Respiratory pharmacology Flashcards
Define asthma
- Chronic inflammatory airway disease
- Intermittent airway obstruction
- Hyper-reactivity of small airways
- Reversible (spontaneously or due to drugs)
- heterogenous disease
What are the aims of asthma control?
- Minimal symptoms during day at night
- Minimal needs for reliever medication
- No exacerbations
- No limitation of physical activity
- Normal lung function
- Early control with stepping up or down as required
What do we need to check before stepping a patient’s asthma treatment up?
- Adherence
- Inhaler technique
- Remove triggers
Give a brief outline of the treatment ladder for asthma
- Regular preventer - low dose ICS
- Initial add-on therapy - add inhaled LABA to low dose ICS
- Additional controller therapies - consider increasing ICS to medium dose or adding LRTA
- Specialist therapies
What indicates that a patient needs to move up the treatment ladder for asthma?
- All asthma patients are given a short acting B2 agonist to use as needed
- Consider moving up if using 3+ doses per week
What are the current NICE guidelines for managing asthma in adults?
- Add LRTA (leukotriene receptor antagonist) after initial low dose LABA
- LRTA is cheaper than LABA
- Though LABA is more effective
Give some examples of inhaled corticosteroids
- Beclomethasone
- budesonide
- Fluticasone
What is the mechanism of action of inhaled corticosteroids?
- Pass through plasma membranes
- Activate cytoplasmic receptors
- Activated receptor passes into nucleus to modify transcription
What are the effects of inhaled corticosteroids on the airways?
- Reduces mucosal inflammation
- Widens airways
- Reduces mucus
- Reduces symptoms, exacerbations and prevents death
What are the adverse side effects of inhaled corticosteroids?
- Can cause a local immunosuppressive action - candidiasis, hoarse voice
What are the contraindications for inhaled corticosteroids?
- Pneumonia risk possible in COPD at high doses
What are the DDIs of inhaled corticosteroids?
- There aren’t really any
Which genes are activated by inhaled corticosteroids?
- Increased B2 receptors
- Anti inflammatory mediators
- Also inhibit release of arachidonic acid
Which genes are repressed by inhaled corticosteroids?
- Those that code for inflammatory mediators
- E.g. interleukins, chemokines, cytokines
Outline the pharmacokinetics of inhaled corticosteroids
- Poor oral bioavailability
- Slow dissolution in aqueous bronchial fluid
- High affinity for glucocorticoid receptor
What happens when a steroid is absorbed p.o.?
- Transported from stomach to liver by hepatic portal system
- Almost complete first pass metabolism
Give some examples of fast-acting B2 agonists?
- Salbutamol and terbutaline (short lasting)
- Formoterol (long lasting)
Give some examples of long-acting B2 agonists?
- Salmeterol (long lasting)
What are the different types of B2 agonists?
- Short acting B2 agonists (SABA) - symptom relief through reversal of bronchoconstriction
- Long acting B2 agonists (LABA) - add on therapy to ICS and SABA
What is the mechanism of action of B2 agonists?
- Major action on airway smooth muscle
- Also increase mucus clearance by action of cilia
- Prevents bronchoconstriction prior to exercise
Why shouldn’t patients use an SABA too often?
- Can reduce asthma control
- Tolerance might build
What are the adverse side effects of B2 agonists?
- Adrenergic - fight or flight effects
- Tachycardia
- Palpitations
- Anxiety and tremor
- Increased glycogenolysis
- Increased renin
What are the contraindications of B2 agonists?
- LABA should only be prescribed alongside ICS
- LABA given alone can mask airway inflammation and near-fatal/fatal attacks
- CVD - tachycardia may provoke angina
What are some problems with LABAs?
- Need to be given in a combined fixed dose inhaler (ICS + LABA)
- Adherence
- Cost
- Safety
What are the DDIs of LABAs?
B blockers may reduce effects of B2 agonists
What are some controller therapies for asthma?
