Asthma (Therapeutics) Flashcards
What is asthma?
A chronic inflammatory disorder of the airways
What does asthma lead to an increase in?
Airway hyperresponsiveness
What are some of the symptoms of asthma?
Recurrent episodes of wheezing, breathlessness, chest tightness and coughing, particularly at night or early in the morning
What are episodes of asthma associated with physiologically?
Widespread, variable airflow obstruction that is often reversible, spontaneously or with treatment
How is asthma usually mediated?
By IgE
Which cells produce mucus?
Goblet cells
What can occur if asthma is poorly managed over a period of years?
Airway remodelling
Does asthma have a cause?
Factors are no longer referred to as ‘causes’ of asthma, but environmental and genetic factors that contribute to its development
What are some of the factors that contribute to the development of asthma?
Family history or other atopic conditions (e.g. eczema, hay fever)
Bronchiolitis in childhood
Exposure to tobacco smoke, especially if mother smokes during pregnancy
Premature birth
Low birth weight
Occupational exposure to plastics, agricultural substances and volatile chemicals
A BMI>30kg/m2
Bottle feeding
Changes in housing, air pollution levels and a more hygienic lifestyle (reducing exposure to allergens)
Is asthma more common in prepubescent girls or boys?
More common in prepubescent boys but boys are also more likely to grow out of their asthma during adolescence
What is a phenotype?
A set of observable characteristics of an individual resulting from the interaction of its genotype with the environment
What is phenotyping?
The process of predicting an organism’s phenotype using only genetic information collected from genotyping or DNA sequencing
What is the relevance of phenotyping in asthma?
Variations in genes that code for beta-adrenoceptors have been linked to differences in how cells respond to beta-agonists
Potential to tailor treatment to individuals in the future
What are some of the possible triggers of asthma?
Common cold Allergens (e.g. dust mites, pollen) Exercise Exposure to hot or cold air Medicines (e.g. NSAID's) Emotions (e.g. anger, anxiety or sadness)
What is the cause of wheezing and coughing in asthma?
Wheezing that occurs as a result of bronchoconstriction and coughing are likely to be caused by stimulation of sensory nerves in the airways
What signs may be present/absent in an acute exacerbation of asthma?
Wheeze may be absent and chest may be silent on listening
In such cases, other signs such as cyanosis (bluish cast to the skin and mucous membranes) and drowsiness may be present
The patient may be unable to complete sentences
What are some of the clinical features that lower the probability of asthma?
Symptoms only when patient has a cold
Isolated cough with no wheeze or difficulty breathing
History of moist cough (in children)
Chronic productive cough with no wheeze or difficulty breathing
Prominent dizziness and peripheral tingling
Repeated normal physical examination of chest when symptomatic
Normal PEV or spirometry when symptomatic
Cardiac disease
Voice disturbance
History of smoking >20 pack years
In such cases, it is likely another disease, not asthma, is present
How is asthma diagnosed?
Based on medical history, physical examination, lung function testing and response to medication
No ‘gold standard’ test
How is diagnosis altered if patient has a high probability of asthma?
Usually start with a treatment trial and response is assessed using spirometry
How is diagnosis altered if patient has a intermediate probability of asthma?
Lung function tests are conducted first such as spirometry, peak flow and airway responsiveness
Do normal spirometry findings exclude a diagnosis of asthma?
No, not if the patient is well at the time of testing
What are some of the spirometric measures used?
FVC
FEV1
FEV1/FVC ratio
What is FVC?
The total volume of air expelled by a forced exhalation after maximal inhalation
What is FEV1?
The volume of air expelled in the first second of a forced exhalation after maximal inhalation
A FEV1/FVC ratio of…
Less than 0.7 suggests airway obstruction, which can increase the probability of asthma but also be caused by other conditions such as COPD
How do you take a peak expiratory flow (PEF) measurement and what does it measure?
Use a peak flow meter to measure the resistance in the airway
Which is more accurate, spirometry or peak expiratory flow measurements?
Spirometry
What are PEF measurements particularly useful for?
