1. BRONCHIAL
ASTHMA

2. Introducation
 Asthma
-
derived from Greek word
To stay awake in order to breath
OR
Difficulty in breathing

3.  Asthma
is a chronic inflammatory
disease in which patient suffers with
reversible
episodes
of
airway
obstruction due to bronchial hyper
responsiveness.
(Damage of bronchial epithelium (mucous layer)
by chemical mediators. So direct expose of
bronchi to irritant stimuli)

4. It has 2phases
 Early phase
(Acute)
-Due to bronchial
smooth muscle
spasm.
- Excessive
secretion of
mucus.
 Chronic
phase
Continuous
Inflammation,
fibrosis, oedma,
necrosis of
bronchial
epithelial cells.

5. Clinical hallmarks
Recurrent episodic coughing
 Shortness of breathing
 Chest tightness
 Wheezing

Symptoms are worsening at night

6. Asthma described as two type
 Extrinsic
(Atopic extrinsic asthma)

It is associated with
exposure of specific
allergen
It is associated with
some non specific
stimulants
Ex:- House dust, pollen
Ex:- chemical
It is episodic and less
prone to develop to
status asthmaticus.
Intrinsic
(Non atopic extrinsic asthma)
irritants
It is perenial and prone
to develop to status
asthmaticus.

7. Pathophysiology
Allergen enter (Foreign body)
Immunological reaction (AG:AB Complex formation)
Circulation in blood
Basophiles, Neutrophilis engulf
Cause neutralization
contd..,

8. Whenever same allergen re exposed
Activation of AG:AB complex
Reacts with lung mast cells
(Degranulation of mast cells)
Spasmogens release
(Like Histamine,5HT,PGs,LT4, Cytokines)

9. IgE-Antigen Complex
Basophil
Eosinophil
Activation
Activation

Mast Cell
Degranulation
Chemical mediators
Histamine, LTC4, LTD4, LTB4,
Cytokines, Adenosine, PGD2, PAF,
ECP and Neuropeptides
Cause inflammation, oedema,
bronchospasm, muscus secretion,
epithelial damage

In early phase these
mediators leads to
bronchoconstriction
Bronchial Tone
In late phase
inflammation,
pulmonary oedema,
mucous secretion
bronchial
hypersensivity and
epithelial damage

10. Asthma therapy

It divided into two categories
1.
Short term relievers.( Bronchodilators)
2.
Long term controllers.

11. IgE-Antigen Complex
SALBUTAMOL
Basophil
Eosinophil
Activation
β2 AGONISTS
Activation
Bronchodilitation
5AMP
THEOPHYLLINE
PDE
cAMP
β2
AC
Mast Cell
Degranulation
Chemical mediators
Histamine, LTC4, LTD4, LTB4,
Cytokines, Adenosine, PGD2, PAF,
ECP and Neuropeptides
ATP
Bronchial Tone
THEOPHYLLINE
GTP
GC
β2 AGONISTS
Inhibit release
Adenosine
cGMP
Cause inflammation, oedema,
bronchospasm, muscus secretion,
epithelial damage
M3
Bronchoconstriction
CARTICOSTEROIDS
Bronchial Smooth Muscle

12. IgE-Antigen Complex
Eosinophil
Basophil
Bronchodilitation
Activation
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
Bronchoconstriction
CARTICOSTEROIDS
INFECTION
Bronchial Smooth Muscle

13. Drugs Used in Bronchial Asthma
BRONCHODILATORS
Selective β2–
Agonists
Short acting
1.





Salbutamol,
Terbutaline,
Remiterol,
Fenoterol,
Bitolterol
Long-acting



Salmeterol,
Formoterol,
Bambuterol
2.
Non-Selective
Sympathomimetics

Adrenaline,
Ephedrine,
Isoprenaline,
Orciprenaline
(Metaproterenol),
Isoetharine





14. 3. Anticholinergics
Ipatropium, Tiotropium, Oxitropium
4. Methyl Xanthines
Theophylline, Aminophylline, Diprophylline,
Choline theophyllinate
Anti inflammatory Drugs (Controllers)
Corticosteroids
1. Oral : Prednisolone, Methylprednisolone
2. Parenteral : Methyl prednisolone,
Hydrocortisone
3. Inhalational : Beclomethasome, Fluticasone,
Triamcinolone, Budesonide, Flunisolide

15. 
Mast Cell Stabilisers
Sodium Cromoglycate, Nedocromil, Ketotifen

Leukotriene Modulators:
1. 5-Lipoxygenase Inhibitor : Zileuton
2. LT – Receptor Antagonists : Zafirlukast,
Montelukast, Iralukast, Pranlukast

Monoclonal Anti-IgE Antibody

Omalizumab
Miscellaneous:
NO, Calcium channel blockers

16. Sympathomimetic agents




ß2 receptors are present in the airway
smooth muscle.
These agents acts on ß2 receptors cause
bronchodilatation
These are only provide relief
M.O.A:

cAMP
 Bonchodilatation
 Release of bronchoconstricting mediators
from mast cells
 Inhibit macrovascular leakage
 Mucociliary clearence

17. 
Epinephrine:

Rapid bronchodilator when inj/SC/inhaled(320µg/puff)
Onset of action 15min after inhalation
Duration of action:60-90min.


ADR:- Acts on β1




receptor cause
Tachycardia
Arrhythmias
Worsening angi
So rarely prescribed.

18. 

Ephedrine: α,β1, β2
Ephedrine has a longer action

Oral activity

Lower potency

Pronounced central effects.

19. β2 Selective

Short acting : Terbutaline, Salnutamol

On inhalation they have rapid onset(1-5Min)
Short duration of action preferred for acute attack
Route: Inhalation 100-200µg/6hourly
Other MDI, Oral, IM, IV




Terbutaline is the only one drug safely used during
the pregnancy.

