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Pharmacology > Asthma Drugs > Flashcards

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
Q

What is mechanism of action of LTRAs

A

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
Q

What are side effects of LTRA

A 
Angiooedema
Anaphylaxis
Arthralgia
Dry mouth 
Fever
GI disturbance 
Night mares
27
Q

Give examples of methylxanthines

A

Aminophylline

Theophylline

28
Q

What is mechanism of action of methylanxines

A

Antagonise adenosine receptor

Inhibit phosphodiesterase - reduce cAMP

29
Q

What are side effects of methylxanthines

A

Nausea, headache, reflux

Arrhythmia, seizures

30
Q

Give examples of LAMA

A

Tiotropium bromide

Not licensed for asthma: aclidinium, umeclidinium

31
Q

What is mechanism of action of LAMA

A

Inhibit M3 muscarinic receptor in airway SM

Slower onset and lower intensity of bronchodilation than beta agonists

32
Q

What are side effects of LAMA

A

Glaucoma
Urinary retention
Dry mouth

33
Q

Give examples of anti-IgE

A

Omalizumab

34
Q

What is mechanism of action of omalizumab

A

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
Q

What are indications of anti-IgE

A

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

36
Q

Give examples of Anti-IL5

A

Mepolizumab

Reslizumab

37
Q

What are indications of anti-IL5

A

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

38
Q

What is mechanism of action of anti-IL5

A

Reduce blood and airway eosinophils

Pharmacology (19 decks)

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