Demonstrating variability of lung function throughout the day
Measurements should be taken in the morning and evening (as a minimum) and recorded in a diary to see if there is diurnal variability
Best of three expiratory blows should be recorded (dependent on technique and effort)
More useful for monitoring those with an established asthma diagnosis rather than for making an initial diagnosis
How can airway responsiveness be measured?
Using inhaled mannitol or methacholine
When is this airway responsiveness test used?
To diagnose patients who have a baseline FEV1 <70% of population data
How does the airway responsiveness test work?
Both drugs induce bronchospasm
A fall in FEV1 of >15% following the test is a specific indicator for asthma
An airway responsiveness test is particularly useful for doing what?
Distinguishing asthma from other common conditions often confused with asthma (rhinitis, gastro-oesophageal reflux, heart failure and vocal cord dysfunction)
What does a treatment trial involve?
Being prescribed a 6-8 week trial of inhaled beclomethasone or prednisolone
What do the results from a treatment trial indicate?
An improvement in FEV1 of 400ml or more is strongly suggestive of asthma
When should spirometry be carried out after a treatment trial?
Spirometric assessment after a trial is more effective for patients with known airway obstruction and less helpful for patients who had near normal lung function between the trial
What other tests aside from spirometry, peak expiratory flow, airway responsiveness and treatment trials can be carried out to help guide a diagnosis of asthma?
Non-invasive testing of sputum eosinophils and exhaled NO concentration
Not routinely used in general practice
What do the results from this additional test indicate?
A raised eosinophil count (>2%) is seen in the majority of patients with uncontrolled asthma
An exhaled NO level of >25 parts per billion supports a diagnosis of asthma
Which conditions could the results from the additional test also indicate?
Patients with COPD or a chronic cough may exhibit similar results and so should not be used for a definite diagnosis
How is asthma management defined?
No day time symptoms or night time waking due to asthma
No need for rescue medication
No exacerbations
No limitations on activity including exercise
Normal lung function (in practical terms FEV1 and/or PEF >80% of predicted or best)
Minimal side effects from treatment
What are some non-pharmacological asthma management strategies?
Allergen and trigger avoidance (e.g. pollen, dust mites)
Stop smoking
Lose weight if obese
Avoid exercise in cold air
Minimise occupational stimuli
Avoid NSAID’s and β-blockers (inc. eye drops)
Holistic remedies such as immunotherapy, breathing techniques
Breast feeding
Air ionisers
Who produces guidance on asthma management?
British Thoracic Society (BTS)
Scottish Intercollegiate Guidelines Network (SIGN)
NICE
Which guidelines do the BNF and other sources mainly refer to?
BTS
Do guidelines differ and how?
NICE guidelines differ greatly to traditional BTS/SIGN and are more conservative with using ICS
How do paediatric guidelines differ?
Do not advocate regular oral steroids and ICS doses are lower
Describe briefly the steps of asthma management.
Step 1 - inhaled SABA to be used as required
Step 2 - add ICS
Step 3 - add LABA
Step 4 - consider increasing ICS doses or adding in a 4th agent (leukotriene receptor antagonist, SR theophylline, oral β2-agonist)
What are SABA’s used for?
To provide short term relief for mild and intermittent asthma
What is increasing use of a SABA a marker of?
Uncontrolled asthma and indicates that the patient should be escalated to the next step
Patients using high doses of SABA’s are more likely to…
Experience side effects such as tremor, cramps, palpitations and headache
What should be checked before a step up in therapy is initiated?
Adherence to inhaled therapy and inhaler technique
How often should patients be reviewed?
Every 3-6 months with a view to stepping down treatment
When is addition of an ICS indicated?
For patients who,
Have had an exacerbation in the previous 2 years
Experience asthma symptoms 3 or more times a week
Are woken up at night with asthma symptoms on 1 or more occasions a week
Name 3 examples of inhaled corticosteroids.
Beclomethasone, budesonide, ciclesonide
ICS are classified as…
Either low, medium or high doses
What is the recommended starting dose of Beclomethasone for adults?
