1. PHARMACOLOGICAL BASIS OF
TREATMENT OF BRONCHIAL ASTHMA

2. Asthma - Greek word meaning “to
stay awake in order to breath” or
“difficulty in breathing”
 Asthma is a chronic inflammatory
disorder of the airways.


3. 
Chronically inflamed airways are
hyper responsive; they become
obstructed and airflow is limited by :
1. Broncho-constriction
2. Mucus plugs
3. Increased inflammation when
airways are exposed to various risk
factors.

4. 
Asthma is a chronic inflammatory disease in
which the patient suffers with reversible
episodes of airways obstruction due to
bronchial hyper-responsiveness.

5. Predisposing factors:
Heredity
 Age: Pediatric group most affected
 Sex: within 10 years of age male:
female ratio(2:1) and equal in adults.
 Allergens – Food, Inhalants, Bacteria .


6. Respiratory infections, pharmacologic
stimulants occupational factors,
exercise, climatic factors, low socioeconomic status.
 Passive smoking.
 Air pollution.
 Obesity.


7. Triggering Factors

Domestic dust mites

Air pollution

Tobacco smoke

Occupational irritants

Cockroach

Animal with fur

Pollen

8. 
Asthma affects 8% in adults and 10% in children.

Asthma is common in industrialized nations such
as Canada, England, Australia, Germany, and
New Zealand, where much of the data have
been collected.

The prevalence rate of severe asthma in
industrialized countries ranges from 2-10%

12. Pathophysiology
IgE-Antigen Complex
SALBUTAMO
L
Eosinophi
l
Activation
β2
Bronchodilitation
AT
P
AC
cAMP
THEOPHYLLINE
Chemical mediators
Histamine, LTC4, LTD4, LTB4,
Cytokines, Adenosine, PGD2, PAF,
ECP and Neuropeptides
β 2 AGONISTS
Inhibit release
PD
E
Bronchial Tone
AMP
Adenosine
M3
cGMP
CORTICOSTEROI
DS
NI
O
G
Bronchoconstriction
O
PI
U
M
Cause inflammation, oedema,
bronchospasm, muscus secretion,
epithelial damage
GT
P
GC
TR
Mast Cell
Degranulation
AN 3
S
TA
Activation
β 2 AGONISTS
IP
M RA
Basophil
Bronchial Smooth Muscle

13. IgE-Antigen Complex
Eosinophi
l
Basophil
Activation
Bronchodilitation
Activation
Mast Cell
Degranulation
NITRIC
OXIDE
DONORS
SOD.
CROMOGLYCATE
Bronchial Tone
Stabilises Mast Cells
Chemical mediators
Histamine, LTC4, LTD4, LTB4,
Cytokines, Adenosine, PGD2,
PAF,
ECP and Neuropeptides
Leukotrienes
LT-ANTAGONIST
Cause inflammation, oedema,
bronchospasm, muscus secretion,
epithelial damage
INFECTION
Bronchoconstriction
CORTICOSTEROI
DS
Bronchial Smooth Muscle

15. NEURAL CONTROL
PARASYMPATHETIC
+
Adenosine
Unmyelinated
Sensory C fiber
SO2,
Cigarette Smoke
Acetylcholine
A3
Mast Cell
+
+
A2
M3
Bronchial
Smooth Muscle
β2
+
Neuropeptides
NO
Circulating Catecholamines
SYMPATHETIC
Neurokinin A
Substance P
Mediators
N
A
N
C

16. ASTHMA MANIFESTS AS
1.
Breathlessness and
2.
Cough
3.
Recurrent episodes of wheezing
4.
Chest tightness

17. 
Goals of asthma therapy
› To prevent chronic and troublesome symptoms
› To maintain near normal pulmonary function
› To maintain normal activity levels (including
exercise and other physical activity)
› To prevent recurrent exacerbations of asthma
and minimise the need for emergency
department visits to hospitalizations

18. › To provide optimal pharmacotherapy with
minimal or no adverse effects
› To meet pts & families expectations and
satisfaction with asthma care.

