Download CH31 Page 1-8

31-1
CHRONIC OBSTRUCTIVE
PULMONARY DISEASE
Treading on Thin Air. . . . . . . . . . . . . . . . . . . . . . . . . . . . . Level II
• Potential overuse of ibuprofen—long-term ibuprofen therapy
has potential toxic effects (eg, acute renal failure, GI ulcer, cardiovascular disease) especially given patient’s medical history.
1.b.What objective information indicates the presence and
severity of COPD?
• Decreased breath sounds.
Joel C. Marrs, PharmD, FCCP, FASHP, FNLA,
BCPS (AQ Cardiology), BCACP, CLS
• Abnormal pulmonary function test:
A 59-year-old man with a number of medical problems presents
to a new primary care provider after moving to Colorado with
complaints of increasing shortness of breath, especially with activity. Review of the history of present illness reveals that this is not
a new problem. The patient has had similar symptoms in the past
with a physically demanding occupation. A change in work activity
appeared to abate the patient’s symptoms. However, a change in
altitude with his move to Colorado has reexposed his disease. It is
unclear if the patient was ever diagnosed with COPD in the past, as
no past medical record is available. Based on the patient’s smoking
history, spirometry report, exacerbation history in the last year, and
current symptoms, the patient is classified into “Group B,” low risk
of exacerbation, but increased symptoms of COPD. The goals of
therapy are to halt disease progression and to enable the patient to
return to his baseline level of functioning. The reader will need to
identify the treatment of COPD with fluticasone/salmeterol as inadequate and potentially inappropriate given the low risk of exacerbation and continued symptoms of COPD. Consistent with the GOLD
guidelines, an additional long-acting bronchodilator will be needed
along with a short-acting bronchodilator for acute symptoms, as
needed. Smoking cessation and appropriate immunizations are also
an important component of the patient’s care.
QUESTIONS
Problem Identification
1.a. Create a list of this patient’s drug-related problems.
• Needs additional therapies for better control of COPD-related
symptoms—patient still having symptoms despite long-acting
bronchodilator therapy with inhaled corticosteroid (fluticasone/salmeterol); in addition, patient may need pneumococcal
and influenza vaccines.
• Unnecessary medication: inhaled corticosteroid—patient
likely does not need as he does not have a reactive component
based on spirometry and does not have a significant COPD
exacerbation history that would indicate the need for this
therapy.
• Needs additional therapy to assist with smoking cessation—
patient continues to smoke despite likely intervention with
bupropion; alternative smoking cessation therapies (eg, varenicline, nicotine replacement) may be needed.
• Overtreatment of coronary artery disease (CAD) with dual
antiplatelet therapy—patient continues to take clopidogrel +
aspirin therapy despite coronary artery stenting 2 years ago.
✓FEV1/forced vital capacity (FVC) <0.7, FEV1 <80% predicted, but >50% predicted
✓Pulse oximetry of 93% on room air
• Lack of signs or symptoms of cyanosis.
• Sputum production.
1.c. What subjective information (eg, patient history) suggests
the diagnosis of COPD in this patient?
• Cigarette smoker (40 pack-year history, plus continued
smoking)
• Chronic bronchitis × 8 years (has had one exacerbation in the
last 12 months; received oral antibiotic treatment but was not
hospitalized)
• Patient history of shortness of breath (decreased exercise
capacity); he most closely fits the Modified Medical Research
Council (mMRC) Grade 2 classification given his shortness of
breath when playing outside with his grandchildren.
1.d. How would you stage and classify this patient’s COPD?
• GOLD 2 (Moderate) via spirometry as evidenced by FEV1/
FVC <0.7, FEV1 <80% predicted, but >50% predicted.
• Patient “Group B” given low risk of exacerbation (only one
exacerbation in last 12 months) and higher symptoms (including mMRC Grade 2 symptoms).
• The patient has not had hospitalization in the past year and
does not have signs or symptoms of respiratory failure.
Desired Outcome
2.What are the desired goals of pharmacotherapy for the treatment of COPD in this patient?
• Although COPD is a preventable and treatable disease, though
not reversible, it is associated with significant extrapulmonary
effects that contribute to disease progression and mortality
despite treatment. Appropriate treatment can relieve symptoms, improve the quality of life (QOL), and extend the
patient’s life span. The goals of treatment in COPD are the
following:
✓Relieve COPD symptoms.
✓Prevent lung disease progression.
✓Improve exercise tolerance.
✓Treat and prevent acute exacerbations and complications.
✓Improve QOL specifically related to physical and psychological well-being.
✓Reduce both morbidity and mortality.
✓Improve/stabilize PFTs (eg, FEV1/FVC ratio, per cent of predicted FEV1).
✓ Encourage and achieve smoking cessation to prevent further
cardiopulmonary damage.
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Chronic Obstructive Pulmonary Disease
Joseph P. Vande Griend, PharmD, FCCP, BCPS
CASE SUMMARY
CHAPTER 31
31
Controversial benefit with increased risk of bleeding and
increased cost. Beta-blocker therapy with metoprolol succinate
is appropriate and safe for this patient with COPD, as it is a
beta-1 selective agent.
31-2
Therapeutic Alternatives
SECTION 3
3.a.What nonpharmacologic therapies would be useful to
improve this patient’s COPD symptoms?
• Enrollment in a smoking cessation program that may include
psychological education as well as additional pharmacologic
support with nicotine patches, gum, or other drug therapy.
(Note: The patient in this case is already receiving treatment
with bupropion but has not yet been successful in quitting
smoking.)
