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Asthma (Therapeutics) Flashcards

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1
Q

What is asthma?

A

A chronic inflammatory disorder of the airways

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2
Q

What does asthma lead to an increase in?

A

Airway hyperresponsiveness

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3
Q

What are some of the symptoms of asthma?

A

Recurrent episodes of wheezing, breathlessness, chest tightness and coughing, particularly at night or early in the morning

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4
Q

What are episodes of asthma associated with physiologically?

A

Widespread, variable airflow obstruction that is often reversible, spontaneously or with treatment

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5
Q

How is asthma usually mediated?

A

By IgE

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6
Q

Which cells produce mucus?

A

Goblet cells

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7
Q

What can occur if asthma is poorly managed over a period of years?

A

Airway remodelling

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8
Q

Does asthma have a cause?

A

Factors are no longer referred to as ‘causes’ of asthma, but environmental and genetic factors that contribute to its development

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9
Q

What are some of the factors that contribute to the development of asthma?

A

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)

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10
Q

Is asthma more common in prepubescent girls or boys?

A

More common in prepubescent boys but boys are also more likely to grow out of their asthma during adolescence

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11
Q

What is a phenotype?

A

A set of observable characteristics of an individual resulting from the interaction of its genotype with the environment

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12
Q

What is phenotyping?

A

The process of predicting an organism’s phenotype using only genetic information collected from genotyping or DNA sequencing

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13
Q

What is the relevance of phenotyping in asthma?

A

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

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14
Q

What are some of the possible triggers of asthma?

A 
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)
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15
Q

What is the cause of wheezing and coughing in asthma?

A

Wheezing that occurs as a result of bronchoconstriction and coughing are likely to be caused by stimulation of sensory nerves in the airways

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16
Q

What signs may be present/absent in an acute exacerbation of asthma?

A

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

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17
Q

What are some of the clinical features that lower the probability of asthma?

A

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

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18
Q

How is asthma diagnosed?

A

Based on medical history, physical examination, lung function testing and response to medication
No ‘gold standard’ test

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19
Q

How is diagnosis altered if patient has a high probability of asthma?

A

Usually start with a treatment trial and response is assessed using spirometry

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20
Q

How is diagnosis altered if patient has a intermediate probability of asthma?

A

Lung function tests are conducted first such as spirometry, peak flow and airway responsiveness

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21
Q

Do normal spirometry findings exclude a diagnosis of asthma?

A

No, not if the patient is well at the time of testing

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22
Q

What are some of the spirometric measures used?

A

FVC
FEV1
FEV1/FVC ratio

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23
Q

What is FVC?

A

The total volume of air expelled by a forced exhalation after maximal inhalation

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24
Q

What is FEV1?

A

The volume of air expelled in the first second of a forced exhalation after maximal inhalation

