Download Short-Acting Beta Agonists (SABA)

Management of stable chronic
obstructive pulmonary disease(06)
1
Dr Mazen Qusaibaty
MD, DIS / Head Pulmonary and Internist Department Ibnalnafisse Hospital
Ministry of Syrian health
Email: [email protected]
General Approach
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Diagnosis Of COPD
Risk Factors
Symptoms
Spirometry
COPD
Assessment
Obstruction
Severity of Obstruction
Post-Bronchodilator
FEV1/FVC < 0.70
Gold IV
FEV1 <30%
Gold III
FEV1
30%-50%
Gold II
FEV1
50%-80%
Gold I
FEV1 ≥80%
mMRC
CAT
Frequent
Exacerbation
C
D
Severe
Obstruction
Less symptoms
++ exacerbations
Very Severe
Obstruction
More symptoms
++ exacerbations
≥ 2 or more
per year
A
B
1 per year
Mild Obstruction
Less symptoms
Few exacerbations
Moderate
Obstruction
More symptoms
Few exacerbations
None
0
1
< 10
2
Symptoms
3
> 10
4
Exacerbation
Worse
More
Severe
• High risk
• Less
symptoms
• Low risk
• Less
symptoms
• High risk
• More
symptoms
C
D
A
B
• Low risk
• More
symptoms
Global Initiative for Chronic
Obstructive
Lung
Disease
© Global Initiative for Chronic Obstructive Lung Disease
The main TWO goals of the
current management of COPD
These goals should be reached
with minimal side effects from
treatment
The main TWO goals of
the current
management of COPD
Reduce the
impact of COPD
on daily activities
Reduce risks of
future events
From the Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease, Global Initiative for
Chronic Obstructive Lung Disease (GOLD) 2014. Available from: http//www.goldcopd.org, © 2014 Global Initiative for Chronic Obstructive Lung
Disease, all rights reserved.
Relieve symptoms
Reduce
symptoms
Improve
exercise tolerance
Improve
health status
Management of
COPD
Prevent
disease
progression
Reduce risks
Prevent and treat
exacerbations
Reduce
From the Global Strategy for the Diagnosis, Management, and Prevention of Chronic
Obstructive Pulmonary Disease, Global Initiative for Chronic Obstructive Lung Disease
(GOLD) 2014. Available from: http//www.goldcopd.org, © 2014 Global Initiative for
Chronic Obstructive Lung Disease, all rights reserved.
mortality
ALL
Categories of COPD
C
D
A
B
Adapted from: Global Initiative for Chronic Obstructive Pulmonary Disease, Executive Summary: Global Strategy
for the Diagnosis, Management, and Prevention of COPD (Accessed November 8, 2013)
Avoidance of risk factor(s), such as
smoking
Adapted from: Global Initiative for Chronic Obstructive Pulmonary Disease, Executive Summary: Global Strategy
for the Diagnosis, Management, and Prevention of COPD (Accessed November 8, 2013)
Reduction of indoor pollution
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Reduction Of Occupational
Exposure
13
• Annual
influenza
vaccination
• Pneumococcal
vaccination
Adapted from: Global Initiative for Chronic Obstructive Pulmonary Disease, Executive Summary: Global Strategy
for the Diagnosis, Management, and Prevention of COPD (Accessed November 8, 2013)
Regular
physical
activity
Adapted from: Global Initiative for Chronic Obstructive Pulmonary Disease, Executive Summary: Global Strategy
for the Diagnosis, Management, and Prevention of COPD (Accessed November 8, 2013)
• Long-term
oxygen
therapy
if chronic
hypoxemia
Bronchodilators
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The Cornerstone of .....
COPD management
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Bronchodilators Inhalers
• It maximizes the bronchodilator's
direct effect on the airways
• While minimizing systemic effects
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Bronchodilators
Inhaled β 2
agonists
Inhaled
Anticholinergics
Short-acting
Short-acting
Long-acting
Long-acting
Theophylline
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Delivery of Inhaled Medication
1. Metered Dose Inhalers ( MDI)
2. Dry Powder Inhalers ( DPI)
3. Nebulizers
Metered Dose Inhalers (MDI)
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(A)
AeroChamber
(B)
AeroChamber with mask
(C)
InspirEase
Examples of various dry powder
inhalers
Panels A, B, E, F, and G: Courtesy of Dean Hess, RRT, PhD.