Respiratory Disorders
• Enrollment in a pulmonary rehabilitation program is strongly
encouraged; components would include the following:
✓Assessment of nutrition and caloric intake
✓An exercise program to improve mechanics of breathing
✓Psychological education regarding the disease and smoking
✓
Education regarding pharmacotherapeutic treatment
options and the proper use of medications
3.b. What pharmacotherapeutic alternatives are available for the
treatment of this patient’s COPD based on the most recent
GOLD guideline recommendations?
• The choice of medications should be based on the severity of
disease, risk of COPD exacerbation, and patient symptoms
using nationally accepted criteria from the GOLD guidelines
and considering the American College of Physicians (ACP)
guidelines.1,2 Based on the GOLD criteria and the patient’s
current status, the patient is in “Group B” given his spirometry
results (GOLD 2, moderate), low risk of exacerbation, and currently uncontrolled symptoms.1
• The patient is currently utilizing Advair (fluticasone/
salmeterol), a long-acting β2-agonist/inhaled corticosteroid
combination. Per the GOLD guidelines, the use of an inhaled
corticosteroid with a long-acting bronchodilator should be
considered for “Group C” or “Group D” COPD patients, which
are categorized as having a higher risk of COPD exacerbation.
For patients with repeated previous exacerbations and/or FEV1
<60% predicted, inhaled corticosteroids can improve symptoms, lung function, and QOL, as well as reduce the frequency
of exacerbations.1,3–7 Similar to Advair, the products Symbicort (budesonide/formoterol) and Breo Ellipta (fluticasone/
vilanterol) also contain the combination of an inhaled corticosteroid and long-acting β-agonist in one inhaler. For this
patient, fluticasone may be inappropriate given the severity of
disease, lack of hospitalization from COPD, and lack of evidence suggesting a reactive component to his disease.
• Options include:
✓Inhaled anticholinergic agents: ipratropium bromide
(Atrovent), aclidinium bromide (Tudorza Pressair),
tiotropium bromide (Spiriva, Spiriva Respimat), umeclidinium bromide (Incruse Ellipta), or glycopyrrolate
(Seebri Neohaler):
■■ Ipratropium bromide (Atrovent): In COPD, there is an
increase in parasympathetic activity, which is a result
of airway inflammation. Acetylcholine exerts its action
through the parasympathetic pathway, causing contraction of airway smooth muscle and increased mucus secretion. Therefore, using anticholinergics to block the action
of acetylcholine results in bronchodilation and decreased
mucus production. The patient is already on a long-acting
β2-agonist (salmeterol); however, this is not sufficient to
control the patient’s symptoms. Addition of this agent
would be beneficial in that it targets a different mechanism of bronchodilation than β2-agonists. However, this
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
agent is short-acting, and the patient would need to use
this medication four times daily in addition to the salmeterol therapy.
■■ Tiotropium bromide (Spiriva, Spiriva Respimat) is a synthetic quaternary ammonium anticholinergic compound
specific for the M1 and M3 muscarinic receptors. Addition
of this agent would also be beneficial in that it targets a
different mechanism of bronchodilation than β2-agonists.
This drug is given as a once-daily inhalation, whether
administered via dry powder inhaler (Spiriva) or metered
dose inhaler (Spiriva Respimat). In general, long-acting
bronchodilators, such as tiotropium, are preferred in
patients with COPD over ipratropium, because of the
need for less frequent dosing (once daily vs four times
daily) and they are more effective at producing maintained symptom relief.1 The GOLD guidelines state that
the combined use of a β-agonist and anticholinergic agent
may be considered if symptoms persist with single treatment. Evidence for this recommendation is limited.8,9 A
recent Cochrane review evaluating combination versus
single treatment found only a slightly better QOL and a
small increase in the postbronchodilator FEV1 with the
combination compared with tiotropium monotherapy.10
■■ Aclidinium bromide (Tudorza Pressair) is a synthetic quaternary ammonium anticholinergic compound with similar affinity to the M1–M5 subtypes of muscarinic receptors.
It exhibits its pharmacologic action through inhibition of
the M3 receptor in the lungs leading to bronchodilation.
Addition of this agent would also be beneficial in that it
targets a different mechanism of bronchodilation than
β2-agonists. This drug is given as a twice-daily inhalation.
It is administered in the form of an inhaled, dry powder,
handheld device. Based on limited clinical trial data, this
agent would be expected to provide similar bronchodilation to tiotropium, but requires twice-daily dosing, and
does not have randomized controlled trial data supporting its benefit.
■■ Umeclidinium bromide (Incruse Ellipta) is a synthetic quaternary ammonium anticholinergic compound with similar affinity to the M1–M5 subtypes of muscarinic receptors.
It exhibits its pharmacologic action through inhibition of
the M3 receptor in the lungs leading to bronchodilation.
Addition of this agent would also be beneficial in that it
targets a different mechanism of bronchodilation than
β2-agonists. This drug is given as a once daily inhalation.
It is administered in the form of an inhaled, dry powder,
handheld device. Based on limited clinical trial data, this
agent would be expected to provide similar bronchodilation to tiotropium, but does not have randomized controlled trial data supporting its benefit.
■■ Glycopyrrolate (Seebri Neohaler) is a synthetic quaternary
ammonium anticholinergic compound with similar affinity to the M1–M5 subtypes of muscarinic receptors. It
exhibits its pharmacologic action through inhibition of
the M3 receptor in the lungs leading to bronchodilation.
Addition of this agent would also be beneficial in that it
targets a different mechanism of bronchodilation than
β2-agonists. This drug is given as a twice daily inhalation.
