Dr. Mei Budi Prasetyo, Sp.P.

RSUD Nganjuk, 24 Juni 2004

Dr. Mei Budi P., Sp.P

 ASMA = INFLAMASI KRONIS SALURAN NAPAS

Melepas
BANYAK SEL : MEDIATOR
-SEL MAST Histamin
-EOSINOFIL PDG 2, LTc 4
-NETROFIL OBSTRUKSI
EPITHELIAL TNF, PAF,
-LIMFOSIT DIFUS
SHEDDING -EPITEL Eo chemo F.
SALURAN
GM-CSF
NAFAS

PENINGKATAN MEKANISME BATUK, WHEEZING, SESAK

NEURAL

SEMBUH
BHR TERHADAP
BERBAGAI STIMULI
Dr. Mei Budi P., Sp.P SPONTAN TERAPI
 1960 1970
GEJALA FISIOLOGIK PENYAKIT
& ALERGI

KONSEP PATOGENESIS

KOMPONEN SELULER
( SAAT INI )
INFLAMMATORY
DISORDER

Dr. Mei Budi P., Sp.P

 SEBELUM 1985
MEREDAKAN GEJALA SESAK NAPAS

KONSEP TERAPI

SESUDAH 1985
PERBAIKAN FAAL PARU &
HIPER REAKTIFITAS BRONKUS

EFIKASI TERAPI
EFEKTIFITAS BIAYA
KUALITAS HIDUP
Dr. Mei Budi P., Sp.P
 FEV1 ( % of baseline )

100

80

60

40 Early Late
Asthmatic Asthmatic
Response Response
20 ( EAR ) ( LAR )

0 60 120 180 240 300 360

T I M E ( minutes )

Antigen Challenge
Dr. Mei Budi P., Sp.P
100
80 DELAYED ASTHMA
60
40
RAS RAL
20

0 60 120 180 240 300 360 420

I N F LA M A S I BHR
Bronko Obstruksi
ENDOTEL
222222222222222222222222222222222222222222222222222222222 DESQUAMASI
Eo Ne , Mo Tc Ba PERMEA
222222222222222222222222222222222222222222222222222222222 BILITY MUCUS
VCAM-1 Secretion
Edema

Leucotrien LTs IL-3.4.5.6.13 Histamin AXON REFLEX

Spasmogenik
IL-3.4.5.8 PGD2 RANTES LTC4
vasoaktif GM-CSF Lipoxy IgE IL-4.13 Fragilitas
ECP genase TXA 2 MIPH Epitel
Mediator
SRSA(LTs)
PGD 2 E N & M T B RANTES
Histamin EOTAXIN
GM-CSF
NEUTROFIL T-Lymp. PAF
EOSINOFIL MAKROFAG (CD4) BASOFIL

SEL
MAST Chemotactic factor, sitokin, TNF-
Dr. Mei Budi P., Sp.P GM-CSF, Pafaceter, LTB4
 1 PREDISPOSITION = GENETIC ( 19 chromosomal region )

VIRAL OCCUPATIONAL ALERGEN

INFECTION EXPOSURE EXPOSURE

2 2 2

3
HYPERSENSITIVITY ( IgE ab )
4

3
NOTE :
1=predisposition
2=initiating
BRONCHIAL REACTIVITY 3=contributing /
promotor
4=trigger
4

Dr. Mei Budi P., Sp.P

AIRWAY OBSTRUCTION
 Klasifikasi Gejala Gejala PEF % PEF
Nokturnal Pred. Variability
Intermittent < 1 x/minggu < 2x/bulan 80 % < 20 %
Tanpa Gejala

Mild 1x/minggu
Eksaserbasi meng
Persistent Ganggu aktifitas > 2x/bulan 80 % 20 30 %
& tidur

Moderate Tiap hari > 60 %

Eksaserbasi meng
Persistent ganggu aktifitas > 1x /mgg < 80 % > 30 %

Severe Terus menerus

Eksaserbasi
Persistent frekuen Frekuen < 60 % > 30 %

Dr. Mei Budi P., Sp.P

 Pertahankan aktivitas normal
Pekerjaan sehari-hari Pertahankan Faal Paru
Mendekati Normal

Penuhi harapan
TUJUAN TERAPI ASMA Perawatan
& Edukasi

Cegah gejala kronis

& Eksaserbasi Hindari efek samping
Obat Asma

Dr. Mei Budi P., Sp.P

 Pencegahan & kontrol lingkungan
Menghindari trigger asma

Edukasi
4 KOMPONEN Terapi
Penderita
KUNCI TERAPI Farmakologis
Asma

Pengukuran Obyektif Faal Paru

( PEFR di rumah )
Menilai & monitor perjalanan penyakit

Dr. Mei Budi P., Sp.P

 Anti cholinergik
Ipratoprium bromide Beta-2 Agonist
Metaproterenol, Terbutalin,
RELEIVER Salmeterol, Procaterol
Methyl Xanthine
Aminophylline
Theophylline

