This document provides information on the treatment of bronchial asthma, including the classification and mechanisms of action of the major drug classes used. The main drug classes discussed are bronchodilators like beta-2 agonists, anticholinergics, and methylxanthines; corticosteroids; mast cell stabilizers; and leukotriene modulators. Routes of administration, indications, benefits, limitations and side effects are summarized for the major drugs in each class.

1. BRONCHIAL ASTHMA

2. LEARNING OBJECTIVES
• To know the commonly used drugs in
bronchial asthma
• To understand the mechanism of action of the
major classes of drugs used in bronchial
asthma
• To know the adverse effects of these drugs

3. BRONCHIAL ASTHMA
• Chronic inflammatory disease
• Reversible episodes of airway
obstruction
• Due to hyperresponsiveness of
tracheobronchial smooth muscle
to various stimuli, resulting in :
-Bronchospasm
-Narrowing of airtubes
-Mucosal edema
-Increased bronchial mucus
secretion and mucus plugging

4. Cardinal symptoms
• Breathlessness
• Wheezing
• Cough
• Chest tightness

5. Trigger factors for asthma
• Infection
• Irritants (pollen, house dust mites, chemical etc.)
• Pollutants
• Exercise
• Exposure to cold air
• Psychogenic

6. Different types of asthma
• Acute asthma
• Chronic asthma
• Extrinsic asthma
• Intrinsic asthma
 Status asthmaticus

7. Pathophysiology
Inflammation underlying hyperactivity
• Early reaction – Reversible airway obstruction
• Late reaction – Worsening of disease
• Increased vagal discharge to bronchial muscle
Bronchoconstriction and increased mucus secretion
• Adenosine - bronchoconstriction

8. Approaches to treatment
• Prevention of Ag-Ab reaction – avoidence of antigen
• Suppression of inflammation and bronchial hyperactivity
– corticosteroids
• Prevention of release of mediators – mast cell stabilizers
• Antagonism of released mediators – LT antagonists
• Blockade of constrictor neurotransmitter –
anticholinergics
• Mimicking dilator neurotransmitter – sympathomimetics
• Directly acting bronchodilators – methylxanthines

9. Classification
A.Bronchodilators
i. Non-selective sympathomimetics – Adrenaline,
ephedrine, isoprenaline
ii. Selective beta2 agonists - Salbutamol, terbutaline,
salmeterol, formoterol
iii.Anticholinergics – Ipratropium bromide, atropine
methonitrate
iv.Methylxanthines – Theophylline, aminophylline, choline
theophyllinate

10. B. Corticosteroids
i. Systemic – Oral: Prednisone
Parenteral : Methylprednisolone,
hydrocortisone
ii. Non- systemic – Inhalational : Beclomethasone,
fluticasone, budesonide
C. Mast cell stabilizers – Nedocromil, ketotifen, sodium
cromoglycate
D.Leukotrine (LT) modulators
i. 5’- lipoxygenase inhibitors – Zileuton
ii. LT receptor antagonist – Zafirlukast, montelukast

12. Role of beta agonists in asthma
MOA
β2 agonists have other beneficial effects including inhibition of
mast cell-mediator release, prevention of microvascular
leakage and airway edema, and enhanced mucocillary
clearance. The inhibitor effects on mast cell actions suggest
that β2 agonists may modify acute inflammation.

13. Sympathomimetics
Mode of administration
• Inhalation – metered dose
inhaler, nebulizer, spinhaler,
rotahaler, spray
• Oral
• i.m. or i.v. injection

14. • Adrenaline – prompt but short-lasting action;
rarely used because of adverse effects
• Isoprenaline – prompt and marked
bronchodilatation; disadvantage – tachycardia
• Ephedrine – mild slowly developing
bronchodilatation; used for mild to moderate
asthma
• Salbutamol – inhaled drug – rapid onset, short
duration of action; used for acute attack
A/E: tremors, tachycardia, palpitation,
nervousness

15. • Terbutaline – can be used safely during
pregnancy
• Salmeterol – slow onset of action, long acting;
used for maintenance therapy and nocturnal
asthma
• Formoterol – faster onset of action, long acting;
used for acute attack and maintenance therapy

16. Limitations
• Non-selective sympathomimetics – cardiac side effects
(β1action) – not preferred in elderly or heart patients
• Long term use of salbutamol and terbutaline –
downregulation of receptors – diminished
responsiveness – worsening of disease

17. Anticholinergics
• MOA
• Atropine and ipratropium antagonize the
actions of Ach at parasympathetic,
postganglionic, effector cell junctions by
competing with Ach for M3 receptor
sites.
• This antagonism of Ach results in airway
smooth muscle relaxation and
bronchodilation.

18. Anticholinergics
• Mode of administration - inhalation
• Slow onset of action – better suited for regular
prophylactic use
• Indications –
– Asthmatic bronchitis
– Psychogenic asthma
COPD
Nebulized ipratropium + salbutamol – refractory asthma

19. Methylxanthines
• MOA –
i. Inhibition of phosphodiesterase – increased
cAMP and cGMP level
ii.Blockade of adenosine receptors
• Mode of administration - oral, i.m., i.v. , rectal
suppositories

20. Plasma therapeutic range – 5-20 µg/ml
Side effects :
• GIT: nausea, vomiting, gastritis, aggravation of
peptic ulcer
• CVS: tachycardis, palpitation, arrhythmias,
hypotension
• CNS: insomnia, headache, delirium,
restlessness, tremor
• Diuresis, flushing
• Rapid i.v. – syncope and sudden death

21. Methylxanthines x Sympathomimetics
potentiate the effects of sympathomimetics
• Bronchodilatation – beneficial
• Cardiac stimulation - harmful

22. Corticosteroids
MOA:
• Decreases the synthesis of inflammatory mediators
• Prevent recruitment, proliferation and activation of
leukocytes
Systemic steroid therapy –
• Severe chronic asthma
• Status asthmaticus
Inhaled steroids –
Long term treatment of asthma

23. • Others Indications
Rhinitis
Nasal polyposis
Adverse effects
Inhaled steroids– drymouth, dysphonia, sore throat,
oropharyngeal candidiasis
Systemic steroids – mood changes, osteoporosis,
hyperglycemia, hypertension, HPA axis suppression

24. • MOA
– They block IgE-regulated calcium channels
essential for mast cell degranulation
– Prevent the release of histamine and related
mediators.
Mast cell stabilizers

25. Mast cell stabilizers
Mode of administration - inhalation, oral
Indications
• Bronchial asthma
• Allergic rhinitis – nasal spray
• Allergic conjunctivitis – eye drops
Adverse effects - irritation, cough, dry mouth,
sedation, headache, rashes

26. Leukotriene modulators
Indications
Prophylactic treatment of mild to moderate
asthma
Adverse effects
Hepatotoxicity, headache, GI distress, rashes
Zafirlukast – Churg-Strauss syndrome

27. Treatment of status asthmaticus
• Humidified oxygen inhalation
• Nebulized salbutamol+ ipratropium
• Systemic steroids – hydrocortisone,prednisolone i.v.
• IV fluids – correct dehydration
• Potassium supplements – correct hypokalemia
• Sodium bicarbonate – treat acidosis
• Antibiotics – treat infection

28. Drugs contraindicated in bronchial
asthma
• Beta blockers
• Cholinergic drugs
• NSAIDs ( expect paracetamol)

29. Recent advances
Omalizumab - anti IgE antibody