clinical features of asthma chemomediators of asthma pathophysiology of asthma Extrinsic asthma: Intrinsic asthma drugs used in asthma

1. DRUGS FOR
BRONCHIAL ASTHMA
Madan Sigdel
Gandaki Medical College

3. Bronchial asthma
• Derived from a Greek word meaning difficulty in
breathing.
• It is the most common chronic disabling disease of
childhood, but it affects all age groups
• CLINICAL FEATURES: Recurrent, episodic bouts of
coughing, shortness of breath, chest tightness, and
wheezing.

4. Bronchial asthma
Etiology

7. Pathology

8. Histopathology of a small airway
in fatal asthma.

10. PATHOPHYSIOLOGY

11. Patho-physiology

12. Inflammatory mediators in
asthma

13. Inflammatory mediators in
asthma

14. Bronchial asthma
Types of asthma based on etiology:
• Extrinsic asthma:
– Allergy-induced
– Commonly suffer from other atopic diseases,
– Mostly episodic, Less prone to status asthmaticus
• Intrinsic asthma:
– No immunological basis for their condition
– Negative skin test to common inhalant allergens
– Normal serum concentrations of IgE,
– Perennial,
– More prone to status asthmaticus

15. Bronchial asthma
• Types of Asthma based on clinical condition:
• Atopic asthma
• Non-atopic asthma
• Drug induced asthma
• Occupational asthma
• Exercise induced asthma

16. Approach for treatment of
Asthma

17. APPROACHES TO TREATMENT
1. Prevention of AG:AB reaction—avoidance of antigen,
hyposensitization—possible in extrinsic asthma and if antigen
can be identified.
2. Neutralization of IgE (reaginic antibody) Omalizumab.
3. Suppression of inflammation and bronchial
hyperreactivity —corticosteroids.
4. Prevention of release of mediators—mast cell stabilizers.
5. Antagonism of released mediators—leukotriene
antagonists, antihistamines, PAF antagonists.
6. Blockade of constrictor neurotransmitter—
anticholinergics.
7. Mimicking dilator neurotransmitter—sympathomimetics.
8. Directly acting bronchodilators—methylxanthines.

18. Classification of drugs for
asthma
• BRONCHODILATORS:
1. β-Sympathomimetics: Salbutamol, Terbutaline, Salmeterol,
Formoterol, Ephedrine
2. Methyl Xanthines: Theophylline, Aminophylline, Choline
theophyllinate, Hydroxyethyl theophylline, Doxophylline.
3. Anticholinergics: Ipratropium bromide, Tiotropium bromide
• LEUKOTRIENE ANTAGONISTS: Montelukast, Zafirlukast
• MAST CELL STABILIZERS: Sodium chromoglycate, Ketotifen
• CORTICOSTEROIDS
1. Systemic: Hydrocortisone, Prednisolone
2. Inhalational: Beclomethasone, Budesonide, Fluticasone,
Flunisolide
• ANTI Ig-E ANTIBODY: Omalizumab

19. Sympathomimetics
• Mechanism of action:
– β2 stimulation increased cAMP formation in bronchial
muscle cell relaxation
– Also decreases mediator release
• E.g. Salbutamol, Terbutaline, Salmeterol, Formoterol,
Ephedrine

20. Mechanism of action

21. Sympathomimetics
Salbutamol
– Highly selective β2 agonist
– Inhaled Salbutamol produces bronchodilatation in 5 min
and action lasts for 2-4 hrs
– Side effects: Palpitations, restlessness, nervousness,
throat irritation, ankle edema
– Uses: Reserved for patients who cannot correctly use
inhalers, Used as an adjuvant in severe asthma
– Not suitable for round the clock prophylaxis
Terbutaline:
– Similar to Salbutamol
– Inhaled Salbutamol and Terbutaline are currently the
most popular drugs for quick reversal of bronchospasm

22. Sympathomimetics
Salmeterol:
• It is the first long acting selective β2 agonist (LABA) with
slow onset of action
• Used by inhalation on a twice daily schedule
• Used for maintenance therapy and nocturnal asthma
Formeterol:
• Another LABA
• Acts for 12 hrs
• Compared to Salmeterol it has faster onset of action

23. • Can you differentiate between salbutamol
and salMETEROl ??
• REMEMBER metro train: that goes long
distance (i.e. long acting )

24. Methyl Xanthines
• Naturally occuring Methyl Xanthine alkaloids are Caffein,
Theophylline and Theobromine
• Mechanism of action:
– Inhibition of phosphodiesterase (PDE)  increased
cAMP Bronchodilatation, cardiac stimulation,
vasodilation
– Blockade of adenosine receptorsrelaxes smooth
muscles
• E.g: Theophylline, Aminophylline, Choline theophyllinate,
Hydroxyethyl theophylline, Doxophylline

