17. Respiratory pharmacology Flashcards
what is asthma?
Chronic inflammatory airway disease
intermittent airway obstruction and hyper-reactivity small airways
reversible both spontaneously and with drugs
a heterogeneous disease
What are the 3 cardinal features of asthma?
- Reversible airflow obstruction,
- airway hyperresponsiveness,
- and airway inflammation
aims of asthma control?
- Minimal symptoms during the day and night
- Minimal need for reliever medication
- No exacerbations
- No limitation of physical activity
- Normal lung function (FEV1 and/or PEF >80% predicted or best)
What should you check before stepping up/down?
- Adherence
- Inhaler technique
- Eliminate trigger factors
what are the steps in asthma management?
- low dose ICS + SABA
- add inhaled LABA
- consider increasing ICS to medium dose or adding LTRA, if no response to LABA consider stopping it
- refer to specialist care
Give examples of inhaled corticosteroids?
- beclometasone
- budesonide
- fluticasone
How do ICS work?
Pass through plasma membrane, activate cytoplasmic receptors, activated receptor then passes in to nucleus to modify transcription
What are the effects of ICS?
- Reduces mucosal inflammation, widens airways, reduces mucus
- Reduces symptoms, exacerbations and prevents death
What genes are activated/repressed by ICS?
Activation: ↑β2 receptors, Anti-inflammatory mediators, also inhibit release of arachidonic acid
Repression: Inflammatory mediators: interleukins, chemokines, cytokines
What are the adverse effects of ICS?
• Can cause a local immunosuppressive action - candidiasis, horse voice
warnings, contraindications of ICS?
Pneumonia risk possible in COPD at high doses
DDIs of ICS?
very few if taken correctly
What is the purpose of the lipophilic side chains added to ICS?
slow dissolution in aqueous bronchial fluid - difficult to enter systemic circulation
high affinity for glucocorticoid receptor
Is there an issue of ICS are absorbed orally?
No:
• Poor oral bioavailability
• if absorbed: Transported from stomach to liver by hepatic portal system
• Almost complete first pass metabolism
High doses have potential to cause systemic side effects
Give examples of SABA.
Salbutamol, Terbutaline (both fast acting)
Give examples of LABA.
- formoterol (fast acting - 12hrs)
- salmerterol (slow acting - 12hrs)
What are the effects of β2 agonists?
- bronchodilation
- also increase mucus clearance by action of cilia
compare how SABA and LABA are prescribed?
- SABA - Only to be used p.r.n (as required)
* LABA – Add on therapy to ICS and p.r.n SABA
What are the adverse effects of β2 agonist?
- Adrenergic - fight or flight effects Tachycardia, palpitations, anxiety and tremor
- ↑Glycogenolysis (liver)
- ↑renin (kidney)
- SVT – (↑SAN activity → ↑HR, ↓refractory period at AVN)
warnings, contraindications of B2 agonists?
CVD – tachycardia may provoke angina
When should LABA be added?
When not controlled on ICS
Can LABA be given without ICS, why?
No, never given alone
- alone can mask airway inflammation and near-fatal and fatal attacks
LABA should only be prescribed alongside ICS
What is the rationale for combined inhaler?
- Ease of use
- Adherence
- less prescriptions - administration, cost?
- SAFETY - LABA comes with ICS
DDIs of B2 agonist?
β-blockers may reduce effects of β2 agonists!
Give an example of a leukotrine receptor antagonist.
montelukast (oral)
How do leukotrienes cause symptoms in asthma?
- LTC4 released by mast-cells/eosinophils
- ↑bronchoconstriction, ↑mucus, ↑oedema
- through CysLT1 receptor - GPCR
How do LTRA work?
LTRA block CysLT1
- Useful in ~ 15% asthmatics most end up taking LABA
WHat are some ADRs of LTRA?
Headache, GI disturbance, dry mouth, hyperactivity