20. Long acting: Salmeterol, bambutarol
Long acting but slow onset of action
 Preferred for maintenance therapy
 Not useful in acute attack due to slow onset of
action
Route: Inhalation 50µg twice daily.

Formoterol:
 Long acting
 Rapid onset
 Preferred for prophylaxis due to long acting
Route: Inhalation 12-24µg twice daily

21. ADR of Sympathomimetics

By oral route stimulate β2 receptors in skeletal
muscle cause tremors, Orthostatic hypotension.

Tachycardia (High dos also stimulate β1
receptors in heart)

Restlessness

Tolarance occurs.

22. Antimuscurnic agent

Less effective then β agonists
MOA: By blocking M3 receptors on air way smooth
muscle and prevents Ach action.
-They acts by cGMP levels in bronchial smooth
muscle.

Ipatropium:-Poor absorption from
circulation
-Do not cross BBB.
-Also mucus secretion
bronchi
into
systemic
Ipatropium + β2 (Salbutamol) work better in serve
asthma and long duration of action

23. Methyl Xanthenes

MOA:
i) Inhibition of PDE 3,4. These enzyme are responsible
for metabolism of cAMP.
ii) Blockade of Adenosine receptors.

Actions:
 Theophyline
exhibits bronchodilatory action
 Anti Inflammatory
 Immunomodulator
 Respiratory stimulation
 Diaphragmatic contractility
 Mucociliary clearance

24. 
Pharmaco Kinetics:

Oral/Parental
 Food delay the rate of absorption
 Well distributed
 Cross placental & BBB
 Metabolized in Liver
 Excreted in urine

25. ADR: Low therapeutic window, CNS stimulant drugs
Plasma levels 10-20µg/ml, Narrow safety
Restlessness, insomnia, headache, tremors
CNS
Nausea,
Vomiting GIT
Peptic ulcer
40µg/ml
20µg/ml
Xanthenes
Diuresis
20µg/ml
Heart
Tachycardia, palpitation, hypotension, arrythimias
Theophyline: potent vasodilator, reflex tachcardia, oral route
Aminophyline: Slow IV infusion

26. Corticosteroids (Controllers)

Glucocorticosteriods induce synthesis of lipocotrin
which inhibits pholipaseA2 there by preventing
formation of mediators such as PGs,TAX2, LTand
other mediators.

Actions:
Anti
allergic,
anti
inflammatory,
immunosuppressant ( AG:AB reactions ), Mucosal
oedema,
bronchial hyperactivity, Enhance β
adrenergic action by up regulation of β2 receptors in
lung.

27. 
Inhalator
glucocorticosteriods
such
as
beclomethasone, budesonide and fluticasone are
used as prophylactic agents in asthma.

PK:
Well tolerated
less systemic side effects.


Common side effects:
 Dryness of mouth
 Voice change
 Oropharangeal candidiats.
Systemic are used in acute severe and chronic severe
asthma.

28. Mast cell stabilizers
Non bronchodilating, Non steroid drugs, used for prophylactic
treat.
MOA:
 Prevent degranulation and release of chemical mediators from
the mast cells.
 They stabilize the mast cells by preventing transmembarane
influx of Ca ions.
PK:
 Highly ionized
 Least systemic absorption
 well tolerated.
Uses: Allergic asthma, allergic conjunctivitis, allergic rhinitis,
allergic dermatitis.
Ketotifen (Mast stab.+ Antihistamincs)


29. LT Modulators








LT are powerful bronchoconstrictors.
Action by preventing their synthesis or blocking
effect on cys LT receptors
Synthesis inhibitors (Lipooxygenase)
Zafirlukast,Montelukast
PK:
Well absorbed after oral administration
Highly bound to plasma protein
Metabolized by liver
Effective for prophylactic treat of mild asthma.

30. ADR:
 Head ache
 skin rashes
 rarely eosinophilia
 Zileuton cause hepatic toxicity.

31. Monoclonal anti IgE antibody







MOA:- AG:Ab complex formation by AB action
Omalizumab:
Recombinant
humanized
monoclonal antibody.
Inhibit the binding site of IgE to mast cells and
basophils
PK: administered parentarally
Uses: Moderate to severe asthma and allergic
disorders.
Indicated for asthmatic patients who are not
adequately
controlled
by
inhalational
corticosteroids.
ADR: Inj site redness, itching, stinging.

32. Miscellaneous
NO: It dilate pulmonary blood vessels and
relax airway smooth muscle.
 Uses: For acute severe asthma and
management of pulmonary hypertension.

Ca channel blockers:
 Broncho constriction ultimately involves
some degree of ca into cells Nefedpine /
Verapamil should provide relief in asthma.


33. RX Status asthmatics (Acute severe asthma)
 Status
asthmatics a severe acute
asthma, which is a life threatening
condition involving exhaustion,
cyanosis, bradicardia,hypotension,
dehydration
and
metabolic
acidosis.

34. 
Humidified O2 inhalation

Inj. Aminophyline 500mg in 10ml of 5% Glucose IV Slow

Neubulized β2 adrenergic agonist + anti cholinergic agent

Systemic glucocorticosteroids IV (Hydrocortisone 200mgIV)
immediately

IV fluids to correct dehydration.

K supplements: To correct hypokalemia produced by
repeated administration of salbutamol.

NaHCo3 (Sodium bicarbonate) to treat acidosis.

Antibiotics to treat infection (Cap. Ampicillin 250mg 1tab tds-

35. DRUGS TO BE AVOIDED IN ASTHMA

β adrenergic blockers

Cholinergic agents

NSAIDS ( cause hyperapoenia) except
paraceatamol.