26. Methyl Xanthines
Theophylline:
– Well absorbed orally, T1/2 is 7-12 hrs
– Side effects: gastric pain (with oral), rectal inflammation (with
rectal suppositories), pain at site of injection (i.m), Rapid IV
can cause precordial pain, syncope and sudden death.
INTERACTIONS:
– metabolism is induced by smoking, phenytoin, rifampicin,
phenobarbitone
– Metabolism is inhibited by erythromycin, ciprofloxacin,
cimetedine, OCPs, allopurinol
USES: Bronchial asthma and COPD, Apnoea in premature
infant,

28. Anticholinergics (Ipratropium bromide,
Tiotropium bromide)
• Atropine drugs cause bronchodilatation by
blocking cholinergic constrictor tone
• Act primarily in larger airways
• Produce slower response than inhaled
sympathomimetics
• Better suited for regular prophylactic use
• Combination of inhaled Ipratropium with β2
agonists produce more marked and longer
lasting bronchodilatation.

29. Leukotriene antagonists
• Competitively antagonize cysLT1 receptor mediated
bronchoconstriction, increased vasodilatation and
recruitment of eisonophils
• Indicated for prophylactic therapy of mild to moderate
asthma as alternative to inhaled glucocorticoids
• May obviate need for inhaled glucocorticoids
• Safe drugs
• Side effetcs: headache, rashes
• E.g: Montelukast, Zafirlukast

30. Mast cell stabilizers
• Inhibits degranulation of mast cells
• Release of mediators like Histamine, LTs, PAF, ILs,
etc is restricted
• Not absorbed orally, administered as an aerosol
through metered dose inhaler (MDI)
• Uses: Long term prophylaxis in mild to moderate
Bronchial asthma, Allergic rhinitis, Allergic
conjunctivitis
• Side effects: Bronchospasm, throat irritation, cough
• E.g: Sodium chromoglycate, Ketotifen

31. Corticosteroids
• These do not cause bronchodilatation,
• Reduce bronchial hyper-reactivity, mucosal edema, by
supressing inflammatory response to AG:AB reaction
• Two forms are used Systemic and Inhalational
1. Systemic/Oral Corticosteroid (OCS)
– Used in severe chronic asthma and Status asthmaticus
– E.g: Hydrocortisone, Prednisolone
2. Inhalational Corticosteroid (ICS)
– Step one for all asthma patients
– Safe during pregnancy
– Side effetcs: mood changes, osteoporosis, bruising, petechiae,
hyperglycemia
– E.g: Beclomethasone, Budesonide, Fluticasone, Flunisolide

32. Pharmacokinetics of inhaled
corticosteroids

33. Using metered dose inhaler
• Remove the cap and hold the inhaler upright.
• Shake the inhaler.
• Tilt your head back slightly and breathe out.
• If your doctor recommends, use a spacer (a hollow, plastic
chamber) to filter the medicine between the inhaler and your
mouth. The chamber protects your throat from irritation from the
medicine.
• Press down on the inhaler to release the medicine as you start
to breathe in slowly.
• Breathe in slowly for 3 to 5 seconds.
• Hold your breath for 10 seconds to allow medicine to go deeply
into your lungs.
• Repeat puffs as directed. Wait 1 minute between puffs to allow
the second puff to get into the lungs better.

34. Guidelines for the Treatment of Asthma

37. Anti-IgE monoclonal antibody
omalizumab
• Omalizumab prevents the binding of IgE to mast cell
and thus prevents mast cell degranulation.
• It has no effect on IgE already bound to mast cells.
• It is administered parenterally.
• It is used in moderate to severe asthma and allergic
disorders such as nasal allergy, food allergy, etc.
• local side effects such as redness, stinging, itching
and induration.

38. Acute severe asthma
• Humidified oxygen inhalation
• Nebulized β2 adrenergic agonist (salbutamol 5mg/
terbutaline 10 mg) + anticholinergic agent (ipratropium
bromide 0.5 mg)
• Systemic glucocorticoids: intravenous hydrocortisone 200
mg i.v. stat followed by i.v. hydrocortisone 100 mg q 6 hrs
or prednisolone30-60 mg depending on patients condition.
• Intravenous fluid to correct dehydration
• Pottasium suppliments: to correct the hypokalemia
produced by the repeted doses of salbutamol/terbutaline.
• Sodium carbonate to treat acidosis.
• Antibiotic to treat nfection.

39. • Drugs to be avoided in patients with
bronchial asthma ?

40. •Thank- you