Respiratory System (cont…)

Functional anatomy of
the respiratory
system: Conducting
Zone
-nose
-nasal cavity
-pharynx
-larynx
-trachea
-bronchi
Respiratory Zone
-respiratory bronchioles
-alveolar ducts 1
Respiratory system
(Cont..)

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Respiratory System (Cont…)
Basic functions :-

 Gas exchange

 Protection

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 PULMONARY EDEMA PULMONARY EMBOLISM

PULMONARY HAEMORRHAGE PNEUMOTHORAX

ASTHMA COPD
RESPIRATORY DISEASES

PNEUMONIA CYSTIC FIBROSIS

RESPIRATORY TUMORS TUBERCULOSIS

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ASTHMA

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 What is Asthma..???
 Chronic inflammatory disease of the

airways.

Characterized by reversible airflow

obstruction and bronchospasm.

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Asthma

□ Asthma is a common chronic inflammatory condition of airway which cause

the lung hyperactive to various stimuli.

□ In susceptible individuals this causes symptoms which usually associated with

widespread but variable airflow obstruction that is often reversible either
spontaneously or with treatment.

Epidemiology:
-In developed countries, the prevalence is about 20%, with about 10-15% of the
10-20 years age group.
- study suggest that up to 20% workers may develop the symptoms if they
exposed to sensitizing agents.
-The prevalence in developing countries is similar but much lower rate in
underdeveloped countries.
□ The incidence peaks at age 10-20 years with about 20% of children wheezing
annually and there is secondary peak at the age of 65 years. These two peaks
corresponds to two main clinical types.

Extrinsic or episodic asthma- tend to occur in younger age group, relatively

mild and is related to atopy
 Intrinsic or cryptogenic asthma- older with more persistent disease.
These distinction has little value as because 30% of the cases have mixed type.

□ Above 20 years age more female are affected than male, the ratio 1:1.5.

□ Interestingly high salt intake has been shown to increase bronchial hyper
responsiveness in men but not in women.

□ Average dietary intake of magnesium shown to improve FEV1 and reduce

hyperactivity and wheezing.
 Symptoms of Asthma
The clinical hallmarks of
Asthma
 Coughing,
 Shortness of breath,
 Chest tightness,
 Wheezing

The Symptom of Asthma

 Smooth muscle contraction
 Vascular congestion
 Bronchial wall edema
 Thick, tenacious secretion
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 Causes of Asthma

Environmental And Genetic

Factors

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Pathophysiology of asthma

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 Diagnosis of Asthma
Based on
 Response to therapy
 Pattern of symptoms
Response to
therapy

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 Diagnosis of Asthma (cont..)
Pattern of symptoms
List of indicators:
 Wheezing
 history of any of the following:
 Cough, worse particularly at night
 Recurrent wheeze
 Recurrent difficulty in breathing
 Recurrent chest tightness
 Symptoms occur or worsen in the presence
of:
 Exercise
 Viral infection
 Animals with fur or hair
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 Diagnosis of Asthma (cont..)
 House-dust mites
 Mold
 Smoke (tobacco, wood)
 Pollen
 Changes in weather
 Strong emotional expression (laughing or crying hard)
 Airborne chemicals or dusts
 Menstrual cycles
Symptoms occur or worsen at night, awakening
the patient
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 Treatment for Asthma
Non-pharmacological
treatment

Pharmacological treatment

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 Non-pharmacological treatment
for Asthma
Risk factor reduction

Pulmonary
rehabilitatation

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includes:

1. Avoiding the contact with allergen.

2. Elimination of trigger factors (rational job placement, changing the residence,
psychological and physical adaptation, careful drug using) is the second condition
for successful asthma treatment.
3. Optimally selected medical care is the base of asthma management.
 Non-pharmacological treatment
for Asthma (cont..)
Bronchial
thermoplasty

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Pharmacological treatment for
Asthma

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Treatment:

Asthma ………. inflammation and bronchoconstriction

increase bronchodilatation reduce inflammation

Main Goals

Restoration of normal airway and prevention of sever attack.

Anti-inflammatory drugs should be given to all patients with all but

mildest of symptoms. Other measures, such as avoidance of
recognized trigger factors.

