Azithromycin –Clarithromycin –Fluoroquinolone with activity against DRSP • (Moxi-, gemi-, levofloxacin) Source- Gilbert, D., Moellering R., Eliopoulos, G., Chambers, H., Saag, M. (2011) The Sanford Guide to Antimicrobial Therapy (41th ed.). Sperryville, VA: Antimicrobial Therapy, Inc. pp. 34. Irwin, R. et al. American College of Chest Physicians (ACCP) Evidence-based Clinical Practice Guidelines: Diagnosis and Management of Cough. Chest. 2006;129:1S-23S. Summary article available at http://www.fhea.com/Newsletter/Fitzgerald%20 Newsletter%20Volume%20VI%20Issue%204.pdf 158 ã Fitzgerald Health Education Associates, Inc. ãLegionella spp. Viral –Rhinovirus –Influenza virus Less common Respiratory Bacteria (Usually in presence of advanced disease and repeated exacerbations) –Enterobacteriaceae spp. –Pseudomonas spp. 155 nC. pneumoniae nM. pneumoniae nM. catarrhalis –Atypical pathogens nH. influenzae nS. pneumoniae –Gram-negative n Fitzgerald Health Education Associates, Inc. Pathogens Associated with COPD Exacerbation Respiratory Bacteria –Gram-positive ã Fitzgerald Health Education Associates, Inc. Initial Empiric Therapy in Outpatients with Acute Bacterial Exacerbation of Chronic Bronchitis Balter MS et al. Can Respir J. 2003;10(Suppl B):3B-32B 154 ã Choice should be based on local bacteria resistance patterns. 153 · Provide antimicrobial coverage for the major bacterial pathogens involved in exacerbation while taking into account local patterns of bacterial resistance. · Fitzgerald Health Education Associates, Inc. Antimicrobial Therapy in COPD Exacerbation (continued) ã Likely indicated when symptoms of breathlessness and cough are accompanied by altered sputum characteristic that are indicative of bacterial infection such as increased purulence and/or change in volume 152 · Fitzgerald Health Education Associates, Inc. Antimicrobial Therapy in COPD Exacerbation ã50% of predicted, add a corticosteroid such as prednisone 40 mg qd for 10 days. Consider using an inhaled corticosteroid such as nebulized budesonide (Pulmicort®) during non-acidotic exacerbations. 151  For children age· Fitzgerald Health Education Associates, Inc. 173 The Honey “Dose” ã In a comparison of honey, DM, and no treatment, parents rated honey most favorably for symptomatic relief of their child's nocturnal cough and sleep difficulty due to upper respiratory tract infection. Honey may be a preferable treatment for the cough and sleep difficulty associated with childhood upper respiratory tract infection. · Fitzgerald Health Education Associates, Inc. 172 Paul et al. Conclusions ã Fitzgerald Health Education Associates, Inc. 171 Honey vs. Dextromethorphan vs. Nothing for Cough: Which won? Paul IM, Beiler J, McMonagle A, et al. Effect of Honey, dextromethorphan, and no treatment on nocturnal cough and sleep quality for coughing children and their parents. Arch Pediatr Adolesc Med 2007;161:1140-6. ã Fitzgerald Health Education Associates, Inc. One tsp BID for cough control 10 mg hydrocodone=5 ml 5 mg hydrocodone=30 mg codeine ã “Robitussin DM® and codeine do nothing but make me and everyone in my family really nervous. I can take Tussionex® or Vicodin® or Percocet® without any problem.” 