Reference: K. D. Tripathi. Essentials of Medical Pharmacology, 6th edition. Jaypee Publication Pg. No. 213-230. This slide deck give detail presentation on causes, pathophysiology and pharmacotherapy of bronchial asthma. For all IV video lecture series of this topic click: https://youtube.com/playlist?list=PLBVbJ9HCa1BYdASIBMWSjjSL7zVHHVW1l - For More Such Learning You Can Subscribe to My YouTube Channel. https://www.youtube.com/channel/UC5o-WkzmDJaF7udyAP2jtgw/featured?sub_confirmation=1 Facebook Page: https://www.facebook.com/asacademylearningforever Website Blog: https://itasacademy.blogspot.com/

1. Prof. Shaikh Abusufiyan
Part-I Bronchial Asthma and
its treatment

2. 2
At the end of this e-learning session you are able to…
q Discuss characteristics, manifestation and
pathophysiology of asthma.
qClassify anti-asthmatic drugs.

3. Characteristics
q Bronchial asthma is characterized
by:
" hyper-responsiveness of bronchial
smooth muscle
" resulting in narrowing of air tubes
" often accompanied by increased
secretion
" mucosal edema and mucus plugging.

4. Causes of Bronchial Asthma

5. Allergens responsible for asthma
Mites
Hair and fur animals
Plant pollen
Food Drugs, Enzymes, Antiobiotics
Dust

6. Genetic factor:
• Excessive production of antibodies
specific to allergy i.e IgE
atopy
(significant factor responsible for asthma).

7. Pathophysiology
q Difficult to predict.
q The disease is mostly related to --> type 1 hypersensitivity
reaction.
q Any allergic reaction consist of 3 phase:
1. Immune phase
2. Patho-chemical phase
3. Pathophysiologic phase

8. Q&A
1. Enlist characteristics of asthma.
2. Give its few symptoms.
3. What are the 3 phase of allergic reactions?
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9. 1. Immune (Ag-Ab phase)
Allergens
Activation of T-cell & B cells
Formation of antibodies

10. In bronchi antibodies
bind to the
Basophils
mast cells
eosinophils

11. 2. Patho-chemical phase
As a result of antigen-antibody reaction:
Basophils, mast cells and eosinophils membrane of
bronchial smooth muscles produces
biologically active substances
(histamine, 5-HT, prostaglandins, leukotrienes,
thromboxane ect)

12. induces:
Ø Inflammation
Ø mucous edema
Ø hypersecretion of mucous
Ø cumulation of exudate in bronchial lumen.
• Patho-chemical phase
3. Patho-physiological phase
Leads to asthmatic attack

13. ManagementIncludes:
1.Preventive measures
Avoid the contact with allergen.
2. If it is impossible
Hypo-sensitization with standard allergens

14. 3. Drug therapy
q 2 drug categories are used:
A. Anti-inflammatory
B. Bronchodilators

15. 3. Drug therapy
A. Anti-inflammatory
I. Hormone containing Ex. Corticosteroids.
— Systemic: Hydrocortisone, Prednisolone.
— Inhalational: Beclomethasone dipropionate,
Budesonide
II. Non-hormone containing
I. Mast cell stabilizers Ex. Sodium
cromoglycate
II. Leukotriene antagonists Ex. Montelukast,
Zahrlukast

16. 3. Drug therapy
B. Bronchodilators
I. Anti-cholinergics: Ex. Ipratropium bromide,
Tiotropium bromide.
II. Beta-2-Agonists: Ex. Salbutamol, Terbutaline,
Formoterol, Ephedrine.
III. Methyl xanthines: Ex. Theophylline
(anhydrous), aminophylline

17. Q&A
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19. Prof. Shaikh Abusufiyan
Part-II Bronchial Asthma and
its treatment

20. 20
At the end of this e-learning session you are able to…
q Discuss mechanism of action and
pharmacology of corticosteroids.
qExplain pharmacotherapy of Status
asthmaticus and COPD.

21. Corticosteroids
Mechanism:
— They act by 3 imp mechanisms:
1. cell membrane stabilization
2. inhibition of inflammatory mediators
3. restoring the sensitivity of beta adrenergic receptors.
Improve air flow, influence air way remodeling and retard
disease progress

22. Systemic corticosteroids:
• Used mainly in case of:
Severe chronic asthma
Not controlled by bronchodilators and
inhaled steroids

23. — Treatment Protocol:
— start with prednisolone 20 to 60 mg daily
attempt dose reduction after 1 to-2 weeks of good control
and finally try to shift the patient onto an inhaled steroid.
— only in few cases patients require long term oral steroids
— then dose should be kept at minimum.

