Asthma Bronkhial

Department of Pharmacology and Therapeutics

Diponegoro University Faculty of Medicine
 Penyakit Paru Obstruktip Kronis
(PPOK)
3 penyakit utama tergolong PPOK:
• Asma bronkhiale
• Bronkhitis kronis
• Emfisema pulmonum
 Asthma
Definisi:
• Asma adalah penyakit inflamasi kronis pada saluran
nafas paru-paru dengan rekurensi obstruksi saluran nafas
yang reversibel, yang penyebabnya belum diketahui
secara jelas.
• Bronkokonstriksi Hipertropi
• Gejala dapat berupa: • Inflamasi & edema mukosa
bronkus
Serangan mengi • Hipersekresi kel mukosa
Dada terasa berat bronkus
Sesak nafas
Batuk (terutama malam hari)
• Karakteristik asma:
1. Inflamasi kronis
2. Hiper-reaktifitas bronkus
3. Obstruksi saluran nafas yan reversibel
Differential Dx of Wheezing
 Asthma
 Bronchiolitis (esp in infants), bronchitis,
laryngotracheobronchitis, tracheitis
 Foreign body aspiration
 Functional abnormalities ( GERD, CF, BPD,
immunodeficiency etc )
 Structural abnormalities ( laryngo-tracheomalacia,
vascular rings, tracheal stenosis / webs, tumors etc )
Pathogenesis of Asthma
 Etiologi dan Pemicu Asma
• Etiologi Asma:
1. Atopi dan Alergi
2. Hiper-reaktifitas saluran nafas

• Faktor Pemicu Asma:

1. Occupational sensitizers: Isocyanates
2. Cold air and exercise
3. Atmosphoric pollution: Sulphur dioxide, Ozone
4. Viral infection: Rhinovirus, RSV, Parainfluenza
virus
5. Drugs: NSAIDs, Beta Bloker
6. Diet
7. Emotion
Risk Factors
 Family Hx of asthma
 Prematurity
 Race ( African and Native Americans )
 Low socioeconomic settings
 Urban settings ( pollutants )
 Increased indoor irritants ( cigarette smoke, dust
mites, pets, recycled air )
 History of Atopy ( eczema, allergies and chronic
rhinitis / sinusitis )
 Macam-macam Obat Asma
Bronkodilator:
1. β2-adrenoreceptor agonist
2. Methylxantine drugs
3. Muscarinic receptor antagonist
4. Leukotriene receptor antagonist
Anti-inflammatory:
5. Corticosteroid
6. Cromoglicate and nedocromil
7. Anti Ig-E
 Terapi thd asma bronkial
• Bronkodilatator
• Obat thd inflamasi dan edema mukosa
• Mengurangi sekret (yang berlebihan)
• Mengatasi hipoxia
• Tindakan supportip lainnya:cairan ,dsb
 3

BRONKODILATOR
 Adrenaline
untuk mengatasi serangan akut:
• Diberikan s.c. dosis kecil 0,2 ml larutan
1:1000
• Efek samping takikardi, hipertensi dan
yg berbahaya bila terjadi aritmia ventrikuler
(fatal).
1
1. β2-adrenoceptor agonists
• The main drugs as bronchodilators
• Primary effect in asthma is to dilate the bronchi by a
direct action on the β2-adrenoceptors on the smooth
muscle whatever the spasmogens involved (physiological
antagonist)
• Other drug mechanisms: Inhibit mediator release from
mast cells and TNF-α release from monocytes; increase
mucus clearance on cilia
• Usually given as: inhalation of aerosol, powder or
nebulised solution, oral and injection
 Macam Obat Asma
• Etiologi Asma:
1. Atopi dan Alergi
2. Hiper-reaktifitas saluran nafas

• Faktor Pemicu Asma:

1. Occupational sensitizers: Isocyanates
2. Cold air and exercise
3. Atmosphoric pollution: Sulphur dioxide, Ozone
4. Viral infection: Rhinovirus, RSV, Parainfluenza virus
5. Drugs: NSAIDs, Beta Bloker
6. Diet
7. Emotion
β2-adrenoceptor agonists
• Two categories:
1. Short-acting agents (SABA): Salbutamol (albuterol),
Terbutaline
 Given by inhalation maximum effect within 30 minutes and the
duration action is 3-5 hours
 Used on an ‘as needed’ basis to control symptoms