Panel C: Image used with permission. Copyright © 2012 Novartis Pharmaceuticals Corporation.
Panel24
D: Image used with permission. Copyright © 2013 Novartis Pharmaceuticals Corporation.
A.
B.
C.
D.
Aerolizer
HandiHaler
Neohaler
Tobi Podhaler
E.
F.
G.
H.
Flexhaler
Diskus
Twisthaler
Ellipta
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Metered Dose Inhalers (MDI)
Dry Powder Inhalers (DPI)
• Improve compliance
• Reduce extra medication usage
and patient cost
Nebulizers
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28
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The Effects of Bronchodilators
Long-term improvements in
symptoms
 Exercise Capacity
 Airflow Limitation (even when
there is no spirometric
improvement following a single
test dose)
Cooper CB, Tashkin DP. Recent developments in inhaled therapy in stable chronic
obstructive pulmonary disease. BMJ 2005; 330:640/Sin DD, McAlister FA, Man SF, Anthonisen NR. Contemporary management of chronic obstructive pulmonary disease: scientific
review. JAMA 2003; 290:2301/Man SF, McAlister FA, Anthonisen NR, Sin DD. Contemporary management of chronic obstructive pulmonary disease: clinical applications. JAMA
2003; 290:2313/Ferguson GT, Cherniack RM. Management of chronic obstructive pulmonary disease. N Engl J Med 1993; 328:1017/Hanania NA, Celli BR, Donohue JF, Martin UJ.
Bronchodilator reversibility in COPD.
Chest 2011; 140:1055.
Short-acting Bronchodilators
31
Short-acting bronchodilators
I.
Short-Acting Beta Agonists
(SABA)
II. Short-Acting Muscarinic
Antagonist (anticholinergics)
(SAMA)
Short-Acting Beta Agonists
(SABA)
β2-agonist
out
β2R
Gs
Gs
AC
cAMP
PKA
(active)
in
ATP
PK
(inactive)
Relaxation
Smooth
muscle
Adapted from Cazzola & Molimard. Pulm Pharmacol Ther 2010
34
Short-acting bronchodilators
SABA / SAMA
• Appropriate medication
 Mild intermittent symptoms .
• The advantage of SABA
 Rapid onset of action
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SABA or SAMA
• Monotherapy is acceptable
In chronic obstructive pulmonary disease, a combination of ipratropium and albuterol is more effective than either agent
alone. An 85-day multicenter trial. COMBIVENT Inhalation Aerosol Study Group. Chest 1994; 105:1411
Change in FEV1 (%)
Short-acting Bronchodilators:
Onset and Duration of Action
40
35
30
25
20
15
10
5
0
-5
N=534
P<0.001 for the combination versus each agent alone
Ipratropium + Albuterol (n=173)
Ipratropium (n=176)
Albuterol (n=165)
0
1
2
3
4
5
Post-dose (hours)
6
Adapted from COMBIVENT Inhalation Aerosol Study Group. Chest. 1994;105:1411-1419. Reproduced with permission from
American College of Chest Physicians.
7
8
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Combination therapy is often
preferred SABA + SAMA
• Achieves a greater bronchodilator
response than either one alone
In chronic obstructive pulmonary disease, a combination of ipratropium and albuterol is more effective than either agent
alone. An 85-day multicenter trial. COMBIVENT Inhalation Aerosol Study Group. Chest 1994; 105:1411
38
Short-Acting Beta Agonists (SABA)
• SABA




Salbutamol
A l b u te ro l
L e va l b u te ro l
Te r b u t a l i n e
• They have been proven in randomized,
controlled trials and meta -analyses to
 I m p ro ve sy m p t o m s
 I m p ro ve l u n g f u n c t i o n
Ram FS, Sestini P. Regular inhaled short acting beta2 agonists for the management of stable chronic obstructive
pulmonary disease: Cochrane systematic review and meta-analysis. Thorax 2003; 58:580
39
Short-Acting Beta Agonists (SABA)
• Prescribed on an as-needed
basis
• Patients A + C ( Less symptoms)
Ram FS, Sestini P. Regular inhaled short acting beta2 agonists for the management of stable chronic obstructive
pulmonary disease: Cochrane systematic review and meta-analysis. Thorax 2003; 58:580
40
Short-Acting Beta Agonists (SABA)
• Regularly scheduled use ?