The lowest possible doses of drug should be given to minimize side

effects.
Approaches of treatment

a. Prevent : AG:AB reaction

b. Suppression of inflammation and bronchial hyperactivity
c. Prevention of mediator release
d. Antagonizing the release mediator
e. Blocked of constrictor neurotransmitter
f. Mimicking dilator neurotransmitter
g. Direct acting bronchodilator
 Drug therapy
2 drug categories are used:
Antiinflammatory drugs
Bronchodilators
(basic)

Are divided into: 3 groups:

hormone-containing
(corticosteroids) b2-agonists

nonhormone-containing anticholinergic drugs

(cromones, leukotriene
receptor antagonists) methylxanthines
Antibodies: Omalizumab
 Bronchodilators
Anticholinergic
b2-agonists drugs

Stimulates reduce tonus

b2-adrenergic of vagus
receptors of bronchi
Smooth
muscle
relaxation

inhibit phosphodiesterase
Methylxanthines
Drugs used in asthma
A. Bronchodilators
β2 Adrenergic Receptor Agonist: Salbutamol,
Terbutaline, Bambuterol, Salmeterol ,
Formoterol, Ephedrine.
Methylxanthine: Theophylline, Aminophylline, Chonine
theophyllinate, Hydroxyethyl theophylline, Theophylline
ethanolate of piperazine, Doxophylline.
Anticholinergics: Ipratropium bromide, Tiotropium
bromide.
B. Glucocorticoids
 Systemic: Hydrocortisone, Prednisolone, and others.

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 Drugs used in asthma (cont..)
Inhalational: Beclomethasone dipropionate, Budesonide,
Fluticasone propionate, Flunisolide, Ciclesonide.
C. Leukotriene-Receptor Antagonists and Leukotriene-
Synthesis Inhibitors
Montelucast , Zafirlucast, Zileuton.
D. Anti-IgE antibody
Omalizumab
E. Mast cell stabilizers
 Cromolyn sodium, Nedocromil sodium

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A. Bronchodilators
β2 Adrenergic Receptor Agonist

Methylxanthine

Anticholinergic Agents

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 Actions of Bronchodilators
Stimulate beta-2 receptor sites

Relax smooth muscle in airway

walls

Dilate airways

Lower resistance to air flow

Decrease respiratory effort

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Mechanism of action of
bronchodilators

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 β2 Adrenergic Receptor Agonist
Short-Acting β2 Adrenergic Receptor Agonists:-
Albuterol , levalbuterol, metaproterenol, terbutaline,
and pirbuterol.
Long-Acting β2 Adrenergic Receptor Agonists:-
Salmeterol xinafoate and formoterol
Oral therapy with β2 Adrenergic Receptor
Agonists:-
Albuterol, metaproterenol, terbutaline

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Cont………
Pharmacological Effects
Inhibit microvascular leakage
Increase mucociliary transport
Affecting the mucus secretions
Increasing ciliary activity

Toxicities
Cardiac arrhythmias,
Hypoxemia acutely,
Tolerance.

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Methylxanthines in comparison with other
bronchodilators have the less bronchodilating
potential. There are long-acting (>12 h) - as well as
short-acting (aminophylline, theophylline) drugs in
this group.
Methylxanthine

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 Anticholinergic drugs

Anticholinergics:

Ipratropium bromide, Tiotropium bromide.

predominantly in nighttime asthma and in
elderly patients because of the least
cardiotoxic effect.

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B. Glucocorticoids
Anti-inflammatory activity
 cell membrane stabilization

 Block leukotriene synthesis

 Inhibit cytokine production

 Reduction of mucosal edema

 Up- regulate β2 adrenoreceptor

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 B. Glucocorticoids (cont..)
Inhalational: Beclomethasone dipropionate,

Budesonide, Fluticasone propionate, Flunisolide,

Ciclesonide.

Toxicity of inhaled corticoid

 Oropharyngeal Candidiasis

 Systemic: Hydrocortisone, Prednisolone, and

others.

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B. Glucocorticoids (cont..)
Side effects
Metabolic effects,
Growth suppression,
Fluid retention, osteoporosis,
Increase susceptibility to
infection,
Cataract, GI symptoms,
Adrenal suppression

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C. Leukotriene-Receptor Antagonists
and Leukotriene-Synthesis Inhibitors
Leukotriene-Receptor Antagonists
Zafirlukast,

Montelukast

Leukotriene-Synthesis Inhibitors
Zileuton

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 Mechanism of action
•Selective and
competitive
receptor antagonist
of Leukotriene
D4 and E4
(LTD4 and LTE4),
components
of slow-
reacting
substance
of anaphylaxis
(SRSA).
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D. Anti-IgE antibody

Omalizumab(Anti-IgEMab)
 Recombinant humanized monoclonal antibody

targeted against IgE.

