Asthma and COPD Flashcards
1
Q
What does SABA stand for?
A
Short acting beta-2 agonists
2
Q
What does LABA stand for?
A
Long acting beta-2 agonists
3
Q
What does SAMA stand for?
A
Short acting muscarinic antagonist
4
Q
What does LAMA stand for?
A
Long acting muscarinic antagonist
5
Q
What does LTRA stand for?
A
Leukotriene receptor antagonists
6
Q
What is an example of a SABA?
A
Salbutamol
Terbutamine
7
Q
What is an example of a LABA?
A
Salmeterol
Formoterol
8
Q
What is an example of a SAMA?
A
Ipratropium
9
Q
What is an example of a LAMA?
A
Tiotropium
10
Q
What is an example of a LTRA?
A
Montelukast
11
Q
What is the common brand name of salbutamol?
A
Ventolin
12
Q
How long does it take SABAs to have a maximum effect and what is the duration of action?
A
Maximum effect within 30 minutes
Duration of action is 4-6 hours
13
Q
What is the duration of action of LABAs?
A
12-24 hours
14
Q
What is special about formoterol?
A
It has a dual action, meaning it has both short and long acting effects. Is used in MART therapy- maintenance and reliever therapy
15
Q
What are the 3 LABAs that are only licensed for the treatment of COPD (can’t be used in asthma)?
A
Indacaterol
Olodaterol
Vilanterol
16
Q
What may be used if a patient is having a severe asthma attack?
A
An IV form of salbutamol or terbutaline
17
Q
What are the adverse effects of SABAs and LABAs if they reach systemic circulation?
A
- Tremors
- nervous tension
- headache
- tachycardia/palpitations
- hyporkalaemia
18
Q
What factors increase the risk of adverse effects from beta 2 agonists?
A
- Taken as a IV or oral form- more likely to reach systemic circulation ( try to void)
- large doses
- Using the reliever inhales frequently during acute exacerbation
19
Q
What causes the tremor sometimes caused by short acting beta-2 agonists?
A
Direct stimulation of beta-2 receptors in skeletal muscle. Often in hands and quick onset
20
Q
What causes tachycardia sometimes caused by short acting beta-2 agonists?
A
The agonistic effects of beta-1 receptors on the heart.
Very disturbing for patients
21
Q
What causes hypokalaemia sometimes caused by short acting beta-2 agonists and what patients are at risk?
A
Caused by increased cellular potassium uptake.
Those already taking medications such as diuretics, xanthines and steroids
22
Q
Why is it important to take care when prescribing beta-2 agonists in those with cardiovascular problems?
A
Those with cardiovascular diseases are often taking beta-blockers which are beta antagonists (e.g. atenolol or propranolol) so would disrupt the action of these beta 2 agonist medications. These drugs are taking for action of b1 receptors on the hearts to slow heart rate however we need to ensure beta agonists are cardio-selective.
23
Q
What are SABA used as?
A
Rescue or reliever therapies
24
Q
SABA counselling points
A
carry at all times
may take before triggers e.g. before excercise
If being used very frequently (more than 3 times a week), it signifies a poorly controlled condition and should be referred.
25
What are LABA used as?
Preventer therapies- usually taken twice a day
26
What does MART therapy contain?
Formoterol + a steroid
27
What is MART therapies used as?
Usually taken twice a day as a preventer therapy but should be carried also to use as a reliever. Only in asthma
28
What type of receptor are the beta-2 receptors?
G-protein coupled receptor (GPCR)
29
What type of receptor are the beta-2 receptors?
G-protein coupled receptor (GPCR)
30
How do Beta-2 agonists work?
Bind to the beta-2 adrenoreceptors ( 7 transmembrane- domain GPCR) on airway smooth muscle cells. This binding induces a conformational change in the g alpha s subunit and it dissociates from the beta-gamma. It then binds to and activates adenyl cyclase to catalyse the conversion of ATP to cAMP. cAMP then activates protein kinase A. PKA and cAMP inhibits the release of calcium ions from intracellular stores. The decrease in calcium ions prevents smooth muscle contraction as it inactivates myosin light chain kinase from being able to perform the power stoke needed for muscle contraction. Normally ca2+ would bind to calmodulin to form a complex that activates MLCK to phosphorylate myosin light chain and form a cross-bridge with actin to cause muscle contraction. But as MLCK has been inactivates, this contraction cannot occur.
31
Aside from the most obvious action of beta-2 agonists, how else can they have an effect?
