1
Q
what would just using B2 agonists for asthma do?
A
desensitisation of receptors, less likely to respond to future doses, doesnt treat underlying cause only the symptoms
2
Q
what is montelukast?
A
long acting muscarinic (leukotriene receptor antagonist)
3
Q
what is an important vasodilator monitor?
A
nitric oxide
4
Q
what is FEV1
A
measure the amount of volume from the lungs in litres
5
Q
what does it mean if FEV1/FVC ratio is <0.7?
A
some sort of obstructive disease eg. asthma or COPD
6
Q
what is MART?
A
maintenance and reliever therapy - step up frequency, dose of corticosteroid may go up
7
Q
what factors can effect FEV1, FVC and PEFR?
A
- time of the day - diurnal rate, breathing dips at 4am (asthma more likely to flare in the morning)
- weight
- age
- ethnicity
- smoking
- fitness level
8
Q
what is a spirometer used for?
A
to measure lung function by gauging the volume and speed of air inhaled and exhaled
9
Q
what is a peak flow meter?
A
to measure how fast you can blow air out of the lungs, helping to diagnose and manage asthma or COPD
10
Q
what is the correct technique for spirometry?
A
- sit upright
- full inhalation to total lung capacity
- tight seal around mouthpiece
- blow out as fast and hard as you can
11
Q
how to use a peak flow meter?
A
- stand or sit upright
- reset marker to zero
- deep breath in
- seal lips tightly
- blow out hard and fast
- repeat 3 times and record higher value
12
Q
what side HF is common with COPD?
A
right handed HF
13
Q
what are examples of non-specific stimuli in asthma?
A
exercise, cold air, hyperventilation, chemical agents
14
Q
what is specific stimuli in asthma?
A
allergens
aspirin; only in those who are hyper-responsive to aspirin
15
Q
what is the inflammatory response in aspirin mediated by?
A
eosinophils, mast cells and neutrophils
16
Q
what smooth muscle substances cause contraction?
A
acetylcholine, histamine and PAF
17
Q
what is neuronal imbalance in asthma?
A
airways are regulated by the parasympathetic and sympathetic system
18
Q
what is hyperplasia and hypertrophy in asthma?
A
hyperplasia - airway smooth muscle proliferate more
hypertrophy - gets bigger
19
Q
what is broncial asthma?
A
far more mucous and prescence of goblet cells which produce mucous and undergo hyperplasia and hypertropy
20
Q
what happes during structural remodelling in the lungs?
A
epithelial damage, mucosal oedema, increased intraluminal secretions, basement membrane thickening, smooth muscle hypertropy and hyperplasia and inflammation
21
Q
what does structural remodeeling do to the airways?
A
obstructs the airways due to mucous and mediates the sensitisation of smooth muscle to contract
22
Q
why is the change in smooth muscles important?
A
- responds to cytokines and mediators (contracts more)
- acetylcholine causesw contraction
23
Q
what is involved in airway muscle proliferation and whst causes it?
A
- hypertrophy and hyperplasia
- stimulated by multiple growth factors and mediators produced
- can release its own mediators
- associated with hyper-responsiveness and increased stiffness
24
Q
what receptors help mediate mucous production?
A
M3 receptors
25
that is the cholinergic response in asthma?
release of ach triggers contraction in smooth muscles. afferent nerves eg. c-fibres respond to substances eg. histamine, bradykinin, prostaglandins to cause a relflex bronchoconstriction
26
what are defects of cholinergic innervation?
- increased vagal tone
- reflex bronchoconstriction
- increased ach release
- increase in post synaptic muscarin receptor function
27
what are A delta fibres stimulated by and what is there effect in asthma?
stimulated by the environment eg. cold air, smoke
activate vagus nerve part of the PNS
hyper-responsivness causes increased mucous and increased contraction
28
what is NANC transmission?
Non-adrenergic non-cholinergic transmission system
- helps regulate opening and shutting of the airways (releases VIP and NO)
29
what does increase in NANC excitory nerves cause?