Directed against cytokines (IL-4, IL-5, and IL-13

Inhibits the binding of IgE to mast cells.

Reduced exacerbations 88%

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Mechanism Of Action of Omalizumab

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E. Mast cell stabilizers

Cromolyn & Nedocromil Sodium

Mechanism of Action:
Inhibit mast cells degranulation

Little inhibitory from basophils

Inhibiting parasympathetic &

cough reflex
Inhibit leukocyte trafficking in
asthmatic airways
Inhibition inflammatory response 45
 E. Mast cell stabilizers (cont..)
Clinical Use
blocks the Bronchoconstriction
by antigen inhalation
by exercise
by aspirin
by allergen
Adverse/Side effects:
Throat irritation, Cough, Wheezing,
Mouth dryness, Chest tightness ,

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Inhaled asthma medication
Drugs used for inhalation:-

 β2 Adrenergic Receptor Agonist

Anticholinergics

Cromoglycate

 Glucocorticoids

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Management:
Chronic asthma
□ The pharmacological management of asthma depends upon the
frequency and severity of patients symptoms

□ The preferred route of drug administration used in management of

asthma is by inhalation. This allows the drug to be delivered directly to
the airway in smaller dose and fewer side effects that if systemic or
parenteral routes were used.

□ Inhaled bronchodialtor has faster onset of action than when

administer systemically and give better protection from
bronchoconstriction.

□ Treatment of chronic asthma is usually give in stepwise progression.

□ If necessary type of inhaler technique should be assessed .

 Flow chart
Bronchodilator- beta agonist
Inhaled steroids- (corticosteroid or cromen
steroids)
Additional Bronchodilator( anti-cholinergic,
Xanthine)
High doses beta agonist( nebulisation)
Oral steroids
Guideline for the management of chronic
Asthma
Step-1
Occasional use of bronchodilator
Inhaled short acting beta agonist as
required for the symptoms relief are
acceptable .
If they are needed more than once daily
move to step 2
Step-2
Regular inhaled anti-inflammatory
agents.
Inhaled short acting beta agonist as
required + Beclomethasone 100-
400µg twice daily
Or, Fluticason 50-200µg twice daily
Alternatively, Cromoglycolate or
Nedocromil sodium. If control is not
achieved start inhaled steroids.
Step- 3
High dose inhaled steroids or Low dose
inhaled steroids + long acting inhaled beta
agonist
Inhaled short acting beta agonist as required
+
either Beclomethasone or Budesonide 800-
2000 µg daily
Or Fluticasone 400-1000µg daily through
large volume spacer.
Or
Beclomethasone or budesonide 100-400 µg
twice daily or Fluticasone 50-200µg daily
twice + Salmetrol 50 µg twice daily
Guideline for the management of chronic
Asthma
Step-4
High dose of inhaled steroids and regular Step- 5
bronchodilators Addition of regular steroids tablets

Inhaled short acting beta agonists as Inhaled short acting beta agonist as
required with inhaled required with inhaled Beclomethasone or
beclomethasone/Budesonide 800- Budesonide 800-2000 µg daily or
2000µg daily or Fluticasone 400-1000 µg Fluticasone 400-1000 µg via large volume
daily via large volume spacer spacer
+ + One or more long acting
Sequential therapeutic trial of Bronchodilators
□ one or more of Inhaled long acting + regular Prednisolone Tablets in single
beta agonist dose
□ Sustained release Theophylline
□ Inhaled Ipratropium or Oxytropium
□ Long acting beta agonist tablets
□ High dose inhaled bronchodilator
□ Cromoglycate or nedocromil
Guideline for the treatment of
Chronic Asthma
Step-6
Review the treatment in every
three to six months. If control is
achieved stepwise reduction in
treatment may be possible

Recent treatment at stage 4 or 5

include steroid tablets.
Devices used for inhalation

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Devices used for inhalation
(cont..)

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Use of spacer in asthma

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