170 · Fitzgerald Health Education Associates, Inc. 169 Truth or fiction? ã Anticipated adverse effects – Visual field distortion, dissociation, bodily perception distortion, excitement, loss of time comprehension · Dissociative psychedelic drug – Effects that are similar to those of ketamine and phencyclidine (PCP) · Fitzgerald Health Education Associates, Inc. 168 Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 31 When Therapeutic Dextromethorphan Dose Exceeded ã Should not be taken with: – Monoamine oxidase inhibitors (MAOIs), serotonin reuptake inhibitors (SSRIs, SSNRIs, TCAs) due to cumulative serotonergic effects – Opiates, opioids, alcohol due to cumulative CNS suppression · Fitzgerald Health Education Associates, Inc. Potential Drug Interactions with Dextromethorphan ã Tylenol® with codeine – #1=7.5 mg – #2=15 mg – #3=30 mg – #4=60 mg 167 · DM 30 mg (10 ml)=Codeine 15 mg – Codeine dose needed for superior cough suppression=30 mg · Fitzgerald Health Education Associates, Inc. Codeine vs. DM in Cough Suppressing Efficacy ã Examples of OTC doses – Robitussin DM®=15 mg/5 ml – Delsym®=30 mg/5 ml – Lee, P. et al., Antitussive efficacy of dextromethorphan in cough associated with acute upper respiratory tract infection J Pharm Pharmacol. 2000 Sep;52(9):1137-42. 166 · Likely marginally effective at recommended doses – 60-120 mg/d total in the adult · Fitzgerald Health Education Associates, Inc. 165 Dextromethorphan (continued) ã Mechanism of action – D-isomer of codeine analog levorphanol – Agonist of receptor sites involved with cough control – Possibly central and peripheral action · Fitzgerald Health Education Associates, Inc. Dextromethorphan ã Central acting antitussive agents such as codeine and dextromethorphan should be considered when other measures fail. In children and adults with cough following an acute respiratory tract infection, if cough has persisted for more 8 weeks, another diagnosis other than post infectious cough should be considered. 164 · Fitzgerald Health Education Associates, Inc. ACCP Recommendations (continued) ãoesophageal reflux disease have been ruled out. 163 < fitzgerald=”” health=”” education=”” associates,=”” inc.=”” 182=”” mild=”” intermittent=”” mild=”” persistent=”” moderate=”” severe=”” intermittent=”” moderate=”” severe=”” persistent=”” avoidance=”” of=”” allergens,=”” irritant=”” and=”” pollutants=”” immunotherapy=”” intranasal=”” decongestant=””>ã Fitzgerald Health Education Associates, Inc. Allergic Rhinitis and Its Impact on Asthma (ARIA) Classification Source: www.whiar.org ã Rescue medication to inactivate formed inflammatory mediators, treat symptoms 181 · Controller therapy to prevent formation of inflammatory mediators · Fitzgerald Health Education Associates, Inc. 180 Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 33 Pharmacologic Intervention in Allergic Rhinitis ã Cost – 30 caps=~$4 (WalMart), dosed TID · Mechanism of action – Anesthetizes respiratory passage, lung, and pleural stretch receptors, reducing cough reflex (antitussive) – Variable reports of efficacy · Fitzgerald Health Education Associates, Inc. Tessalon Perles ã Pediatric, 2-6 years – 300 mg q 12 hr, not to exceed 600 mg/day 179 · Child age 6-12 years – 600 mg q 12 hr, not to exceed 1.2 g/day · Adult dose – Not to exceed 2.4 g per day · Fitzgerald Health Education Associates, Inc. 178 Guaifenesin ã Conclusion – Guaifenesin inhibits cough reflex sensitivity in subjects with URI, whose cough receptors are transiently hypersensitive, but not in healthy volunteers. – Source- CHEST 2003; 124:2178–2181, available at http://chestjournal.chestpubs.org/content/124/6/2178.full .pdf, accessed 2.7.12. · Fitzgerald Health Education Associates, Inc. 177 Guaifenesin Efficacy: Limited Study ã Mechanism of action – Possible mechanisms include a central antitussive effect, or a peripheral effect by increased sputum volume, serving as barrier and shielding cough