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Many cells and mediators are involved in

asthma and lead to several effects on the


airways.
Prevent mast cell degranulation
Anti-IgE antibody
Block the action of the products released
Cromolyn, Nedocromil
Inhibit acetylcholine released from vagus nerve
Muscarinic antagonists
Relax smooth muscle
Sympathomimetics,
Methylxanthines

Asthma is characterized by:


Increased responsiveness of the bronchi
Contraction of airway smooth muscle
The most easily reversed
pathology
Mucosal thickening
Viscid plugs of mucus

Sympathomimetic Agents
Along with corticosteroids, are the most widely
used drugs for asthma.
They relax smooth muscle and inhibit release of
bronchoconstricting substances from mast cells.
They also inhibit microvascular leakage, increase
ciliary activity and increase cAMP.
They cause tachycardia and tremor as side
effects.
Adrenoceptor agonists are best delivered by
inhalation for greatest effect and least systemic
toxicity.
Even in best conditions, 80-90% of the aerosol is
deposited in the mouth or pharynx.
Effectiveness can be increased by holding the
breath in inspiration.
Side effects include tremor and nervousness.
Short acting 2 selective drugs:
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Albuterol (salbutamol)
Terbutaline
Metaproterenol
Pirbuterol
Bronchodilation is maximal within 15-30 min. and
persists for 3-4 hr.
All can be diluted in saline for administration
from a nebulizer.
Long-acting 2 selective agonists:
Salmeterol
Formoterol
Their duration of action is 12 hr.
They are usually used with other drugs (eg:
inhaled corticosteroids)

Methylxanthines
Methylxanthines:
Theophylline (tea)
Theobromine (cocoa)
Caffeine (coffee)
Theophylline is most selective in its smooth
muscle effects.
Caffeine has the most marked CNS effects.
Theophylline is not an ideal drug, but has a low
cost.
Aminophylline is an injectable derivative of
theophylline.
They Inhibit phosphodiesterase (PDE) and
increase cAMP.
Adenosine causes airway contraction and
histamine release.
Theophylline derivatives also nay inhibit
adenosine receptors.
Theophylline also improves contractility and
reverses fatigue of the diaphragm in patients
with COPD.
So theophylline can diminish dyspnea even in
patients with irreversible airflow obstruction.
Rate of metabolism: Children > adults > neonates
and young infants
Cigarette smoking induces metabolizing enzymes.
Theophylline has a narrow therapeutic window.
Improvement in lung function is seen at 5-20
mg/L.
Vomiting, abdominal discomfort, headache, and
anxiety occur at 15 mg/L in some, and at >20
mg/L in all patients.
Higher levels (> 40 mg/L) causes seizures or
arrhythmias.
These may NOT be preceded by GI or neurologic
warning symptoms.
Methylxanthines stimulate secretion of both
gastric acid and digestive enzymes.

Even decaffeinated coffee has a potent stimulant


effect on GI secretion.
Methylxanthines decrease blood viscosity and
may improve blood flow.
For this reason pentoxifylline is used in the
treatment of intermittent claudication.
Caffeine causes mild arousal with increased
alertness and deferral of fatigue.
Very high doses cause convulsions and even
death.
Caffeine has positive chronotropic and inotropic
effects on the heart.
In very sensitive individuals, consumption of a
few cups of coffee may result in arrhythmias.

Caffeine Amount In Drinks


Amount (gram)

Caffeine (mg)

Coffee
Brewed, regular
Instant
Espresso

142227
142227
57

40180
30120
120

Tea
Brewed, leaf or bag
Instant
Iced

227
227
340

80
50
70

Soft Drinks
Pepsi, Diet Pepsi

340

38

9/24/2014

empperezmd2014

Antimuscarinic Agents
Involvement of parasympathetic system in
respiratory diseases varies among individuals.
Antimuscarinic agents are used:
Instead of inhaled -agonists in
asthmatics
In addition to inhaled -agonists in
asthmatics
In COPD patients
Ipratropium is a polar drug used for asthma.
Tiotropium is used for COPD.
Corticosteroids
Their most important action is inhibition of
airway mucosal inflammation.
Inhalational therapy minimizes their adverse
effects.
Inhalational drugs include:
Beclomethasone
Budesonide
Fluticasone
Triamcinolone
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They do not relax airway smooth muscle directly.


