Asthma Drugs Flashcards

1
Q

Describe pathophysiology of asthma

A

Th2/eosinophilic inflammation

Mucosal oedema, mucus secretion, bronchoconstriction

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

Bronchial hyperresponsiveness

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2
Q

What is heterogenous about asthma

A

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

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3
Q

What is BTS guidelines for asthma management

A

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

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4
Q

What is nice guidelines for asthma management

A

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

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5
Q

What is stepwise approach to management of asthma

A

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

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6
Q

What constitutes good asthma control

A
Minimal symptoms day + night 
Minimal use of reliever therapy
No exacerbations 
No limitations to physical activity 
Normal lung function
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7
Q

What are the classes of beta agonist

A

Short acting:
Salbutamol, Terbutaline

Fast onset long acting:
Formoterol, Olodaterol

Slow onset long acting:
Salmeterol, Vilanterol

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8
Q

What are indications for SABA

A

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

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9
Q

What is mechanism of action of beta agonists

A
Agonist at beta 2 adrenoceptor in airway SM 
Activate Alpha S subunit
Activate AC
Increase cAMP
Inhibit MLCK, activate PKA
Smooth muscle relaxation
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10
Q

Why should SABA not be used regularly

A

Reduces asthma control

Regular use causes increased mast cell degranulation in response to allergens

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11
Q

What are side effects of beta agonists

A

Tachycardia
Palpitations
Tremor

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12
Q

Give examples of ICS

A

Budenosine
Beclomethasone
Fluticasone

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13
Q

What are indications of ICS

A
Step 2: 
Symptoms >3/week
Use of reliever >3/week
Awakening >1/week
W
Exacerbation requiring oral steroids in last 2 years
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14
Q

What is mechanism of action of ICS

A

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

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15
Q

What are the effects of ICS

A

Reduce symptoms
Reduce exacerbations
Improve lung function
Reduce mortality

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16
Q

What are the benefits of having lipid side chain on ICS

A

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

17
Q

Why do you get systemic availability of ICS

A

Absorption from lungs

Absorption from gut (some enters oesophagus)

18
Q

Why is there low systemic availability of ICS

A

ICS undergoes Extensive first pass metabolism

19
Q

What are indications of LABA

A

Step 3

When not controlled on 400 mcg/day on ICS

20
Q

What are the effects of LABA

A

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

21
Q

What is the difference in PK properties bw Formoterol and Salmeterol

A

Both 12 hr duration
Greater potency
Greater efficacy
Faster onset

22
Q

Give examples of combined inhalers

A

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

23
Q

What are the benefits of combine inhalers

A

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

24
Q

Give examples of LTRAs

A

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