dr. ELLY NURUS SAKINAH, M.

Si

PHARMACOLOGY OF RESPIRATORY
DRUG
OBAT ASTHMA
 Obstruksi Jalan Nafas
Kontraksi otot polos
bronkus
produksi mukus
berlebih
Bronchial tube
Edema mukosa sal
nafas
Bronchial
smooth Inflamasi jalan nafas
muscle
Hiperreaktifitas jalan
Bronchiole Tight muscle nafas

Mucus lines the Inflamed Alveoli w/trapped air Extra mucus

bronchial tubes airway
Inflamed swollen
airway

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GAMBARAN KLINIS ASTHMA
Breathlessness

Hyper-responsive
lower airway
Cough

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Hyperinflated
lungs
Wheezing

Chest
tightness

Treatment
pertama : Inflamasinya
Kedua : bronkokostriksinya
 Pathophysiology of
asthma

Exposure to allergen
Hindari paparan alergen

Agen stabilisator sel mast Release mediator radang

Glucocorticoids: inhaled, oral, Inflamasi

intravenous

-adrenoceptor agonists; Konstriksi otot polos Increased capillary

methylxanthines bronkus permeability

Chemotactic factor release with cellular

recruitment

Chronicity with epithelial and Widespread effect

neural damage

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 Terapi Asma

Relievers
Short-acting bronchodilators
2-adrenergic agents
Anti-cholinergic (Parasympatholytic) agents

Controllers
Corticosteroids
Long-Acting bronchodilators
2-adrenergic agents
Methylxanthines
Cromolyn sodium
Leukotriene inhibitors
Anti-IgE monoclonal antibodies
 ATP
Bronchodilation AC + AR
agonist
+ cAMP
Bronchial tone _ Theophylline
PDE
AMP

Acethycholine Adenosine
+ +
Muscarinic _
_ Theophylline
antagonists
Bronchoconstriction

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 Drugs Used in Asthma

Bronchodilators
Beta-adrenergic agonists merelaksasikan otot
polos bronkus dan menurunkan permeabilitas
vaskular
Muscarinic antagonists / Antikolinergik
menghambat efek Asetilkolin pada otot polos
bronkus shg mjd bronkodilatasi
Theophylline/ metilxantine menurunkan
frekuensi kekambuhan bronkospasme
 Drugs Used in Asthma (cont.)

Non-bronchodilators (for chronic

use)
Corticosteroids kontrol produksi mukus
dan menurunkan edema jalan nafas
Cromolyn kontrol release mediator
radang
Leucotriene modulators antagonis
mediator reseptor dan menurunkan
sintesisnya
 Short Acting beta agonis
Catecholamines
Epinephrine
Isoproterenol
Isoetharine
Resorcinol agents
Metaproterenol
Saligenin agents
Albuterol
Pirbuterol
Bitolterol
 Beta-2 Adrenergic Agonists Short acting
agents
Rute Pemberian
Inhalasi/ parenteral cegah efek sistemik
Bronkodilator paling efektif

Mekanisme kerja
Meningkatkan cAMP pada sel otot polos
bronkus menurunkan tonus otot
bronkodilatasi
Merelaksasikan otot polos jln nafas
mempertahankan fungsi mukosiliar
Menurunkan permeabilitas vaskular
 Side Effects Seen with Beta Agonist
Tremor
Papitations and tachycardia
Headache
Insomnia
Rise in blood pressure
Nervousness
Dizziness
Nausea
 Anticholinergic (Parasympatholytic)
Bronchodilators
Tertiary Ammonium Compounds
Atropine sulfate
Scopalamine
Quaternary Ammonium Compounds
Ipratropium
Tiotropium
 Anticholinergic (Parasympatholytic)
Bronchodilators
Rute pemberian
Inhalasi (MDI, solution for nebulization, nasal spray)
Mekanisme kerja
Block reseptor muskarinik M1 dan M3 Hambat efek
release asetilkolin (hambat bronkokonstriksi)
menurunkan tonus otot polos jalan nafas.
Kurang potent jikan dibanding inhaled beta-2 agonists,
onset of action lambat (30-60 min after inhalation persists
for up to 8 h).
 ATP
Bronchodilation AC + AR
agonist
+ cAMP
Bronchial tone _
PDE Theophylline
AMP

Acethycholine Adenosine
+ +
Muscarinic _
_ Theophylline
antagonists

Bronchoconstriction

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 Anticholinergic (Parasympatholytic)
Bronchodilators
Role in therapy
Menambah efek short-acting beta-2 agonist pada kasus
eksaserbasi asma
Combivent
Tx COPD
Digunakan pada pasien yang tidak toleran dg efek samping dari
beta agonis seperti tachycardia, arrhythmias, and tremor.
Tx vasomotor rhinitis : Ipratoprium nasal spray Menurunkan
sekresi kelenjar (decongestan)
Side effects
Dryness of the mouth and bitter taste, blurred vision, urinary
retention
CONTROLLERS
 Controllers
Corticosteroids
Long-Acting bronchodilators
2-adrenergic agents
Methylxanthines
Cromolyn sodium/Nedrocromil
Leukotriene inhibitors
Anti-IgE monoclonal antibodies
 INHALED CORTICOSTEROIDS