TERAPI FARMAKOLOGIS
Kombinasi
Albuterol
Ipratoprium CONTROLLER
Anti Leukotrien
Zafirlukast

Cromoglycate Corticosteroid
Cromolin sodium Inhaler
Nedokromil Oral, parenteral

Dr. Mei Budi P., Sp.P

 ANTI INFLAMASI KEMOTAKSIS
PALING POTEN EOSINOFIL

REKRUTMEN,AKTIVASI &
PELEPASAN
PROLIFERASI SEL RADANG
BERBAGAI
MEDIATOR

KORTIKOSTEROID PELEPASAN
- METABOLIT ASAM
ARAKIDONIK
- LEUKOTRIEN
MIKRO - SITOKIN
VASKULER - GM-CSF
LEAKASE
Dr. Mei Budi P., Sp.P
 MEMPERBAIKI PEMAKAIAN
KERUSAKAN EPITEL INHALASI
SEDINI MUNGKIN

DOSIS AWAL BESAR

KORTIKOSTEROID TAPERING KE
DOSIS MINIMAL
EFEKTIF

MEMPERBAIKI
HIPER-REAKTIFITAS MENCEGAH
BRONKUS FIBROSIS
BRONKUS

Dr. Mei Budi P., Sp.P

 INHALED STEROID

- Less Systemic
CORNER STONE IN Side Effect
THE MANAGEMENT OF - Lower doses used
CHRONIC ASTHMA - Get to Airway

BECLOMETHASONE
BUDESONIDE DECREASE IN AIRWAY
FLUTICASONE OBSTRUCTION
MOMETASONE IMMEDIATE & LATE
REACTION

DECREASE AIRWAY
REACTIVITY
Dr. Mei Budi P., Sp.P
 ORAL STEROID

SHORT TERM ROLE

STILL HAS IN
AN IMPORTANT ACUTE ASTHMA
&
SEVERE CHRONIC
ASTHMA

LONG
TERM
THERAPY RISK OF SEVERE
SYSTEMIC
SIDE EFFECT

Dr. Mei Budi P., Sp.P

 RELIEVER PALING EFEKTIF MENGHAMBAT
PELEPASAN MEDIATOR

MENGHAMBAT
AKTIVASI ADENYL CYCLASE
CHOLINERGIC
MENINGKATKAN cAMP
NEUROTRANSMISSION

BETA AGONIS

MENGURANGI HIPOKSEMIA MENINGKATKAN

PERMEABILITAS TEMPORER KLIRENS
VASKULER 10-20 MENIT MUKOSILIER
& EDEMA OKSIGEN
Dr. Mei Budi P., Sp.P
 Rationale for Combination Therapy

Smooth muscle Airway

LABA dysfunction inflammation CS

Bronchoconstriction Inflammatory cell

Bronchial hyper- infiltration/activation
reactivity Mucosal oedema
Hyperplasia Cellular proliferation
Inflammatory Epithelial damage
mediator release Basement membrane
thickening

Symptoms\exacerbations
Dr. Mei Budi P., Sp.P
 KOMPETITOR ANTAGONIS
ACETYLCHOLIN

ANTI KOLINERGIK

MENGURANGI TONUS VAGAL

PADA PARASIMPATIS GANGLION

Dr. Mei Budi P., Sp.P

 INTRAVENOUS
PERANNYA DIGESER
PADA ASMA BERAT
BETA 2 AGONIS

METIL XANTIN

PREPARAT
EFEKTIF
LEPAS LAMBAT
TERAPI MAINTENANCE
MENGURANGI
ASMA KRONIS
EFEK SAMPING
Dr. Mei Budi P., Sp.P
 GTP ATP

BRONKO
KONSTRIKSI

c GMP c AMP

BRONKO
DILATASI

GMP AMP
Dr. Mei Budi P., Sp.P
 KORTIKOSTEROID KOMBINASI OBAT
INHALASI MEMBERI MANFAAT
SEDINI MUNGKIN MAKSIMAL
FIRST LINE ANTI ( LABA & STEROID )
INFLAMMATION DRUG

