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Flashcards in Asthma Drugs Deck (38):
1

Describe pathophysiology of asthma

Th2/eosinophilic inflammation

Mucosal oedema, mucus secretion, bronchoconstriction

Airway remodelling: gland hyperplasia, increased SM, thickening, fibrosis

Bronchial hyperresponsiveness

2

What is heterogenous about asthma

Pathophysiology: eosinophilic, neutrophilic
Presentation: symptoms, triggers
Response to treatment

3

What is BTS guidelines for asthma management

1) SABA
2) SABA + ICS
3a) SABA + ICS + LABA
3b) If LABA unresponsive: medium dose ICS
If responsive: LABA + md ICS / additional therapy: methylxanthines, LTRA, LAMA
4) high dose ICS or additional therapy
5) oral ICS or biological therapy

4

What is nice guidelines for asthma management

1) SABA
2) SABA + ICS
3) SABA + ICS + LTRA
4) SABA + ICS + LABA +/- LTRA
5) SABA + MART +/- LTRA
6) Medium dose ICS MART / separate md ICS+LABA
7) High dose ICS + LABA / additional therapy / specialist referral

5

What is stepwise approach to management of asthma

Step up as required to achieve asthma control
Step down to maintain lowest controlling treatment
Keep patent on minimum effective dose of ICS

6

What constitutes good asthma control

Minimal symptoms day + night
Minimal use of reliever therapy
No exacerbations
No limitations to physical activity
Normal lung function

7

What are the classes of beta agonist

Short acting:
Salbutamol, Terbutaline

Fast onset long acting:
Formoterol, Olodaterol

Slow onset long acting:
Salmeterol, Vilanterol

8

What are indications for SABA

Step 1:
As required reliever therapy
Relieves symptoms by reversal of bronchoconstriction
Prevents bronchoconstriction

9

What is mechanism of action of beta agonists

Agonist at beta 2 adrenoceptor in airway SM
Activate Alpha S subunit
Activate AC
Increase cAMP
Inhibit MLCK, activate PKA
Smooth muscle relaxation

10

Why should SABA not be used regularly

Reduces asthma control
Regular use causes increased mast cell degranulation in response to allergens

11

What are side effects of beta agonists

Tachycardia
Palpitations
Tremor

12

Give examples of ICS

Budenosine
Beclomethasone
Fluticasone

13

What are indications of ICS

Step 2:
Symptoms >3/week
Use of reliever >3/week
Awakening >1/week
W
Exacerbation requiring oral steroids in last 2 years

14

What is mechanism of action of ICS

Bind to intracellular GC receptor and control gene transcription
Transactivation: upregulation of gene expression for beta adrenoceptors, anti inflammatory cytokines, ILRI
Transrepression: downregulation of gene expression for inflammatory cytokines

15

What are the effects of ICS

Reduce symptoms
Reduce exacerbations
Improve lung function
Reduce mortality

16

What are the benefits of having lipid side chain on ICS

increased binding affinity
increased absorption into tissues on local admin
Rapid inactivation by first pass metabolism

17

Why do you get systemic availability of ICS

Absorption from lungs
Absorption from gut (some enters oesophagus)

18

Why is there low systemic availability of ICS

ICS undergoes Extensive first pass metabolism

19

What are indications of LABA

Step 3
When not controlled on 400 mcg/day on ICS

20

What are the effects of LABA

Improve symptoms
Improve lung function
Reduce exacerbations
No effect on inflammation - must be used with ICS

21

What is the difference in PK properties bw Formoterol and Salmeterol

Both 12 hr duration
Greater potency
Greater efficacy
Faster onset

22

Give examples of combined inhalers

Budenosine/Formoterol
Beclomethasone/Formoterol
Fluticasone/Formoterol
Fluticasone/Salmeterol

23

What are the benefits of combine inhalers

Ease of use
Compliance
Cheaper
Safety: improved lung function, reduced exacerbations

24

Give examples of LTRAs

Montelukast
Zafirlukast

25

What is mechanism of action of LTRAs

Eosinophils and mast cells produce leukotrienes
Leukotrienes cause mucosal oedema, mucus production, bronchoconstriction, recruitment of inflammatory cells
LTRAs inhibit LT receptors to inhibit LT activity

26

What are side effects of LTRA

Angiooedema
Anaphylaxis
Arthralgia
Dry mouth
Fever
GI disturbance
Night mares

27

Give examples of methylxanthines

Aminophylline
Theophylline

28

What is mechanism of action of methylanxines

Antagonise adenosine receptor
Inhibit phosphodiesterase - reduce cAMP

29

What are side effects of methylxanthines

Nausea, headache, reflux
Arrhythmia, seizures

30

Give examples of LAMA

Tiotropium bromide

(Not licensed for asthma: aclidinium, umeclidinium)

31

What is mechanism of action of LAMA

Inhibit M3 muscarinic receptor in airway SM
Slower onset and lower intensity of bronchodilation than beta agonists

32

What are side effects of LAMA

Glaucoma
Urinary retention
Dry mouth

33

Give examples of anti-IgE

Omalizumab

34

What is mechanism of action of omalizumab

Bind to free IgE and inhibit binding to IgE receptors
Does not bind to bound IgE thus does not cause cross linking/ mast cell degranulation

35

What are indications of anti-IgE

Step 5:
Asthma not adequately controlled on oral steroids
Taper off oral steroids

36

Give examples of Anti-IL5

Mepolizumab
Reslizumab

37

What are indications of anti-IL5

Step 5:
Reduce no of severe exacerbations (most effective)
>3 exacerbations/year with raised blood eosinophils
Taper off oral steroids

38

What is mechanism of action of anti-IL5

Reduce blood and airway eosinophils