9.2.1 Asthma Drugs Flashcards
What is asthma?
Chronic inflammatory airway disease
Intermittent airway obstruction
Hyper-reactivity of small airways
Reversible inflammation with drugs and spontaneously
How do airways look in asthma?
Mucosal oedema and plugging
More eosinophils than COPD
What symptoms are present in asthma exacerbation?
Coughing
Wheezing
SOB
Caused by bronchospasm
What features are considered good asthma control?
(5)
- Minimal symptoms during day and night
- Minimal need for reliever medication
- No exacerbations
- No limitation to physical activity
- Normal lung function - FEV1/PEFR >80% predicted)
What is the aim for asthma control overall?
Early control with steeping up or down as needed
What must be checked before stepping up or down the treatment ladder?
- Adherence
- Inhaler technique
- Trigger removal- eg animal hair
What are the features of uncontrolled asthma?
- 3 or more days a week with symptoms or:
- 3 or more days a week with required use of SABA for symptomatic relief or:
- 1 or more nights a week with awakening due to asthma
Outline the asthma treatment ladder
1) Start with (short acting beta 2 agonists) to use when needed
2) Add preventer if needed - low dose ICS
3) LABA - long acting beta agonist
4) LTRA - leukotrine receptor antagonist
Why do NICE recommend leukotrine receptor antagonist before long acting beta agonists?
LTRAs are cheaper
Evidence shows most patients end up on LABA eventually anyway
When do you give inhaled corticosteroids?
When SABA alone is not enough
Give some examples of inhaled corticosteroids
Beclometasone
Budesonide
Fluticasone
How are ICS absorbed and how do they work?
ICS pass through plasma membrane
Activate cytoplasmic receptors
Activated receptor then passes into nucleus to modify transcription
What do ICS do?
- Reduced mucosal inflammation, widens airways
- Reduces mucus
- Reduces symptoms, exacerbations and prevents death
What are the adverse effects of ICS?
Local immunosupression causing
- Candidiasis
- Hoarse voice
What can ICS possibly cause in COPD patients?
Pneumonia risk possible at high doses
What are some important drug to drug interactions with ICS?
If taken correctly very few DDIs and adverse effects
How do steroids work?
Gene Activation:
- Increase B2 receptors
- Increase anti-inflammatory mediators
- Inhibit release of arachidonic acid
Gene Repression:
- Inflammatory mediators- interleukins, chemokines
What are the pharmacokinetics of ICS?
- Poor oral bioavailability
- Have lipophilic side chain added causing slow dissolution in aqueous bronchial fluid
- High affinity for glucocorticoid receptor
What happens if steroid is absorbed p.o?
Transported from stomach to liver by hepatic portal system
Almost complete first pass metabolism - litte gets to systemic circulation
But at high doses all ICS have potential to produce systemic side effects
When do you use SABAs?
Symptom relief through reversal of bronchoconstriction - only to be used when needed
When do you use LABAs?
- Add on therapy to ICS and SABA and in MART (maintenance and reliever)
- LABA and ICS together - as LABA cannot be taken without ICS
What effect do beta 2 agonists SABA and LABA have?
Major action on airway smooth muscle - bronchorelaxation
Also increase mucus clearance action by cilia
Normal B2 binding mechanism
Why can SABAs only be used when required?
When SABA is used regularly it can reduce asthma control, if not well managed, patient at high risk
What are the different B2 agonists and their onset speeds?
Fast onset:
Salbutamol and terbutaline (turbo-speedy)- short acting
Formoterol - long acting
Slow onset:
Salmeterol - long acting
What are the adverse effects of Beta 2 agonists?
Adrenergic - fight or flight effects:
- Tachycardia
- Palpitations
- Anxiety
- Tremor
- Increased glycogenolysis in liver
- Increase renin release from kidney
- SVT - increases SAN activity, increases HR, decreases refractory period at AVN
What are the warnings/contraindications for beta 2 agonists?
- LABA should only be prescribed alongside ICS if alone can mask airway inflammation and near fatal and fatal attacks can occur
- CVD - tachycardia may provoke angina
What is a combined fixed dose inhaler?
- ICS and LABA together
- Improves adherance as only 1 inhaler
- Improved safety - LABA needs to be taken with ICS
What are some important drug interactions for beta 2 agonists?
Beta blockers - reduce effects of beta 2 agonists
Why are LABA and ICS used together?
Synergistic - using at same time better than using alone
When are leukotrine receptor antagonists used and how are they taken?
Used as add on therapy to SABA and ICS
Orally
What is an example of a leukotrine receptor antagonist?
Montelukast
How do leukotrine receptor antagonists work?
Leukotrines are usually released by mast cells/eosinophils causing:
- Bronchoconstriction
- Increased mucus
- Increased oedema
Through CysLT1acting on a GPCR
Leukotriene receptor antagonists block CysLT1 from binding to CYSLTR1
How useful are LRTAs?
Most move on to LABA
Useful in 15% of asthmatics
What are some adverse effects of LTRAs?
Headache
GI disturbance
Dry mouth
Hyperactivity
What warnings andcontraindications are there for LTRAs?
Neuropsychiatric reactions can happen
What important drug interactions are there with LTRAs?
None reported
