Asthma Drugs Flashcards
Describe pathophysiology of asthma
Th2/eosinophilic inflammation
Mucosal oedema, mucus secretion, bronchoconstriction
Airway remodelling: gland hyperplasia, increased SM, thickening, fibrosis
Bronchial hyperresponsiveness
What is heterogenous about asthma
Pathophysiology: eosinophilic, neutrophilic
Presentation: symptoms, triggers
Response to treatment
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
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
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
What constitutes good asthma control
Minimal symptoms day + night Minimal use of reliever therapy No exacerbations No limitations to physical activity Normal lung function
What are the classes of beta agonist
Short acting:
Salbutamol, Terbutaline
Fast onset long acting:
Formoterol, Olodaterol
Slow onset long acting:
Salmeterol, Vilanterol
What are indications for SABA
Step 1:
As required reliever therapy
Relieves symptoms by reversal of bronchoconstriction
Prevents bronchoconstriction
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
Why should SABA not be used regularly
Reduces asthma control
Regular use causes increased mast cell degranulation in response to allergens
What are side effects of beta agonists
Tachycardia
Palpitations
Tremor
Give examples of ICS
Budenosine
Beclomethasone
Fluticasone
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
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
What are the effects of ICS
Reduce symptoms
Reduce exacerbations
Improve lung function
Reduce mortality
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
Why do you get systemic availability of ICS
Absorption from lungs
Absorption from gut (some enters oesophagus)
Why is there low systemic availability of ICS
ICS undergoes Extensive first pass metabolism
What are indications of LABA
Step 3
When not controlled on 400 mcg/day on ICS
What are the effects of LABA
Improve symptoms
Improve lung function
Reduce exacerbations
No effect on inflammation - must be used with ICS
What is the difference in PK properties bw Formoterol and Salmeterol
Both 12 hr duration
Greater potency
Greater efficacy
Faster onset
Give examples of combined inhalers
Budenosine/Formoterol
Beclomethasone/Formoterol
Fluticasone/Formoterol
Fluticasone/Salmeterol
What are the benefits of combine inhalers
Ease of use
Compliance
Cheaper
Safety: improved lung function, reduced exacerbations
Give examples of LTRAs
Montelukast
Zafirlukast
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
What are side effects of LTRA
Angiooedema Anaphylaxis Arthralgia Dry mouth Fever GI disturbance Night mares
Give examples of methylxanthines
Aminophylline
Theophylline
What is mechanism of action of methylanxines
Antagonise adenosine receptor
Inhibit phosphodiesterase - reduce cAMP
What are side effects of methylxanthines
Nausea, headache, reflux
Arrhythmia, seizures
Give examples of LAMA
Tiotropium bromide
Not licensed for asthma: aclidinium, umeclidinium
What is mechanism of action of LAMA
Inhibit M3 muscarinic receptor in airway SM
Slower onset and lower intensity of bronchodilation than beta agonists
What are side effects of LAMA
Glaucoma
Urinary retention
Dry mouth
Give examples of anti-IgE
Omalizumab
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
What are indications of anti-IgE
Step 5:
Asthma not adequately controlled on oral steroids
Taper off oral steroids
Give examples of Anti-IL5
Mepolizumab
Reslizumab
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
What is mechanism of action of anti-IL5
Reduce blood and airway eosinophils