- Reduce mediator release from mast cells
- Reduce plasma exudation
- Reduce cholinergic transmission
- Increases mucus clearance
- Increase in pulmonary surfactant
32
Why is monotherapy with just a LABA or SABA strongly discouraged?
Because once the agonist has bound, the GPCRs on the immune cells (eosinophils, neutrophils, t-cells) can be quickly desensitised meaning no prolonged anti-inflammatory effects. Hence why not used as a monotherapy. Has been linked with increased hospitalisation, poorly controlled asthma and deaths. Now usually use a low dose of an inhaled corticosteroid as a first step.
33
Why is monotherapy with just a LABA or SABA strongly discouraged?
Because once the agonist has bound, the GPCRs on the immune cells (eosinophils, neutrophils, t-cells) can be quickly desensitised meaning no prolonged anti-inflammatory effects. Hence why not used as a monotherapy. Has been linked with increased hospitalisation, poorly controlled asthma and deaths. Now usually use a low dose of an inhaled corticosteroid as a first step.
34
What are some examples of inhaled corticosteroids used in asthma?
- Beclometasone
- Budosonide
- Fluticasone
35
How can ICS be used in the treatment of COPD ?
Must be used in combination with a LABA such as salmeterol or formeterol or a LAMA such as tiotropium.
36
What are the two available brands of beclometasone in a MDI?
Qvar
Clenil
37
What is an important factor when receiving a prescription for beclometasone MDI?
That the two brands (Qvar and Clenil) are not interchangeable and therefore cannot give if the prescription is generic and doesn't specify.
38
Why are the different brands of beclometasone MDIs not interchangeable?
Because they have different particle sizes.
Qvar particles are extra fine so are nearly twice as potent as Clenil.
39
What is the typical starting dose for an adult with beclometasone ( Qvar)?
2 puffs (50mcg) Twice a day
40
What is the typical starting dose for an adult with beclometasone (Clenil)?
2 puffs (100mg) twice a day
41
If a patient has had an asthma exacerbation, what may they be given to bring down the inflammation?
A short course of oral corticosteroids to reduce inflammation and open the airways.
42
What may be given if a patient has had an acute Asthma exacerbation?
IV corticosteroids to prevent late phase reaction
43
When may oral corticosteroids be prescribed in COPD?
If the patient contracts an upper respiratory tract infection. Will usually be given in combination with antibiotics.
44
What does a rescue pack for COPD contain?
Oral corticosteroid e.g. prednisolone
Broad spectrum antibiotic e.g. amoxicillin
45
What are some adverse effects of inhaled corticosteroids?
- Hoarseness
- Throat irritation
- Dysphonia- changes in voice
- Candida (Oral thrush)
46
How can you reduce the chances of oral thrush caused by ICS?
- Use a spacer e.g. aerochamber or volumatic
- Wash mouth out or brush teeth after- steroid promotes fungal growth
47
What is the classification of asthma?
An inflammatory disease of the airway characterised by recurrent attacks of breathlessness and wheezing. Airway is mostly reversible with treatment or spontaneously.
48
What can cause asthma?
Host causes or environmental causes
Host e.g.
genetic predisposition
age
gender
ethnicity
Environmental e.g.
Allergens
pollutants
tobacco smoke
diet
drugs
obesity
exercise
49
What are the two classifications of asthma?
Intrinsic and extrinsic
50
What is extrinsic asthma?
Most common type
Have an atopic phenotype- raised IgE antibody levels
often has an early onset- in childhood
is episodic- attacks of breathlessness etc but not all of the time, usually caused by a trigger e.g. dust, pollen, fur
51
What is intrinsic Asthma?
Less common and is usually onset in adulthood
- it is non-atopic- normal levels of IgE antibodies
- more chronic- more frequent and apparent breathlessness
Can be caused by occupational exposure, obesity, stress, exercise, medications
52
What is the classification of COPD?
A disease characterised by airflow obstruction. It is usually progressive and non-reversible. It can be divided into emphysema and bronchitis.
53
What causes the airflow obstruction in COPD?
Is due to airway and parenchyma damage as a result of chronic inflammation.
54
What percentage of COPD cases are associated with smoking?
Greater than 90% of patients are current smokers out have smoked previously. However, only 10% of smokers will develop the disease
55
Aside from smoking, what other factors can cause COPD?