400µg equivalence per day
What are some of the long term side effects of ICS therapy?
Diabetes, skin thinning and bruising, cataracts
High does of ICS have the potential to…
Induce adrenal suppression
What should all patients taking ICS be given?
Steroid card
What are some of the local side effects associated with ICS?
Dysphonia (difficulty in speaking)
Oral candidiasis
How can local side effects of ICS be minimised?
Spacer device
Rinsing mouth with water after each use, but do not swallow water
How should patients be taken off ICS?
Discontinuation can worsen clinical outcomes significantly, patients need to be weaned off treatment
Which agent should not be used as single therapy for asthma treatment, and should only be used alongside ICS?
LABA
What effect do LABA’s have on airway inflammation?
They have no effect
Induce bronchodilation, do not affect inflammation
What are some of the adverse effects of LABA’s?
CV stimulation
Anxiety
Tremor
Name 2 leukotriene receptor antagonists (LTRA’s).
Montelukast and zafirlukast
How do LTRA’s work?
Interfere with the pathway of leukotriene mediators which are released from mast cells, eosinophils and basophils
How are LTRA’s administered?
Orally
What are some of the side effects of LTRA’s?
Abdominal pain Headache Thirst Rash Sleep disturbances CNS effects
Give 2 examples of methylxanthines and how they are administered.
Oral theophylline
IV/oral aminophylline
Why are SR preparations of methylxanthines used?
Have a narrow therapeutic index
SR preparations are used to give a more predictable effect
The brand must remain constant
What effects does a subtherapeutic dose of methylxanthine have?
Nausea, diarrhoea, nervousness, headache
What effects does an overdose of methylxanthine have?
Vomiting, insomnia, arrhythmias
What effects does a serious overdose of methylxanthine have?
Hyperglycaemia, arrhythmia, convulsions, death
How are methylxanthines cleared?
CYP450 metabolism
What impact does the clearance of methylxanthines have on their use?
ADR's as CYP450 is a common route of drug metabolism Enzyme inhibition (decreased clearance, increased concentration, overdose) e.g. by cimetidine, erythromycin, allopurinol, ciprofloxacin Enzyme induction (increased clearance, decreased concentration, subtherapeutic dose) e.g. carbamazepine, rifampicin, phenytoin, smoking
How does Theophylline work to treat asthma?
Promotes bronchial smooth muscle relaxation, increase mucocilliary transport and contractility of the diaphragm, and acts as a central respiratory stimulant
What are some of the side effects of Theophylline?
Tachycardia Palpitations Headache Insomnia Nausea GI disturbance
What can be said about the side effects of Theophylline?
More common than with alternative treatments
How are oral β2-agonists formulated?
As slow release tablets
What is the only licensed LAMA for asthma?
Tiotropium
What is meant by ‘maintenance and reliever therapy’?
An approach for those who struggle using multiple inhalers
Employs the use of combination products that contain a LABA and an ICS to provide maintenance and reliever therapy without the need for an additional SABA
Patient receives a maintenance dose of ICS/LABA in the morning and at night
When should you consider reviewing a patients ‘maintenance and reliever therapy’?
If the patient is using the inhaler one or more times during the day on a regular basis in addition to their maintenance dose
When is oral corticosteroid maintenance therapy required?
For a small number of patients who have severely uncontrolled asthma
What is the most commonly used oral corticosteroid?
Prednisolone
What are some of the side effects of long term oral corticosteroids?
Hypertension Diabetes Hyperlipidaemia Osteoporosis Obesity Cataracts Glaucoma Skin thinning and bruising Muscle weakness
How can you minimise the side effects of long term oral corticosteroid use?
Use the lowest dose possible
What is Omalizumab?
A humanised anti-immunoglobulin E (IgE) monoclonal antibody
How is Omalizumab given?
Administered by SC injection
Name 3 immunosuppressants used in asthma.
Methotrexate
Ciclosporin
Liquid gold
Why are immunosuppressants used in asthma?
