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Peran NAC Pada PPOK Eksaserbasi Akut
Peran NAC Pada PPOK Eksaserbasi Akut
Definition of COPD
Mechanisms Underlying
Airflow Limitation in COPD
Small Airways Disease
Parenchymal Destruction
Airway inflammation
Airway fibrosis, luminal plugs
Increased airway resistance
AIRFLOW LIMITATION
2013 Global Initiative for Chronic Obstructive Lung Disease
Burden of COPD
Genes
Infections
Socio-economic
status
Aging Populations
2013 Global Initiative for Chronic Obstructive Lung Disease
PATOGENESIS COPD
Noxious particles and
gases
Host factors
Antioxidants
Lung Inflamation
Oxidative stress
Antiproteinase
Proteinase
COPD pathology
Repair mechanism
PROBLEM UTAMA
RESPIRASI PADA PPOK
1. OXIDATIVE STRESS
Basic problem di tingkat selluler
3. Bacterial adherence
Timbul kolonisasi bakteri pada saat eksaserbasi Akut
Impaired
mucociliary
clearance
Damaged to
airways
epithelium
Proggress of
COPD
Altered elastase
anti-elastase
balance
Bacterial Colonisation
(Bacterial Adhesion)
Bacterial Product
Increased Oxidative
Stress (oxidant)
(consumption of antioxidant)
Increased elastolytic
activity
Inflammatory
Response
SOCIAL DEATH
(Faisal Yunus93, ERS98)
Pasien tidak mampu melakukan aktivitas sosial
Disability of Lung Function
FEV1 <30% Predicted Value < 750 ml.
Pengobatan PPOK
(ERS95, PDPI2010)
Strategi :
Terapi
Alasan
Bronkhodilator Terjadi proses fibrosis,metaplasia sel goblet dan
hipertropi
otot polos yang menyebabkan
obstruksi jalan napas
Antiinflamasi
Antioksidan
Note : Pemberian antibiotik hanya pada saat eksaserbasi akut COPD (AECOPD) (NLHEP98 &
ERS;95)
Therapeutic Options
Manage Exacerbations
Manage Comorbidities
UPDATED 2013
Manage Exacerbations
An exacerbation of COPD is:
an acute event characterized by a
Impact on
symptoms
and lung
function
EXACERBATIONS
Accelerated
lung function
decline
Increased
economic
costs
Increased
Mortality
2013:Global
for Chronic Obstructiveduring
Lung Diseasean exacerbation.
Spirometric tests
notInitiative
recommended
PERANAN NAC
DALAM MENGATASI
Problem Respirasi
Dosis / Hari
ANTIOXIDANT
I.C.U.
Activity
MUCOLYTIC
I.V. INFUS.
FLUIMUCIL
600 mg x 3
4 Amp / hr
600 mg x 2
COPD
600 mg x 2
Chronic bronchitis
600 mg x 2
Acute bronchitis
Influenza
600 mg
200 mg x 3
100 mg x 3
1800 mg
Activity
ORAL
HIDONAC 600 -
NAC EFFECTIVENESS
3. Anti-adhesi bakteri
4. Anti inflamasi
S
S
5. NAC
sebagai IMMUNOMODULATOR
N = 36
P = 0.034
54 ml/tahun
ml/tahun
50
40
30 ml/tahun
30
20
10
0
NAC
Placebo
20
P = 0.001
15
10
N = 254
5
0
50
N = 259
P = 0.001
40
30
40%
20
10
NAC
800
739
N = 28
600
260
400
N = 27
200
19%
Control
P = 0.088
1000
Jumlah Hari
25
Placebo
NAC
Mengurangi Eksaserbasi
Placebo
(6 bulan)
NAC
Mengurangi Incident
(G.Boman)
Meningkatkan Effektifitas
(Rasmussen, et al.)
(NAC)
2,5
ADJUSTED MEANS
CORR. COEFF. = 0.36
P < 0.001
2
Tickness Score
2
1,5
1,5
0,5
0,5
0
0
NAC
2
1,5
1
0,5
0
bulan
Placebo
ADJUSTED MEANS
CORR. COEFF. = 0.28
P < 0.001
2,5
ADJUSTED MEANS
CORR. COEFF. = 0.27
P < 0.001
2,5
bulan
Placebo
NAC
6
bulan
Placebo
NAC
Batuk
Viscositas Sputum
Difficulty Expectoration
n mol/g
275
200
150
n = 27
100
No NAC
+ NAC
+ NAC
(1-3 jam)
(16-20 jam)
(Bridgeman, 1991)
Safety
Aman dalam dosis tinggi
38