- Leukotriene receptor antagonists
- Long acting muscarinic antagonists
Give an example of a leukotriene receptor antagonist (LRTA)
- Montelukast
What is the mechanism of action of leukotriene receptor antagonists?
- Leukotrienes released by mast cells/eosinophils
- Increased bronchoconstriction, mucus, and oedema through CysLT1 - a GPCR
- LRTAs block CysLT1
What are the adverse side effects of leukotriene receptor antagonists?
- Headache
- GI disturbance
- Dry mouth
- Hyperactivity
What are the contraindications for LRTAs?
- Neuropsychiatric reactions
What are the DDIs for LRTAs?
- None reported
Give some examples of long acting muscarinic antagonists (LAMA)
- Tiotropium
- Theophylline
What are the indications of tiotropium?
- Severe asthma
- COPD
What is the mechanism of action of tiotropium?
- Block vagally mediated contraction of airway smooth muscle
What are the adverse side effects of tiotropium?
- Infrequent
- Anticholinergic effects
- E.g. dry mouth, urinary retention, dry eyes
- Generally ok for most with inhaled route
What are the indications for theophylline?
- p.o.
- Poorly controlled asthma
What is the mechanism of action of theophylline?
- Adenosine receptor antagonist
- Decreased bronchoconstriction
- Phosphodiesterase inhibitor
- Taken on short term basis alongside ICS, LABA or muscarinic antagonist
What are the contraindications of theophylline?
- Narrow therapeutic index
- Potentially life-threatening complications including arrhythmia - must measure plasma concentration
What are the DDIs of theophylline?
- CYP450 inhibitors increase concentration of theophylline
Why are self-management plans given to asthmatic patients?
- For all asthmatic patients
- Written instructions on when and how to step up and down treatment
- Allows better day to day management and reduced exacerbations
What values indicated that asthma is acute or severe?
- Unable to complete sentences
- Peak flow 33-50% best or predicted
- Respiratory rate > 25/min
- Heart rate >110/min
Which values make asthma life-threatening?
- All criteria for acute and severe asthma plus one of the following:
- Peak flow <33% best or predicted
- Arterial oxygen saturation <92%
- PaO2 <8kPa
- Normal PaCO2 4.6-6.0 kPa
- Silent chest
- Cyanosis
- Poor respiratory effort
- Arrhythmia
- Exhaustion
Which medications should be given in acute severe and life-threatening asthma?
- Oxygen
- High dose nebulised B2 agonist (oxygen driven)
- Prednisolone
- Ipratropium
- Consider i.v. aminophylline if life-threatening/near fatal and no success with the above
What type of drug is prednisolone?
- Oral steroid
- Continue ICS alongside
What type of drug is ipratropium?
- Taken nebulised as ipratropium bromide
- Short acting muscarinic antagonist
- Take alongside B2 agonist if poor response alone
What are the 5 tasks of management of COPD?
- Confirm diagnosis
- Smoking cessation
- Breathlessness score
- Vaccination
- Medication
What medications are given to COPD patients suffering from acute exacerbations and requiring hospitalisation?
- Nebulised salbutamol and/or ipratropium
- If patient is hypercapnic or acidotic, nebuliser should be driven by air
- Oral steroids
- Antibiotics
- Review of chronic treatment and action plan
What factors influence which inhalers you prescribe?
- Need to find an inhaler that the patient can use
- Should be assessed by an appropriately trained healthcare professional
- Dose needs to be titrated against clinical response
- Reassessed as part of regular medication review
What are some different types of inhaler that can be prescribed?
- Pressurised metered dose inhalers (pMDI)
- Breath-actuated pMDI
- Dry powder inhalers
- Inhalers often prescribed by brand and not generic
Why is inhalation technique important?
- Inhaler, technique and drug formulation dictate particle size and deposition
- If inspiratory flow is too slow, drug deposits in mouth
- But if it’s too fast, drug deposits in the throat
- If drug is too small it is inhaled to the alveoli and then exhaled without being deposited
- If drug id too big, it is deposited in the mouth and oropharynx
How can we check a patient’s inhaler technique?
- In-check DIAL device