Constriction - release of substance p and neurokinins from C-fibre sensory nerve endings in repsonse to prostaglandins and bradykinin released as consequence of inflammation
30
why does cold air worsen asthma?
causes reflex constriction due to release of Ach to mucus glands and cold air contains less moisture so epithelium becomes dried out and damaged
31
why do NSAIDS not work in asthma?
reduce PGE2 and PGFa and TXA2 in the lungs, may redirect activation of leukotriene pathway which is contractile
32
what are examples of SABAs
salbutamol
33
what is examples of LABAs?
salmeterol, formoterol, vilanterol
34
how do B2 andrenoreceptor agonists work?
function via cyclic AMP dependant relaxation of the airways smooth muscle (interferes with calcium)
35
what does the LABAs structure have attached to them?
lipophillic groups attaxched which interact with exosites on the receptor
36
what is more potent salmeterol or salbutamol?
salmeterol (binds for longer and more strongly to receptor, 12hrs actionm less desensitisation
37
what is the major problem with B2 adrenoreceptor agonists?
relatively short action, so can lead to loss in respose to the agonist over time (desensitisation)
38
what mechanism is desensitisation brought about by?
phosphorylation of the occupied receptor by a specific receptor kinase, termed GRK. This enables binding of beta-arrestin and subsequent internalisation of the receptors (cannot be activated)
39
why may salmeterol have less desensitisation?
partial agonist, less phosphorylation of the GRK, less internalisation of the beta-2 adrenoceptor
40
what are routes of administration of B2 agonists?
- inhaled - metered dose is commonly use or nebulisers or dry powders
- oral route - side effects make this last option
- IV or IM - necessary for acute asthma (risk of death) most commonly used with terbutaline
41
how much b2 agonist enters the lungs?
10%
42
what are systemic issues with b2 agonists?
- increased blood flow and a fall in BP - reflex increased tacycardia and cardiac output
- increased metabolic processes, increased glucose, fatty acids, ketone bodies and HDL
- increase in tremor
43
why are ICS used in asthma?
dampen down inflammation of the lungs, increase expression of B2 receptors on smooth muscles in the lungs, inhibits adhesion molecules required to get WBCs in the area
44
what are examples of ICS?
beclomethasone, budesonide, fluticasone as prophylatic therapy
45
what is oral steroid theapy in asthma?
prednisolone
46
what are IV steroids used in asthma?
hydrocorisone and methylprednisolone
47
how does steroid action occur?
- interact with nuclear receptors - gets through plasma membrane withv receptor in the cytosol (glucocorticoid)
- translocates to nucleus when activated
- sits on promoter regions of genes - transcription factors turn the genes on or off and can bind to response elements to turn on or off
48
what is lipocortin?
natural inhibitor of phosphilipase A2- strating enzyme to make prostaglandins and leukotrienes
49
what is the affect of steroids inhibiting cytokine mediators?
endothelial cell leaks less and inhibits mucous production
50
what are the beneficial effects of steroids?
- reduction in the synthesis or mediators LTC&D4, histmaine etc.
- inhibition of cytokine synthesis eg. TNFa, IL-1
- inhibits chemokine synthesis and adhesion molecule expression on endo cells
- inhibits migration and activation of immune cells (B and T)
- causes apoptosis of immune cells
51
what is the synergistic reaction between beta 2 agonists and steroids?
- inhibition of cytokine production (because the promoter regions of genes have more than one regulation site)
- steroids increase beta2 receptor expression
- salbutamol increases glucocorticoid receptor expression
52
what are side effects of steroids?
weight gain
water retention
sweating or rahses
increased apetite
mood changes
shortness of breath
blurred vision or dizziness
moon face
supressed immune system
headache
sleep problems (nightmares)
53
what type of antagonist is montelukast?
CysLT1 receptor antagonist
54
what does leukotriene C4 and D4 cause?
bronchoconstriction, increased bronchial reactivity, mucousal oedema and mucous hypersecretion
55
what are examples of leukotriene D4 receptor antagonists?
zafirlukast, zileuton and montelukast
56
what is zileuton useful in and what is the major side effect?
aspirin induced asthma
side effect: liver toxicity
57
what is the unique side effect of montelukast?
eosinophillia (too high) and churg Strauss syndrome (eosinophillic granulomatosis in small blood vessels)
58
what is a xanthine?
commonly used anti-asthmatic drugs eg. theophylline, profylline
59
what is the mechanism of action of adenosine receptor antagonists?
these drugs can block the inhibitory action of adenosine upon adenylyl cyclase, and thus allow intracellular cyclic AMP to accumulate and promote
60
how does phosphodiesterase inhibitors work?
block reduction in intracellular cAMP and relax smooth muscle
61
what is the effects of throphylline in asthma?
smooth muscle relaxation
inhibits anaphylactic release of mediators (mast cells)
suppresses oedema
central stimulation of ventilation
62
what are side effects of theophylline?