Menurunkan inflamasi dan edema jalan nafas

Mek kerja : menghambat enzim fosfolipase A2
hambat pembentukan asam arakidonat
hambat pembentukan leukotriene
Digunakan untuk asma kronik
Bukan bronkodilator
Tidak digunakan pada serangan akut
Contoh : fluticasone
 Phospholipid
(from cell membrane)

Corticosteroids -

Phospholipase A2

Arachidonic acid
Cyclooxygenase
5-Lipoxyenase

Prostacyclin (PGI2)

Leukotrienes PGE2
PGF2 PGH2
PHARMACOLOGY of METHYLXANTHINES
Theophylline
Rangsang pusat respirasi meningkatkan
sensitivitas pusat nafas terhadap pCO2
Merelaksasikan otot polos bronkus.
Tidak efektif aerosol, lebih efektif oral
Kurang efektif sebagai bronkodilator
Onset of action lambat dibanding inhaled 2-
adren. agonists
Mekanisme kerja: hambat reseptor adenosin
serta hambat fosfodiesterase bronkodilatasi
Used in chronic asthma
 ATP
Bronchodilation AC + AR
agonist
+ cAMP
Bronchial tone _ Theophylline
PDE
AMP

Acethycholine Adenosine
+ +
Muscarinic _
_ Theophylline
antagonists
Bronchoconstriction

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PHARMACOLOGY of METHYLXANTHINES
Theophylline, cont.

narrow safety index (10-20 ug/ml),

it is used as an second line or additional therapy
Toxicity is dependent on plasma concentration
Mild (30 mg/L): nausea, vomiting, headache,
insomnia, and nervousness
Potentially serious (40 mg/L): sinus
tachycardia
Severe (45 mg/L): cardiac arrhythmias,
seizures
 Asma selama hamil dan menyusui
Untuk ibu hamil sebenarnya seua obat asam
masuk kategori C
Agonis Beta 2 selektif yang inhalasi cegah
efek samping takikardi pada janin (albuterol)
Glukokortikoid inhalasi juga aman untuk
kehamilan
Teofilin merupakan pilihan terapi ke tiga
Upper Respiratory Problems
 Pharmacologic Agents
Decongestants
Corticosteroids
Antihistamines
Antitussives
Mucolytics/Expectorants

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 Decongestants
Mek. Kerja : stimulasi -adrenergic receptors
pada otot polos pembuluh darah hidung
vasokonstriksi penurunaneksudasi edema
mukosa hidung
Respon dalam bentuk topikal lebih cepat
Not recommended beyond 3-5 days.
Rebound effect possible

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 Decongestants (cont.)
Adverse Effects:
CNS, Respiratory, Cardiovascular, GI
Containdications and Precautions
Hati-hati pada pasien dg hipertensi, pembesaran
prostat dan penggunaan antidepressants

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 Decongestants (cont).
Ephedrine
Epinephrine (adrenaline)
Naphazoline
Oxymetalozone (Afrin, Neo-Synephrine)
Phenylephrine (Neo-Synephrine)
Pseudoephedrine (Sudafed)
Tetrahydrozolone
Xylometazoline

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 Antihistamines
Reduce the effects of histamine release by one of the
following mechanisms:
act at different receptor sites
reduce the degranulation of mast cells and inhibit
histamine release
antagonize the effects of histamine at the receptor
site (H1)

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 First generation antihistamines
Chlorpheniramine (Chlor-Trimeton)
Diphenhydramine (Benedryl)
More sedating
Anticholinergic effects:
Dry mouth
Constipation
Urinary hesitancy

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 Second and third generation
antihistamines
Most do not cross blood-brain barrier and
have minimal CNS side-effects.
Desloratadine (Clarinex)
Loratadine (Claritin, Claritin-D)
Fexofenadine (Allegra)
Cetirizine (Zyrtec) - has some sedative effects
Azetastine (Astelin) - only intranasal preparation

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Treatment of Cough

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 The cough reflex arc. Coughing
may be triggered by mechanical or
chemical stimuli of the upper
respiratory tract or by central
stimuli.

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Purpose: expel unwanted material from
the airways.

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 Antitussives
Mechanism of action is either central
(suppressing cough center in the medulla
oblongata) or peripheral (lessen irritation of
the respiratory tract).
Therapeutic objective is to decrease the
intensity and frequency of the cough.
Narcotic (opioid) and non-narcotic (non-
opioid) agents are used.

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 Opioid Antitussives
Codeine: most effective antitussive available
Can suppress respirations
Potential for abuse
Hydrocodone:
More potent than codeine
Potential for abuse

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 Non-Opioid Antitussives
Dextromethorphan
Derivative of codeine, acts in CNS
Diphenhydramine
Has sedation and anticholinergic properties
Benzonatate (Tessalon)
Decreases sensitivity of respiratory tract stretch
receptors
May have CNS effect

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Drugs that reduce the sensitivity of the
cough center: opioids
codeine
dextromethorphan
noscapine
levopropoxyphene
benzonatate
pholcodine

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 Mucolytics/Expectorants
Break up respiratory mucoprotein into smaller
strands.
Facilitate coughing and the removal of mucus from
the respiratory tract.
Acetylcysteine (Mucomyst) is used in cystic
fibrosis, atelectasis, acetaminophen overdose.
Guaifenesin (Robitussin - Mucinex) decreases
cough frequency and reduces sputum thickness.

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