ASTHMA

DRUGS USED IN ASTHMA

BRONCHODILATORS ( ANTIASTHMATICS )
A. Xanthines
- * Theophylline
- aminophylline
- dyphylline
B. Sympathomimetics
- * Epinephrine
- Ephedrine
- Isoproterenol
C. Beta2 Selective Drugs ( Beta adrenoreceptor stimulants
)
- albuterol
- terbutaline
- metaproterenol
- pirbuterol
- salmeterol
D. Anti Cholinergics ( Antimuscarinic Agents )
- Ipratropium
- Tiotropium
E. Inhaled Steroids
- * flunisolide
- beclomethasone
- budesonide
- fluticasone
- triamcinolone
F. Leukotrienne Receptor Antagonists
- * Zafirlukast
- Montelukast
- zileuton
G. Lung Surfactants
- Beractant
H. Mast Cell Stabilizers
- Cromolyn
- Nedocromil
ASTHMA
- Recurrent bouts of shortness of breath
- Chest tightness
- Wheezing often associated with coughing
- Physiologically by widespread, reversible
narrowing of the bronchial airways and a
marked increase in bronchial responsiveness
to inhaled stimuli
- Pathologically by lymphocytic, eosinophilic
inflammation of the bronchial mucosa
- In mild asthma, symptoms occur only
occasionally for instance
a. exposure to allergens or certain pollutants
b. on exercise
c. after viral upper respiratory infections
- More severe form of asthma are associated
with frequent attacks of wheezing, dyspnea
especially at night or with chronic airway
narrowing, causing chronic respiratory
impairment
- Effective treatment is for relief of acute
broncho constriction ( short term relievers )
and for reduction in symptoms and prevention
of attacks ( long term controllers )
 Causes of Airway Narrowing in acute Asthmatic
Attacks ( Asthma Exacerbation )
a. Contraction of airway smooth muscle
b. Inspissation of viscid mucus plugs in the
airway lumen
c. Thickening of the bronchial mucosa from
edema, cellular infiltration and hyperplasia of
secretory, vascular and smooth muscle cells
 SHORT TERM RELIEF
Short Term Relief most effectively achieved by
agents that relax airway smooth muscle
a. Beta adrenoceptor stimulants are the most
effective and most widely used
b. Theophylline
c. Antimuscarinic agents ( anticholinergic )
- for reversal of airway constriction
 LONG TERM CONTROL
Long term control is most effectively achieved
with an
a. Anti inflammatory agent such as an inhaled
corticosteroid
b. Leukotriene pathway antagonist
c. Inhibitor of mast cell degranulation such as
cromolyn or nedocromal
Efficacy of Treatment for Severe Asthma
- Monoclonal antibody
- Omalizumab which is specially targeted
against IgE the antibody responsible for
allergic sensitization
 Pathogenesis of Asthma
- A disease mediated by a reaginic immune
globulin ( IgE )
- Foreign materials that provoke IgE production
are described as allergens
- Most common allergens are
a. proteins from house dust mite, cockroach,
animal danders, molds and pollens
- Asthma and other allergic diseases cluster in
families
- Once produced, IgE antibodies bind to mast
cells in the airway mucosa
- On re exposure to a specific allergen, antigen
antibody interaction on the surface of the
mast cell triggers both the release of
mediators stored in the cells granules and the
synthesis and release of other mediators
Other Mediators are the following;
- Histamine
- Tryptase
- leukotrienes C4 and D4
- Prostaglandin D2
* Diffuse through the airway mucosa triggering the
muscle contraction and vascular leakage
responsible for acute broncho constriction of the
Early Asthmatic Response
Second More Sustained Phase of Broncho
Constriction ( 4 6 Hours ) called the Late
Asthmatic Response occurs
- this is associated with an influx of inflammatory
cells into the bronchial mucosa and with an
increase in bronchial reactivity that may last for
several weeks after a single inhalation of allergen
- the mediators responsible for this late response
are the cytokines produced by TH2 lymphocytes
especially the interleukins ( IL )
- These cytokines attract and activate
eosinophils, stimulate IgE production by B
lymphocytes and stimulate mucus production
by bronchial epithelial cells
* The benefits of the corticosteroid therapy are
attributed to their inhibition of the production
of pro inflammatory cytokines in the airway
 Most asthma attacks are not triggered by
inhalation of allergens, they are triggered by
viral respiratory infections
Bronchoconstriction seems to result from the
direct effect of the release mediators and also
from the activation of neural or humoral
pathway
 Asthmatic Bronchospasm Might Be Reversed