receptors within respiratory epithelium from tussive stimulus · Fitzgerald Health Education Associates, Inc. Guaifenesin (continued) ã Mechanism of action – Likely act as irritant to gastric vagal receptors, recruits efferent parasympathetic reflexes that cause glandular exocytosis of a less viscous mucus mixture – Potentially thins tenacious, congealed mucopurulent material from obstructed small airways 176 · Fitzgerald Health Education Associates, Inc. 175 Guaifenesin ã Antioxidant properties · Increased salivary production · Sweet taste induces endogenous opioids · Fitzgerald Health Education Associates, Inc. 174 Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 32 Proposed Mechanisms of Action: Honey ã 12-18 years – 2 tsps (9.86 ml) · 6-11 years – 1 tsp (4.93 ml) · 2-5 years – ½ tsp (2.46 ml) ·1 y – Do not use due to botulism risk < for=”” instructions=”” to=”” take=”” this=”” test=”” on-line,=”” go=”” to=”” www.fhea.com/testinstructions.htm=”” 186=”” drugs=”” that=”” affect=”” the=”” respiratory=”” system=”” copyright,=”” fitzgerald=”” health=”” education=”” associates,=”” inc.=”” all=”” rights=”” reserved.=”” reproduction=”” is=”” prohibited.=”” 34=”” production=”” credits=”” recorded=”” and=”” produced=”” in=”” the=”” studios=”” of=”” fitzgerald=”” health=”” education=”” associates,=”” inc.=”” this=”” program=”” is=”” intended=”” for=”” individual=”” use.=”” no=”” reproduction=”” or=”” institutional=”” use=”” is=”” permitted=”” without=”” a=”” specific=”” license=”” from=”” fitzgerald=”” health=”” education=”” associates,=”” inc.=”” 187=”” fitzgerald=”” health=”” education=”” associates,=”” inc.=”” 85=”” flagship=”” drive=”” north=”” andover,=”” ma=”” 01845-6154=”” 978.794.8366=”” fax-978.794.2455=”” web=”” sites:=”” on-line=”” store:=”” store.fhea.com=””>· Fitzgerald Health Education Associates, Inc. ã Fitzgerald Health Education Associates, Inc. End of Presentation! Thank you for your time and attention. Margaret A. Fitzgerald, DNP, FNP-BC, NP-C, FAANP, CSP, FAAN, DCC Website: www.fhea.com E-mail: cs@fhea.com 185 ã Fitzgerald Health Education Associates, Inc. Questions? Comments? 184 ã10 days) or oral decongestant intranasal steroid oral or local non-sedative H1-blocker Management of Allergic Rhinitis: ARIA Guidelines Source- http://www.jacionline.org/article/S0091-6749(10)01057-2/fulltext#sec4.3, accessed 2.7.12. leukotriene receptor antagonists 183  & Testing Center: www.npexpert.com www.facebook.com/fitzgeraldhealth 188 Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 35 Classification of Asthma Severity (Youths≥12 Years of Age and Adults) Classifying severity for patients who are not currently taking long-term control medications Components of Severity Persistent Impairment Normal FEV1/FVC: 8-19 yr 85% 20-39 yr 80% 40-59 yr 75% 60-80 yr 70% Symptoms Intermittent Mild Moderate Severe ≤2 days/week >2 days/week
but not daily Daily Throughout the day
Nighttime
awakenings ≤2x/month 3-4x/month >1x/week but
not nightly Often 7x/week
Short-acting beta2-
agonist use for
symptom control
(not prevention of
EIB)
≤2 days/week
>2 days/week
but not
>1x/day
Daily Several times per day
Interference with
normal activity None Minor limitation Some limitation Extremely limited
Lung function
Normal FEV1
between
exacerbations
FEV1>80%
predicted
FEV1>80%
predicted
FEV1>60% but
5%
Risk
Exacerbations
requiring oral
systemic
corticosteroids
0-1/year (see note) ≥2/year (see note)
Consider severity and interval since last exacerbation. Frequency and severity
may fluctuate over time for patients in any severity category.
