FARMAKOTERAPI II

OLEH :
FRANSISKA MARIA C.
BAG. FKK-FFUJ
 References

 GINA, 2018
 DEFINITION

 “Asthma” (Greek)  Panting (terengah-engah)

 Asthma is a chronic inflammatory disorder of the
airways in which many cells and cellular elements play a
role: in particular, mast cells, eosinophils, T-lymphocytes,
macrophages, neutrophils, and epithelial cells.
(The National Institutes of Health, National Asthma Education and Prevention
Program (NAEPP) Expert Panel Report 3 (EPR3) in Dipiro, 2014)

 Asthmais a heterogeneous disease, ussualy characterized

by chronic airway inflammation
(GINA, 2018)
 Respiratory symptoms

Vary over time in their

A occurrence, frequency,
Wheezing & intensity
+ variable
B expiratory airflow
Shortness of breath limitation

C
Chest tightness

D
Cough

(GINA, 2018)
Etiology & Risk Factor

Some drugs,
e.g. -blocker,
aspirin, etc.
Patophysiology

Inflamasi

Bronkrokonstriksi

Hipersekresi mukus

Hiperresponsif
 Asthmatic bronchus VS Normal bronchus

A. Normal
B. Asthma
(Dipiro, 2018)
(Dipiro, 2018)
Allergic Respone in Asthma

(Nature Reviews Immunology 8, 2008)

 Pulmonary Function Test

• Normal
Ratio
FEV1/FVC
•  75-80 %
(adult)
•  90%
(children)
• FEV1
increases
> 12% or 0,2L
ASTHMA..??? Spirometry  FEV1 & FVC after inhaling
broncodilator
PEF variability
Peak flow meter  PEF in asthma
> 10% (adult)
> 13% children)
 Pulmonary Function Test

 FEV1 (Force
Expiratory
Volume in the
first second of
expiration)
 FVC (Force
Vital Capacity =
total amount of
air that can be
exhaled during
a force
exhalation)
 PEF (Peak
expiratory
Flow)
 Clasifiying asthma severity
& initiating therapy (NHLBI, 2012)
Management for SEVERE ACUTE
ASTHMA (EXACERBATION)
 MANAGEMENT FOR SEVERE ACUTE ASTHMA
(EXACERBATION)

 Exacerbation (flare-ups or attack)

  Suatu kejadian pemburukan yang akut atau sub akut dari suatu
gejala dan fingsi paru dibandingkan status pasien umumnya

 Goals of treatment:
 Correct significant hypoxemia
 Rapidly reverse airway obstruction (within minutes)
 Reduce likelihood of reccurent of severe airflow obstruction
 Develop a written asthma action plan in case of future exacerbation
 Pharmacologic Treatment

• Repeat inhaled SABA

• eg: Salbutamol & terbutalin (1st choice)
• Inhaled anticholinergic
• eg: ipratropium bromide (tambahan
SABA/alternatif bila SABA tdk efektif)
• Sistemic Corticosteroid
• short course  mencegah eksaserbasi berulang
• Oksigen
• menjaga SaO2 > 93-95% (remaja & dewasa) atau
>94-98% (anak & wanita hamil dg gangguan
jantung)
 Beta Adrenergic (2 Agonist)

Effect:
 Relax bronchial smooth muscle (bronchodilatation)
 Inhibit mediator release from mast cells, eosinophils,
macrophages
 Increase mucous secretion (submucosal gland)
 Increase mucociliary transport
 Inhibit bronchial oedema
 Inhibit cholinergic transmisssion
 Decrease airway hyperresponsiveness
Mechanism

• Activating adenylyl
cyclase  increase
cAMP level 
activating Protein
Kinase A (PKA) 
bronchial muscle
relaxation
 2-AGONIST BRONCHODILATORS

Salbutamol …..???
Quick relief medications
 Corticosteroids

 Short course systemic

corticosteroids (IV or oral)
 Indicated for all patients with
acute severe asthma
exacerbations not responding
completely to initial SABA (every
20 minutes for 3-4 doses)
 Warning ESO..!!
Corticosteroids for asthma
Anticholinergics
Blockade of
muscarinic M3
receptor at
bronchial muscle

Inhibit
contraction
mediated by PLC
signaling

Relaxation of
bronchial
smooth muscle
 Anticholinergics

 Ipratropium Bromide
 May mix in some nebulizer with
albuterol
 Do not use as 1st line therapy

 Only add to 2 agonist therapy

 12 years old  12 years old

(Dipiro, 2014)
Quick Relief Medication (Cont’)
 Alternative therapy

 Methylxantine (Teophylline/Aminophylline)
 not recommended
(Risk > benefit)
 Eleminated primarily by metabolism via hepatic CYP450
enzymes  drug interaction
 Interpatient variability  routine monitoring of serum
theophylline concentration
AC = Adenilyl Cyclase
PDE = Phospodiesterase
Home management
of acute asthma
exacerbation
(Dipiro, 2018)
Emergency department & hospital care of acute asthma exacerbation
(Dipiro, 2014)

To be continued
Cont’
Moderate exacerbation Severe exacerbation
 Management for
CHRONIC ASTHMA
 MANAGEMENT OF CHRONIC ASTHMA

 Long-term GOALs:
 Symptom control

 Risk reduction (risk of exacerbations, airway limtation &

damage, lung function, medication side-effects)

(Asthma Care-Quick Ref, 2012)

