Pathophysiology + Pharmacology of Asthma

Question 1

What is asthma?

Answer 1

Recurrent + reversible (in short term) obstruction to airways in response to stimuli

Question 2

What are the causes of asthma attack?

Answer 2

Allergens
Exercise
Respiratory infections
Smoke, dust, environmental pollutants

Question 3

Describe structure of smooth muscle in airways in acute asthma

Answer 3

Contraction of smooth muscle
Mucus hypersecretion
Air inflammation

Question 4

What are the symptoms of acute asthma?

Answer 4

Dyspnoea
Wheezing
Coughing

Question 5

What is dyspnoea?

Answer 5

Loss of breath

Question 6

What hypersensitivity reaction is sensitisation of asthma?

Answer 6

Type I

Question 7

Describe what happens in sensitisation to asthma

Answer 7

IL-4 stimulates production of IgE by B cells + activate mast cells
IL-13 stimulate mucus secretion from bronchial submucosal glands
+ stimulate IgE by B cells + activate mast cells
IL-5 activates locally recruited eosinophils

Question 8

What is basic immediate response?

Answer 8

Bronchospasm

Question 9

What is basic delayed response?

Answer 9

Inflammatory reaction

Question 10

Describe immediate phase

Answer 10

Bronchoconstriction
Increased mucus production
Vasodilation
Release of mediators

Question 11

Describe delayed phase

Answer 11

Recruitment of leukocytes + T cells by cytokines, produced by mast cells
Release of mediators of inflammation

Question 12

Describe the immediate response on re-exposure to antigen

Answer 12

Antigen binds to IgE-IgE receptor complex
Cross links IgE receptors
Stimulates Ca2+ entry into mast cells evoking …
Release of histamine + leukotrienes = smooth muscle contraction
Release of eosinophils that attract cells causing inflammation

Question 13

What are the effects of mast cell mediators?

Answer 13

Bronchospasm
Increased vasodilation
Mucus production
Recruit mediator-releasing cells

Question 14

What are examples of mast cell mediators?

Answer 14

Histamine + leukotrienes

Question 15

Describe what happens in late phase

Answer 15

More pro-inflammatory mediators released =
Eosinophil major basic protein = epithelial damage + airway constriction
Cytokines = contribute to amplification of inflammation

Question 16

Describe chronic asthma

Answer 16

Increased smooth muscle
Accumulation of interstitial fluid
Increased mucus
Exposed sensory nerve endings

Question 17

How do you diagnose?

Answer 17

Demonstrate increased airflow obstruction (spirometry)
Wheezing
Eosinophil count in blood test
Allergy tests

Question 18

What does parasympathetic intervention do?

Answer 18

Worsen symptoms of asthma

Question 19

Describe what happens in parasympathetic intervention

Answer 19

IP3 increases = Ca2+ increases
= bronchoconstriction + increased mucus

Question 20

What does sympathetic innervation?

Answer 20

Improve symptoms

Question 21

Describe what happens in sympathetic intervention

Answer 21

Adrenaline acts on beta-2 receptors = bronchodilation

Question 22

What does chromolyn do?

Answer 22

Prevents mast cells from exploding

Question 23

What treatments are used for immediate phase (bronchospasm)?

Answer 23

Bronchodilators
- Beta-2 agonists
- Muscarinic antagonists
- Xanthines

Question 24

Describe what beta-2 agonists do in immediate phase

Answer 24

Direct action on beta-2 receptors on smooth muscle
= smooth muscle relaxation
Decrease mucus

Question 25

How are beta-2 agonists given?

Answer 25

Inhalation

Question 26

What are the 2 types of beta-2 agonists (inhaler)?

Answer 26

Short acting = salbutamol Long acting = salmeterol

Question 27

What are the side effects of beta-2 agonists?

Answer 27

Tolerance Tremor

Question 28

Describe the action of salbutamol on beta-2 receptors

Answer 28

Stimulation receptors = activation of adenalyl cyclase + increase cAMP + PKA activation = smooth muscle relaxation

Question 29

Describe what muscarinic antagonists do in immediate phase

Answer 29

Dilate bronchi Decrease mucus

Question 30

Describe how muscarinic antagonist dilate bronchi

Answer 30

Block Gq signalling pathway = increased Ca2+ conc

Question 31

What is an example of muscarinic antagonists?

Answer 31

Ipratropium

Question 32

Describe how ipratropium is used

Answer 32

Inhalation

Question 33

Why can ipratropium not cause many side effects?

Answer 33

NOT well absorbed so doesn't get into circulation

Question 34

What do xanthines do in immediate response?

Answer 34

Bronchodilation Anti-inflammatory properties

Question 35

Describe how xanthines cause bronchodilation

Answer 35

Block phosphodiesterase = increase cAMP = bronchodilation

Question 36

What is an example of xanthine?

Answer 36

Theophylline

Question 37

What is the problem with theophylline?

Answer 37

Narrow therapeutic window

Question 38

What are the side effects of theophylline?

Answer 38

HR change Arrhythmias CNS stimulation GI disturbances

Question 39

What treatments are involved in the inflammatory phase?

Answer 39

Glucocorticoids

Question 40

Describe what glucocorticoids do in the inflammatory response

Answer 40

Inhibit transcription of phospholipase A2 = decrease production of inflammatory mediators

Question 41

What are examples of glucocorticoids?

Answer 41

Beclomethasone = inhalation Prednisolone = orally (short term) Hydrocortisone = injection

Question 42

What are examples of glucocorticoids?

Answer 42

Oral candidiasis Cushing like syndrome

Question 43

What does sodium cromolyn do?

Answer 43

Prevents the release of histamine + inflammatory mediators

Question 44

What do cysteinyl-leukotriene receptor antagonists do?

Answer 44

Block leukotrienes induced bronchospasm

Question 45

What are cysteinyl-leukotriene receptor antagonists effective for?

Answer 45

Mild persistent asthma

Question 46

What is an example of cysteinyl-leukotriene receptor antagonists?

Answer 46

Montelukast

Question 47

Why can't propanolol be used to treat hypertension with patients with asthma?

Answer 47

Because beta 1 + 2 blockers = beta-2 blocked = bronchospasm

Question 48

Why can ACE inhibitor captopril not be used in patients with asthma?

Answer 48

Induce cough

Question 49

Why can NSAIDs precipitate asthma?

Answer 49

= in aspirin = COX1/2 blocked = increase leukotriene generation