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Definition
Asthma is a chronic inflammatorydisorder of the airways in which manycells and cellular elements play a role.
The chronic inflammation is associatedwith airway hyperresponsiveness thatleads to recurrent episodes of wheezing,
breathlessness, chest tightness, andcoughing, particularly at night or in themorning.
Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma, updated 2009
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Epithelial
damage
Inflammatory
cell infiltration
Vascular
dilation
Mucous gland
hypertrophy
Edema
Mucus
Thickeningof basement
membrane
Adapted from National Asthma Education and Prevention Program. Expert PanelReport. Guidelines for the Diagnosis and Management of Asthma. August 1991.
Changes in Airway Morphology in
Asthma
Airway smooth
muscle
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These episodes are usually associated
with widespread, but variable, airflow
obstruction within the lung that is often
reversible either spontaneously or with
treatment. Clinical manifestations of
asthma can be controlled withappropriate treatment.
When asthma is controlled, there shouldbe no more than occasional flare-ups
and severe exacerbations should be
rare.
Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma, updated 2009
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Asthma Prevalence, 2004
Global burden of Asthma, 2004
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Global Strategy for Asthma Management and Prevention, Global Initiative for Asthma, updated 2009
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Treatment Cycle, GINA, updated 2009
Assessingasthma control
Treating to
achieve control
Monitoring to
maintain control
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reliever
Rapid acting B2-
agonist inhaledand oral
Systemic steroid
Anticholinergics
Xanthines
controller Inhaled and systemic
glucocorticosteroid
Leukotriene modifiers Inhaled LABA
Theophylline
Cromones Oral LABA
Asthma Medication
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Medication Routes
1. Inhalation
2. Orally
3. Injection
Benefits:
Delivered directly into the airwaysProducing higher local concentrations
Significantly less systemic side effects
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Inhalation Medications
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Quick Relief Medicines
(Rapid Acting 2-Agonist)
Act fast, generally within 15-20 minutes
Relaxes the smooth muscles around the bronchial
tubes Must have available at all times
Is only medicine that helps breathe quickly
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BETA2AGONIST
ACTION
IN ASTHMA
BRONCHODILATATION
INCREASED
MUCOCILIARYCLEARANCE
DECREASEDNEUTROPHILFUNCTION
DECREASED
BACTERIALADHERENCE
DECREASEDCHOLINERGIC
NEUROTRANSMISSION
DECREASEDPLASMA
EXUDATION
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Onset of Action
Rapid or Slow
Duration of Action
Short or Long
Efficacy at Receptor Site
Partial or Full Agonist
CHARACTERISTICS OF 2AGONIST
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Full-agonist Fast-onset Long-duration
Salbutamol - + -
Terbutaline - + -
Fenoterol - + -
Salmeterol - - +
Formoterol + + +
Procaterol + + +
Fast onset and full-agonis for relieverLong duration for add on controller
Choosing Beta-2 agonist
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PROCATEROL
Was found by Yoshizaki et al. at Japan
in 1976
Procaterol is a potent bronchodilator
even on a low dose
Has the effect of ten times stronger than
salbutamol and terbutalline
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PROCATEROL
TABLET (ORAL)
METERED DOSE INHALER (MDI)
SOLUTIO (NEBULIZED)
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Mean % FEV1 - Change from baseline (Initial Dosage)
35%
15%
0
M5 M30 H1.0 H2.0 H3.0 H4.0 H5.0 H6.0 H7.0 H8.0
Double-blind, randomized, 2 weeks study in 40-80% from predicted FEV-1 patients
M = minute H= hour
Ref: Storm; W,at.al.1985.Annals of Allergy, 55: 476-478
20 gMeptinair tid,n=71
10 gMeptinair tid,n=68
Placebo, n=67
:p< 0.05
PROCATEROL has fast bronchodillating effect
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Fast onset of action and longer duration than salbutamol
Comparative study of Meptinair vs salbutamol inhaler
Initial dose Week 12
50
40
30
20
10
Meptinair20 g tid,n=171
Salbutamol 200 g tid,n=162
0 1 2 3 4 5 6 7 8 0 1 2 3 4 5 6 7 8
Duration of Action (Hours) Duration of Action (Hours)
50
40
30
20
10
The horizontal (dashed) line represent 15% clinical improvement in FEV1from baseline.