It is administered in the form of an inhaled, dry powder,
handheld device. Based on limited clinical trial data, this
agent would be expected to provide similar bronchodilation to other long-acting anticholinergic agents, but does
not have randomized controlled trial data supporting its
benefit.
31-3
■■ Salmeterol (Serevent), formoterol (Foradil, Perforomist),
indacaterol (Arcapta), or olodaterol (Striverdi Respimat):
The patient is currently on scheduled salmeterol (a longacting β2-selective agonist) as provided in the combination product Advair, which is appropriate based on the
patient’s “Group B” COPD classification. Generally, utilizing one of these agents on a regularly scheduled basis is an
appropriate step when COPD patients are not adequately
managed on an as-needed short-acting bronchodilator
and/or scheduled inhaled long-acting anticholinergic.
Indacaterol and olodaterol are both 24-hour long-acting
β2-agonists dosed once daily, and all other agents are
dosed twice daily. Formoterol is currently available alone
as Foradil, an inhalation powder, alone as Perforomist, a
nebulized solution, or in combination with the inhaled
corticosteroid budesonide (Symbicort). Indacaterol is
currently only available alone as a once-daily dry powder
inhalation. Olodaterol is currently only available alone
as a once-daily inhalation spray. Neither indacaterol nor
olodaterol are available in nebulized form, nor are they
available in combination with an inhaled corticosteroid.
✓Combined inhaled anticholinergics and β-agonists:
albuterol/ipratropium (Combivent Respimat), vilanterol/
umeclidinium (Anoro Ellipta), tiotropium/olodaterol
(Stiolto Respimat), and indacaterol/glycopyrrolate
(Utibron Neohaler):
■■ Ipratropium bromide/albuterol (Combivent Respimat):
Each dose of Combivent Respimat contains 100 mcg
of albuterol and 20 mcg of ipratropium bromide per
actuation. The dose is one inhalation four times daily; the
number of inhalations should not exceed six in 24 hours.
This medication could be added to the patient’s regimen
for as-needed symptom control. Alternatively, it could be
utilized on a scheduled basis for this patient, but would
need to be given four times daily (a disadvantage relative
to the available once-daily option of tiotropium). This
combination agent would provide bronchodilation from
both anticholinergic and β2-agonist mechanisms. However, long-acting bronchodilators are preferred in patients
with COPD over scheduled short-acting bronchodilators
because of the need for less frequent dosing (once daily
■■ Vilanterol/umeclidinium (Anoro Ellipta): Each dose of
Anoro Ellipta contains 25 mcg of vilanterol and 62.5 mcg
of umeclidinium per actuation. The dose is one inhalation once daily. This medication could be added to the
patient’s regimen for maintenance symptom control, and
provides two long-acting bronchodilators in one inhalation. This combination agent provides bronchodilation
from both anticholinergic and β2-agonist mechanisms.
This may improve patient and adherence and has the
potential to reduce overall cost.
■■ Tiotropium/olodaterol (Stiolto Respimat): Each dose of
Stiolto Respimat contains 2.5 mcg of tiotropium and
2.5 mcg of olodaterol per actuation. The dose is two inhalations once daily. This medication could be added to the
patient’s regimen for maintenance symptom control, and
provides two long-acting bronchodilators in one inhalation. This combination agent provides bronchodilation
from both anticholinergic and β2-agonist mechanisms.
This may improve patient adherence and has the potential
to reduce overall cost.
■■ Indacaterol/glycopyrrolate (Utibron Neohaler): Each dose
of Utibron Neohaler contains 27.5 mcg of indacaterol
and 15.6 mcg of glycopyrrolate per inhalation. The dose
is administered via the inhalation of powder from one
capsule twice daily. This medication could be added to
the patient’s regimen for maintenance symptom control,
and provides two long-acting bronchodilators in one
inhalation. This combination agent provides bronchodilation from both anticholinergic and β2-agonist mechanisms. The medication is dosed twice daily, so it may be
less convenient than once daily options.
✓Oral theophylline:
■■ Theophylline use is not ideal for this patient. His theophylline levels would need to be monitored regularly
to evaluate risk of toxicity, especially given his current
smoking that can interact with theophylline. Theophylline
is not preferred as it is less well tolerated and less effective
compared with available inhaled bronchodilator therapy.
✓Phosphodiesterase-4 inhibitor: roflumilast (Daliresp):
■■ Roflumilast is a phosphodiesterase-4 inhibitor. The inhibition of phosphodiesterase-4 increases intracellular cyclic
AMP, which, in turn, results in inhibition of inflammatory cells within the lungs. Roflumilast is indicated as
a treatment to reduce the risk of COPD exacerbations
in patients with severe COPD (FEV1 <50%) associated
with chronic bronchitis and a history of exacerbations.
According to the GOLD guidelines, it can be considered
in “Group C” or “Group D” COPD in combination with
a long-acting β-agonist or in combination with dual longacting β-agonist/inhaled corticosteroid therapy. Because
it works to reduce inflammation, its efficacy, when used in
combination with inhaled corticosteroids, is not entirely
clear. In one published study, the benefits of adding roflumilast to a long-acting β-agonist in combination with
an inhaled corticosteroid were minimal in patients with
severe COPD at risk for exacerbations. The medication is
not indicated for this patient at this time.