or Prevented By
a. Drugs that reduce the amount of IgE bound
to mast cells
- anti IgE antibody
b. Prevent mast cell degranulation
- cromolyn, nedocromil, sympathomimetic
agents, calcium channel blockers
c. Blocked the action of the products released
- antihistamines
- leukotriene receptor antagonist
d. Inhibit the effect of acetylcholine released
from vagal motor nerve
- muscarinic antagonists
e. Directly relax airway smooth muscle
- sympathomimetic agents and theophylline
Second Approach to the treatment of asthma is
-aimed at reducing the level of bronchial
responsiveness >> because this is linked to
airway inflammation >> is a feature of late
asthmatic responses
- By reducing exposure to the allergens that
provoke inflammation
- By prolonged therapy with anti inflammatory
agents especially INHALED CORTICOSTEROIDS
 DRUGS USED TO TREAT ASTHMA
BRONCHODILATORS / ANTIASTHMATICS
- are medications used to facilitate respiration
by dilating the airways
- helpful in symptomatic relief or prevention of
bronchial asthma and for bronchospasm
associated with COPD
 DRUGS USED TO TREAT ASTHMA

A.Sympathomimetic Agents
- adrenoceptor agonists
- relax airway smooth muscle
- inhibit release of broncho constricting
mediators from mast cells
- best delivered by inhalation
 DRUGS USED TO TREAT ASTHMA
Sympathomimetics ( Cont )
a. Epinephrine is an effective, rapid acting
bronchodilator when injected subcutaneously
or inhaled as a microaerosol from a
pressurized canister
b. Ephedrine
c. Isoproterenol
B. Beta2 Selective drugs
a. Albuterol most widely used
sympathomimetics for treatment of the
bronchoconstriction of asthma
b. Terbutaline
c. Metaproterenol
d. Pirbuterol
- Bronchodilation is maximal within 15 30
minutes and duration of action is 3-4 hours
Salmetrol and formoterol a new generation of
long acting Beta2 selective agonist
Adverse Effects;
- Hypertension
- tachycardia
C. METHYLXANTHINE DRUGS
- 3 important methylxanthines
a. theophylline preparation commonly used for
therapeutic purpose is aminophylline
b. theobromine
c. caffeine
Mechanism of Action
- Relaxation of smooth muscle
- Reduction in the immune and inflammatory
activity of specific cells
Adverse Effects:
- Therapeutic theophylline levels are from 10 to
20 mcg. / ml.
- Tachycardia, seizures, brain damage , coma
and death
Drug Drug Interactions
- Nicotine increases the metabolism of xanthines
D. Antimuscarinic agents ( anticholinergics )
- Patients who cannot tolerate the sympathetic effects of the
sympathomimetics
Therapeutic or Mechanism of Action:
- Normally vagal stimulation results in a stimulating effect on
smooth muscle causing contraction
- By blocking the vagal effect, relaxation of smooth muscle in
the bronchi occurs leading to bronchodilation
- Ipratropium is the only anticholinergic recommended for
bronchodilation
- Maintenance treatment of patients with COPD
Pharmacokinetics:
- Ipratropium onset of action in 15 minutes
when inhaled
Adverse Effects
- Dry mouth
- Palpitations
- Urinary retention
E. INHALED STEROIDS
- All of the inhaled steroids are used for the
prevention and treatment of asthma
- For treatment of chronic steroid dependent
bronchial asthma
- Adjunctive therapy for asthma patients who
do not respond to traditional bronchodilators
Inhaled Steroids ( cont )
- Action: are used to decrease the inflammatory
response in the airway.
- In an airway that is swollen and narrowed by
inflammation and swelling, this action will
increase air flow and facilitate respiration
- Decreased swelling associated with inflammation
and promotion of beta adrenergic receptor
activity which promote smooth muscle relaxation
and inhibit broncho constriction
- Are used for the prevention and treatment of
asthma
- These drugs are rapidly absorbed but take from 2
to 3 weeks to reach effective levels
Adverse Effects
- Pharyngeal and laryngeal fungal infections
- Sore throat
- Hoarseness
- Dry mouth
F. Leukotriene Receptor Antagonists
- Developed to act more specifically at the site
of the problem associated with asthma
- Zafirlukast was the first drug to be developed
- Montelukast and Zileuton are the other drugs
- Prophylaxis and chronic treatment of
bronchial asthma
Action:
- Leukotriene receptor antagonists selectively and
competitively block ( Zafirlukast, Montelukast ) or
antagonize ( zileuton ) receptors for the
production of leukotrienes D4 and E4 component
of SRSA.