2. Longer-acting agents (LABA): Salmeterol, Formoterol

 Given by inhalation with duration of action 8-12 hours
 Not used ‘as needed’ but given regularly, twice daily, as
adjunctive therapy (inadequately controlled by steroid)

Unwanted effects: tremor, tachycardia, dysrhytmia

Sympathomimetic Agents
 2. Methylxanthine Drugs
Mekanisme Kerja:
1. Hambat Phosphodiesterase(PDE)4…increase cAMP & cGMP
2. Hambat Adenosine
3. Pacu deasetilase Histone
Methylxantine drugs

• Drugs: Theopylline, Aminophylline (theophylline

ethylenediamine)
• Given orally in sustained-release preparations;
aminophylline given by slow IV injection of a loading
dose followed by IV infusion
Theophylline dose: adult 3-4 mg/kg/6 h
• Actions:
1. Bronchodilator
2. CNS: alertness, tremor, insomnia
3. Cardiovascular: chronotropic, inotropic, vasodilator
4. Kidney: weak diuretic
• Perhatian: Narrow therapeutic window (5-20 mg/L)
Methylxantine drugs

• Theophylline is metabolised by the P450 system in liver

• Drug interaction:
1. Plasma concentration decreased by P450 inducer drugs:
Rifampicin, phenobarbital, phenytoin, carbamazepine
2. Plasma concentration increses by P450 inhibitor drugs:
Erythromycin, clarithromycin, ciprofloxacin, diltiazem,
fluconazole

• Clinical use:
1. Second line drugs, in addition to steroid (inadequate
respons to beta agonist)
2. Acute severe asthma
3. Muscarinic receptor antagonist (anticholinergic)
• Despite their commonly used name, the “anticholinergic”
drugs antagonize only the muscarinic receptors.
• Ipratropium and tiotropium are the two anticholinergics (or
parasympatholytics) currently used. Both are only available
for administration via the inhalational route.
• Ipratropium (the older drug) has no selectivity for M1, M2,
or M3 receptors and lasts for about 6 hours. However,
tiotropium is a long-acting anticholinergic which can be
used once daily.
• Anticholinergic drugs also effect mucus secretion.
Since systemic anticholinergic drugs can block all
muscarinic receptors, tachycardia, increased contractility,
blurred vision, dry mouth, decreased sweating, constipation,
and confusion are effects that can be expected in a dose
dependent manner.
3. Muscarinic receptor antagonist (anticholinergic)
Clinical use:
1. Not particularly effective against allergen challenge
2. No effect on late inflammatory phase
3. Not well absorbed into the circulation, so safe and well
tolerated
4. Combination with β2-adrenoceptors agonist
Leukotriene Pathway Inhibitors
Leukotriene modifiers

• There are two types of agents that modify leukotriene

response, inhibitors of LT synthesis that block lipo-
oxygenase, and LT receptor antagonists.
• The drugs zafirlukast and montelukast belong to the latter
group and are used more clinically.
• Zileuton is an inhibitor of leukotriene synthesis
• In theory, these LT modifying agents could have a major
role in the treatment of asthma. However theory and
practice are not identical; many asthmatics appear not to
have any benefit from LT modifiers, which now are
prescribed mainly for mild asthma or asthma with
profound exercise-induced symptoms.
ANTI-INFLAMASI
Corticosteroids
5. Corticosteroid
• Asthma controller drugs:
1. Efektif dalam memperbaiki kontrol asma:
2. Keparahan gejala
3. Tes airway caliber and bronchial reactivity
3. Frekwensi kekambuhan
4. Kualitas hidup

• Clinical use:
1. Urgent: oral 30-60 mg prednisone/day OR IV I mg/kg
methyprednisolon every 6 hours
2. Aeorosol treatment (beclamethasone, budesonide,
ciclesonide, flunisolide, flucitasone, mometasone,
triamcinolone)
3. Prednisolone p.o; prolonged treatment w/ inhaled
bronchodilators & steroid in severely patients
Corticosteroids
Corticosteroid

• Unwanted effects:
1. Oropharyngeal candidiasis, hoarseness
reduced by spacing device
2. Adrenal supression
less likely with flucitasone, mometasone and ciclesonide
(poorly absorbed from GI tract and complete presystemic
metabolism)

Clinical trial showed:

Inhaled corticosteroid are not curative, but
CONTROLLER
 6. Mast cell stabilizers

Antigen trigger on mast cell

• The IgE-Fc receptor (membrane of mast cells) binding
triggers:

1. the degranulation process (releasing histamine, proteases,

TNF and interleukins)

2. the increased synthesis of interleukins

3. the release of leukotrienes as well as prostaglandins.