✓Inhaled corticosteroids:
■■ Inhaled corticosteroids should be considered in patients
with “Group C and D” COPD, specifically those with
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Chronic Obstructive Pulmonary Disease
■■ Albuterol (short-acting β2-selective agonists) could be
added to the patient’s regimen for as-needed symptom control in addition to the scheduled, long-acting
β2-selective agonist (salmeterol). Although short-acting
β2-agonists are sometimes used on a scheduled basis in
the chronic treatment of COPD, it would be inappropriate to schedule both a long-acting and a short-acting
β2-selective agonist together for chronic maintenance
treatment. Although albuterol could be given scheduled
four times daily, the GOLD guidelines indicate that the
long-acting agents, such as salmeterol, indacaterol, or
formoterol, are preferred in patients with “Group B–D”
COPD. Thus, the primary role for the use of albuterol in
COPD is as a supplemental as-needed (PRN) medication
to treat intermittent symptoms and exacerbations, which
is indicated in all patients with COPD. The maximum
number of inhalations of albuterol should not exceed
12 per day. The recommended maximal dosing should
not be exceeded because of an increased risk of systemic
toxicity (eg, tachycardia, tremor, hypokalemia).
vs four times daily) and their demonstrated efficacy in
maintaining symptom relief.1
CHAPTER 31
✓Inhaled β-agonists: albuterol, levalbuterol (Xopenex),
salmeterol (Serevent), indacaterol (Arcapta), formoterol
(Foradil, Perforomist), or olodaterol (Striverdi Respimat):
31-4
SECTION 3
FEV1 <60% predicted and/or those with high risk for
exacerbation.1,3–7 This patient only has stage 2 COPD and
has never been hospitalized for an exacerbation. In addition, his history and PFTs do not suggest a reactive component to his disease. He is currently receiving fluticasone
propionate as a component of Advair, which may not be
appropriate in this patient.
✓Systemic corticosteroids—prednisone and methylpred­
nisolone:
Respiratory Disorders
■■ Systemic corticosteroids may be beneficial when given
for up to 2 weeks in patients with moderate or severe
exacerbations who are not already receiving long-term
oral corticosteroids. A short course of systemic steroids
improves spirometry and decreases the relapse rate in
these patients. The optimal dose and duration of systemic
corticosteroid therapy remain uncertain. Routine daily
use of oral corticosteroids in chronic COPD management
should be avoided given the lack of consistent improvement and associated adverse effect profile (eg, osteoporosis, diabetes, adrenal insufficiency).1
✓Influenza and pneumococcal vaccination:
■■ The patient’s immunization status should be determined.
This patient should receive an annual influenza vaccine
and the pneumococcal vaccine (if he has not received one
in the past) if not contraindicated. Patients with COPD
are more prone to respiratory tract infections that can be
life-threatening, making vaccination an important component of care in this population.
3.c. Should home oxygen therapy be considered for the patient
at this time? Why or why not?
• No, the patient is at 93% oxygen saturation per pulse oximetry
and does not need home oxygen therapy at this time. His
medication regimen should be optimized today. A decision to
use home oxygen therapy would be indicated after medication
optimization if the patient had any of the following:
✓A resting PaO2 of <55 mm Hg, or SaO2 below 88%
✓Evidence of pulmonary hypertension, peripheral edema suggesting congestive heart failure, or polycythemia (hematocrit
>55%) with a PaO2 of <60 mm Hg, or SaO2 of 88% or below
Optimal Plan
4.Evaluate the patient’s current COPD regimen, and develop
recommendations to continue or change the current COPD
medication regimen at his clinic visit today. Make sure to
include specific doses, route, frequency, and duration of
therapy.
• Based on the GOLD treatment guidelines, the patient’s low
risk of exacerbation, and his increased symptoms, the patient
should be on two long-acting bronchodilators (ie, a long-acting
inhaled anticholinergic and a long-acting inhaled β-agonist) and
a short-acting agent (either albuterol or albuterol/ipratropium)
for as-needed symptoms. While the guidelines recommend this
approach, data to support benefit (eg, quality of life, exacerbations, improved symptoms) from two long-acting bronchodilators is limited and conflicting.8–10 Alternatively, short-acting
Combivent Respimat (albuterol/ipratropium) could be utilized
and given as a scheduled dose (one puff four times daily) with
up to a total of six puffs every 24 hours. It could be argued
whether the short-acting Combivent Respimat (one inhalation
four times daily) or two long-acting inhalers (salmeterol twice
daily + tiotropium once daily) would provide better adherence
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
or be more cost-effective. The GOLD guidelines point out
that the longer-acting anticholinergic and β-agonist products
are preferred for most patients with COPD given maintained
symptom relief and convenience.1
• Inhaled corticosteroid therapy should be considered in
patients with “Group C and D” COPD, specifically those with
FEV1 <60% predicted and/or those with high risk for exacerbation.1,3–7 The patient does not fit this criteria and therefore does
not need an inhaled corticosteroid at this time.
• An optimal plan would be to discontinue Advair (salmeterol/
fluticasone), one inhalation twice daily, and substitute with salmeterol (Serevent) 50 mcg twice daily (taken 12 hours apart),
indacaterol (Arcapta) 75 mcg once daily, olodaterol (Striverdi
Respimat) 5 mcg once daily, or formoterol (Foradil), one inhalation twice daily (taken 12 hours apart). Salmeterol (Serevent)
may be preferred for this patient over indacaterol (Arcapta),
olodaterol (Striverdi Respimat) and formoterol (Foradil), since
the Advair and Serevent inhalation devices are the same. Indacaterol (Arcapta) and olodaterol (Striverdi Respimat) are only
given once daily, which could potentially improve adherence.
