Asthma by jitendra bhangale

7/19/2012

By- Jitendra Bhangale
Assistant Professor & Head,
Department of Pharmacology,
Smt N. M. Padalia Pharmacy College,
Ahmedabad

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© 2010 Delmar, Cengage Learning

Introduction
Etiology
Pathophysiology
Symptoms
Diagnosis
Management
References

By Jitendra Bhangale
Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad2
© 2010 Smt N. M. Padalia

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7/19/2012

Asthma is a chronic inflammatory disorder of the airways in
which many cells and cellular elements play a role, in particular,
mast cells, eosinophils, T lymphocytes, macrophages, neutrophils,
and epithelial cells.
In susceptible individuals, this inflammation causes recurrent
episodes of wheezing, breathlessness, chest tightness, and
coughing, particularly at night or in the early morning.
The inflammation also causes an associated increase in the
existing bronchial hyperresponsiveness to a variety of stimuli.



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7/19/2012

Immediate phase Late phase
Infiltration of cytokine-
Eliciting agent:
Releasing Th2 cells,
Allergen or & monocytes, & activation of
Non-specific stimulus inflammatory cells, particularly
eosinophils
Mast cells,
Mononuclear cells Mediators
e.g. cysLTs,
NO
Spasmogens Epithelial damage
Chemotaxins,
cysLTs, Airway
chemokines
H, PGD2 inflammation Airway
hyper-reactivity
Bronchospasm Bronchospasm,Wheezing,
coughing


Allergens

T lymphocytes activated
& secrete lymphokines

Lymphokines activates eosinophils
& secrete mediators & damaging proteins

Mediators potentiate inflammation
& damage epithelium
Enhancing BHR


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7/19/2012

 Hypoxemia  Hypersecretion production
 Airway Inflammation  Cough
Acute Chronic  Wheezing
 Bronchospasm  Dyspnoea



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7/19/2012

Chronic asthma:
Acute severe asthma:  Dyspnoea on exertion,

 Upright position,  wheeze,

 Can’t complete sentences in one  chest tightness and cough on
breath, daily basis, usually at night
 Tachypnea > 25/min, and early morning;

 Tachycardia > 110/min,  productive cough (mucoid
 PEF < 50% of pred or best, sputum),

 Prolonged expiration,  recurrent respiratory infection,
 Breath sounds decreased,
 expiratory rhonchi throughout
 Inspiratory and expiratory rhonchi, and accentuated on forced
expiration.
 Cough

1) Spirometer
In asthma, the following results may be obtained on spirometry:

Sr.no Interpretation

Asthma in remission or
1 Normal spirometry
asthma under control
Airflow obstruction
present (can be graded
2 FEV1 <80% FVC
based on amount of
reduction)
FEV1 increase by 15% or more Significantly reversible
3
than 200 mL after bronchodilator airflow obstruction

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Asst. Prof. Dept of Pharmacology, Delmar, Cengage Learning Pharmacy College, Ahmedabad

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7/19/2012

2) Peak Expiratory Flow Rate:

Mini Wright's peak flow meter

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Chest X-Ray

Allergy Tests

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7/19/2012

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Clinical features before treatment
Night time Daily
Symptoms PEF
symptoms medications
STEP 4 Continuous,
≤60% predicted High dose inhaled
Severe Limited physical Frequent
Variability >30% CS & LAβA
Persistent activity
Low to medium
STEP 3
>60%-<80% predicted dose CS & LAβA
Moderate Daily >time/weak
Variability >30% Alternative:-LA or
Persistent
theophylline
STEP 2
≥1 time a week >2 times a ≥80% predicted
Mild Low dose CS
But <1 time a day months Variability 20-30 %
Persistent
STEP 1 < 1 time a week
No daily
Mild Asymptomatic & ≤2 times a ≥80% predicted
medication
Intermitte Normal PEF betw months Variability <20%
needed.
nt attacks
Quick relief Short acting bronchodilator
all patients Use of short acting β2 agonists
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7/19/2012

Initial assessment
History, physical examination, PEFR

Initial therapy
Inhaled β2 agonist.o2 if needed

Incomplete/ poor response
Good response Respiratory failure

Add systemic corticosteroids
Observe for at least 1 hr

Admit to ICU
If stable Good response Poor response
Discharge to
home Discharge
Admit to hospital

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7/19/2012

SR.NO. DEVICE DRUGS

I Metered dose Inhaler (MDI)

a CFC MDI All classes
b HFA MDI Albuterol
c Autohaler MDI Beclomethasone Pirbuterol

II Dry powder Inhaler (DPI)

a Rotahaler Albuterol
b Terbuhaler Budesonide
Fluticasone
c Diskus Salmeterol
Fluticasone/salmeterol
d Aerolizer Formoterol
e Twisthaler mometasone

III Nebulizer

All classes except long acting β2-
a Jet Nebulizer
agonists
Cromolyn solution
b Ultrasonic Nebulizer
Short acting β2-agonist solution