19. Drugs used in Bronchial Asthma
Bronchodilators
Selective β2- Agonists
Short acting

Salbutamol

Terbutaline

Remiterol

Fenoterol
1.
Long-acting

Salmeterol,

Formoterol,

Bambuterol.
2. Non-selective
Sympathomimetics
 Adrenaline
 Ephedrine,
 Isoprenaline,
 Orciprenaline,
(Metaproterenol).
 Isoetharine.

20. 3. Anticholinergics - Ipratropium, Tiotropium,
Oxitropium,
4. Methyl Xanthines- Theophylline, Aminophylline,
Diprophylline, choline theophyllinate.
Anti inflammatory drugs.
Corticosteroids
1.
Oral: Prednisolone, Methylprednisolone,
2.
Parenteral: Mehtyl Prednisolone, Hydrocorticsone
3.
Inhalational: Beclomethasone, fluticasone,
Triamcinolone, Budesonide, Flunisolide

21. 
Mast Cell Stabilisers
Sodium Cromoglvcate, Nedocromil, Ketotifen,

Leukotriene Modulators:
1. 5-Lipoxygenase inhibitor: Zileuton
2. LT-rceptor Antagonists: Zafirlukast,
Montelukast, Iralukast, Pranlukast,

Monoclonal Anti-lgE Antibody
omalizumab

22. 1. β2-Selective adrenoceptor
agonist
most widely used sympathomimetics for the
treatment of asthma at the present time.
1.
Short acting:- albuterol-Terbutaline
used only for acute attack of bronchospasm
1.
Long acting:- salmeterol –formeterol
used for only prophlaxis and not for acute
attack of bronchospasm.

23. Selective β2 receptor agonist
mechanism of action
Stimulation of
β2-receptors
Bronchial smooth
muscle relaxation
Intracellular
cAMP

24. Selectively β2 receptor agonist
Route of administration:
Usually delivered via a metered dose inhaler
with immediate effect

Orally used in children.

i.v used for acute attack.

S.C. (terbutaline)
2. Adverse effect:

Cardiac arrhythmias (at high dose has β1
effects)

Tolerance to β agonist (tachyphylaxis)

Skeletal muscle tremors.
1.


25. Non-selective Sympathomimetics
Adrenaline/epinephrine:
Adrenaline/epinephrine

Agonist of α and β receptor

Adverse effect of cardiovascular system usually
occurs thereby less usable

S.C. injection
Ephedrine:

Orally administered

Similar action to Adrenaline

Less usable for central excitation

26. Mechanism of Action: It stimulates the β2 receptors
and cause bronchodilation.
Rout of administration:

As aerosol
Adverse effects:

Tachycardia,

Hypertension

Worsening of angina and even arrhythmias

27. They are divided into two types:

1. Salt complex: increased water solubility
without augmentation of pharmacological
action, such as: aminophylline.

2. Slow-release form: small fluctuation of blood
concentration after oral administration thus used
for nocturnal attack of asthma.

28. Theophylline
Mechanism of action

Inhibit activity of PDE
cAMP
bronchial relaxation
cAMP
PDE
AMP
3. Inhibition of the cell surface receptor of
adenosine

29. Theophylline
1.
Route of administration:

Orally

Metabolised by P450 enzyme system
2. Pharmacodynamics

Direct positive chronotropic and inotropic
effects on the heart.

In large dose, these agents also relax
vascular smooth muscle.

30. Theophylline:
Adverse effect

It has a narrow therapeutic index

Its therapeutic and toxic effects are related to
its plasma concentration.

<20mg/L: nausea, vomiting, headache,
anxiety, abdominal discomfort.

20-40mg/L: arrhythmia

31. Muscarinic antagonist
1. Mechanism:

Act by competitive blocking of muscarinic
receptors (M3 subtype)
2. Route of administration:

Metered dose inhaler e.g Ipratropium bromide
3. indication:

Used as adjuncts to β2-adrenoceptor agonist in
treatment of asthma.

32. Anti-inflammatory drug
Glucocorticoids

Mechanism:
1.
Depress the inflammatory response in bronchial
mucosa thus diminish bronchial
hyperresponsiveness.
2.
Anti-inflammatory effect (inhibit phospholypaseA2)
3.
Immunosuppressive effect.