- As a result, these drugs block many of the signs
and symptoms of asthma, such as neutrophil and
eosinophil migration, neutrophil and monocyte
aggregation, leukocyte adhesion and smooth
muscle contraction
Adverse Effects:
- Abdominal pain
- Elevated liver enzymes concentration
- Vomiting
Lung Surfactants
- Reduce the surface tension within the alveoli,
allowing expansion of the alveoli for gas exchange
- Beractant, calfactant, colfosceril and the newest
drug poractant
Action- used to replace the surfactant that is
missing in the lungs of neonates with respiratory
distress syndrome ( RDS )
- prophylactic treatment of infants at high risk for
RDS.
G. Mast Cell Stabilizers
- Cromolyn
- Nedocromil
Actions: works at the cellular level to inhibit the
release of histamine ( released from mast cells in
response to inflammation or irritation ) and
inhibits the release of SRSA >> thus preventing
the allergic asthmatic response when the
respiratory tract is exposed to the offending
allergen.
- Inhaled from a capsule and may not reach its
peak effect for 1 week
- Nedocromil: inhibit the mediators of
inflammatory cells ( eosinophils, neutrophils,
macrophages and mast cells ) >> by blocking
these effects it decreases the release of histamine
and blocks the over all inflammatory response
- Indicated for the mgt. of patients with mild to
moderate bronchial asthma who are older than
12 years of age.
H. Anti IgE Monoclonal Antibodies
P Omalizumab
Action:
- Inhibits the binding of IgE to mast cell and
thus does not provoked mast cell
degranulation
- Also inhibit IgE synthesis by B lymphocytes
- Administration of Omalizumab to asthmatic
individuals for 10 weeks lowers plasma IgE to
undetectable levels and significantly reduces the
magnitude of both the early and the late
broncho - spastic responses to antigen challenge.
- Repeated administration lessens asthma severity
and reduces the corticoid requirement in patients
with moderate to severe disease especially those
with a clear environmental antigen precipitating
factor
 PREVENTIVE AND TREATMENT
MEASURES OF ASTHMA AND OTHER
COPD
Reduce environmental exposure to irritants
Stop smoking
Filter allergens from the air
Avoid exposure to known irritants and allergens
Open the conducting airways through muscular
bronchodilation
Decrease the effects of inflammation on the
airway lining
 POINTS TO REMEMBER
Pulmonary Obstructive Diseases include
asthma, emphysema, and chronic obstructive
pulmonary disease ( COPD ) which cause
obstruction of the major airways, and
respiratory distress syndrome ( RDS ) which
causes obstruction at the alveolar level
Drugs used to treat asthma and COPD include
drugs to block inflammation and drugs to
dilate bronchi
 The xanthine derivatives have a direct effect
on the smooth muscle of the respiratory tract
both in the bronchi and in the blood vessels
The adverse effects of the xanthines is directly
related to the theophylline concentration in
the blood and can progress to coma and death
 Sympathomimetics are drugs that mimic the
effects of the sympathetic nervous system;
they are used for dilation of the bronchi and
to increase the rate and depth of respiration
Anticholinergics can be used as
bronchodilators because of their effect on the
vagus nerve, resulting in a relaxation of
smooth muscle in the bronchi, which leads to
bronchodilation
 Steroids are used to decrease the
inflammatory response in the airway. Inhaling
the steroids tends to decrease the numerous
systemic effects that are associated with
steroid use
Leukotrienne receptor antagonists block or
antagonize receptors for the production of
leukotrienes D4 and E4, thus blocking many of
the signs and symptoms of asthma
 Lung surfactants are instilled into the
respiratory system of premature infants who
do not have enough surfactant to ensure
alveolar expansion
The mast cell stabilizers are anti asthmatic
drugs that block mediators of inflammation
and help to decrease swelling and blockage in
the airways
END