Relative annual risk of exacerbations may be related to FEV1
 Fitzgerald Health Education Associates, Inc. 189ã
Classification of Asthma Control
12 Years of Age and Adults)³(Youths 
Components of Control
Impairment
Symptoms Well-controlled Not Wellcontrolled
Very Poorly
Controlled
≤2 days/week >2 days/week Throughout the day
Nighttime awakenings ≤2 x/month 1-3x/week ≥4x/week
Interference with normal
activity None Some limitation Extremely limited
Short-acting beta2-agonist
use for symptom control
(not prevention of EIB)
≤2 days/week >2 days/week Several times per day
FEV1 or peak flow >80% predicted/personal
best
60-80%
predicted/personal
best
³ Fitzgerald Health Education Associates, Inc. 194 Stepwise Approach for Managing Asthma in Patients Agedã Fitzgerald Health Education Associates, Inc. 192 Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 37 193 ã12 Years: NAEPP EPR-3 Guidelines Step 1 Preferred: SABA PRN Step 2 Preferred: Low-dose inhaled corticosteroid (ICS) Alternative: Mast cell stabilizer (Cromolyn nedocromil), leukotriene receptor antagonist (LTRA), or theophylline Step 3 Preferred: Medium-dose ICS or Low-dose ICS + LABA Alternative: Low-dose ICS and either LTRA, theophylline, or zileuton Step 5 Preferred: High-dose ICS + LABA and omalizumab (Xolair) use can be considered for patients who have allergies. Step 4 Preferred: Medium-dose ICS + LABA Alternative: Medium-dose ICS and either LTRA, theophylline, or zileuton Step 6 Preferred: High-dose ICS + LABA + oral corticosteroid and consider omalizumab for patients who have allergies Severe Persistent Moderate Mild Persistent Persistent Intermittent ³ Fitzgerald Health Education Associates, Inc. Stepwise Approach for Managing Asthma in Patients Agedã60% predicted/personal best Validated Questionnaires ATAQ ACQ ACT 0 ≤0.75* ≥20 1-2 ≥1.5 16-19 3-4 N/A ≤15 Exacerbations 0-1/year ≥2/year (see note) Consider severity and interval since last exacerbation Risk Progressive loss of lung function Evaluation requires long-term follow-up care Treatment-related adverse effects Medication side effects can vary in intensity from none to very troublesome and worrisome. The level of intensity does not correlate to specific levels of control but should be considered in the overall assessment of risk. *ACQ values of 0.76-1.4 are indeterminate regarding well-controlled asthma. Key: EIB, exercise-induced bronchospasm; FEV1, forced expiratory volume in 1 second. See figure 3-8 for full name and source of ATAQ, ACQ, ACT. 190 Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 36 Monitoring Control in Clinical Practice: Asthma Control Test™ for Patients Aged≥12 Years http://www.asthma.com/resources/asthma-control-test.html, accessed 2.7.12. Level of Control Based on Composite Score ≥20 = Controlled 16-19 = Not Well Controlled ≤15 = Very Poorly Controlled Regardless of patient’s selfassessment of control in Question 5 191   Fitzgerald Health Education Associates, Inc. 196 Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 39 197 I: Mild II: Moderate III: Severe IV: Very Severe Figure 9-3: Therapy at Each Stage of COPD •FEV1/FVCã Fitzgerald Health Education Associates, Inc. 195 Improved Bronchodilation in Severe* Patients (First Dose) ã Fitzgerald Health Education Associates, Inc. Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 38 Clearance of Albuterol Isomers: (S)-Albuterol is Cleared Slowly ãStep 6 Preferred: High-dose ICS + LABA + oral corticosteroid and consider omalizumab for patients who have allergies Severe Persistent Moderate Mild Persistent Persistent Intermittent <>§70%  >80%
predicted
FEV1/FVC<>§70% <><=””>
exacerbations in 3 years
Add long term oxygen if
chronic respiratory failure.
Consider surgical treatments
Active reduction of risk factor(s); influenza vaccination
Add short-acting bronchodilator such as albuterol (salbutamol) (when needed)
Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 40
Safety Data from Pooled Analysis of
Tiotropium Trials and UPLIFT
Michele TM et al. N Engl J Med 2010;363:1097-1099.
199
 Fitzgerald Health Education Associates, Inc.ã
Peters SP et al. N Engl J Med 2010;363:1715-1726.