 Pharmacological Treatment
• Inhaled Corticosteroids (ICS) or OCS
• ICS & long acting 2-agonist broncodilator (LABA)
combination (ICS/LABA)
• Methylxantines (theophylline)
CONTROLLER
• Leukotriene modifiers (zafirlukast, montelukast,
MEDICATIONS zileuton)
• Anti-IgE (omalizumab)
• Chromones (Na-cromoglycate)
• Long acting anticholinergic (Triotropium)*
• Anti IL-5 (mepolizumab)*

• Short acting inhaled 2-agonist

broncodilator (SABA) RELIEVER
• Low dose ICS & SABA combination MEDICATIONS
• Short acting anticholinergic
(Ipraptropium Br)
INHALED CORTICOSTEROIDS (ICS)

(GINA, 2018)
Leukotriene
modifiers

 Zileuton

 Montelukast
 Pranlukast
 Zafirlukast

J Allergy Clin Immunol, 124 (3) 422-427 (2009)

Anti-IgE (Omalizumab)
 Omalizumab (Xolair®)

 Bermanfaat pada pasien yg asmanya tdk terkontrol

dg ICS & nilai pemeriksaan antibody IgE-nya tinggi
(> 30 IU/mL)  asma persisten sedang &/ berat
 Sebelumnya (th 2003) digunakan utk dewasa, saat
ini (mulai th 2016) dpt digunakan pd anak 6-11 th
 Dosis disesuaikan dg kadar IgE dan berat badan
pasien
 Injeksi subkutan setiap 4 minggu
 Harga..??
 Chromones (Na-cromoglycate)

 Mast cell stabilizator  prevent degranulation

 Mediator release is restricted
 Long time use prevents hypereactivity bronchus
> not for acute case
 Not absorbed orally, given via MDI – 1 mg/dose,
4.d.d 2 puff
 Anticholinergic long acting
(triotropium bromide)

 16 September 2015  FDA approved triotropium

bromide inhaler for use in the treatment of asthma
 Long term, once daily, maintenace therapy
Anti IL-5 (mepolizumab)

 IL-5 : kemotaktik faktor bagi

eosinofil menuju jaringan
inflamasi
 s.c injection, once every 4
weeks
 4 Nop 2015 – FDA approved

Nature Reviews Drug Discovery 3, 831-844 (2004)

Asthma medications mechanism
Stepwise approach to asthma treatment
Clinical Guidelines for the Diagnosis, Evaluation and Management of Adults and Children
with Asthma, 2013
 Patients
counseling
ASSESSING ASTHMA CONTROL

(GINA, 2016)
ASSESSING ASTHMA CONTROL
& ADJUSTING THERAPY
ACT
 Obyektif pemakaian ACT

1. ACT  menilai kontrol asma berdasarkan angka

yang sudah divalidasi, dg ketentuan:
  19 = asma tidak terkontrol
 20-24 = terkontrol baik (well controlled)
 25 = totally controlled
2. Meningkatkan komunikasi pasien/dokter
3. ACT sudah divalidasi dg memakai uji spirometri &
penilaian spesialis
0-19 : Belum terkontrol
20-27 : Terkontrol
 ADJUSTING THERAPY

3 4
2
1
ADJUSTING THERAPY 4
3

2 1

STEP-DOWN
ASTHMA DEVICES
Device dalam terapi inhalasi

INHALER

MDI DPI
(Metered (Dry Powder Nebulizer
Dose Inhaler) Inhaler)

Ultrasonic-
Jet-nebulizer
nebulizer
 PERBEDAAN

MDI DPI

 Aerosol, suspensi,  Serbuk kering, tanpa

larutan dg propelan propelan
CFC/HFA  Inspirasi cepat, kuat &
 Inspirasi pelan & dalam
dalam  Tidak perlu dikocok
 Perlu dikocok  Tanpa spacer
 Dapat menggunakan  Sulit pada anak kecil
spacer
 MDI
(Metered Dose Inhaler)
Cara Penggunaan MDI
DPI type Device name Company

Single-unit dose Aerolizer Novartis

Cyclohaler Pharmachemie

Rotahaler GSK

Spinhaler Aventis

Inhalator

Handihaler
B-Ingelheim

B-Ingelheim
DPI
(Dry powder Inhaler)
Multi-dose Clickhaler Innovata Biomed
reservoir
Easyhaler Orion Pharma

Pulvinal Chiesi

Turbuhaler Astra Zeneca

Twisthaler Schering-Plough

Novolizer Asta Medica

Multi-unit dose Aerohaler B-Ingelheim

Diskhaler GSK

Diskus/Accuhaler GSK
Turbuhaler
Diskus
 Cara penggunaan nebulizer
1. Udara dalam ruangan harus segar, ventilasi
baik
2. Pasien duduk tegak, rileks atau tidur miring
setengah duduk
3. Bernafas biasa (volume tidal), sesekali
menarik nafas dalam
4. Pergunakan mouthpiece atau masker
5. Waktu pengguaan 5-15 menit, jika
diperlukan dapat dilakukan bbrp kali dlm
sehari
 Cara penggunaan nebulizer
6. Jika ada bronkokontriksi, berikan bronkodilator
dahulu (atau bisa digabung dg kortikosteroid)
7. Jangan memberikan mukolitik saat pasien masih
sesak, terutama pd serangan akut berat
8. Sekret yg dikeluarkan jgn sampai tertelan 
sediakan wadah
9. Perhatikan tanda2 yg tidak biasa (sianosis atau
sesak semakin parah, dll)
10. Pergunakan alat yg disposable, pisahkan terhadap
pasien tertentu
11. Jika selesai, bersihkan peralatan yg dipakai
See U next time …