GI, seizures, palpitations
63
if it is a Th2 condition then what leukotrienes do you want antibodies against?
IL 4, 5 and 13
64
what is the target of BARa
adrenoreceptors beta 2 selective vasodilation in lungs
both are GCPRs
65
why is molecular specificity important in steroids?
- basic structure is similar
- interacion with many steroid receptors that have steroids as their ligand
- selectivity is difficult to get - some offside side effects
66
what is the mineralcorticoid receptor for?
water/ electrolyte control eg. hypotension
67
what is the effects of the glucocorticoid receptor?
immune system, inflammation
68
why is molecular specificity important in BARs?
- binding sites similar but key amino acid residues differences in binding a lipophillic pockets
- permits selective agonism against beta 2 receptor
69
what is the steroid backbone structure?
- organic 4 ring containing compound
A,B and C= 6 and D=5
70
what carbons in the steroid backbone are needed for biological activity?
3,4,5
71
what carbons are needed for MR and GR activity?
6,9,10,13,16
72
what carbons in the steroid backbone increase GR selectivity?
1,2,11,17
73
what receptor does aldosterone interact with?
MR
74
what receptor does dexamethasone interact with?
prefers GR
75
what is catechol-O-methyltransferase?
enzyme which deactivates catecholamines
76
what is the side effects of isoprenaline?
cardiac side effects (not specific as its a full agonist)
77
how does the structure of salmeterol affect the release?
larger hydrophobic tail so diffuses slowly from the cell membrane into aqueous envirnoment in the cytosol (LABA) - higher log P
77
what structure in salbutamol prevents COMT
methylene group - by taking the hydroxyl group further away
78
what are LABAS used for?
as a preventor
- selective and potent
- increased duration of action
- no good for acute attacks
- no insomnia
79
what is the onset of action and duration of eformoterol
- lower lipophillicity than slameterol so diffuses quicker into the cytosol
- use prophylaxis
80
how does molecular functionality of the steroids increase selectivity for GR and MR receptor?
- amino acid sequence similar between GR and MR
- subtle difference give rise to different binding
- concentration dependant
- too much of the drug would flood the active sites so need to tease out selectivity with the correct dose
81
what are symptoms of asthma?
better or worse at different times
wheezing
difficulty breathing
chest tightness and cough
82
why does it become difficult to breath out with asthma?
the airways become narrower (bronchoconstriction), airway walls become thicker and there is more mucous
83
what are clinical tests for asthma?
- FeNO (exhaled nitric oxide)
- bronchodilator reversiblity with spirometry
- PEFR
- bronchial challenge test
84
what is the aim of asthma management?
- no daytime symptoms
- no night time wakening
- no need for rescue medication
- no attacks
- no limitations on activity including exercise
- normal lung function (PEFR >80%)
- minimal side effects from medication
85
how is asthma monitored?
at every review
ask:
- time of work or school due to asthma
- amount of reliver used
- number of courses of oral steroids
- admission to hospital or attending A&E
86
what are the questions in the asthma control test?
1. in the past 4 weeks how much of the time did you asthma keep you from doing as much at work, school or home?
2. how often did you have shortness of breath
3. how often did your asthma symtpoms wake you up at night or earlier in the morning
4. how often have you used your rescue inhaler or nebulizer medication
5. how would you rate your asthma control
score <15 = very poorly controlled asthma
87
what is non-pharmcological managment of asthma?
identify triggers and manage these
- pollution
- house dust mites
- pollen
- pets
- occupation
- foods
- infection
- smoking and secondhand smoke
88
how is asthma managed in pregnancy?
- asthma review early in pregnancy (need control to be good)
- advice smoking cessation
- Use SABA, LABA, ICS and theophylline as normal
- use oral steroids to treat asthma attacks
- LTRA should not be stopped but also not started
89
how is asthma managed in labour?
- attacks rare during labour
- continue medicartion as normal
- regional blocks are preferable to general anaesthetic
- if taking more than 7.5mg predisolone for more than 2 weeks before labour, they would require IV hydrocortisone
90
what do you need to discuss with asthma in adolescence?
- career choices
- smoking and vaping
- factors that may affect use of inhaler in school and social situations
91
what do you need to consider with people with asthma paying sports at high levels?