Reduce the need for long term oral corticosteroids
What are Cromones?
Mast cell stabilisers used as preventer therapy in 5-12 year olds
Give an example of a Cromone.
Nedocromil
How do Cromones work?
Inhibit mediator (histamine) release from mast cells
What are some of the side effects of Cromones?
N&V
Bitter taste
Dyspepsia
What is a bronchoplasty?
A procedure involving the delivery of radio frequency energy to the airway wall to heat the tissue and remove smooth muscle present
Novel therapies are…
Invasive, expensive and often associated with a higher level of risk
What is a ‘reliever’ in terms of asthma therapy? Give an example.
Produces quick symptom relief
Usually dosed PRN
SABA’s e.g. Salbutamol
What is a ‘preventer’ in terms of asthma therapy? Give an example.
Act on underlying inflammation
Usually dosed BD
Corticosteroids e.g. Beclomethasone
What is a ‘controller’ in terms of asthma therapy? Give an example.
Slow onset and long acting
Usually dosed BD
LABA’s e.g. Salmeterol
Inhalers were traditionally defined by…
Colour i.e. blue for reliever, but this is often not the case now
What are nebulisers do?
Vaporise aqueous solution of drug to a mist for inhalation through a mask or mouthpiece
When and where are nebulisers used?
Used to delivery high doses and are particularly useful in acute or chronic/severe asthma since coordination is not needed
Used a lot in hospital settings
What is ‘difficult asthma’?
Patients who have persistent symptoms, frequent exacerbations, or both, despite treatment at steps 4 or 5 are described as having ‘difficult asthma’
What is ‘difficult asthma’ a result of?
Often a result of poor adherence, incorrect inhaler technique, environmental factors, psychological issues or co-existing conditions
What is ‘severe refractory asthma’?
Patients who have difficult asthma but remain uncontrolled despite resolution of contributing factors are described as having ‘severe refractory asthma’
Why are personalised asthma action plans (PAAP’s) used?
To help patients recognise the deterioration of their asthma control and to provide tailored advice on how they can treat their exacerbations at an early stage (detailing when and how they should modify their medicines in response to worsening asthma and when to see a HCP)
What should a patients PAAP include?
Instructions on how to recognise signs of worsening asthma
Advice on the prompt use of SABA’s and oral corticosteroids
Monitoring of response to medicines
Contact information/telephone numbers
Follow up to assess asthma control
What are the 4 features determining ‘severe’ asthma?
PEF<50% of normal/best
Ability to talk
RR>25
HR>110
What are the additional features present in ‘life threatening’ asthma?
Silent chest Cyanosis Bradycardia Confusion Exhaustion Coma Difficulty speaking full sentences PEF<33% of normal/best
What should be immediately prescribed in an acute asthma attack?
Oxygen - highest possible concentration (40-60%), aim for arterial oxygen saturation 94-98%
β-agonist - nebuliser or multiple doses (10-20 puffs) via spacer
Corticosteroid - oral prednisolone or IV hydrocortisone
What else could be prescribed for an acute asthma attack for immediate treatment?
Ipratropium nebuliser
Single dose IV magnesium sulphate (stabilises T-cells and mast cells)
IV aminophylline/salbutamol
What monitoring requirements are there for a patient experiencing an acute asthma attack?
PEF O2 saturation (aim 94-98%) Arterial blood gases HR and RR (tachycardia/ponea) CRP WCC (if infection is suspected) Theophylline levels (if continued >24 hours) Serum K+ (if taking nebuliser SABA) Glucose Hydration Blood pH ~7.4 (risk of acidosis)
What symptoms indicate the patient requires a transfer to ITU?
Deteriorating PEF Persistent hypoxia Hypercapnia Exhaustion and drowsiness Coma and respiratory arrest
Whilst the patient is hospitalised, the following should be done/put in place…
IV to nebuliser to inhaler transition Oral steroid 40-50mg 5/7 depending on severity of exacerbation Restart steroid inhaler Discharge criteria Action plan Check inhaler technique