The bronchodilator effect of indacaterol is superior to that of
formoterol and salmeterol, although the clinical significance
of this is unknown.1 A long-acting anticholinergic should also
be added to this patient’s regimen. Options include tiotropium (Spiriva, Spiriva Respimat), the contents of one capsule
(18 mcg) via two inhalations once daily with the HandiHaler
device or as two inhalations (2.5 mcg each) once daily via the
Spiriva Respimat, aclidinium (Tudorza) 400 mcg given twice
daily with the Pressair device, glycopyrrolate (Seebri Neohaler)
as one inhalation (15.6 mcg) of dry powder twice daily, or
umeclidinium (Incruse Ellipta) 62.5 mcg administered once
daily as a dry powder inhaler should be initiated. Tiotropium
would be preferred since it is once daily and has significant
clinical trial evidence to support its effectiveness in COPD.
The combination of a long-acting β-agonist and long-acting
anticholinergic is available as vilanterol/umeclidinium (Anoro
Ellipta) in a single dry powder inhaler once daily, tiotropium/
olodaterol (Stiolto Respimat) as two inhalations once daily, or
indacaterol/glycopyrrolate (Utibron) in a single dry powder
inhaler twice daily. Vilanterol/umeclidinium and tiotropium/
olodaterol have the advantage of once daily inhalation. These
options could be utilized in place of separate long-acting
β-agonist and long-acting anticholinergic inhalers. Depending on the patient’s insurance coverage, this could reduce
cost. A short-acting bronchodilator (albuterol, levalbuterol, or
ipratropium/albuterol) should also be initiated for as-needed
shortness of breath.
• The patient should be instructed on the use of all inhalers.
Proper inhalation technique should be reviewed with him, and
he should then be asked to demonstrate it.
• Recommend that this patient receive an annual influenza vaccine and the pneumococcal vaccine (if he has not received one
previously) if not contraindicated.
Outcome Evaluation
5.a.What clinical parameters will you monitor to assess the
COPD pharmacotherapy regimen in this patient?
• Prospectively monitor medical resource utilization, with the
goal to reduce the rate of hospitalizations and emergency
department (ED) visits.
• Monitor patient refills on medications during routine office
visits to ensure that the patient is using them within prescribed
31-5
• Monitor frequency of upper respiratory tract infections over
time. Have the patient notify you or his physician in the event
of increased sputum quantity, change in sputum color, cough,
fever, or other symptoms consistent with pneumonia.
• Monitor tobacco use, promote smoking cessation, and continue long-term follow-up with cessation plans.
• Monitor pulse oximetry during scheduled office visits. The
values should be maintained within normal limits. The room
air PaO2 should be used as a gauge for when to initiate home
oxygen therapy if necessary.
• Prevent rapid decline in pulmonary function over time. Measure PFTs annually and compare the values with previous
years.
• Monitor for other long-term comorbidities such as rightsided heart failure (eg, monitor heart function via ECG) and
increased hematocrit at least annually during scheduled office
visits.
Patient Education
6.What information should be provided to the patient to
enhance adherence, ensure successful therapy, and minimize
adverse effects?
General notes for the clinician:
• Refer to USP DI Volume 2 for drug-specific information
on the use of tiotropium, albuterol, levalbuterol, ipratropium, umeclidinium, vilanterol, aclidinium, glycopyrrolate,
salmeterol, indacaterol, formoterol, and olodaterol. Emphasis
should be placed on proper inhaler technique and adherence
to the medication regimen to ensure successful therapeutic
outcomes and to minimize adverse effects.
• Numerous holding chambers (spacers) are available for use
with MDIs. In general, the patient should be instructed to
use them as outlined in the individual package insert for each
agent, but emphasis on timing of actuation and inhalation is
not necessary.
• All inhaled medications must be “ozone friendly.” For this
reason, many new delivery devices have entered the market.
Specific examples of environmentally safe inhaler devices
include MDIs with hydrofluoroalkane (HFA) propellants
(rather than chlorofluorocarbons [CFCs]), dry powder inhalers (DPIs), and mechanically delivered spray. In contrast to
MDIs and mechanically delivered spray, DPIs require that the
patient properly load each dose, prevent loss of product before
inhalation (ie, avoid spilling the dose), and inhale the medication with a deep and rapid breath. DPIs cannot be used with
spacers or holding chambers and do not require coordination
between actuation and inhalation. Therefore, it is important
that the clinician be prepared to educate patients on the unique
attributes of each delivery device and look for ways to consolidate the medication regimen, when possible, to enhance
patient adherence.
• Instruct patients on how to routinely clean their inhaler
devices and properly determine the amount of drug in the
canister or device.
• Inhaled anticholinergic agents: ipratropium bromide
(Atrovent), aclidinium bromide (Tudorza), tiotropium
bromide (Spiriva), umeclidinium (Incruse Ellipta), or glycopyrrolate (Seebri Neohaler):
✓These medications are inhaled into the lungs in order to
open up the airways and make breathing easier. Side effects
are not common, but can include dry mouth, dry eyes, dry
nose, and constipation. If you experience difficulty urinating, you should contact your healthcare provider immediately. This is especially important if you have an enlarged
prostate or if you have existing urinary symptoms. If eye
symptoms develop while using this medication, contact your
healthcare provider immediately.
✓Ipratropium bromide (Atrovent): This medication is shortacting and can be taken as needed when you develop
shortness of breath. Your healthcare provider may ask you
to take it regularly even if you do not have symptoms of
shortness of breath. In this case, you would take two inhalations by mouth four times daily, or every 6 hours. You can
take a maximum of 12 inhalations per day. This medication
is delivered via an inhalation as a solution aerosol. This
medication does not require shaking prior to use. To use,
breathe in slowly and deeply through the mouth and at the
same time spray the medication into your mouth. Hold your
breath for 10 seconds, and then breathe out slowly through
your mouth. Wait 15–30 seconds and repeat the dose for the
second inhalation as needed. This medication has a unique
side effect of bad taste in the mouth that does not go away
quickly. Let your healthcare provider know if this occurs.