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25
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
26
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
27
Which is more accurate, spirometry or peak expiratory flow measurements?
Spirometry
28
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
29
How can airway responsiveness be measured?
Using inhaled mannitol or methacholine
30
When is this airway responsiveness test used?
To diagnose patients who have a baseline FEV1 <70% of population data
31
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
32
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)
33
What does a treatment trial involve?
Being prescribed a 6-8 week trial of inhaled beclomethasone or prednisolone
34
What do the results from a treatment trial indicate?
An improvement in FEV1 of 400ml or more is strongly suggestive of asthma
35
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
36
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
37
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
38
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
39
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
40
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
41
Who produces guidance on asthma management?
British Thoracic Society (BTS) Scottish Intercollegiate Guidelines Network (SIGN) NICE
42
Which guidelines do the BNF and other sources mainly refer to?
BTS
43
Do guidelines differ and how?
NICE guidelines differ greatly to traditional BTS/SIGN and are more conservative with using ICS
44
How do paediatric guidelines differ?
Do not advocate regular oral steroids and ICS doses are lower
45
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)
46
What are SABA's used for?
To provide short term relief for mild and intermittent asthma
47
What is increasing use of a SABA a marker of?
Uncontrolled asthma and indicates that the patient should be escalated to the next step
48
Patients using high doses of SABA's are more likely to...
Experience side effects such as tremor, cramps, palpitations and headache
49
What should be checked before a step up in therapy is initiated?
Adherence to inhaled therapy and inhaler technique
50
How often should patients be reviewed?
Every 3-6 months with a view to stepping down treatment
51
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
52
Name 3 examples of inhaled corticosteroids.
Beclomethasone, budesonide, ciclesonide
53
ICS are classified as...
Either low, medium or high doses
54
What is the recommended starting dose of Beclomethasone for adults?
400µg equivalence per day
55
What are some of the long term side effects of ICS therapy?
Diabetes, skin thinning and bruising, cataracts
56
High does of ICS have the potential to...
Induce adrenal suppression
57
What should all patients taking ICS be given?
Steroid card
58
What are some of the local side effects associated with ICS?
Dysphonia (difficulty in speaking) | Oral candidiasis
59
How can local side effects of ICS be minimised?
Spacer device | Rinsing mouth with water after each use, but do not swallow water
60
How should patients be taken off ICS?
Discontinuation can worsen clinical outcomes significantly, patients need to be weaned off treatment
61
Which agent should not be used as single therapy for asthma treatment, and should only be used alongside ICS?
LABA
62
What effect do LABA's have on airway inflammation?
They have no effect | Induce bronchodilation, do not affect inflammation
63
What are some of the adverse effects of LABA's?
CV stimulation Anxiety Tremor
64
Name 2 leukotriene receptor antagonists (LTRA's).
Montelukast and zafirlukast
65
How do LTRA's work?
Interfere with the pathway of leukotriene mediators which are released from mast cells, eosinophils and basophils
66
How are LTRA's administered?
Orally
67
What are some of the side effects of LTRA's?
``` Abdominal pain Headache Thirst Rash Sleep disturbances CNS effects ```
68
Give 2 examples of methylxanthines and how they are administered.
Oral theophylline | IV/oral aminophylline
69
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
70
What effects does a subtherapeutic dose of methylxanthine have?
Nausea, diarrhoea, nervousness, headache
71
What effects does an overdose of methylxanthine have?
Vomiting, insomnia, arrhythmias
72
What effects does a serious overdose of methylxanthine have?
Hyperglycaemia, arrhythmia, convulsions, death
73
How are methylxanthines cleared?
CYP450 metabolism
74
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 ```
75
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
76
What are some of the side effects of Theophylline?
``` Tachycardia Palpitations Headache Insomnia Nausea GI disturbance ```
77
What can be said about the side effects of Theophylline?
More common than with alternative treatments
78
How are oral β2-agonists formulated?
As slow release tablets
79
What is the only licensed LAMA for asthma?
Tiotropium
80
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
81
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
82
When is oral corticosteroid maintenance therapy required?
For a small number of patients who have severely uncontrolled asthma
83
What is the most commonly used oral corticosteroid?
Prednisolone
84
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 ```
85
How can you minimise the side effects of long term oral corticosteroid use?
Use the lowest dose possible
86
What is Omalizumab?
A humanised anti-immunoglobulin E (IgE) monoclonal antibody
87
How is Omalizumab given?
Administered by SC injection
88
Name 3 immunosuppressants used in asthma.
Methotrexate Ciclosporin Liquid gold
89
Why are immunosuppressants used in asthma?
Reduce the need for long term oral corticosteroids
90
What are Cromones?
Mast cell stabilisers used as preventer therapy in 5-12 year olds
91
Give an example of a Cromone.
Nedocromil
92
How do Cromones work?
Inhibit mediator (histamine) release from mast cells
93
What are some of the side effects of Cromones?
N&V Bitter taste Dyspepsia
94
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
95
Novel therapies are...
Invasive, expensive and often associated with a higher level of risk
96
What is a 'reliever' in terms of asthma therapy? Give an example.
Produces quick symptom relief Usually dosed PRN SABA's e.g. Salbutamol
97
What is a 'preventer' in terms of asthma therapy? Give an example.
Act on underlying inflammation Usually dosed BD Corticosteroids e.g. Beclomethasone
98
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
99
Inhalers were traditionally defined by...
Colour i.e. blue for reliever, but this is often not the case now
100
What are nebulisers do?
Vaporise aqueous solution of drug to a mist for inhalation through a mask or mouthpiece
101
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
102
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'
103
What is 'difficult asthma' a result of?
Often a result of poor adherence, incorrect inhaler technique, environmental factors, psychological issues or co-existing conditions
104
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'
105
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)
106
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
107
What are the 4 features determining 'severe' asthma?
PEF<50% of normal/best Ability to talk RR>25 HR>110
108
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 ```
109
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
110
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
111
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) ```
112
What symptoms indicate the patient requires a transfer to ITU?
``` Deteriorating PEF Persistent hypoxia Hypercapnia Exhaustion and drowsiness Coma and respiratory arrest ```
113
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 ```

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