Lecture 13 - Respiratory Pharmacology

Question 1

What phases does asthma have?

Answer 1

Early and late phases

Question 2

What is asthma characterised by?

Answer 2

Airway Inflammation
Bronchial hyper-reactivity
Reversible airway obstruction

Question 3

When is asthma observed as reversible?

Answer 3

Once allergens that are responsible for reaction has been removed

Question 4

What can degree of obstruction be monitored by?

Answer 4

Spirometry (lung function)

Question 5

What is FEV1?

Answer 5

Forced expiratory volume in 1 second

Question 6

What is FVC?

Answer 6

Forced vital capacity

Question 7

What is the equation for spirometry?

Answer 7

FEV1/FVC

Question 8

What is PEFR?

Answer 8

Peak expiratory flow rate

Question 9

What is bronchospasm?

Answer 9

Smooth muscle constriction

Question 10

When does late phase occur?

Answer 10

After immediate phase because of certain mediators that are generated and released during the immediate phase

Question 11

Immediate phase of asthmatic attack

Answer 11

Occurs abruptly
Caused by spasm of bronchial smooth muscle
Allergen interaction with mast cell-fixed IgE cause release of histamine, leukotriene B4 and prostaglandin

Question 12

What are other mediators of immediate phase?

Answer 12

IL-4
IL-5
IL-13
Macrophage inflammatory protein-1alpha 
Tumour necrosis factor TNA-alpha

Question 13

When the allergens are inhaled what does it cause?

Answer 13

Mast cell degranulation

Question 14

How do you relieve smooth muscle constriction?

Answer 14

Beta-2 adrenoceptor agonist

Question 15

What does inflammatory cell include?

Answer 15

Activated eosinophils

Question 16

What does activated eosinophils release?

Answer 16

Cysteinyl leukotrienes 
Interleukin IL-3
IL-5
IL-8
Toxic proteins (eosinophil cationic protein)
Major basic protein 
Eosinophil derived neurotoxin

Question 17

What can late phase be inhibited by?

Answer 17

Glucocorticoids

Question 18

What is Glucocorticoid and what does it do?

Answer 18

Steroid hormone

Interrupt the link between T helper cells and accumulation of eosinophils

Question 19

What is the long term effect of changes occurring in the bronchioles?

Answer 19

Hypertrophied smooth muscle

Question 20

What is hypertrophied smooth muscle?

Answer 20

Changes in the smooth muscles which make it more reactive/liable to reduce the diameter of the bronchioles

Question 21

What is an example of changes to be lining of bronchioles?

Answer 21

Thickened basement membrane

Question 22

What formation is seen during asthma attack?

Answer 22

Formation of mucus plug with eosinophils and desquamated epithelial cells
Further restrict the flow of air through the bronchioles

Question 23

What are the main drugs used for bronchodilators?

Answer 23

B2-adrenoceptor agonist

Theophylline

Question 24

What are examples of bronchodilators?

Answer 24

Cysteinyl leukotriene receptor antagonist

Muscarinic receptor antagonist

Question 25

What does bronchodilators do?

Answer 25

Reverse the bronchospasm of the immediate phase

Question 26

What are anti-inflammatories and what do they do?

Answer 26

Steroids | Inhibit or prevent the inflammatory components of both phases

Question 27

What is step 1 of the stepwise approach ?

Answer 27

Mild intermittent asthma | Inhaled short-acting B2 agonist as required

Question 28

What is step 2 of stepwise approach?

Answer 28

Regulator preventer therapy Add inhAled corticosteroid 200-800 micrograms/day 400 micrograms are an appropriate starting dose for many patients Start at dose of inhaled corticosteroid appropriate to severity of disease

Question 29

What is step 3 of step wise approach?

Answer 29

Add inhaled long-acting B2 agonist (LABA)

Question 30

What is step 4 of step wise approach?

Answer 30

Persistent poor control Increase inhaled corticosteroid up to 2,000 micrograms/day Addition of 4th drug e.g. leukotriene receptor antagonist SA theophylline, B2 agonist tablet

Question 31

What is step 5 of stepwise approach?