KESIMPULAN
FARMAKOTERAPI

DAPAT DIKOMBINASI RASIONAL

SECOND LINE DRUG LEUKOTRIEN
ANTI KOLINERGIC & ANTAGONIS
METILXANTIN EFEK BRONKODILATOR
& ANTI INFLAMASI
Dr. Mei Budi P., Sp.P
 Severity of Asthma
Attacks
Respiratory
Parameter1 Mild Moderate Severe arrest
imminent
Breathless Walking Talking At rest
Infant-softer Infant-stops
shorter cry; feeding
difficulty
feeding
Can line Prefers sitting Hunched forward
down
Talks in Sentence Phrases Words
Alertness May be Usually Usually agitated Drowsy or
agitated agitated confused
Dr. Mei Budi P., Sp.P
 Respiratory
Parameter1 Mild Moderate Severe arrest
imminent
Respiratory Increased Increased Often > 30/min
rate
Guide to rates breathing associated with
respiratory distress in awake children :
Age Normal rate
<2 months <60/min
2-12 months <50/min
1-5 years <40/min
6-8 years <30/min
Accessory Usually Usually Usually Paradoxical
muscles & not troraco-
suprasternal abdominal
retractions
Dr. Mei Budi P., Sp.P
movement
 Respiratory
Parameter1 Mild Moderate Severe arrest
imminent
Wheeze Moderate, Loud Usually loud Absence of
often only end wheeze
expiratory
Pulse/min < 100 100-120 > 120 Bradycardia
Guide to limits of normal pulse rate in children :
Infants 2-12 months -Normal rate<160/min
Preschool 1-2 years -Normal rate<120/min
School age 2-8 years -Normal rate<110/min
Pulsus Absest May be Often present
paradoxus <10 mm Hg present >25 mm Hg
10-25 mm Hg (adult)
20-40 mm Hg
Dr. Mei Budi P., Sp.P (child)
 Respiratory
Parameter1 Mild Moderate Severe arrest
imminent
PEF Over 80% Approxima- <60% predicted or
After initial tely personal best
bron- 60-80% (<100 L/min
chodilator adults)
% prediced or Or response lasts
% personal <2 hours
best
PaO2 (on air)* Normal >60 mm Hg <60 mm Hg
and/or Testnot Possible cyanosis
usually
necessary
PaO2* <45 mm Hg <45 mm Hg >45 mm Hg:
Possible
respiratory failure
Dr. Mei Budi P., Sp.P (see text)
 Respiratory
Parameter1 Mild Moderate Severe arrest
imminent
SaO2% (on >95% 91-95% <90%
air)*
Hypercapnia (hypoventilation) develops more
readily in young children that in adults and
adolescents

Dr. Mei Budi P., Sp.P

 Management of Asthma Attacks
Initial Assessment
History (hx) physical ecamination (auscultation, use of
accessory muscles, heart rate, repiratory rate, PEF or FEV1,
oxygen saturation, Arterial blood gas of patient in extremis,
and other tests as indicated)

Initial Treatment
Inhaled short-acting beta2-agonist, usually by nebulization,
one done every 20 minutes for 1 hour
Oxygen to achieve O2 saturation > 90% (95% children)
Systemic corticosteroids if no immediate response, or if patient
recently took steroid tablets or syrups, or if episode is severe
Sedation is contraindicated in the treatment of attacks.

Dr. Mei Budi P., Sp.P Repeat Assessment

 Repeat Assessment
PE, PEF, O2 saturation, other tests as needed

Moderate Episode Severe Episode

PEF60-80% predicted
Physical exam: moderate
symptoms, accessory muscle
use
Inhaled beta2-agonist every 60
minutes
Consider corticosteroids
Continue treatment 1-3 hours,
provided there is improvement
PEF <60% predicted
Physical exam: severe symptoms at
rest, chest retraction
Hx : high-risk patient
No improvement after initial
treatment
Inhaled beta2-agonist, hourly of
coninouus inhaled anticholinergic
Oxygen
Systemic corticosteroid
Consider subcutaneous,
intramuscular, or intravenous beta2-
agonist

Good Response
Dr. Mei Budi P., Sp.P Incomplete Response Poor Response
 Good Response Incomplete Poor Response
Response Response Within Within 1 Hour
sustained 60 1-2 Hours Hx : high-risk
minutes after last Hx : high-risk patient
treatment patient Physical exam :
Physical exam : Physical exam : symptoms severe,
normal mild to mederate drowsiness,
No distress symptoms confusion
O2 saturation PEF >50% but PEF <30%
>90% (95% <70% PCO2 >45 mm
children) O2 saturation not Hg
improving PO2 <60 mm Hg

Admit to Intensive
Discharge Home Admit to Hospital
Care
Dr. Mei Budi P., Sp.P
 Discharge Home Admit to Hospital Admit to Intensive
Contonue treatment Inhaled beta2- Care
with inhaled beta2- agonist inhaled Inhaled beta2-agonist
agonist anticholinergic anticholinergic
Consider, in most Intravenous
Systemic
cases, corticosteroid corticosteroid
corticosteroid Consider
tablets or syrup
Patient adeucation
Oxygen subcutaneous
: Take medicine Consider intramuscular, or
correctly review intravenous intravenous beta2-
action plan close aminophylline agonists
medical follow up Monitor PEF, O2 Oxygen
saturation, pulse, Consider intravenous
treophylline aminophylline
Possible intubation
and mechanical
ventilation
Discharge Home
improve Not Improved

Dr. Mei Budi P., Sp.P

Admit to Intensive Care
 improve Not Improved

Discharge Home Admit to

If PEF > 70% Intensive Care
predicted/personal If no
best and improvement
sustained on within 6-12 hours
tablets or
syrup/inhaled
medication

Note : Preferred treatments are inhaled beta2-agonist in high doses

and corticosteroids. If inhaled beta2-agonists are not available
Theophylline may be be considered

Dr. Mei Budi P., Sp.P

Dr. Mei Budi P., Sp.P