Learning objective

• Describe the effect of ANS and other agents

to bronchus smooth muscle, and able to
describe the mechanism of action and the
side effects of drugs used as bronchodilator
 Role of ANS
on bronchiolar smooth muscle

• Sympathetic division
- bronchodilatation (ß2 receptor)
• Parasympathetic division
- vagus nerve:
. Bronchoconstriction (M receptor)
. Secretion of mucus

In asthma bronchiale there is hyperactivity

of the parasympathetic division and may
contibute to the hyperreactivity.
 Effect of other agents to bronchial
smooth muscle

β2 α

L c AMP M

H1
cAMP :
Bronchodilatation
Mediator release
• The high level of c GMP:
.release of mast cell mediators
.bronchoconstriction
.increased secretion of mucus
.mucosal edema
.leucocyte infiltration
 Histamine

PG F2 α

ECF. A
Mast
cell
SRS.A

Leukotriene

Cytokine
Sign and symptom of bronchial asthma

- Bronchoconstriction

- Mucosal edema

- Inflammation

- Mucus secretion
 ATP
Bronchodilatation AC B2 agonist
+ +

cAMP
+
PDE Theophylline
_- -

5’AMP
Bronchial tone
Ach
Adenosine
+ +

- - Theophylline
Muscarinic
Antagonist
Bronchoconstriction
 Exposure to antigen

Avoidance
-
Ag – Ab reaction ( Ag – IgE
on mast cell)
- Cromolyn
- Steroid
- - zileuton

( Mediators )
Histamine, ECF.A,
SRS.A, leukotriene,
-β agonist Cytokine -Steroid
-Theophylline -Cromolyn
-Muscarinic antagonis -Zafirlukast
- -
-Zafirlukast

Early response
Late Response
Bronchoconstriction
inflammation

Acute symptom Bronchial hyperreactivity

 Drug used in the treatment of
asthma
• Reliever ( bronchodilator)

• Preventer ( controler)
. Corticosteroid
. Leucotriene antagonist
. DSCG (cromolyn)
Bronchodilator

Short –acting β2 agonist

Long acting B2 agonist (LABA)
Muscarinic antagonist ( anticholinergic)
Methylxantine
β agonist
Non selective
Epinephrine
Ephedrine
Isoprotrenol

Selective β2
Terbutalin
Salbutamol (albuterol)
Salmeterol
Clenbuterol
Short acting B2 agonist

• Salbutamol, Terbutalin
• Increase cAMP ( relaxation smooth muscle)
• For acute symptom
• Side effect:
. Tachycardia
. Tremor
. Nervous
. Tolerance
Long acting B2 agonist (LABA)

• Salmeterol, Formeterol
• Effect up to 12 jam
• Better for preventer
• Combination inhaler;
.Salmeterol + fluticasone
.Formeterol + budesonide
Muscarinic antagonist

Non selective ( atropin )

( M1, M2, M3 )

Selective ( ipratropium )
( M3 )
Ipratropium, Oxitropium

• Antagonizing M receptor on bronchial

smooth muscle (reduction of bronchocon
striction)
• Antagonizing M receptor on Goblet cell
(reduction of mucous secretion)
• Poorly absorbed orally
• The main used is in COPD
• Side effect: Dry mouth, Urinary retention,
constipation, blurred of vision
Methylxanthine

Caffeine

Theobromine

Theophylline ( aminophylline )
Theophylline

• Preventing the breakdown of PDE

• For severe acute attack that do not respond
to B2 agonist
• Clearance increased by enzyme inducer
(nicotine, rifampicin) and childhood
• Clearance decreased by enzyme inhibitor
(cimetidine, clarithromycin) and old age
• Side effect: diuresis
Preventer

• Corticosteroid

• Leucotriene receptor antagonist

• Cromolyn
Antiinflammatory

Corticosteroid
Prednisone
Prednisolone
Methylprednisolone

Inhibit release of mediator

Cromolyn
Ketotifen
Nedocromil

Leukotriene antagonist (Leucotriene modi

fiers)
Corticosteroid
Activated GREs Substance ?

Prevent inflammation & alergy

Reduced activity of Phospholipase A2

Phospholipid
Phospholipase A2

Arachidonic acid
Lipoxygenase Cyclooxygenase

Leukotriene PG

R. leukotriene R. PG
Inhaled Corticosteroid

• Beclometasone
• Budesonide
• Fluticasone
• Mometasone
• Side effect : hoarsenes, oral candidiasis
Oral Corticosteroid

• Prednisolone
• Side effect:
. Adrenal suppression
. Growth retardation
. Diabetes mellitus
. Increase susceptibility to infection
. Weight gain
Leucotriene receptor antagonist
(leucotriene modifier)
• Antiinflammatory effect
• Bronchodilator effect
• Zileuton inhibit Lypoxygenase
• Zapirlukast block the receptor
Disodium cromoglycate (DSCG)

• Stabilized Mast Cell

• Has no bronchodilator effect
• Can not be used in acute attack
• Route of administration: Inhalation