Ref: Mazza J.A,et.al. 1992. Annals of Alergy, 68: 267-273
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Faster and longer duration of action than fenoterol
= P< 0.05 P vs F= P< 0.05 P vs S
= P< 0.05 S vs F
Fenoterol (F), n=35
Meptinair (P), n=35
Salmeterol (S), n=35
2000
1800
1600
1400
1200
0 5 15 30 300 540 (minute)
Change of FEV1value
Ref: Yunus F.,et.al. 2001. Indonesia Allergologist Association. 4 th National Congress Medan
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The Utility of a Long-Acting
Sympathomimetic Agent, Procaterol, for
Nocturnal AsthmaR. P. Baughman and R. G. Loudon. Chest February 1988
Ten patients with nocturnal asthma
Procaterol 0.1mg at night
Measured FEV1 every 2 hours from10PM to 8AM
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The use of long-acting -adrenergic
sympathomimetic agent reversed the
obstruction of the airway seen in
nocturnal asthma
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Twenty (20) asthmatic patients
Two puffs of procaterol (20g) or two
puffs of salbutamol (200g) MDI
PEF, FVC and FEV1were measured
after 5, 15, 30, 60, 120 and 180 min
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Pengaruh pemberian prokaterol dibandingkan
dengan salbutamol secara inhalasi dosis terukur
terhadap gejala klinis dan faal paru pada penderita
asmaMaimunah, T. Syafiuddin. Jurnal Respirologi Indonesia, 1999
Thirty (30) asthmatic patients
Procaterol 20g TID and Salbutamol
200g TID
PEFR, FEV1, FVC, bronchodilator test
every 2 weeks for 8 weeks
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Within the first two weeks, both drugs
showed equal efficacy dan clinical
improvements
After 2 weeks, the salbutamol group
showed deterioration while theprocaterol group still showed some
improvements
The decline in spirometry was greater in
salbutamol group than in procaterol
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A long-term trial of procaterol in
steroid-dependent patientsD.P. Tashkin. Journal of Respirology 1997
Seventy five (75) cocticosteroid-
dependent with moderate to severeasthmatic patients
Oral or inhaled corticosteroid andprocaterol for 28 weeks in five centers
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Procaterol has corticosteroid-sparing
effect of procaterol without a
compensatory increase in bronchodilator
use
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PURPOSE
The present study aimed to compare the
efficacy of nebulized procaterol with
nebulized salbutamol in the treatment of
moderate acute asthma
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METHODS
This was a randomized, double-blind, parallel group
study in 140 patients with moderate acute asthmaaccording to modified GINA 1998
Patients visiting the Emergency Room of PersahabatanHospital - Jakarta, male or female, aged 15 to 60 years,
were eligible for entry into this study
Excluded from the study were pregnant or lactatingwomen, smokers, patients with chronic obstructivepulmonary disease (COPD), heart disease,
hyperthyroidism, diabetes mellitus, severe infections, orother chronic diseases
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METHODS
Patients were randomly assigned to receive three
doses of either nebulized procaterol or salbutamol
The primary efficacy variable was the
improvement in predicted PEFR, while the
secondary efficacy variable was the improvement
in asthma score and the incidence and severity ofadverse events
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A total of 156 patients were screened and
there were 140 patients eligible for safety
evaluation, 137 patients eligible for ITTevaluation and 133 patients eligible for PP
analysis (Figure 1)
RESULT
P t l S lb t l
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Procaterol
(n=68)
Salbutamol
(n=69)
VITAL SIGNS
Temperature (0C) mean (SD)
Heart rate (beats/min) mean (SD)
Blood pressure (mm Hg) mean (SD)
SystolicDiastolic
Respiratory rate (resp/min) mean (SD)
36.9 (0.36)
104.2 (11.7)
121.5 (10.8)77.9 (8.9)
27.3 (2.6)
36.8 (0.48)
102.9 (12.7)
120.0 (9.7)75.2 (7.0)
27.4 (2.2)
PHYSICAL EXAMINATIONSn (%)
Normal
Abnormal (hyperemic pharynx)
64 (94.1)
5 (5.9)
66 (95.7)
3 (4.3)
ASTHMA SCOREmean (SD) 8.8 (1.5) 8.4 (1.6)
PEFRmedian (range)
PEFR value (L/min)
% predicted
< 25% - n(%)
125 (70 - 300)
30.5 (12 - 57)
19 (27.9)
120 (80 - 320)
26.0 (15 - 64)
32 (46.4)
ARTERIAL BLOOD GAS ANALYSESmean (SD)
PaO2 (mm Hg)
PaCO2 (mm Hg)
SaO2 (%)
HCO3-(mEq/L)
pH
LABORATORY ABNORMALITIESn (%)
ECG ABNORMALITIESn (%)
75.8 (16.28)
33.9 (6.67)
94.4 (4.37)
22.4 (3.84)
7.4 (0.06)
23 (33.8)
18 (26.5)
79.8 (22.18)
32.8 (5.46)
95.3 (2.66)
21.8 (2.64)
7.4 (0.06)
23 (33.3)
14 (20.3)
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PEFR (% predicted) improvements in each
group
Mean PEFR (% predicted) was markedly improved
compared with baseline value at every timepoint (20,
40, 60 and 120 minutes) in both groups (Figure 2).