✓Aclidinium bromide (Tudorza): This medication is longeracting and should be taken as one inhalation twice daily,
even if you do not have symptoms of shortness of breath.
This medication is delivered to the lungs as a dry powder.
Aclidinium is administered using the Pressair device. This
device has a large green button. While holding the device
upright, press the green button down firmly and release it
to prepare a dose of medication. The control window on the
inhaler will turn green to let you know the medication is
ready for inhalation. Put your lips tightly around the inhaler
and breathe in deeply and quickly to deliver the medication
to your lungs. Continue breathing in until you hear a “click”
sound, and then hold your breath for as long as is comfortable. The control window will turn red if you have inhaled
correctly. If it is still green, administer the dose again until
the window turns red. The Pressair device has a counter to
let you know how many inhalations are left. The medication
should be refilled when the counter shows few doses left.
✓Tiotropium bromide (Spiriva, Spiriva Respimat): This medication is long-acting and should be taken as two inhalations once daily (Spiriva) or two puffs once daily (Spiriva
Respimat), even if you do not have symptoms of shortness
of breath. This medication is delivered to the lungs as a dry
powder (Spiriva) or an inhalation spray (Spiriva Respimat). For administration using the HandiHaler device,
first remove one capsule from the blister pack. The capsule
contains the dry powder medication needed to help your
lungs. Place this one capsule in the center chamber of your
HandiHaler device, and then close the mouthpiece. Hold
the mouthpiece upright, and then press the green piercing button on the side of the HandiHaler all the way in.
This puts a hold in the capsule to release the dry powder.
The medication is now ready to be delivered. Breathe out
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Chronic Obstructive Pulmonary Disease
5.b.What laboratory tests can be performed and how often
should they be performed to assess the efficacy of the current
COPD regimen as well as progression of the patient’s lung
disease?
Medication-specific patient education:
CHAPTER 31
guidelines. A goal is to see reduction in shortness of breath
from COPD with the addition of the tiotropium.
31-6
SECTION 3
Respiratory Disorders
completely in one breath, and then wrap your lips around
the HandiHaler mouthpiece and breathe in deeply until
your lungs are fully inflated. You must again breathe out
deeply, and then breathe in deeply until your lungs are fully
inflated for a second time. This ensures that all medication
in the capsule is delivered into your lungs. For administration using the Respimat device, first time use requires
actuation of the inhaler toward the ground until an aerosol
cloud is visible. This process should be repeated 3 times to
ensure the device is ready for use. You should breathe out
fully and slowly, then close your lips around the end of the
mouthpiece. The inhaler should be pointed to the back of
your mouth, and while inhaling slowly the dose should
be administered and inhaled into your lungs. Your breath
should be held for 10 seconds to ensure inhalation into the
lungs. A second inhalation is required to achieve the recommended 5 mcg daily dose.
✓Albuterol, levalbuterol (ProAir, Ventolin, Proventil, Xopenex):
These medications are delivered via a metered-dose inhaler.
Albuterol is available as three different brand name products
(ProAir, Ventolin, and Proventil). Levalbuterol is available
as brand name Xopenex. These medications are short-acting
and can be taken as needed when you develop shortness of
breath. Your healthcare provider may ask you to take one of
them even if you do not have shortness of breath symptoms.
In this case, your healthcare provider would provide you
with a scheduled dose. Both albuterol and levalbuterol are
administered the same way. Shake the inhaler for at least
10 seconds prior to use. When ready to inhale, breathe in
slowly and deeply through the mouth and at the same time
spray the medication into your mouth. Hold your breath for
up to 10 seconds, and then breathe out slowly through your
mouth. Wait 1 minute and repeat the dose if a second inhalation is needed.
✓Umeclidinium bromide (Incruse Ellipta): This medication
is long-acting and should be taken as one inhalation once
daily, even if you do not have symptoms of shortness of
breath. This medication is delivered to the lungs as a dry
powder. The medication is available as a plastic inhaler containing a double-foil blister strip with 30 blisters containing
powder for inhalation. For administration, first open the
cover of the inhaler. A “click” will be heard and the medication is now ready for inhalation. If the cover is closed at
this point, the medication will be wasted. After opening the
cover and hearing the “click” you should breathe out, then
place the mouthpiece between your lips, and take one long,
steady, deep breath through your mouth. The inhaler should
be removed from your mouth and your breath should be
held for at least 3–4 seconds. You may then breathe out
slowly and close the inhaler.
✓Salmeterol (Serevent): this medication is long-acting and
should be taken as one inhalation twice daily, even if you do
not have symptoms of shortness of breath. This medication
is delivered to the lungs as a dry powder. It is administered
using the Diskus device. To administer this medication, first
hold the device in one hand and put the thumb of your other
hand on the thumb grip. Push your thumb away from you
as far as it will go until the mouthpiece appears and snaps
into position. Hold the device in a level, flat position with
the mouthpiece toward you. Slide the lever away from you
as far as it will go until it clicks. The device is now ready to
use. Breathe out completely in one breath, and then put the
mouthpiece to your lips and breathe in deeply until your
lungs are full. Hold your breath for about 10 seconds, and
then breathe out slowly. Close the Diskus device until you
are ready to use again for the next dose.
✓Glycopyrrolate (Seebri Neohaler): This medication is longacting and should be taken as one inhalation twice daily,
even if you do not have symptoms of shortness of breath. It
should be taken as one inhalation of powder twice daily. This
medication is delivered to the lungs as a dry powder. It is
administered using the Neohaler device. To administer this
medication, first remove one capsule from the blister pack.