- Occupational dust exposure (e.g. silica, chemicals, wood, grain etc)
- Biomass
- Air pollution
- An alpha anti-trypsin deficiency- the enzyme neutrophil elastase is needed to breakdown elastin in the lungs. Alpha-anti trypsin is an enzyme that. inhibits this enzyme so the lungs isn't broken down consistently, without this enzyme, elastin will break down the extracellular matrix causing alveolar collapse and lung damage
56
What is a genetic cause of COPD?
An alpha anti-trypsin deficiency.
This is an autosomal recessive condition.
This alpha anti-trypsin enzyme is needed to inhibit neutrophil elastase. Without this inhibitor, the elastase will continue to break down the extracellular matrix, leading to lung damage and alveolar collapse.
57
What are the symptoms of asthma?
- Wheeze- especially on expiration (air gets trapped due to obstruction and resistance)
- Breathlessness (not enough oxygen due to bronchoconstriction)
- Coughing ( especially in morning and at night)- can be due to spasm of smooth muscle or mucus
- Chest tightness- not being able to get air due to narrowing of airways
- Diurnal variation (varies during the day)
- Night time waking
58
What are the symptoms of bronchitis?
- Excess mucus production
- Wheeze and shortness of breath
- Low o2 (hypoxia) and high co2 (hypercapnia) in system
- chronic productive cough
- loose ability to control rate and depth of breathing
- are often overweight
59
What are the symptoms of emphysema?
- Usually breathlessness even at rest due to breakdown of alveoli
- Breathing rate is increased- hyperventilating
- less likely to have a cough or bronchial infection than in bronchitis
- Often appear flushed, pink, thin and have pursed lips- have to put a lot of effort into expiration which is usually a passive process
60
What is an exacerbation?
A sustained worsening of the patients symptoms from the usual state. It is acute in onset and increase likeliness of hospitalisation, morbidity and costs of NHS.
61
Describe the histopathology of asthma airways?
(Describe the structural changes)
- Narrowed lumen
- Increase in goblet cells (hyperplasia), therefore increased mucus production and secretion
- Increased layer of smooth muscle- larger and more cells
- Increase in blood vessels= oedema- vessels become leaky and contents leaking makes this area thicken
- Increased volume of submucosal glands
- in the sub-epithelial layer there are large deposits of collagen, restricting the airway
61
Describe the histopathology of asthma airways?
(Describe the structural changes)
- Narrowed lumen
- Increase in goblet cells (hyperplasia), therefore increased mucus production and secretion
- Increased layer of smooth muscle- larger and more cells
- Increase in blood vessels= oedema- vessels become leaky and contents leaking makes this area thicken
- Increased volume of submucosal glands
- in the sub-epithelial layer there are large deposits of collagen, restricting the airway
62
What happens in the early stage reaction of asthma?
- A response to an allergen or irritant. Within minutes to hours:
- Hypersensitivity:
- Spasm of smooth muscle layer
- Hyper-secretion of mucus from increase in goblet cells and increased size of mucus glands
- Bronchoconstriction- smooth muscle constricts and narrows the airways
- vasodilation- vessels dilate and can cause oedema- leaking of blood vessels
63
What happens in the late phase of asthma?
The release of the substances in the early phase, recruits inflammatory cells and causes a cellular infiltration.
- Inflammation- injury to epithelial layer and disrupt the barrier function and exposes the nerve endings
- cilia are damaged- can't move and clear the mucus
- Bronchoconstriction
64
Why do we need short acting and long acting treatments in asthma?
Because bronchoconstriction, which most of these drugs target to open the airways happens in both the early and late reaction phase of asthma.
65
What is the difference in pathophysiology of emphysema and bronchitis?
- Bronchitis: Inflammation of bronchioles and bronchi
- Emphysema: more in the alveoli
66
What happens in bronchitis?
- Thickened smooth muscles
- fibrosis and structural recomposition of airways- often impairs the function as elasticity is reduced
- increase in mucus and goblet cells
- Increase in collagen deposits
67
What happens in emphysema?
- membranes holding the alveoli are broken down, leading to holes and airspaces, reducing efficient gaseous exchange
- Also reduces the elastic recoil of the lungs as elastin is broken down
68
What is the difference in airflow obstruction in asthma and COPD?
- In asthma, the obstruction is reversible by using bronchodilators
- In COPD, the obstruction is not fully reversible
69
If the probability of a patient having asthma is high, what would you do?
Make a record of likely to be asthma
Give them six weeks course of an ICS- reduces inflammation in the airways
After 6 weeks reassess, to see if symptoms have improved. Can measure FEV1 ration or PEF
70
If the probability of a patient having asthma is intermediate what would you do?