Procaterol was statistically better in improving PEFR
value at 120 minutes compared with salbutamol but notclinically significant. The minimum clinically significant
difference in PEFR improvements between procaterol
and salbutamol groups according to the investigators
judgment as defined in the protocol was 5%. At othertimepoints, PEFR improvements by procaterol was
similar to salbutamol
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PEFR(%
predicted)
Procaterol (n=68) Salbutamol (n=69)
Timepoints(minutes)
Figure 2. PEFR (% predicted) values at different timepoints in procaterol and salbutamol groups, ITT population.
The improvements from baseline were significant at all timepoints (**p
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Asthma score improvements from baselinein procaterol and salbutamol groups
The asthma scores in procaterol and salbutamol groupswere markedly improved at every timepoint (20, 40, 60and 120 minutes) (Figure 3). At 120 minutes, meanasthma score in procaterol group was 2.0 and insalbutamol group was 2.1. Asthma score improvementsin procaterol group were compared with those insalbutamol group. It was shown that procaterol gavegreater improvements in asthma scores at the first 40minutes (20 and 40 minutes, p
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Time (minutes)
Procaterol (n=68) Salbutamol (n=69)
Figure 3. Asthma scores at several timepoints in procaterol and salbutamol groups, ITT population.
The improvements from baseline were significant at all timepoints (** p
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Arterial blood gas analyses
Arterial blood gas analyses at 120 minutes aresummarized in Table 2. Number of patients analyzed forblood gas was 62 patients in procaterol group and 65patients in salbutamol group. Six patients in procaterolgroup and 3 patients in salbutamol group could not be
included in the blood gas analysis due to the missingdata on either at baseline or at 120 minutes. Overall,PaO2 in procaterol group was slightly increased, while itwas slightly decreased in salbutamol group. SaO2 wasunchanged in procaterol group and slightly decreased in
salbutamol group, while PaCO2 slightly decreased inboth procaterol and salbutamol groups
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Blood Gas Analysis
PP analysis
Procaterol
(n=62)
Salbutamol
(n=65)
PaO2 (mmHg) 0 minutes
120 minutes
76.8
81.4
80.0
76.2
SaO2 0 minutes
120 minutes
95.0
95.0
95.3
94.3
PaCO2
(mmHg)
0 minutes
120 minutes
33.4
31.6
32.8
31.7
Table 2. Mean PaO2, PaCO2and O2saturation (SaO2)
before and after treatment (120 minutes)in procaterol
and salbutamol groups, PP analysis
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Adverse events
Incidences of adverse events were very low in thepresent study. Adverse events recorded were sinustachycardia and palpitation, which were common after2agonist administration. Palpitation was recorded as asubjective symptom.
There were 2 subjects in salbutamol group experienced
palpitation, and no one in procaterol group. Thepalpitation was considered as mild.
Sinus tachycardia was found during electrocardiographyat 120 minutes, which was recorded and analyzed forany changes from baseline. There were 2 (2.9%) cases
of changes in ECG recordings in procaterol group and 6(8.6%) cases in salbutamol group.
No serious adverse event was found in the presentstudy
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CONCLUSIONS
Beta 2 agonists have been used as reliever inasthma management
In moderate acute asthma, nebulized procateroland nebulized salbutamol were both effective in
improving PEFR and decreasing asthma score.
Both treatments were well tolerated, and adversereactions were rare, lower incidence with procaterolthan with salbutamol
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