6. Mast cell stabilizers

• Antihistamines block the effects of histamine already

released into the system. Another means of blocking the
effects of histamine is by preventing it's release from
inflammatory cells.
• Nedocromil and cromoglycate are substances that are
thought to work by preventing degranulation of mast
cells. These agents are only available by inhalation and are
indicated for the prophylaxis of mild asthma. Unfortunately,
poor clinical results with these agents limit their utility.
• Not interfere the growth, good for children.
Anti-IgE Monoclonal Antibodies
7. Anti IgE monoclonal antibody

• Omalizumab (Xolair®)  monoclonal anti-IgE

antibody
• Effective in allergic asthma
• Considerable theoretical interest
• Very expensive
• Place in therapeutics  UNCLEAR!!!
Management of acute exacerbation
 Asthma exacerbation is a medical emergency. Don’t delay
evaluation and treatment.
1) Early/Immediate Phase : characterized by
bronchoconstriction.
2) Late Phase (6-8 hours) : airway inflammation and hyper-
responsiveness
 Management should emphasize
◦ 1) Initial stabilization
◦ 2) progressive monitoring and treatment
◦ 3)eventually discharge planning
 O2 to keep sats >92%

 Bronchodilators :
Beta Agonist (Albuterol) : via nebulizer Q 15-20 minutes times three then
Q2 twice if needed and then Q4-6 hrs ATC/PRN
If needed more frequently PICU admisision
Ipratropium ( Atrovent ) via nebulizer may be given with the first three
albuterol treatments then Q4-8 ATC/PRN

Levalbuterol ( Xopenex ) : selective beta 2 agonist. Not routinely used.

Good alternative for continuous therapy if side effects from albuterol
experienced
 Start Corticosteroids if;
◦ No response after one nebulised t/t
◦ Patient is steroid dependent
◦ Has had a recent ER visit for asthma
◦ Previous admission to ICU

 Steroid PO (Prednisolone 2mg/k/d) or Steroid IV

(Solumedrol 2mg/k IV/IM bolus then 1-2mg/k/d
divided Q6) x 3-10 days
 If greater than 5 day course, will need to wean
COPD

41
COPD Epidemiology
U.S. Adults

6.4%
15,700,000

Wheaton. MMWR. 2015. 42

 COPD Epidemiology
15,694
Medicare hospitalizations for COPD as primary diagnosis (PA)

$1.05 billion
Annual cost for Medicare COPD readmissions (US)

Ford. Chest. 2013. 43

AHRQ Statistical Brief #196
 COPD GOLD Guidelines
2011
1998 GOLD Major Revision
GOLD (ABCD multimodal grading)
formed

2017
GOLD Major Revision
2001 (refined ABCD grading)
1st GOLD report
(spirometric grading)

GOLD = Global Initiative for Chronic Obstructive Lung Disease 44

 COPD Goals of Therapy
Reduce Symptoms
 Relieve symptoms
 Improve exercise tolerance
 Improve health status

Reduce Risk
 Prevent disease progression
 Prevent and treat exacerbations
 Reduce mortality

45
GOLD 2017
 COPD Definition

“….a common, preventable and treatable disease

that is characterized by persistent respiratory
symptoms and airflow limitation that is due to
airway and/or alveolar abnormalities usually caused
by significant exposure to noxious particles or gases”

46
www.ginasthma.org
Assessment of COPD: GOLD 2001

47
Assessment of COPD: GOLD 2011

48
Assessment of COPD: GOLD 2017

49
 Treatment of COPD: GOLD 2017
GOLD Preferred Treatment For Continued Symptoms
Grade or Exacerbations
PRN SABA or LABA or
A SAMA or LAMA Use alternative class

B LABA or LAMA LAMA + LABA

C LAMA LAMA + LABA*

[or] LABA + ICS
LAMA + LABA + ICS
D LAMA + LABA [or] LABA + ICS

*preferred

GOLD 2017 50