24. `
Status asthmaticus/acute asthma attack:
— Asthma not responding to --> bronchodilator therapy
— Treatment Protocol:
1. start with high dose or; 2. use rapidly acting i.v. glucocorticoid
generally acts in 6 to 24hours
shift to oral therapy for 5 to 7 days and then discontinue abruptly.

25. `
Chronic obstructive pulmonary disease (COPD)
— COPD
A short course (1-to 3 weeks) of glucocorticoid

26. Inhaled corticosteroids:
Ø These are glucocorticoids with -->
high topical & low systemic activity
due to:
Ø poor absorption
Ø Marked first pass effect
ØEg. beclamethazone, budesonide,
fluticazone

27. Advantage:
Ø Most effective and safe
Ø Considered to be the first line drugs --> for asthma treatment.
Indications of inhaled corticosteroids:
Ø It is used when;
1. inhaled B2 agonist are needed on daily basis
2. disease is not just episodic.

28. Treatment strategy for Inhaled corticosteroids
ØStart with 100 to 200 micro g BD
ØTitrate dose upward every 3 to 5
days
ØMaximum 400 micro g.

29. Treatment strategy for Inhaled corticosteroids
ØNo role --> during an status asthmaticus or
in case of acute attack
— Short courses of oral steroid may be
initiated --> if asthma is exacerbation.
— If patients asthma well controlled for long
period ---> can even stop inhaled steroid
— Safe during pregnancy

30. — COPD:
— High dose inhaled steroids --> is
needed in advanced COPD
— Precaution:
— Should not be used in early/ mild
cases

31. Q&A
1. Enlist characteristics of asthma.
2. Give its few symptoms.
3. What are the 3 phase of allergic reactions?
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32. Prof. Shaikh Abusufiyan
Part-III Bronchial Asthma and
its treatment

33. 33
At the end of this e-learning session you are able to…
q Discuss pharmacology of cromons and
leukotriene receptor antagonists.
qExplain pharmacology of Beta2 agonist.

34. Cromones
Ex. cromolyn sodium and nedocromil
— MoA: Stabilize mast cell membranes
Use: in case of:
— Aasthma of pediatric practice
— intermittent or mild type of
persistent asthma.
Leukotriene R antagonists
Ex. montelukast, zafirlukast
— Moderate Anti-inflammatory activity
Use: in case of:
— Asthma induced by aspirin
— Physical exertion induced asthma

35. LEUKOTRINE RECEPTORS ANTAGONISTS
— Montelukast and Zafirlukast:
— Both have almost similar action i.e it
produces
1. Bronchodilatation
2. Reduced sputum eosinophil count
3. Suppression of bronchial inflammation
and Hyperactivity

36. LEUKOTRINE RECEPTORS ANTAGONISTS
– MoA: Competitive antagonism of cys LT1 R mediated
— Bronchoconstriction
— Eosinophil recruitment
— Increase vascular permeability

37. Clinical effectiveness of LTR antagonist:
• Some patients are:
— Responders
— And some are Non-responder to
the anti-LT therapy.

38. Clinical effectiveness of LTR antagonist:
They are indicated for:
— mild to moderate asthma as alternative to
inhaled glucocorticoids.
— More acceptable to children’s
— Severe asthma
— they permit reduction in steroid dose
— and need for rescue B2 agonist inhalations.

39. Pharmacokinetics
— Plasma half life:
— Montelukast is 3 to 6 hrs
— While that of zafirlukast is 8 to 12 hrs.

40. Side effects
— Are Very few like:
— Eosinophilia
— Rashes
— Headache
— Neuropathy – but infrequent

41. Q&A
1. What is MOA of cromones?
2. Blocking of ______ receptors by Montelukast and
Zafirlukast responsible for anti-asthmatic action.
3. Name category of anti-asthmatic drugs which are more
acceptable in pediatrics patients.
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42. Bronchodilators
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43. — Inhalation Beta2-agonists
One of the basic drug among bronchodilators.
• 2 types:
— Short-acting (duration of action 5 to 6 h)
Beta2-agonists Ex. Fenoterol, salbutamol.
- Use: for quick relief of asthma.

44. oLong-acting (t1/2: 12 h) Beta2-
agonists:
- Ex. Farmoterol, salmoterol
- Use: for prevention of asthma
symptoms

45. 1. Beat2 R stimulation
Increase cAMP formation in bronchial muscles
Relaxation of bronchi (Bronchodilatation)
2. In addition, increase cAMP in mast cell and other inflammatory cells
Decrease release of mediators
Mechanism of Action

46. — Adrenaline and isoprenaline are effective
bronchodilators
Non selective (Produces cardiac SE)
— The selective agonists are used in asthma -
-> to minimize cardiac SE.

47. — Salbutamol (Albuterol) --> A highly selective B agonist
cardiac side effects are less prominent.
— Selectivity is further increased by ---> inhaling the drug.