IV Spacer Devices 17

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7/19/2012

I) Bronchodilators II) Leukotriene antagonists
a. Sympathomimetics Montelukast
Adrenaline Zafirlukast
Ephedrine Zileuton
Salbutamol III) Mast cell stabilizers
Terbutaline Sodium cromoglycate
Bambuterol Nedocromil
Salmeterol Ketotifen
Formoterol IV) Corticosteroids
b) Methylxanthines Systemic
Theophyline Hydrocortisone
Aminophylline Prednisolone…etc
Choline theophyline • Inhalational
Hydroxyethyl theophylline Beclomethasone
c) Anticholinergics dipropionate
Atropine methnitrate Budesonide
Ipratropium bromide Fluticasone propionate
flunisolide 19
Tiotropium bromide Delmar, Cengage Learning
© 2010

 Therapeutic action of β2 agonists:-
 Relax contracted bronchial smooth muscle
 Prevent bronchial smooth muscle contraction by various stimuli
 Increase mucous clearance
 Prevent mast cell mediator release
 Prevent edema induced by histamine, etc. by preventing increase
in endothelial permeability
 Delivery
 By Aerosol:
 mild to moderately severe asthma only
 often used in conjunction with other drugs; e.g. to promote better
delivery of cromolyn or corticosteroids to the distal airways.
 Systemically:
 available orally and for injection

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7/19/2012

 Adverse effect
 Muscle tremor due to skeletal muscle β-receptors

 Tachycardia and palpitations due to reflex cardiac stimulation secondary
to peripheral vasodilation, stimulation of myocardial β1 receptors

 Metabolic effects: increased FFA, glucose, lactate after large systemic doses

 Hypokalemia (due to stimulation of K+ entry into skeletal muscle

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Major therapeutic actions
Relaxes bronchial smooth muscle
Decreases mast cell mediator release
Increases mucocilliary clearance
Mechanisms of action
Inhibition of phosphodiesterases
Increase intracellular cAMP
Adenosine receptor antagonism
Adenosine causes bronchoconstriction in asthmatics
Bronchoconstriction prevented by theophylline at therapeutic
concentrations
Other
Increased epinephrine secretion form adrenal medulla; increase small
and cannot account for the bronchodilation
Antagonizes some prostaglandins in smooth muscle

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7/19/2012

Delivery
Ineffective by inhalation; requires build-up of effective plasma
concentration
Intravenous; for severe acute asthma only

Side effects of Methylxanthine
Nausea
Vommiting
Headache
Restlessness
Increased acid secretion
Diuresis
Convulsions
Cardiac arrhythmias
CNS stimulation

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Mechanism of Action

Mast cell stabilization

Inhibition of degranulation by a variety of stimuli, including cell-bound IgE
allergen Interactions
Inhibition of leukotriene production
Above actions due to blockage of calcium influx into mast cells
 No bronchodilator or antihistamine activity

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7/19/2012

Delivery
Less than 1% of an oral dose of cromolyn is absorbed, so
therapeutic effects are achieved through local administration via
inhalation:
In 4% solution - By aerosol spray or nebulizer
Powdered drug - as capsules to use in powered turbo-inhaler or as a
metered dose Inhaler
Adverse reactions:
Bronchospasm,
Cough,
Laryngeal edema,
Joint swelling or pain
Headache
Rash,
Nausea

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Mechanisms of action due to anti-inflammatory properties

Reduces number and activity of inflammatory cells in airways
Inhibits release of arachidonic acid metabolites
Prevents increased vascular permeability
Suppresses IgE binding
Increases β-adrenergic responsiveness

Delivery
Aerosol
Oral or IV
for severe episodes: prednisone

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7/19/2012

Side Effects of Inhaled Preparations
Dysphonia

Oropharyngeal candidiasis

Both can be reduced by mouth rinsing with water after
administration and through use of appropriate spacers with the inhaler
to avoid oral deposition

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PDE4 inhibitors
Inhaled ciclosporin A
Monoclonal antibodies against IgE, CD4 cells, and Th2 cytokines (e.g.,
interleukin 4 and 5)
More specific immunotherapy
Antagonists to chemokines, adhesion molecules, proinflammatory cytokines,
tumour necrosis factor , interleukin 1
Antisense oligonucleotides and gene therapy
Inhibitory cytokines interleukin 10

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7/19/2012

Action of PDE4 inhibitors
Relax airway smooth muscle
Reduce bronchoconstriction
Decrease oedema
Reduce secretion of inflammatory mediators, such as histamine, leukotrine
and chemokines (IL-4, IL5)
Block leukocyte adhesion to vascular endothelial cells
Block generation of oxygen derived free radicals

E.g..
Roflumilast (Altana pharma)
Cilomilast (GSK)
S-5751 (Shionogi)

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Mechanism of action:-
Monoclonal antibodies blocks the attachment of the IgE to
the Fc receptors on mast cells and basophils and the subsequent release of
histamine by those cells upon exposure to allergen.

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7/19/2012

Thank you

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Asthma by jitendra bhangale

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