To prevent adrenal insufficiency they are used in
the morning.
If nocturnal asthma happens they have to be
given in the afternoon.
Oropharyngeal candidiasis may occur which can
be managed by gargling water and spit after each
dose.
Hoarseness happens by their effect on vocal
cords.
Chronic use of inhaled corticosteroids reduces
bronchial reactivity.
Corticosteroids are not curative, asthma returns
after stopping them even if they have been taken
for > 2 years.

Zafirlukast, montelukast
They are weaker than inhaled corticosteroids, but
reduce the frequency of exacerbations
One advantage is that they are taken orally;
children comply poorly with inhaled therapies.
Montelukast is approved for children as young as
6 years of age.
5-10% of asthmatics are exquisitely sensitive to
aspirin and other NSAIDs.
It is thought to result from inhibition of
cyclooxygenase.
LT antagonists are useful for preventing this
problem.

Cromolyn & nedocromil


They effectively inhibit both antigen and exercise
induced asthma.
Alter the function of delayed chloride channels in
the cell membrane, inhibiting cellular activation.
They inhibit cough and mast cell (but not
basophil) degranulation in the lung.
Are only of value when taken prophylactically.
Young patients with extrinsic asthma are most
likely to respond.
A 4 weeks trial determines whether a patient will
respond.
Cromolyn solution is also useful for allergic
rhinoconjunctivitis.
Because the drugs are so poorly absorbed,
adverse effects are minor and are.
Leukotriene Pathway Inhibitors
LTC4 & LTD4 exert many effects known to occur in
asthma
There are two treatment strategy:
Inhibition of lipoxygenase and
leukotriene synthesis
Zileuton
Antagonizing leukotriene D4 receptor

Anti-IgE Antibodies
Omalizumab inhibits the binding of IgE to mast
cells but does not activate IgE already bound.
It also inhibits IgE synthesis by B lymphocytes.
The murine antibody has been humanized and it
does not cause sensitization.
Omalizumab's effect is reduction of both the
severity of asthma and corticosteroid dosage.
Patients most likely to respond are those with the
greatest need:
Patients with a history of repeated
exacerbations
A high requirement for corticosteroid
treatment
Poor pulmonary function
Omalizumab treatment reduced exacerbations
requiring hospitalization by 88%.
These benefits justify the high cost of this
treatment in severe disease.
Treatment strategy
All asthmatics should be instructed for severe,
attacks:
To take up to four puffs of albuterol
every 20 minutes over 1 hour.
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If they do not note clear improvement


after the first four puffs, refer to
emergency department.
Children exposed to allergens (pets) may be
protected from asthma in later stages of life.
Mild asthma
Inhaled beta receptor agonist (Albuterol)
on an "as-needed" basis
In these cases inhaled corticosteroid is added:
Asthma attacks more than twice a week
Nocturnal symptoms more than twice a
month
FEV1 less than 80% predicted
Cromolyn or LT antagonist may be used
alternatively, but inhalational steroids are
superior.
If FEV1 is <50% predicted, oral corticosteroid is
added to control the symptoms and then
stopped.
Anti-IgE antibody, is reserved for Patients :
Unresposive to long-acting -agonist plus
high-dose inhaled corticosteroid
With demonstrated IgE-mediated
sensitivity

Acute Asthma
In mild attacks subcutaneous epinephrine or
inhalation of a receptor agonist are equally
effective.
Both of them are superior to IV aminophylline.
For severe attacks:
Oxygen
Frequent administration of aerosolized
albuterol
Systemic treatment with corticosteroids.
Patients should be closely watched.

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