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.
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.
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.
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
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.