The capsule contains the dry powder medication needed to
help your lungs. Place this one capsule in the capsule chamber of your Neohaler device, and then close the mouthpiece.
Hold the mouthpiece upright, and then press the piercing
buttons that are located on each side of the Neohaler device
until you hear a “click.” This puts a hole in the capsule to
release the dry powder. The medication is now ready to be
delivered. Breathe out completely in one breath, then wrap
your lips around the Neohaler mouthpiece, and then breathe
in deeply until your lungs are fully inflated. Hold your breath
for at least 5–10 seconds. Open the device to see if there is
powder remaining in the capsule. If there is, you must again
breathe out deeply, and then breathe in deeply until lungs are
fully inflated for a second time. This ensures that all medication in the capsule is delivered into your lungs.
✓Indacaterol (Arcapta): This medication is long-acting and
should be taken as one inhalation once daily, even if you do
not have symptoms of shortness of breath. This medication
is delivered to the lungs as a dry powder. It is administered
using the Neohaler device. To administer this medication,
first remove one capsule from the blister pack. The capsule
contains the dry powder medication needed to help your
lungs. Place this one capsule in the capsule chamber of your
Neohaler device, and then close the mouthpiece. Hold the
mouthpiece upright, and then press the piercing buttons that
are located on each side of the Neohaler device until you
hear a “click.” This puts a hole in the capsule to release the
dry powder. The medication is now ready to be delivered.
Breathe out completely in one breath, and then wrap your
lips around the Neohaler mouthpiece and breathe in deeply
until your lungs are fully inflated. Open the device to see if
there is powder remaining in the capsule. If there is, you must
again breathe out deeply, and then breathe in deeply until
lungs are fully inflated for a second time. This ensures that all
medication in the capsule is delivered into your lungs.
• Inhaled β-agonists: albuterol, levalbuterol (Xopenex), salmeterol (Serevent), indacaterol (Arcapta), formoterol (Foradil,
Perforomist), or olodaterol (Striverdi Respimat):
✓These medications are inhaled into the lungs in order to
open up the lungs and make breathing easier. Side effects
are not common, but more common ones include fast heart
rate, nervousness, throat irritation, and tremor. If these side
effects do not go away or are more severe, you should contact
your healthcare provider immediately.
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
✓Formoterol (Foradil): This medication is long-acting and
should be taken as one inhalation twice daily, even if you do
not have symptoms of shortness of breath. This medication
is delivered to the lungs as a dry powder. It is administered
using the Aerolizer device. To administer this medication,
first remove one capsule from the blister pack. The capsule
contains the dry powder medication needed to help your
lungs. Place this one capsule in the capsule chamber in the
base of your Aerolizer device, and then twist the mouthpiece
to close the device. Hold the mouthpiece upright, and then
press the piercing buttons that are located on each side of the
31-7
• Combined inhaled anticholinergics and β-agonists: albuterol/
ipratropium (Combivent Respimat), vilanterol/umeclidinium
(Anoro Ellipta), tiotropium/olodaterol (Stiolto Respimat), and
indacaterol/glycopyrrolate (Utibron Neohaler):
✓These medications are inhaled into the lungs in order to
open up the lungs and make breathing easier. Side effects
are not common, but more common ones include fast heart
rate, nervousness, throat irritation, tremor, dry mouth, dry
eyes, dry nose, and constipation. If these side effects do not
go away or are more severe, or if you experience difficulty
urinating, you should contact your healthcare provider
immediately. If eye symptoms develop while using this
medication, contact your healthcare provider immediately.
✓Albuterol/ipratropium (Combivent Respimat): This medication is inhaled into the lungs in order to open up the lungs
and make breathing easier. It works very quickly to make
breathing easier. It is short-acting and can be taken as
needed when you develop shortness of breath. Your healthcare provider may ask you to take it regularly even if you
do not have symptoms of shortness of breath. In this case,
you would take one inhalation by mouth four times daily, or
every 6 hours. You can take a maximum of six inhalations
per day. Side effects are not common, but can include fast
heart rate, nervousness, throat irritation, tremor, dry mouth,
dry eyes, and constipation. If these side effects do not go
away or are more severe, you should contact your healthcare
provider immediately. If you experience difficulty urinating,
you should contact your healthcare provider immediately.
This is especially important if you have an enlarged prostate
or if you have existing urinary symptoms. This medication is
administered as a slow mist using the Respimat device that
provides a mechanically delivered spray. Point the Respimat
inhaler at the back of the throat. While taking a slow, deep
breath through your mouth, press the dose release button
and continue to breathe in slowly for as long as you can.
Hold your breath for 10 seconds or as long as is comfortable.
✓Vilanterol/umeclidinium (Anoro Ellipta): This inhaler contains both a long-acting β-agonist and a long-acting anticholinergic administered together. It should be taken as
✓Tiotropium/olodaterol (Stiolto Respimat): This inhaler contains both a long-acting β-agonist and a long-acting anticholinergic administered together. It should be taken as two
inhalations once daily. This medication is delivered to
the lungs as an inhalation spray. For administration using
the Respimat device, first time use requires actuation of the
inhaler toward the ground until an aerosol cloud is visible.
This process should be repeated 3 times to ensure the device
is ready for use. You should breathe out fully and slowly,
then close your lips around the end of the mouthpiece.
The inhaler should be pointed to the back of your mouth,
and while inhaling slowly the dose should be administered
and inhaled into your lungs. Your breath should be held for
10 seconds to ensure inhalation into the lungs. A second inhalation is required to achieve the recommended daily dose.
