Bronchodilators and other drugs used in Asthma
Category/Class
Alpha 1-2, Beta 1-2
agonists 
Bronchdilators
Prototype
Epinephrine -
Mechanism of Action
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Selective beta 2
agonists
Short Acting – Albuterol,
Terbutaline

Toxicities/Side Effects
Stimulation of B1 and B2
sympathetic receptors.
Beta 2 stimulation of
adenylate cyclase gives
cAMP which relaxes the
vascular smooth muscle
and may inhibit release of
LTR’s from mast cells.
SO overall, inhibit release
of bronchoconstricting
substances from mast cells
and increase mucociliary
transport.

As above but specific for
B2 receptors so less side
effects.
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Long Acting – Salmeterol
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As above

1
Treatment
Other / Pharmacodynamics/kinetics
Most effective and less
side effects when inhaled
into bronchial tree.
Less effective with
excessive repeated use
(Beta down regulation)
Skeletal muscle tremor,
tachycardia and
arrhythmias, angina
symptoms, nausea,
vomiting, HA due to
stimulation of B1 and B2
receptors.

First to be used in
acute Asthma but
found more
specific B2
agonists with less
sideffects.

Skeletal muscle tremor,
tachycardia, nausea,
vomiting, HA due to loss
of B specificity at high
doses.
Hypokalemia at high
doses from due to an
increase in Na/K atpase
ti accelerate entry of K
into cell.
As above

Acute
bronchospasm
and prevention of
exercise induced
asthma.

Used in conjuction
with inhaled
corticosteroid
effective for long term
control of symptoms
(especially nocturnal
and exercise) but not
acute exacerbations.
Maximal
bronchodilation of
inhaled at 30 min
lasting 3-4hr. SubQ
tablet and syrup ok but
not as good.
As above
Asthma = inflammatory dissorder of the airway & bronchial hyperresponsiveness (autonomic reflex where airway afferent receptors sensitized at a lower threshold to give
efferent cholinergic impulses). Inflammation leads to hyperesponsiveness and constriction of smooth muscle  increased mucous volume and viscosity  airway edema 
narrowing airway lumen  increased airway resistance. Eosinophils and mast cells release mediators (PAF, PG’s, LTR’s) which propogate the response. Management: 1objective measures of lung function 2-Eliminate enviromental factors 3-comprehensive long term therapy. Note: COPD refers to physical obstruction of airways as seen in
smokers and varies from chronic bronchitis to emphysema and can be treated with some of the above drugs.
Bronchodilators and other drugs used in Asthma
Prototype
Category/Class
Methylxanthines
Theophylline

Mechanism of Action

Other methyxanthines
include coffee, tea and
cola and affect CNS,
Heart, Vessels, skeletal
and smooth muscle.

Increase intracellular
calcium in skeletal and
cardiac muscle to increase
contractility. In Bronchial
muscle they inhibit
phosphodiesterase activity
to increase
CAMPvasodilation.
Some like theophylline
antagonize adenosine
receptors in CNS and
periphery (so cAMP not
broken down to AMP) –
thus inhibits contraction.
Toxicities/Side Effects
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Leukotriene Modifiers
Zarflukast

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Modulates (lowers) LRT’s
from mast cells and
basophils to lessen the
contraction of airways,
decrease vascular
permeability, decrease
mucus secretions, and stop
attraction and activation of
inflammatory cells.
Zafirlukast – LRT
antagonist
Zileuton – inhibits 5lipoxygenase


Oral has more N, V and
GI irritation less if taken
with food.
Duration altered by
drugs and diseases that
alter hapatic metabolism.
CNS stimulation 
corticol arousal,
nervousness,
restlessness, insomnia,
tremors, hyperesthesia.
CV stimulation 
increase HR, dilate to
decrease resistance but
constrict cerebral vessels
GI – stimulate gastric
acid and digestive
enzyme secretion.
Skeletal Muscle 
increase Ca to contract
MISC – high dose =
insomnia, nervousness,
diarrhea, tachycardia,
arrhythmias,
hypokalemia,
hypergylcemia, seizure.
Well tolerated orally
some GI distrubancesm
mild HA
Will increase warfarin
conc if taken together
2
Treatment
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effective
prophylactically
and to a lesser
extent during an
acute attack.
Chronic Asthma
to decrease
frequency and
severity of
symptoms and
decrease oral
steroid
requirements
Not used much in
acute unless
started
immediately to
maintain previus
levels – by IV
takes 15-20 min
to theraputic
levels.


mild to moderate
asthma
If taken with food
decreases
bioavailability
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Other / Pharmacodynamics/kinetics
FIGURE 1 – pg 6!!!
Absorbed oral, rectal,
parenteral.
Metabolized in liver
and excreted in urine.
Rapidly absorbed in
HY tract
Peak blood levels 3 hr
Liver metabolize
excrete in feces ½ life
10 hrs
Bronchodilators and other drugs used in Asthma
Category/Class
Glucocorticoid
Prototype
Hydrocortisone
Methylprednisolone
Mechanism of Action
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Cromolyn
Cromolyn sodium


Muscarinic antagonist
Ipratropium (atropine,
Glycopyrrolate)

Toxicities/Side Effects
Most effective at treating
inflammatory response
Reduce the respiratory
inflammation and
hyperresponsiveness of
asthma by: inhibition of
mediator synthesis,
stabalization of cell
membranes, redistribution
and inhibition of
leukocytes.
Restore beta adrenergic
receptor response
facilitatin bronchodilation.
Inhibits mast cell influx of
Ca to stop release of
histamine, LTR’s, others..
May also inhibit
phosphodiesterase or alter
neuronal transmission

Similar to atropine – weak
bronchodilator limited to
muscarinic receptors in the
lung due to low
ammonium lipid solubility
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Daily use can cause
glucose intolerance,
weight gain, HTN, bone
demineralization,
cataracts,
immunosuppression, and
decrease growth in kids.
Will suppress adreno-pit
axis (so taper off)
Oral thrush in inhaled
steriods but less of above
side effects seen.
Inhaled used a lot with
Beta agonists.
Localized to site of
application: throat
irritation, cough, dry
mounth, chest tightness,
wheezing
Very usefull in treating
allergic asthma
especially in children
and young adults.
Like atropine: dry
mouth, palpitations,
blurred vision,
constipation. At high
doses: hallucinations,
tachycardia, urinary
retention, glaucoma
3
Treatment
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Useful in severe,
acute asthma (or
chronic
unresponsive
asthma
Use 8-10 days
after acute attack
to prevent relapse.
Taper off.
Only effective
prophylactically
Not used for acute
response.
Prevent
bronchspasm due
to exercise or cold
(not as well as
beta agonists)
COPD
Less effective to
treat asthma
May have
additive effects if
combined with
beta agonists
(give in nebs)
Other / Pharmacodynamics/kinetics
* Parenteral oral or
inhaled. Oral and injected
most effective for acute
exacerbation (unresponsive
to bronchdilators takes 4-6
hrs for relief)
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Does not directly relax
bronchial smooth
muscle
Inhalation only less
than 10% absorbed,
t1/2 is 80 min, not
metabolized, excreted
in urine and bile
No antiinflamatory
activity
Does not decrease
bronchial
hyperesponsiveness.
Max effect 1-2 hrs
lasts 4-6 hrs