4.1- Review Pathophysiology & Introduction to Pharmacology of Respiratory 07avril2014-jan2021_102114.ppt

Pathophysiology and pharmacology of respiratory system

1. Review Pathophysiology &
Introduction to Pharmacology of
Respiratory Tract
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2. Learning Objectives
–List mediators of inflammations (pro-inflammatory and anti-
inflammatory) in respiratory diseases and describe the origin,
physiologic and pathogenic effects
–Describe the synthesis of prostaglandins, thromboxanes,
leukotrienes from arachidonic acid.
–Explain physiologic and pathophysiologic roles of esicosanoids
in regulation of local blood flow, airway resistance,
inflammation and nociception
–Identify Respiratory Tract Pathologies that require drug
therapy (Asthma, bronchitis, Pulmonary Artery Hypertension)
•Describe Pathophysiology of each disorder
•Describe Airway elements involved disease pathogenesis
–(muscle, nerves, secretory cells, blood vessels, blood cells, epithelium, immune
cells)
–list Drug Targets for the Treatment of Respiratory Pathologies
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3. Figure 4-4Trachea, lung, bronchi, bronchioles, and alveoli

4. Figure 4-7Gas exchange

5. Airway Anatomy
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6. Control of bronchomotor tone
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7. Sensory nerves
Bertrand & Geppetti (1996) TiPS 17,255-9
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8. Control of Airway Smooth
Muscle
•Neural control
–SNS-beta receptors causing dilatation
•direct effect weak
•indirect effect predominates
–Parasympathetic-muscarinic receptors
causing constriction
–NANC nerves (non-adrenergic, non-
cholinergic)
•Inhibitory release VIP and NO bronchodilitation
•Stimulatory bronchoconstriction, mucous
secretion, vascular hyperpermeability, cough,
vasodilation “neurogenic inflammation”
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9. Control of Airway Smooth
Muscle (cont.)
•Local factors
–histamine binds to H1 receptors-constriction
–histamine binds to H2 receptors-dilation
–slow reactive substance of anaphylaxsis-
constriction-allergic response to pollen
–Prostaglandins E series-dilation
–Prostaglandins F series-constriction
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10. Control of Airway Smooth
Muscle (cont)
•Environmental pollution
–smoke, dust, sulfur dioxide, some acidic
elements in smog
•elicit constriction of airways
–mediated by:
•parasympathetic reflex
•local constrictor responses
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11. Obstructive airway disease
Chronic obstructive pulmonary disease (COPD),
including emphysema, chronic bronchitis and chronic
asthma
Asthma -triggers,
allergic, non-allergic (intrinsic). Atopic disorders (rhinitis,
eczema, urticaria)
Factors:
hereditary -polygenetic, environment, viruses, allergens,
drugs, irritants, smoking
Heterogeneous disorders, generally of unknown
aetiology. Similarities and differences in treatment
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12. Cellular mechanisms involved in the pathogenesis
of asthma
•A large variety of inflammatory cells are both recruited and activated
in the airways of the lung, where they release many different
cytokines and inflammatory mediators.
•These substances result in bronchoconstriction, vasodilation,
edema, mucus hypersecretion, and activation of sensory nerves.
•Over time, structural changes develop including epithelial shedding,
thickening of the basement membrane (subepithelialfibrosis),
angiogenesis, hyperplasia of mucus-secreting cells, and smooth
muscle hypertrophy & hyperplasia.
•Associated with the late-phase response to allergen exposure there
is a recruitment of multiple subtypes of immune cells, in particular
eosinophils, neutrophils and memory T-cells.
•In severe cases of asthma, the release of multiple inflammatory
mediators can cause cholinergic hyper-reactivity that increases both
mucus secretion and bronchoconstriction, effects that can be
reduced by inhaled antimuscarinics
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Simplified view of allergic inflammation in the airways
aI: anti-IgE cr: cromolyn l: leukotriene inhib. t: theophylline
: beta
2agonists cs: corticosteroids m: antimuscarinics
G&G 11th Ed
(cr)

15. The Real Story
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16. Pathophysiology of asthma
ImagesMD.com
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18. Bronchial asthma –airways
Two phases in an asthma attack, immediate (narrowing -mins) and late
(inflammation –lasting for hours/days) phases
•Asthma triggered by damaging
stimuli
•Spasm of smooth muscle by IgE
mediators released from
various cells of immune system
•Mucus secretion, cough,
oedema, swelling
•Remodelling –cytokines and
growth/repair of wall
•Permanent narrowing and
plugging –“twitchy”
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20. Allergen-induced degranulation of
mast cells and basophils
ImagesMD.com
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21. Inflammatory mechanisms in COPD
Barnes (1998) Thorax, 53, 137-147
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22. Asthma –triggers; mast cells
Busse (1998) J Allergy Clin Immunol
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23. Pathogenesis of asthma: abnormal
repair response to epithelial injury
ImagesMD.com23

24. Drugs for Asthma
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25. Drug therapy –current
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