Bronchial astham treatment

1. BRONCHIAL ASTHMA

2. Bronchial asthma is a chronic inflammatory disorder
characterized by hyper-responsiveness tracheobronchial
smooth muscle and reversible airflow obstruction
Cardinal symptoms
• Cough
• Dyspnea
• Wheezing
• Limitation of activity

3. Pets
Pharmacologi
cal
• Beta blockers
• NSAIDs
• Morphine
Pollen
Patholog
y (repeated
RTI)
Pollution

7. PATHOPHYSIOLOGY
Phase I – Early allergic response
Phase II – Late allergic response

8. Early allergic response
Sensitized individual – antigen binds to IgE on mast cells
Release of preformed mediators (Histamine, protease enzymes, TNFα)
Short term effects
1. Increased vascular permeability
2. Increased mucous secretion
3. Bronchospasm

9. Late allergic response
PLA2 on membrane phospholipids PGs, LTs (B4, C4, D4 - SRS-A) & Pro-
inflammatory cytokines (PAF, IL-6, IL-14)
Amplification of allergic response
Short-term + long-term effects
 Smooth muscle hypertrophy &
proliferation
 Angiogenesis
 Basement membrane thickening
Airway remodeling
• Fibrosis
• Narrowing of airway
• Increased resistance to airflow
Chronic persistent asthma

10. TYPES OF ASTHMA
Extrinsic
 Childhood asthma
 Family history present
 Allergen implicated
 Increased IgE
 Responds to selective b2 agonists
Intrinsic
 Middle age onset
 No allergen
 No increase in IgE
  expression of cholinergic
receptors
 Inhalational corticosteroids

11. CLINICAL CLASSIFICATION
Mild intermittent - symptoms less than 2 times a week, FEV1≥ 80%
Chronic persistent -
 Mild - symptoms more than 2 times a week, FEV1≥ 80%
 Moderate - symptoms daily, FEV1 60-80%
 Severe - continuous symptoms, FEV1 < 60%
Acute severe asthma - Repeated attacks of bronchospasm without
recovery in between the attacks (Status asthmaticus)

12. DRUGS FOR BRONCHIAL ASTHMA
CLASSIFICATION:
1. Bronchodilators:
 b2 agonists: Salbutamol, Terbutaline, Salmeterol, Formoterol
 Methyl xanthines: Theophylline, Hydroxyethyl theophylline
 Anticholinergics: Ipratropium bromide, Tiotropium bromide

13. DRUGS FOR BRONCHIAL ASTHMA
2. Leukotriene antagonists: Montelukast, Zafirlukast
3. Corticosteroids:
 Inhalational: Beclomethasone, Budesonide, Fluticasone,
Ciclesonide
 Systemic: Hydrocortisone, Prednisolone
4. Mast cell stabilisers: Sodium cromoglycate, Ketotifen
5. Anti-IgE antibody: Omalizumab

14. BRONCHODILATORS

15. β2 Agonists
Selective β2 agonist
• SABA – salbutamol, terbutaline
• LABA – salmeterol, formoterol
MOA:- binds to β2 receptors adenylyl cyclase cAMP
dephosphorylation of myosin light chain kinase
Relaxes airway smooth muscle- bronchodilation

16. Advantages:
 Rapid onset of action – Rx of acute attacks
 β2 receptors Bronchial smooth muscle - relaxation
Mast cells - stabilize
 Increased cAMP- stabilizes mast cells - prevents mediator release
 Can dilate up to the level of terminal bronchiole
 Additive action with anticholinergics
 Decreases cholinergic tone to a certain extent
 Synergistic action with methylxanthines
Safe bronchodilator in pregnancy- terbutaline

17. 6/26/2023

18. Disadvantages:
 Drug tolerance
 Muscle tremors
 Not 100% selective - palpitations, restlessness

19. Uses:
1. Mild intermittent asthma
2. Mild to Moderate chronic persistent asthma
LABA:-
1. Maintenance therapy
2. Nocturnal asthma
3. COPD
4. Chronic persistent asthma- severe- always with inhaled corticosteroids

20. Methylxanthines (Theophylline)
MOA:-
1. Inhibition of PDE3 – cAMP – bronchodilation
2. Adenosine receptor antagonism (A1), A3 in mast cells
3. Sub-bronchodilator doses - enhance histone
deacetylation & blocks transcription of inflammatory
mediators

21. Advantages:
 Can be combined with β2 agonists
 Improved mucociliary clearance
 Stimulation of medullary respiratory centre
 Augment diaphragmatic contractility

22. Disadvantages:
 GI irritation
 Irritant
 Rectal inflammation
 Pain at site of IM injection
 Rapid IV- precordial pain, arrhythmias, sudden death
 Narrow margin of safety >10-20mcg/ml - CVS & CNS toxicity
 Drug interactions; enzyme inducers will decrease levels,