Use a reverse spirometry test when giving a patient bronchodilator.
- Do a test before and then after taking a bronchodilator and see if the symptoms have improved.
71
How can peak flow be used to monitor their condition in asthma?
Measures volume of air expelled from the lungs
Process:
- Either be sitting straight to standing up, once chosen keep to this forever
- Push the small arrow on the meter up towards the mouthpiece and then hold the meter on the sides to ensure you're not toughing the arrow
- Take a deep breath and blow hard and fast into the mouthpiece
- the number at which the arrow is now at is your peak flow reading and should be plotted in a peak flow diary
72
What is the medicine research council (MRC) Dyspnoea scale used for?
Used to rate a patients breathlessness, on a grade scale 1-5. where 1 is not troubled by breathlessness unless during strenuous activity and 5 is so breathless they can't leave the house and get breathless when just getting undressed.
73
How can spirometry be used
Measure lung function
Process:
- Put a clip on your nose to ensure you are only breathing out of your mouth
- Blow into a tube connected to a computer- ensure the mouth is tightly sealed around the mouthpiece.
- Take a deep breath and then breath out as fast as you can for as long as you can
- Repeat
- sometimes may be asked to do after taking your reliever inhaler
74
What is the FVC of a traditional healthy patient?
About 4 litres
75
What should FEV1/PEF readings be?
(FEV1 and or PEF >80% predicted/best)
76
What must an ICS be used in combination with in COPD?
A LABA or LAMA- so won't see as individual products e.g. ciclesonide and mometasone are only used as individual medications so won't be given in COPD
77
What are some examples of ICS?
Used in COPD and asthma:
Beclometasone
Budesonide
Fluticasone
Just used in asthma as are single-ingredient inhalers and in COPD, ICS must be in combination with a LABA or LAMA:
ciclesonide
Mometasone
78
Can steroids be given my multiple routes at the same time?
yes
e.g. oral, inhaled, nasal spray etc
79
Why may patients taking steroids not see any effect for a couple of days?
because it takes time for them to have their effect due to the method of action.
80
What are ICS used as?
A preventative therapy
81
What is the usual dose for an ICS?
Usually BD- morning and evening
82
What is the mechanism of action of corticosteroids?
Steroids can cross the plasma membrane and into the cytoplasm.
Corticosteroids then bind to the glucocorticoid receptors in the cytoplasm.
Ligand binding allows homodimerisation (when two receptors with a ligand bound can come together).
Once this has occurred, they translocate to the nucleus and bind to hormone-response elements (specialised sequences within DNA for binding)
This causes proteins to either be brought to the complex or not and causes transcriptional activation or transcriptional repression.
In asthma and COPD want to know how this reduces pro-inflammatory cytokines and help to reduce inflammation.
83
What are the cellular effects of corticosteroids in asthma?
- Reduction in number of dendritic cells- needed for sampling antigens from epithelial surface- crucial in initiating initial hypersensitivity reactions
- Reduction in mast cell numbers- needed for mast cell degranulation and concurrent effects
- Reduction of cytokine production from t-lymphocytes, smooth muscle cells, macrophages and epithelial cells. this decreases the pro-inflammatory environment
- Smooth muscle cells increase expression of the B2 receptors- important in co-therapy when using a bronchodilator and will block the desensitisation of b2.
- Reduction in leakage of epithelial cells, reduce airway mucosa from filling up with fluid
- reduction in eosoniphils- dining by apoptosis
- reduction in goblet cells- reduction in mucus production
84
What cytokines and chemokine are reduced by use of corticosteroids?
- Cytokines- interleukin-1 and interleukin-6 (IL-1 & IL-6)
- Chemokines- interleukin-8, eotaxin
- adhesion molecules- cam-1
85
How does this action of ICS actually have an effect in asthma?
- Suppresses the cytokine interleukin-2 which is important in expansion of t-helper-2 cells (Th2 cells). This is the key cell driving asthma- as it produces cytokines that promote eosinophils to promote production of the IgE antibodies that cause the hypersensitivity reaction.
- Can also inhibit vasodilators e.g. prostaglandin-2
- May inhibit leukotrienes
- Upregulate the B2 adrenoreceptor which is important to prevent receptor desensitisation.
86
Where are muscarininc receptors found?
Found in target organs of the parasympathetic nervous system. The post-ganglionic neurone releases acetylcholine which stimulates muscarinic receptors on the target organ to have its downstream effects.