48. — Inhaled Salbutamol
bronchodilatation within 5 min and the action
lasts for 2 to 4 hours.
— It is, therefore, used to terminate attacks
of asthma

49. — Because of its s.E --> not suitable for round the clock prophylaxis
— SE:
— Muscle tremors.
— Palpitation
— restlessness
— nervousness
— throat irritation
— and ankle oedema.

50. ORAL DOSE
— Salbutamol undergoes --> pre-systemic metabolism in the gut wall
— oral bioavailability --> is 50%.
— Oral Salbutamol acts for --> 4 to 6 hours
— Because of more frequent side effects, oral Beat2 agonist therapy
is reserved for patients who
— cannot correctly use inhalers
— or as alternative/adjuvant drugs in severe asthma.

51. Q&A
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53. Prof. Shaikh Abusufiyan
Part-IV Bronchial Asthma and
its treatment

54. 54
At the end of this e-learning session you are able to…
q Explain pharmacology of anti-cholinergic
and Methylxanthines.
qDiscuss management of Sever asthmatic
status.

55. — Anti-cholinergic drugs
— Ex. atrovent, ipratropium bromide
— used predominantly in Nocturnal asthma.
— and in geriatric patients --> due to its
minimum cardio-toxic effect.

56. • Methylxanthine
as compared to other bronchodilators
less Broncho-dilating potential.
• 2 types:
— long-acting (t1/2 - 12 h) --> Ex. Theodur, theopec,
theolong
— short-acting --> Ex. Aminophylline, Caffeine, theophylline

57. Pharmacological actions
CNS:
— Caffeine, theophylline:
CNS stimulants
Primarily affect the higher centers.

58. Pharmacological actions
• Caffeine: 110 to 250 mg produces
— a sense of well-being
— alertness
— Clear thinking
— allays fatigue
— Tends to improve performance
and motor activity.

59. CVS:
— Directly stimulate the heart and increases --> force of
myocardial contractions & HR.
— Theophylline --> Tachycardia common with theophylline
— Caffeine --> Unpredictable effect
- CO & cardiac work ---> increased.
- HR --> decreases
- Cardiac arrhythmias --> At high doses .

60. Effect on BP is variable and unpredictable:-
- Vasomotor centre & direct cardiac
stimulation --> tends to raise BP.
- Vagal stimulation & direct vasodilatation
--> tends to lower BP.
- Usually a rise in systolic and fall in diastolic
BP is observed.

61. — Smooth muscles:
— Relaxation
— Most prominent effect exerted on -->
bronchi of asthmatics
— Theophylline is more potent than caffeine
— But the effect is much less marked compared
to inhaled beta R agonists
— Kidney:
- Mild diuretics

62. Q&A
1. Give action of methylxanthines on CNS.
2. What is action of Methylxanthines on bronchial smooth
muscles?
3. Name category of anti-asthmatic drugs which are more
acceptable in geriatric patients.
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63. — Skeletal muscles: 3 Types of actions
— Caffeine enhances --> contractile power of skeletal muscles.
— Increases --> release of Ca2* from sarcoplasmic reticulum
— facilitates neuromuscular transmission --> by increasing release of Ach

64. • Stomach:
Enhances secretion of acid & pepsin
Gastric irritant

65. • Mast cells and inflammatory cells:
Decreases the release of histamine
contribute to anti-Inflammatory action in bronchial asthma.

66. Mechanism of action:
— 3 distinct actions:-
(a) Release of Ca2+ --> from sarcoplasmic reticulum
(b) Inhibition of phosphodiesterase (PDE)
Inhibit conversion of cAMP & cGMP --> 5-AMP & 5-GMP
Increase in level of cAMP & cGMP
Bronchodilatation, cardiac stimulation & vasodilatation

67. c) Blockade of adenosine receptors:
— Adenosine acts as a local mediator --> in CNS, CVS and other organs.
The following effect of adenosine are inhibited
• Contracts smooth muscles especially bronchial
• Depresses cardiac pacemaker
• Inhibits gastric secretion.
• Dilates cerebral blood vessels

68. Management of asthmatic status (Severe asthma)
— Systemic corticosteroids: (Methyl prednisolone 125 mg every 6 h IV or
Prednisolone 50 mg/day per os or Hydrocortisone 200 mg)
— Oxygen
— Inhalations of short-acting Beta-2-agonists --> Salbutamol 5 mg or Fenoterol 2
mg given through nebulizer
- 3 times at 1st hour
- then once an hour till distinct improvement is achieved
- then 3 to 4 times a day.
— Inhaled anti-cholinergic drugs or IV Aminophylline.
— If non is effective --> artificial lung ventilation is needed.

69. Q&A
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