 No clear benefits
Cook D, Guyatt G, Wong E, et al. Regular versus as-needed short-acting inhaled beta-agonist therapy for chronic
obstructive pulmonary disease. Am J Respir Crit Care Med 2001; 163:85.
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Short-Acting Beta Agonists (SABA)
• Safe
When used at the recommended
doses
Cook D, Guyatt G, Wong E, et al. Regular versus as-needed short-acting inhaled beta-agonist therapy for chronic
obstructive pulmonary disease. Am J Respir Crit Care Med 2001; 163:85.
Overuse
 Risks of β 2 -agonist
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β2 –agonist Peripheral arterial dilation
Reflex tac hycardia
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β2 –agonist  Hypokalemia
Extreme
Cases
45
• A serum potassium level of
less than 3.5 mEq/L (3.5 mmol/L)
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• A serum potassium level of
less than less than 2.5 mEq/L
48
• β2 agonists taken as tablets can
cause more severe side effects
such as:
 Ner vousness
 Palpitation
 Cramps in the muscles
 Drowsiness
 Tremors
S. Ramaiah - Asthma - 2005
49
Risks of beta-agonist overuse
• Oral beta-2 agonists are generally
Not Prescribed because their
incidence of side effects is
particularly high
Tachyphylaxis
• An acute rapid decrease in
response to a drug after its
administration
Bunnel, Craig A. Intensive Review of Internal Medicine, Harvard Medical School 2009
Tachyphylaxis
It can occur after an Initial Dose
Or
After a series of Small Doses
Bunnel, Craig A. Intensive Review of Internal Medicine, Harvard Medical School 2009
Tachyphylaxis
• Increasing the dose of the
drug
 May be able to restore the original
response
Lehne, Richard A. (2013). "Tachyphylaxis". Pharmacology for Nursing Care. Philadelphia: Saunders. p. 81. ISBN 978-14377-3582-6.
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Tachyphylaxis
• Polymorphisms of the beta-2
receptor play a role in
tachyphylaxis
• Glycine at position 16 (greater
receptor downregulation by
endogenous catecholamines) >
Arg-16
Somme
Studies
Safety
Short-Acting
Beta Agonists
(SABA)
Wilchesky M, Ernst P, Brophy JM, et al. Bronchodilator use and
the risk of arrhythmia in COPD: part 2: reassessment in the
larger Quebec cohort. Chest 2012; 142:305
55
Safety : SABA
• The rate of severe cardiac
arrhythmia 
 New use of oral or inhaled short acting beta agonist ( R R 1 . 2 7 , 9 5 % C I
1.03-1.57)
Wilchesky M, Ernst P, Brophy JM, et al. Bronchodilator use and the risk of arrhythmia in COPD: part 2: reassessment in
the larger Quebec cohort. Chest 2012; 142:305
56
Safety : SABA
Cardiac arrests
Atrial fibrillation /flutter was
most common
Wilchesky M, Ernst P, Brophy JM, et al. Bronchodilator use and the risk of arrhythmia in COPD: part 2: reassessment in
the larger Quebec cohort. Chest 2012; 142:305
57
Sinus Rhythm
Atrial fibrillation
The purple arrow indicates a P
wave, which is lost in atrial
fibrillation
https://commons.wikimedia.org/wiki/File:Afib_ecg.jpg
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https://commons.wikimedia.org/wiki/File:Afib_ecg.jpg