The Role Combination of

Salbutamol and Ipratropium in

Asthma and COPD
31 Mei 2015

dr. Prasna Pramita, SpPD, MARS, FINASIM

Chronic Respiratory Disease is a Leading Cause

of Chronic Disease Deaths Worldwide

The World Health Organization (WHO) projected that, in 2005, chronic respiratory disease would be the
third-leading cause of deaths from chronic disease worldwide

Adapted from: World Health Organization. Preventing chronic diseases: a vital investment. (2005) Available at:
http://www.who.int/chp/chronic_disease_report/contents/en/index.html (accessed Mei 2015)

Prevalence Asthma and COPD in Indonesia 2013

The prevalence of asthma (4.5 percent), COPD (3.7

percent) and cancer (1.4 percent) based on interviews in
Indonesia per mile. Pravelence of asthma and cancer is
higher in women, the prevalence of COPD is higher in
men

Riskesdas 2013

Definition of Asthma (GINA Definition of COPD (GOLD

2015)
2015)
Asthma is a common and potentially COPD, a common preventable and
serious chronic disease that imposes a
treatable disease, is characterized by
substantial burden on patients, their
persistent airflow limitation that is usually
families and the community. It causes
progressive and associated with an
respiratory symptoms, limitation of activity,
enhanced chronic inflammatory response
and flare-ups (attacks) that sometimes
in the airways and the lung to noxious
require urgent health care and may be
particles or gases
fatal
Exacerbations and comorbidities contribute
to the overall severity in individual patients
Asthma causes symptoms such as wheezing,
shortness of breath, chest tightness, and
cough that vary over time in their
occurrence, frequency and intensity

Professor Peter J. Barnes, MD

National Heart and Lung Institute, London UK

Differential Diagnosis

ASTHMA

COPD

Onset early in life (often childhood)

Onset in mid-life

Symptoms vary from day to day

Symptoms slowly
progressive
Long smoking history

Symptoms worse at night/early

morning
Allergy, rhinitis, and/or eczema also
present
Family history of asthma

Adaptation from GOLD 2015

Asthma Triggers

Adaptation from www.aafatexas.org (accessed Mei 2015)

COPD Facts

Adaptation from www.copdandtreatment.com

Assessment of Asthma (GINA

2015)

Assessment of COPD
(GOLD 2015)

1.

Asthma control - two domains

1. COPD Assessment Test (CAT)
Assess symptom control over the last 4
2. Clinical COPD Questionnaire (CCQ)
weeks
Assess risk factors for poor outcomes, 3. mMRC Breathlessness scale
including low lung function

2.

Treatment issues
Check inhaler technique and adherence
Ask about side-effects
Does the patient have a written asthma
action plan?
What are the patients attitudes and goals
for their asthma?

3.

Comorbidities
Think of rhinosinusitis, GERD, obesity,
obstructive sleep apnea, depression,
anxiety
These may contribute to symptoms and
poor quality of life

GINA 2015, Box 2-1

Inflammation and Remodelling

Pedoman Diagnosis dan Penatalaksanaan Asma Indonesia 2004

Stepwise Approach to Control Asthma Symptoms and Reduce

Risk

STEP 5
STEP 4

Other
controller
options

Consider
low dose
ICS

RELIEVER

REMEMBER
TO...

STEP 2

STEP 3

Low dose ICS

Low dose
ICS/LABA*

Leukotriene receptor
antagonists (LTRA)
Low dose theophylline*

Med/high dose ICS

Low dose ICS+LTRA
(or + theoph*)

As-needed short-acting beta2-agonist (SABA, misal Berotec)

Med/high
ICS/LABA
Add tiotropium#
High dose ICS
+ LTRA
(or + theoph*)

Refer for add-on

treatment
e.g.
anti-IgE
Add tiotropium#
Add low dose
OCS

As-needed SABA or
low dose ICS/formoterol**

Adaptation from GINA 2015

PREFERRED
CONTROLLER
CHOICE

STEP 1

The Role Combination of Salbutamol and Ipratropium

in Asthma Attacks
MILD or MODERATE

SEVERE

Talks in phrases
Prefers sitting to lying
Not agitated
Respiratory rate increased
Accessory muscles not used
Pulse rate 100120 bpm
O2 saturation (on air) 9095%
PEF >50% predicted or best

Talks in words
Sits hunched forwards
Agitated
Respiratory rate >30/min
Accessory muscles being used
Pulse rate >120 bpm
O2 saturation (on air) < 90%
PEF 50% predicted or best

Short-acting beta2-agonists
Consider ipratropium bromide
Controlled O2 to maintain
saturation 9395% (children 94-98%)
Oral corticosteroids

Short-acting beta2-agonists
Ipratropium bromide
Controlled O2 to maintain
saturation 9395% (children 94-98%)
Oral or IV corticosteroids
Consider IV magnesium
Consider high dose ICS
Adaptation from GINA 2015