33. Glucocorticoids
Route of administration
1.
Metered dose inhaler: (deeply & slowly inhale)
Beclomethasone, dexamethasone
2.
Intravenous used for: severe asthma status
asthmaticus (prednisolone or hydrocortisone)
3.
oral

34. Monoclonal anti IgE antibody
Omalizumab
Mechanism of action:

It prevents the binding of IgE to mast cell & thus
prevents mast cell degranulation
Rout of administration:

i.v or s.c
Side effects:

Redness, stinging, itching, induration.

35. 1.
NSAIDS like aspirin,ibuprofen,diclofenac etc.
(paracetamol can be used)
2.
Beta-adrenergic blockers
3.
Cholinergic agents.

36. 1. Mild episodic asthma
Inhaled short-acting beta2
agonist at onset of each episode (step-1)
2. Seasonal asthma
start regular inhaled cromoglycate/low dose
inhaled steroid(200-400micro g/day) 3-4 wks before
anticipated seasonal attacks continue till 3-4 wks
after the season is over treat individual episodes
with inhaled short acting β2 agonist.

37. 3. Mild chronic asthma with
occasional exacerbations:
regular inhaled cromoglycate, episodic-short
acting β2 agonist(step-2)
4. Moderate asthma with frequent
exacerbations:
increases doses of steroid (up to 800μg/day)
+inhaled long acting β2 agonist(step-3)

38. 5. Severe asthma:
Regular high dose inhaled (steroids 800-2000μg/day)
though a large volume spacer device + inhaled longacting β2 agonist (salmeterol) twice daily
.

39. 6. Status asthmaticus

Any pt of asthma has the potential to develop
acute severe asthma which may be life
Threatening.

upper respiratory tract infection is the most
common precipitant.

40. Management of status asthmaticus

Hydrocortisone hemisuccinate 100mg
I.V stat
followed by 100-200mg 4-8 hourly infusion

Nebulized salbutamol (2.5-5mg)+ipratropium
bromide (0.5mg) intermittent inhalations driven
by 02.

41. 
High flow humidified oxygen inhalation.

Salbutamol/terbutaline 0.4mg i.m/s.c may be
added, since inhaled drug may not reach
smaller bronchi due to severe
narrowing/plugging.

Intubation & mechanical ventilation, if needed.

42. 
Treat chest infection with intensive antibiotic
therapy.

Correct dehydration and acidosis with
saline+sod. bicarbonate/lactate infusion.

43. Aerosol Delivery of Drugs

High local concentration in bronchioles

Low systemic side effect.

Increased bioavailability.

Optimal particle size for deposition in
airways – 1to 5μm
small

44. 
Four classes of antiasthma drugs, i.e β2 agonists,
anti-cholinergics, cromoglycate and
Glucocorticoids are available for inhalational use.

They are aimed at delivering the drug to the site
of action so that lower dose is needed and
systemic side effects are minimized.

Most asthma patients are now maintained on
inhaled medication only.

45. Aerosol Delivery Devices:
Liquid aerosols

Metered dose inhaler (MDI)

Nebulizer
Powdered drugs

Dry powder inhaler (DPI), Spinhaler, Rotahaler

46. Pressurized Metered Dose Inhaler
(pMDI)

In pMDI drug is dissolved or suspended in
propellant under pressure and when actuated
releases a predetermined dose.

Pressurized MDI can be used with spacer or
without spacer.

User of spacer improves drug deposition in lungs
and reduces oropharyngeal drug deposition.

Use of spacer reduces oropharyngeal drug
deposition by 10-15 folds when compared to pMDI
alone.

47. 
Spacer acts as reservoir for drug from which
patients can breathe easily.

Depending on patient’s technique, drug
delivery varies from 7 to 20%.

An oropharyngeal drug deposition is about
80% with pMDI.

48. 
The particle size distribution through HFA was 1.07
micrometer and that of with CFC is 3.36
micrometer.

Lung deposition of drug with HFA is 50% while with
CFC it is 10-20%.

With HFA the oropharyngeal deposition is 30%
whereas with CFC it is 90-94%.

49. 
Spacer/holding chamber
 Slow (3-5 secs) inhalation or tidal breathing
immediately following actuation
 Easier to use than MDI alone
 Recommended for anyone using MDI
Spacer

50. Nebulizers

Nebulizer convert a liquid solution or
suspension into an aerosol using either a jet
or ultrasonic energy.

