BRONCHIAL ASTHMA

Dr. PRATIVA SAHOO

SENIOR RESIDENT
Dept. of pharmacology
VIMSAR, Burla
ANTI-INFLAMMATORY
 Phospholipids STEROIDS
PLA2

Arachidonic acid ZILEUTON

COX LOX

PG LT

MONTELUKAST
ZAFIRLUKAST LT Receptor

Bronchoconstriction
Vascular permeability
Mucus secretion
 ( A ) CORTICOSTEROIDS

Inhalation : Beclmethasone dipropionate, Budesonide, Fluticasone, Ciclesonide

Oral : Prednisolone, Methylprednisolone.
Parenteral : Hydrocortisone, Methylprednisolone

DOSE and FORMULATIONS

Inhalation

• Patient needing - β2 agonist inhaler control more than twice weekly

• ICSs - twice daily dose 400μg
• Dose > than 800 μg daily via pMDI - a spacer device - reduce the risk of
oropharyngeal side effects.
 ( A ) CORTICOSTEROIDS

Systemic

• Intravenous  Acute asthma

Hydrocortisone hemisuccinate- steroid of choice - (5–6 h) rapid
Given until a satisfactory response is obtained
• Oral  Prednisolone – most commonly used - 30-40mg/day
Patients who show no significant improvement with nebulized β2 agonist
Dose may be tapered over 1 week
 ( A ) CORTICOSTEROIDS

inhibit the formation of multiple inflammatory cytokines, particularly cytokines released from TH2 cells

decrease eosinophil survival by inducing apoptosis.

effects on gene transcription, increasing the transcription of several anti-inflammatory genes and
suppressing transcription of many inflammatory genes.

prevent and reverse the increase in vascular permeability due to inflammatory mediators

have no direct effect on contractile responses of airway smooth muscle

potentiate the effects of β agonists on bronchial smooth muscle and prevent and reverse β receptor
desensitization in airways

increase the transcription of the β2 receptor gene

 ( A ) CORTICOSTEROIDS

Adverse effects

Inhalational
Hoarseness of voice STATUS
Dysphonia • Exacerbations in pts on regular low dose
Sore throat
Oropharyngcal candidiasis inhaled SABA
Systemic • Add on with LABA moderate asthma with
Mood changes
Osteoporosis frequent exacerbations
Growth retardation in children • Systemic steroids in acute severe
Early cataract
Bruising, petechiae asthma/status asthmaticus
Hyperglycaemia
Pituitary adrenal suppression
 ( B ) MAST CELL STABILIZERS
CROMONES KETOTIFEN
• Cromolyn sodium H1 anti
• Nedocromil sodium histaminic Antihistaminic with
cromoglycate like
action

Mechanism of action Pts with multiple

allergy disorder
Inhibits degranulation of mast cells (as well as other inflammatory cells)

Release of mediators of asthma like histamine, LTs , PAF, interleukins is reduced

Broncospasm induced by allergens restricted

Not a bronchodilator- not useful in attack

 ( B ) MAST CELL STABILIZERS

DOSE and FORMULATIONS

Cromones :
• Sodium cromoglycate is not Ketotifen :
absorbed orally • Well absorbed orally
• Aerosol through MDI • 1-2mg BD
• 5mg/puff MDI, 2 puffs 4 times
daily

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 ( B ) MAST CELL STABILIZERS

Adverse effects
STATUS
Cromones :
Throat irritation, cough • Prophylaxis - chronic and seasonal
asthma  reduce the need for
Ketotifen : bronchodilator / corticosteroid
Sedation therapy
Dry mouth • Not used - acute attacks
Dizziness • Other uses : allergic rhinitis
Nausea
Weight gain
 ( C ) LEUKOTRIENE ANTAGONISTS

Zafirlukast
Montelukast
Zileuton

Mechanism of action

Courtesy : Harrison’s Principles of Internal Medicine, 20th edition 11

 ( C ) LEUKOTRIENE ANTAGONISTS

STATUS
• Adjuvants with inhaled corticosteroids
• Poorly responding patients.
• Reduce the dosage of β2 agonists and inhaled corticosteroids for maintenance.

ADVERSE EFFECTS:
Headache
DOSE
Dyspepsia
Montelukast - 10 mg at bedtime.
Elevate Sr. Hepatic enzymes
Zafirlukast - 20 mg BD
Neuropathy
Zileuton - 600 mg QID

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IMMUNOMODULATOR THERAPY
 ANTI - IgE ANTIBODY

OMALIZUMAB

Mechanism of action
Recombinant humanized monoclonal
antibody

Binds to IgE , prevents it from

binding to IgE receptors on mast
cells and basophils

Prevents their activation by allergens

Inhibits chronic inflammation

Courtesy : Harrison’s Principles of Internal Medicine, 20th edition Reduces levels of circulating IgE
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 ANTI - IgE ANTIBODY

DOSE
s.c once in 2-4 wks

Adverse effects
• Anaphylaxis
• Not all pts respond – trial of 4 months
necessary
STATUS
• Reduces dependence on steroids and decrease
• High cost –
• Pts poorly controlled on steroids with frequency of exacerbations
• In patients - severe asthma - poorly controlled
concomitant allergic rhinitis
• Given prior to exacerbation season with conventional therapy
Treatment of Asthma
Mild Asthma
• Acute episode:-occasional episode of bronchospasm need rapidly acting
inhaled β2 stimulants like salbutamol
Moderate asthma
• Prophylaxis:- regular prophylactic cromoglycateif symptom persist
inhaled steroids(if c/Ileukotriene antagonist)
• Acute episodeLABA
Severe asthma
• Repeated episodes of bronchospasm with frequent exacerbation and
symptoms interfere day today life
• Regular inhaled steroid+inhaled β2 agonist+oral steroid+additional inhaled
ipratropium br/oral theophylline
Treatment of Asthma
Treatment of Asthma
Treatment of Asthma