Answer 31

Continuous or frequent use of oral steroids Use daily steroid tablet in lowest dose providing adequate control Maintain high dose inhaled corticosteroid at 2,000 micrograms/day Refer patients for specialist care

Question 32

What are examples of short-acting (5 hours) of B2-Adrenoceptor agonist?

Answer 32

Salbutamol Terbutaline Given as needed

Question 33

What are examples of long-acting (12 hours) of B2-adrenoceptor agonist?

Answer 33

Salmeterol Formoterol Given as adjunct to other treatment/prophylactically

Question 34

What is the administration for B2-adrenoceptor agonist?

Answer 34

Inhalation Metered dose inhalers Spacers Nebulisers

Question 35

How is the duration of action for B2-adrenoceptor agonist prolonged?

Answer 35

Incorporation of lipophilic side-chain which bonds to area adjacent to receptor active site

Question 36

What does formoterol enter?

Answer 36

Lipid bilayer

Question 37

How are short acting compounds administered (B2-adrenoceptor agonist)?

Answer 37

Orally Subcutaneously IntrVenously

Question 38

What can B-adrenoceptor stimulation lead to?

Answer 38

``` Tremor Tachycardia, arrythmia Acute metabolic response Paradoxical bronchospam Headache ```

Question 39

Membrane phospholipid

Answer 39

Generation of inflammatory mediators through action of enzyme: phospholipase A2 and cyclo-oxygenase

Question 40

PGE2

Answer 40

Potent vasodilator

Question 41

LTBB4

Answer 41

Potent chemotaxin

Question 42

When is corticosteroid introduced?

Answer 42

Using bronchodilator more than once daily

Question 43

What is corticosteroid skewed to?

Answer 43

``` Glucocorticoid action Beclometasone Budesonide Fluticasone Mometasone Cuclesonide Prednisone ```

Question 44

What are the actions of corticosteroid?

Answer 44

``` Decrease cytokines formation Inhibit production of leukotriene Inhibit allergen-induces influx of eosinophils into lung Upregulate B2-adrenoceptors Decrease microvascular permeability Reduce mast cell number ```

Question 45

What are unwanted effects of corticosteroid?

Answer 45

Limited by route of administration Oropharyngeal thrush Sore throat Adrenal suppression

Question 46

What are 3 types of Muscarinic receptor associated with airway function?

Answer 46

M1 M2 M3

Question 47

M1

Answer 47

Facilitate parasympathetic Ganglia transmission

Question 48

M2

Answer 48

Presynaptic inhibitory auto receptors

Question 49

M3

Answer 49

Postsynaptic Mediate bronchoconstriction Mucus secretion - generation of CGMP

Question 50

How are antimuscarinic compound administered?

Answer 50

Inhalational route

Question 51

Ipratropium

Answer 51

Short acting

Question 52

Tiotropium

Answer 52

Medium

Question 53

What are antimuscarinic compound use for?

Answer 53

Reduced secretion | Increase clearance

Question 54

What are side effects of antimuscarinic compounds?

Answer 54

Dry mouth Constipation Contribute to glaucoma

Question 55

Methylxanthenes

Answer 55

Theophylline and related derogate aminophylline

Question 56

What are multiple actions of methylxanthene?

Answer 56

Phosphodiesterase inhibition Increased contraction of diaphragm Adenosine receptor antagonism Activation of histone deacetylsse

Question 57

What are unwanted effect of methylxanthene

Answer 57

Hypotension | CNS and GI disturbance

Question 58

Metyhlxanthene

Answer 58

Metabolised by CYP3A4 | Low TI

Question 59

Leukotriene receptor antagonist

Answer 59

Monteluklast Oral agents with additive affect when given with corticosteroid Inhibit early and late stage bronchoconstriction

Question 60

Status asthmaticus

Answer 60

``` Medical emergency - prompt attention High conc oxygen Use of nebuliser to deliver salbutamol IV corticosteroid, e.g hydrocortisone Oral prednisolone ```

Question 61

How is status asthmaticus monitored by?

Answer 61

Spirometry | Blood gas