Aerosol is then delivered to the patient
through either a face mask or a
mouthpiece.

51. 
Nebulzer requires least patient
cooperation and coordination.

Nebulzers are preferred in patients who
are unable to use other devices or in
acute attacks when inspiratory flow is
limited.

52. 
Only about 13% of the dose used is deposited
in the lungs.

The doses used in nebulizers are higher than
those used in other aerosol devices.

Therefore patients will receive 10-20 times the
dose received from a MDI.

53. Dry Powder Inhaler (DPI)

In PDI drug is provided as micronized particles in
large aggregates with or without carrier
substances.

Drug delivery in DPI depends on patient’s
inspiratory effort to disperse the drug and deliver it
to the lungs.

Drugs deposition in lungs with DPI is 15-40% with
considerable inter device variability and drug
deposition in oropharynx is <60%.

DPI dose not require propellants and hand breath
coordination

54. › Rapid (1-2 secs), deep inhalation; dose lost if
client exhales through device
› Population: > 4-5 years
Rotahaler

55. Spinhaler
1. Hold spinhaler upright with mouthpiece
downwards, and unscrew body
2. Put coloured end of spincap into cup of
propeller, making sure it spins freely
3. Screw the two parts together and hold
horizontal. Move grey sleeve up and down

56. once or twice, this will pierce capsule
4. Breathe out gently, tilt head back, put
spinhaler into mouth so lips touch flange and
breathe in quickly and deeply
5. Remove spinhaler from mouth and hold
breath for about 10 seconds, then breathe out
slowly
6. If any powder is left in spincap, repeat steps
4 and 5 until it is empty
Always Demonstrate To The Patient How To Use
The Spinhaler

57. Route of Administration & Dose
Drug
1. Selective β2
Agonists
 Salbutamol
 Formoterol

Salmeterol

Terbutaline
Route & Dose
Inhalant: 90 μg/puff aerosol; 0.83,
0.5% solution for nebulized
Oral: 2,4 mg tab; 2mg/5ml syrup.
Inhalant: 12 μg/puff aerosol.
12mg/unit inhalant powder.
Inhalant aerosol: 25 μg salmeterol
base/puff in 60 & 120 dose
containers inhalant powder
50 μg/ unit
Inhalant: 0.2mg/puff aerosol.
Oral: 2.5, 5 mg tab.

58. Cont….
2. Selective
Sympathomimetics
 Ephedrine

Epinephrine
3. Anti-cholinergics

Ipratropium.
Oral: 25mg capsules
Parenteral: 25,50mg/ml/ injection
Inhalant: 0.1,1, 2.25% for nebulization
Parenteral: 1:10000 (0.1mg/ml)
Aerosol: 18mg/μg/puff in 200 metereddose inhaler.
4. Methyl xanthenes
 Aminophylline
Oral: 105mg/5ml liquid, 100, 200mg
tablet
5. Leukotriene Inhibitors
 Montelukast
 Zafirlukast
 Zileuton
Oral: 10 mg tablets, chewable tablets
Oral: 20 mg tablets
Oral: 600 mg tablets

59. Cont…
6. Corticosteroids
 Beclomethasone
Budesonide
 Dexamethasone

Aerosol Powder: 42 μg/puff in 200 dose
container
Aerosol Powder: 160 μg/activation
Aerosol powder: 84 μg/puff in 170 dose
container
7. Mast cell
stabilisers
Pulmonary aerosol: 800 μg/puff in 200 dose
 Cromolyn sodium
container; 20mg/2ml for nebulization.
 Nedocromil sodium Pulmonary aerosol: 1.75 mg/puff in 113
metered-dose container.

60. 
Asthma cannot be cured but can be
controlled with regular use of medications.

Asthma is treated with two types of medicines:

Long term control

Quick-relief medicines

61. 
Long term control medicines help to reduce
airway inflammation and prevent asthma
symptoms.

Quick-relief,or “rescue", medicines relieve
asthma symptoms that may flare up.

Initial asthma treatment will depend on severity
of the disease.

62. 
Patient counseling on drug therapy should
concentrate on drugs used to relieve
symptoms, drugs used to prevent asthma
attacks and those drugs which are given only
as reverse treatment for severe attacks.