23. Uses:
 Chronic persistent asthma
 Nocturnal asthma
 COPD
 Cardiac asthma (Bronchospasm precipitated by uncompensated congestive heart failure)

24. Anticholinergics
MOA: Binds to M3 receptors & block the increased parasympathetic tone
USES:
1. Chronic persistent asthma
2. COPD
3. Exercise induced asthma
4. Asthmatic bronchitis
5. Psychogenic asthma

25. 6/26/2023

26. Advantages:
 No tolerance
 Suited for regular prophylactic use
 Additive action with β2 agonists
 Nebulized ipratropium + salbutamol - refractory asthma
 Reduce mucus secretion
Disadvantages:
Less effective than β2 agonists (not a bronchodilator - no action on smooth
muscle)

27. BRONCHODILATORS
Relieve symptoms rapidly, but do not control the disease process
“RELIEVERS”

28. LEUKOTRIENE ANTAGONISTS
Montelukast, Zafirlukast
 MOA:- competitively blocks the actions of cysteinyl leukotrienes at
cysLT1 receptor

29. Advantages:
 Blocks the effects of leukotrienes – Bronchoconstriction, mucous
secretion, recruitment of eosinophils
 Prevents airway remodeling
 Improves lung function tests & QOL
 Steroid sparing effect
 Decreased need for rescue β2 agonist inhalations
 Accepted for children ≥ 2yrs

30. Disadvantages:
 Eosinophilia
 Skin rashes
 Churg-strauss syndrome (blood vessel inflammation)
 Increased serum transaminases
 No value in COPD (not a bronchodilator)

31. Uses:
 Chronic persistent asthma
 Childhood asthma
 Aspirin induced asthma
 Exercise induced asthma
 Seasonal allergic rhinitis

32. INHALATIONAL CORTICOSTEROIDS
Cornerstone therapy for bronchial asthma – “CONTROLLERS”

33. MOA:-
 Potent anti-inflammatory drugs
 Block the synthesis and release of prostaglandins and leukotrienes
 Stabilize lysosomal membranes
 Decrease recruitment of inflammatory cells
 Upregulates β2 receptors
 Prevents bronchial/airway remodeling

34. Advantages:
 High topical : systemic activity ratio
 No growth retardation in children
 No osteoporosis/HPA suppression
 Decrease need of rescue β2 agonist inhalations
 Prevent episodes of acute asthma
 Increase FEV1
Uses: Chronic persistent asthma

35. Disadvantages:
 Hoarseness of voice
 Sore throat
 Oropharyngeal candidiasis
 > 600 mcg/day --> osteoporosis, cataract, glaucoma

37. MAST CELL STABILISERS
MOA:- Stabilize mast cell & inhibit degranulation
 Block release of phase I & formation of phase II mediators
 Inhibit leucocyte activation and chemotaxis
Prophylactic – need 3-4 weeks for action

38. Uses:
 Seasonal asthma - to be started 1 month prior
 Seasonal allergic rhinitis
Ketotifen: Also an antihistaminic (H1 blocker)
 Chronic idiopathic urticaria
 Atopic dermatitis
 Food allergies

39. OMALIZUMAB
 Humanized monoclonal antibody against IgE
 Severe asthma - reduces exacerbations and steroid requirement
Disadvantage
 Expensive - Reserved for resistant asthma patients

40. 6/26/2023

41. BRONCHIAL ASTHMA - THERAPY
Mild intermittent: Short acting b2 agonist at onset of each episode
Chronic persistent:
 Mild: Regular low dose (100-500 mg/day) ICS + Short acting b2
agonist rescue

42. BRONCHIAL ASTHMA - THERAPY
 Moderate: Increasing doses of ICS (up to 800 mg/day) + Inhaled
long acting b2 agonist/leukotriene antagonist + Short acting b2
agonist rescue
 Severe: Regular high dose ICS (800-2000 mg/day) + Inhaled long
acting b2 agonist + Leukotriene antagonist/sustained release oral
theophylline/inhaled ipratropium bromide + Short acting b2
agonist rescue

44. BRONCHIAL ASTHMA - THERAPY
Acute severe asthma (Status asthmaticus):
 High flow humidified oxygen inhalation 100%
 Hydrocortisone 200 mg i.v. stat
 Nebulised salbutamol 5 mg + ipratropium bromide (0.5 mg)
 Correct dehydration and acidosis – saline + sodium bicarbonate infusion
 Treat chest infection – intensive antibiotic therapy
 Aminophylline iv

45. BRONCHIAL ASTHMA - THERAPY
Refractory asthma:
Aminophylline 250-500 mg
 diluted in 20-50 ml glucose solution
 injected slow i.v. over 20-30 minutes
 with cardiac monitoring
(Use restricted to resistant cases only)
MgSO4

46. Thank you