✓Indacaterol/glycopyrrolate (Utibron Neohaler): This inhaler
contains both a long-acting β-agonist and a long-acting
anticholinergic administered together. It should be taken
as one inhalation of powder twice daily. This medication is
delivered to the lungs as a dry powder. It is administered
using the Neohaler device. To administer this medication,
first remove one capsule from the blister pack. The capsule
contains the dry powder medication needed to help your
lungs. Place this one capsule in the capsule chamber of your
Neohaler device, and then close the mouthpiece. Hold the
mouthpiece upright, and then press the piercing buttons
that are located on each side of the Neohaler device until
you hear a “click.” This puts a hole in the capsule to release
the dry powder. The medication is now ready to be delivered.
Breathe out completely in one breath, and then wrap your
lips around the Neohaler mouthpiece and breathe in deeply
until your lungs are fully inflated. Hold your breath for at
least 5–10 seconds. Open the device to see if there is powder
remaining in the capsule. If there is, you must again breathe
out deeply, and then breathe in deeply until lungs are fully
inflated for a second time. This ensures that all medication
in the capsule is delivered into your lungs.
REFERENCES
1. Global Initiative for Chronic Obstructive Lung Disease. Global strategy
for the diagnosis, management, and prevention of chronic obstructive
pulmonary disease. Updated 2015. Available at: http://www.goldcopd
.org. Accessed March 1, 2016.
2. Qaseem A, Wilt TJ, Weinberger SE, et al. Diagnosis and management
of stable chronic obstructive pulmonary disease: a clinical practice
guideline update from the American College of Physicians, American
College of Chest Physicians, American Thoracic Society, and European
Respiratory Society. Ann Intern Med 2011;155:179–191.
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
Chronic Obstructive Pulmonary Disease
✓Olodaterol (Striverdi Respimat): This medication is longacting and should be taken as two inhalations once daily at
the same time each day, even if you do not have symptoms
of shortness of breath. This medication is delivered to the
lungs as an inhalation spray. First time use requires priming the device. To do this, the inhaler is actuated toward
the ground until an aerosol cloud is visible. This process
should be repeated 3 times to ensure the device is ready for
use. You should breathe out fully and slowly, then close your
lips around the end of the mouthpiece. The inhaler should
be pointed to the back of your mouth, and while inhaling
slowly the dose should be administered and inhaled into
your lungs. Your breath should be held for 10 seconds to
ensure inhalation into your lungs. A second inhalation is
required to achieve the recommended 5 mcg daily dose.
one inhalation once daily. This medication is delivered to
the lungs as a dry powder. The medication is available as
a plastic inhaler containing a two double-foil blister strips
with 30 blisters containing powder for inhalation. One strip
contains umeclidinium (62.5 mcg per blister) and the other
strip contains vilanterol (25 mcg per blister). For administration, first open the cover of the inhaler. A “click” will be
heard and the medication is now ready for inhalation. If the
cover is closed at this point, the medication will be wasted.
After opening the cover and hearing the “click” you should
breathe out, then place the mouthpiece between your lips,
and take one long, steady, deep breath through your mouth.
The inhaler should be removed from your mouth and your
breath should be held for at least 3–4 seconds. You may then
breathe out slowly and close the inhaler.
CHAPTER 31
Aerolizer device until you hear a “click.” This puts a hole in
the capsule to release the dry powder. The medication is now
ready to be delivered. Breathe out completely in one breath,
and then wrap your lips around the mouthpiece and breathe
in deeply until your lungs are fully inflated. Open the device
to see if there is powder remaining in the capsule. If there is,
you must again breathe out deeply, and then breathe in deeply
until lungs are fully inflated for a second time. This ensures
that all medication in the capsule is delivered into your lungs.
31-8
SECTION 3
Respiratory Disorders
3. Mahler DA, Wire P, Horstman D, et al. Effectiveness of fluticasone propionate and salmeterol combination delivered via the diskus device in
the treatment of chronic obstructive pulmonary disease. Am J Respir
Crit Care Med 2002;166:1084–1091.
4. Calverley PM, Anderson JA, Celli B, et al. Salmeterol and fluticasone
propionate and survival in chronic obstructive pulmonary disease.
N Engl J Med 2007;356:775–789.
5. Calverley P, Pauwels R, Vestbo J, et al. Combined salmeterol and fluticasone in the treatment of chronic obstructive pulmonary disease: a
randomized controlled trial. Lancet 2003;361:449–456.
6.Szafranski W, Cukier A, Ramirez A, et al. Efficacy and safety of
budesonide/formoterol in the management of chronic obstructive
pulmonary disease. Eur Respir J 2003;21:74–81.
Copyright © 2017 by McGraw-Hill Education. All rights reserved.
7. Jones PW, Willits LR, Burge PS, Calverley P. Disease severity and the
effect of fluticasone propionate on chronic obstructive pulmonary disease exacerbations. Eur Respir J 2003;21:68–73.
8. Tashkin DP, Pearle J, Iezzoni D, Varghese ST. Formoterol and tiotropium compared with tiotropium alone for treatment of COPD. COPD
2009;6:17–25.
9. van Noord JA, Aumann JL, Janssens E, et al. Comparison of tiotropium
once daily, formoterol twice daily, and both combined once daily in
patients with COPD. Eur Respir J 2005;26:214–222.
10. Karner C, Cates CJ. Long-acting beta(2)-agonist in addition to tiotropium versus either tiotropium or long-acting beta(2)-agonist alone for
chronic obstructive pulmonary disease. Cochrane Database Syst Rev
2012;4:CD008989.