Anticholinergic Use in Asthma
 Fitzgerald Health Education Associates, Inc. 200ã
Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 41
Allergic Rhinitis and Its Impact on
Asthma (ARIA) Classification
Source: www.whiar.org
 Fitzgerald Health Education Associates, Inc. 201ã
mild
intermittent
mild
persistent moderate
severe
intermittent
moderate
severe
persistent
avoidance of allergens, irritant and pollutants
immunotherapy
intranasal decongestant (< fitzgerald=”” health=”” education=”” associates,=”” inc.=”” drugs=”” that=”” affect=”” the=”” respiratory=”” system=”” copyright,=”” fitzgerald=”” health=”” education=”” associates,=”” inc.=”” all=”” rights=”” reserved.=”” reproduction=”” is=”” prohibited.=”” 42=”” peak=”” serum=”” concentration=”” dosage=””>ã10 days) or oral decongestant intranasal steroid oral or local non-sedative H1-blocker Management of Allergic Rhinitis: ARIA Guidelines Source- http://www.jacionline.org/article/S0091-6749(10)01057-2/fulltext#sec4.3, accessed 2.7.12. leukotriene receptor antagonists 202  < 9.9=”” mcg/ml=”” if=”” symptoms=”” are=”” not=”” controlled=”” and=”” current=”” dosage=”” is=”” tolerated,=”” increase=”” dose=”” about=”” 25%.=”” recheck=”” serum=”” concentration=”” after=”” three=”” days=”” for=”” further=”” dosage=”” adjustment.=””>‐14.9 mcg/mL If symptoms are controlled and current dosage is tolerated, maintain dose and recheck serum concentration at 6‐12 month intervals. If symptoms are not controlled and current dosage is tolerated consider adding additional medication(s) to treatment regimen. 15‐19.9 mcg/mL Consider 10% decrease in dose to provide greater margin of safety even if current dosage is tolerated.   20‐24.9 mcg/mL Decrease dose by 25% even if no adverse effects are present. Recheck serum concentration after 3 days to guide further dosage adjustment. 25‐30 mcg/mL Skip next dose and decrease subsequent doses at least 25% even if no adverse effects are present. Recheck serum concentration after 3 days to guide further dosage adjustment. If symptomatic, consider whether overdose treatment is indicated (see recommendations for chronic OVERDOSAGE). > 30 mcg/mL
Treat overdose as indicated (see recommendations for
chronic overdosage). If theophylline is subsequently
resumed, decrease dose by at least 50% and recheck
serum concentration after 3 days to guide further
dosage adjustment.
Dose reduction and/or serum theophylline concentration measurement is
indicated whenever adverse effects are present physiologic abnormalities
that can reduce theophylline clearance occur (e.g. sustained fever), or a
drug that interacts with theophylline is added or discontinued  
Source‐ www.purduepharma.com/PI/Prescription/Uniphyl.pdf, accessed 1.18.10.  
Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 43
Fanta C. N Engl J Med 2009;360:1002‐1014
Drugs that Affect the Respiratory System
Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 44
Fanta C. N Engl J Med 2009;360:1002‐1014
Drugs that Affect the Respiratory System
Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 45
Fanta C. N Engl J Med 2009;360:1002‐1014
Drugs that Affect the Respiratory System
Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 46
Fanta C. N Engl J Med 2009;360:1002‐1014
Drugs that Affect the Respiratory System
Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 47
Fitzgerald Health Education Associates, Inc. provides continuing
education seminars on a regular schedule, as well as, on-demand for
state and local groups for advanced practice nurses and ambulatory
care nurses. We also provide home study continuing education for
Nurse Practitioners.
We enjoy hearing feedback and we’d appreciate your taking the time to
let us know how we are doing and what we can do to serve you better.
Please comment about our products or services. We also appreciate
your suggestions for live and taped seminars as well.
Customer service email: comments@fhea.com
Margaret Fitzgerald email: cs@fhea.com
Website and on-line store: www.fhea.com, store.fhea.com
Subscribe to our on-line newsletter for Pointers from Peg, new
products, new seminar schedules: ezine@fhea.com
Would you like to host a seminar? Contact services@fhea.com
We appreciate your business and welcome feedback on this and any of
our products or services.
Sincerely,
All of us at Fitzgerald Health Education Associates, Inc.
Drugs that Affect the Respiratory System Copyright, Fitzgerald Health Education Associates, Inc. All rights reserved. Reproduction is prohibited. 48

 

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