Therapeutic Options for COPD Medications

Beta2-agonists
Short-acting beta2-agonists ( misalnya Berotec )

Long-acting beta2-agonists
Anticholinergics
Short-acting anticholinergics ( misalnya Atrovent )
Long-acting anticholinergics

Combination short-acting beta2-agonists + anticholinergic in one inhaler

( misalnya Combivent UDV )
Combination long-acting beta2-agonist + anticholinergic in one inhaler
Methylxanthines
Inhaled corticosteroids
Combination long-acting beta2-agonists + corticosteroids in one inhaler
Systemic corticosteroids

Phosphodiesterase-4 inhibitors
Adaptation from GOLD 2015

Mechanism of Action
Salbutamol
Sympathetic Way

2 Agonist

2
Reseptor

Ipratropium
Parasympathetic Way

Anti Cholinergic

Cholinergic
Reseptor

The effect of bronchodilatation is more superior compared

to administration of each component1
1. Information Local Product of Combivent UDV 2012

Factors Affecting Inhaled Drug Delivery

Patient variables
Aerosol characteristics
Particle size
Particle velocity

Device type
Nebulizers
Pressurized Metered-Dose Inhalers (pMDIs)
Dry-Powder Inhalers (DPIs)

Interface / Attachment
Mouthpieces
Facemasks

Spacers
Extension device
Holding chambers

Barry et al. Adv Drug Deliv Rev. 2003;55:879-923; Bisgaard et al. Chapter 12. Drug Delivery to the Lung. Marcel Dekker 2001;162:389-420.

Aerosol Particle Size & Location

Aerosol Size

Upper Respiratory Lower Respiratory

>10m

7 - 10m

4 - 6m

2 - 3m

1m

<1m

No Deposition

Usmani OS, Biddiscombe MF, Barnes PJ

Regional lung deposition and bronchodilator response as a function of beta2-agonist particle size.
Am J Respir Crit Care Med 172 (12), 1497 - 1504 (2005)

Advantages of Inhalation Therapy

topical

low dose

directly to
resp system

minimal
side effects

high
th/. ratio

safety of
longterm use

fast onset

reliever
DBS 2004

controller

Combivent UDV better in terms of improving lung function

(FEV1) compared with salbutamol alone
in adult asthma patients

Garrett JE, Town GI, Rodwell P, Kelly AM. Nebulized Salbutamol with and without ipratropium bromide in the treatment of acute asthma, J Allergy Clin
Immunol 1997; 100(2): 165-170

Increase of PEFR (%)

Combivent UDV >2x Increase PEFR Higher to Adult Patients

with Acute Asthma compared to Salbutamol alone

77%

31%
Salbutamol

Combivent UDV

ODriscoll BR Nebulized Salbutamol with & without Ipratropium Bromide, Lancet 1989; 333 (8652): 1418-1420

Combivent UDV Increased FVC better in COPD

compared to Salbutamol alone

Change of FVC (%)

40

30

Kombinasi UDV
Combivent
Salbutamol

20

10

0
0.25 0.5 0.75

Time after dose (hour)

Levin DC, et al. Am J Med. 1996; 100(suppl 1A): 40S-48S.

Aerosol therapy devices

1. Nebulizer easiest
2. Dry Powder Inhaler (DPI)
3. Metered Dose Inhaler (MDI) most difficult
fortunately: spacer (addition closed space
between device and mouth)
extension device
holding chamber

1 - Nebulizer
Preparation of the device and the drug
Place the interface
Patient breath normally, sometimes with deep
breathing

2 - Dry powder inhaler (DPI)

The power source is the flow of inspiration / inhalation of the
patient
Breath-actuated inhaler, no propelan
Fast & strong inspiration, effort dependent
Less oropharynx deposition
Not suitable for under 5 children
For older children easier to use than MDI
No need of spacer, easy to carry

3 - MDI, How to use

Shake the canister, open the cap
Hold it up right, exhaled slowly
Put the canister mouthpiece between
lips tightly, inhaled slowly
Anytime after the beginning until the
middle of inspiration, push down the
canister
Continue the inspiration gently until
maximal inspiration
At maximal inspiration, hold the
breath for 10 seconds
Rinse the mouth and spill it out

Combivent UDV in Local and

Internasional Guideline

Updated 2015

1.
2.
3.
4.
5.

Buku Lengkap Diagnosis dan Penatalaksanaan PPOK PDPI, Juli 2011

Pedoman Tata Laksana Asma DAI 2011
Pedoman Nasional Asma Anak 2004
GOLD 2015
GINA 2015

SUMMARY
The goal of asthma and COPD treatment is to
improve the quality of life
ICS can be use for Asthma but not effective for COPD
Combivent UDV is better in terms of improving
lung function (FEV1) compared with salbutamol
alone in adult asthma patients
Combivent UDV is recomended in Local and
Internasional Guideline
Combivent UDV availables in JKN/BPJS