ICS needs to be declared on drug tests - might cause you to get banned if not
92
what is the management of occupational asthma?
relocate away from exposure as soon as diagnosis is confirmed
93
when would you consider reducing ICS?
if stable for 6 month
94
what is moderate acute asthma in adults?
- increasing symptoms
- PEFR 50-75% best or predicted (based on age, sex and height)
- no features of acute severe
95
what is the treatment of moderate acute asthma in adults?
- treat at home
- SABA through spacer
- Prednisolone 40-50mg daily
- continue or increase therapy
- only admit to hospital if life theatening features
96
what is acute severe asthma in adults?
Any 1 of:
- PEFR 33-50% of predicted/best
- unable to talk in sentences
- RR > 25 breaths/min
- pulse >110 bpm
97
what is the treatment of acute severe asthma in adults
- consider admission to hospital
- oxygen by venturi mask to maintain oxygen saturation at 94-98%
- prenisolone 40-50mg daily
- nebulised SABA (or spacer)
98
why would you not give oxygen through nasal canula in acute severe asthma?
dont know exactly how much oxygen they are getting or how well they can breath through there nose
99
what is life threatening asthma in adults?
- oxygen saturation < 92%
- PEFR <33% best or predicted
- PaO2 < 8kPa
- normal PaCO2 (4.6-6.0 kPa)
- clinical signs:
altered conciousness
exhaustion
arrythmias
hypotension
cyanosis
silent chest
poor respiratory effort
100
what is the treatment of life threatening asthma in adults?
- immediate hospital admission
- nebulised beta agonists and ipratropium
- 40-50mg prednisolone
- oxygen via venturi mask
101
what IV treatment might someone get in hospital with life threatening asthma?
IV aminophylline, salbutamol or terbutaline
IV magnesium
IV fluids/electrolytes especially K
102
what is near fatal asthma in adults?
raised PaCO2 and/or requiring mechanical ventilation
treatment - ICU
103
when is an asthma patient discharged?
- when stable and diurnal variation in PEFR less than 25%
- on inhaler therapy (preferably 24hrs after nebuliser)
- seen in primary care within 24hrs
- asthma action plan for the patient
104
what is moderate acutre asthma in children?
- able to talk
- SpO2 > 92%
- HR <140 aged 1-5 or <125 > 5yrs
- RR <40breaths/min aged 1-5 or <30 breaths/min aged >5
105
what is acute severe asthma in children?
- cant complete sentences in one breath or too breathless to feed
- SpO2 < 92%
- PEF 33-50% best or predicted
- HR and RR the same as moderate acute asthma
106
what is life threatening asthma in children?
- SpO2 <92% plus any of the following:
- exhaustion
- hypotension
- cyanosis
- silent chest
- poor respiratory effort
- confusion
- PEF <33% best or predicted
107
what is the treatment of asthma attacks in children?
- high flow oxygen
- SABA - space if nebuliser isnt available
- steroids - as BNF doses based on weight
108
what is the compliance issue with using ICS and LABA separately?
patient may be unlikely to use the ICS as they arent getting immediate effects (takes up to 10 days to work)
109
what is AIR therapy?
LABA/ICS given as required
110
what is the problem with AIR therapy?
used as required so not constantly treating the underlying inflammation
111
what is vilanterol?
ultra long acting LABA so only required once a day
112
how do leukotriene receptor antagonists work?
blocks leukotriene receptors on smooth muscle cells and macrophage, reduces inflammation, reduces bronchostriction, decreases mucous secretion
113
how to use bronchodilator with spacer in acute severe asthma?
one puff at a time in and out and can be done up to 10-15 times, until the ambulance comes or until the patient feels better
114
why is prenisolone given in the morning?
nightmares
cortisol is higher in the mornings and lower at night
115
how long will you be kept on oral steroid after asthma attack?
for 5 days or at least 2 days after symtpoms have gone (dont need to reduce slowly, would only do this if used for longer than 21 days as it can lead to adrenal suppression)
MP324
flashcards
Decks in class (16)
# Cards
-
Immune system57
-
autoimmune disorders43
-
skin conditions108
-
Asthma116
-
formulation of medicines of respiratory system31
-
COPD139
-
bronchiectasis and interstitial lung disease42
-
Chemistry and ADME30
-
Pulmonary embolism14
-
Pharmacology of coughs44
-
pharmacokinetics of theophylline19
-
Health promotion7
-
Cystic fibrosis39
-
personalised medicine11
-
fungal lung disease27
-
emerging challenges8
