Transcript  The mechanisms underlying bronchial hyperreactivity are somehow related to inflammation of airway mucosa.  The agents that increase bronchial reactivity, such as ozone exposure,

 The
mechanisms underlying bronchial
hyperreactivity are somehow related to
inflammation of airway mucosa.
 The agents that increase bronchial reactivity,
such as ozone exposure, allergen inhalation,
and infection with respiratory viruses, also
cause airway inflammation.
 Its
pathologic characters are contraction of
airway smooth muscle, mucosal thickening
from edema and cellular infiltration, and
inspissation in the airway lumen of
abnormally thick, viscid plugs of mucus.
 The products of cells in the airways, such as
eosinophil, lymphocytes, macrophages,
mast cells, sensory nerves, and epithelial
cells, have been shown to alter airway
smooth muscle function.
 Asthma
therapies are divided into two
categories: short-term relievers and longterm controllers.
 short-term relievers: β-adrenoceptor
stimulants, theophylline, antimuscarinic
agents.
 long-term controllers: anti-inflammatory
agents, inhibitor of mast cell degranulation.
Ⅰ. Adrenoceptor agonists
//mechanism
1. Stimulation of β2 receptor in bronchial
smooth muscle cell mb →cAMP →Ca2+↓
→SM relaxation .
2. Also activateβreceptor on mast cell mb. ,
thus used in prophylaxis of allergic
asthma .
3. Stimulation of αreceptor in bronchial
vessels contraction of vascular smooth
muscle edema .
4. The density of β receptor will decrease after
prolonged treatment.
• Adrenaline/epinephrine (肾上腺素):
//agonist of α and β receptor
//adverse effect of cardiovascular system
usually occurs thereby less usable
//s.c. injection
• Ephedrine （麻黄碱）
//orally administered
//similar action to Adr.
//less usable for central excitation
• Isoproterenol （异丙肾上腺素）
//agonist of β1&β2 receptor
//no action on α receptor
//used for acute attack of bronchoasthma
by inspiration route
//orally ineffective
//involved in adverse effect of β1 receptor
excitation.

Selectively β2 receptor agonist
Salbutamol (沙丁胺醇，舒喘灵)
Terbutaline （特布他林，博利康尼）
Clenbuterol （克仑特罗）
The β2-Selective adrenoceptor agonist drugs
are the most widely used sympathomimetics for
the treatment of asthma at the present time.
//Mechanism : Air way smooth muscle has
little sympathetic nervous supply
but contain lots of ß2-adrenoceptors
that respond to circulating adrenaline.
The stimulation of ß2-receptors leads
to a rise in intracellular cAMP levels
and the subsequent bronchial smooth
muscle relaxation
 They
are effective after inhaled or oral
administration and have a long duration of
action and significant β2 selectivity.
 Given
by inhalation , these agents cause
bronchodilation equivalent to that produced
by isoproterenol.
ß2-adrenoceptor agonist may also help
to prevent the activation of mast cell
in a minor degree .
Modern selective ß2-receptor agonists
are potent bronchodilators and have
very few ß1 -stimulating properties.
//Route of administration :
• usually delivered via a metered dose
inhaler with immediate effect
• orally used in children
• iv used for acute-care.
• S.C. (terbutaline)
//Adverse effect :
cardiac arrhythmias
tolerance to ß agonist
hypoxemia
Ⅱ.Theophylline :
derivatives of methylxanthine
• The importance of theophylline as a
therapeutic agent in the treatment of asthma
has waned .
• But theophylline's very low cost is
important advantage for economically
disadvantaged patients .
They are divided into two types :
1. Salt complex :
increased water solubility without
augmentation of pharmacological
action , such as :
aminophylline（氨茶碱）
choline theophylline（胆茶碱）
2. Agent of delayed release :
small fluctuation of blood concentration
after oral administration
thus used for nocturnal attact of asthma
protheo (优喘平）
//Mechanism :
• Anti-inflammation
• inhibit activity of PDE cAMP
Ca 2+
bronchial relaxation
• increase the release of NA, Adr
• inhibition the cell surface receptor of adenosine
• interfere with the transportation of Ca 2+
//pharmacodynamics
The bronchodilation is the major therapeutic action
in asthma.
 Potent effects in improving contractility and in
reversing fatigue of diaphragm in patients with
chronic obstructive lung diseases.
 Direct positive chronotropic and inotropic effects
on the heart.
 In large doses, these agents also relax vascular
smooth muscle.

//Administration route : orally effective
but different from adrenergic agent for
metabolism by P450 enzyme system
//Indications :
• Bronchial asthma (+βreceptor agonist)
•Chronic obstructive lung diseases
•Cardiogenic asthma
•Sleep apenea syndrom
//Adverse effect :
it has a narrow therapeutic window and its
therapeutic and toxic effects are related to its
plasma concentration.
<20mg/L : nausea, vomiting, headache,
anxiety, abdominal discomfort
20-40mg/L: arrhythmia
Ⅲ. Muscarinic antagonist :
Ipratropium bromide (异丙托溴铵)
Ipratropine(异丙托品)
//Mehanism :
act by blocking muscarinic receptors
esp. the M3 subtype , which responds
to this parasympathetic bronchial
constrictor tone .
//Route of administration :
metered dose inhaler
//Indication :
used as adjuncts to ß2-adrenoceptor
agonist in treatment of asthma and more
effective in vagus-induced asthma .
//Therapeutic note :
synergism when administered with
ß2-adrenoceptor agonist.
Ⅳ. Anti-inflammatory drug
Glucocorticoids include :
beclomethasone (倍氯米松)
budesonide（布地奈德）
//Mechanism :
depress the inflammatory response in
bronchial mucosa thus diminish bronchial
hyperresponsiveness.
 Anti-inflammatory
effect
 Immunosuppressive
 Increase
 Inhibit
effect
the response to catecholamines
the activity of PDE
Adenoceptor-upregulation
//Route of administration :
• orally
i.v
used for : severe asthma
status asthmaticus
• metered dose inhaler
//Indications :
Because of the efficacy and safety of inhaled
corticosteroids, they are now routinely prescribed
for patients who require more than occasional
inhalations of β agonist for relief of symptom.
// Adverse effect:
 Oropharyngeal candidiasis
it can be reduced by having patients
gargle water and spit after each inhaled
treatment.
 Hoarseness
Ⅴ. Anti-allergic agents
i.e. mast-cell-stabilizers
cromolyn sodium (色甘酸钠)
//Mechanism :
They appear to stabilize antigen-sensitized
mast cell by reducing calcium influx and
subsequent release of inflammatory
mediators .
 On
mast cells, for inhibition of the early
response to antigen challenge
 On
eosinophils, for inhibition of the
inflammatory response to inhalation of
allergens
// Route of administration :
metered dose inhaler of cromoly sodium
// Indications :
pretreatment with cromolyn blocks the
bronchoconstriction caused by antigen
inhalation ,by exercise, by aspirin, and by
a variety of cause of occupational asthma.
// Adverse effect
 Throat
irritation
 Cough
 Mouth
dryness
 Chest tightness and so forth