Asthma Flashcards
prevalence of asthma
1/12 adults
1/11 children
classification of asthma
extrinsic
intrinsic
what is extrinsic asthma?
allergic
what is intrinsic asthma?
non-allergic
different types of asthma
chronic severe acute early/ late onset episodic/ seasonal exercise induced type 1 and 2 brittle eosinophilic/ non-eosinophilic
type 1 brittle
rare but severe form of asthma, on medication but still experience asthma attacks
type 2 brittle
rare but severe form of asthma, experience severe life-threatening attacks with no warning
eosinophilic and non-eosinophilic asthma
same as allergic and non-allergic
triggers of asthma
exercise pollen bugs in home chemical fumes cold air fungus spores dust smoke strong odours pollution anger stress pets
Immunological mechanism of asthma
mediated by IgE
formed in response to an allergen
first exposure - sensitisation occurs
re-exposure - allergen binds to specific IgE molecule on mast cell surface
degranulation of mast cells releasing histamines, chemokines, cytokines etc.
Airway narrowing
smooth muscle goes into spasm - narrows airway
lining of the lungs become inflamed
mucus production is increased
in some parts of the airway mucus can form plugs that block the airway
Histology of section asthmatic lung
thickening of basement membrane
mucous hyperplasia and hypersecretion
volume of smooth muscle increased
phases of asthma attack
- early phase
2. late phase
what happens in early phase of an asthma attack?
degranulation of mast cells, spasmogens released causing bronchospasm.
Chemotaxins and chemokines released leading to late phase
what happens in late phase of an asthma attack?
infiltration of Th2 cells, activation of inflammatory cells, cysLTs and other mediatorys, more eosinophils . Airway inflammation, more bronchospasm, airway hyper-reactivity and eosinophils cause epithelial damage
signs and symptoms of asthma
coughing
wheezing/ whistling noise in chest
shortness of breath
tightness in chest - dyspnoea
initial assessment of asthma
clinical history
physical examination
lung function tests
moderate asthma
PEF> 50-75% oxygen sats > 92% speech normal respiration <25/m pulse <110bpm
acute severe asthma
PEF 33-50% oxygen sats >92% cannot complete sentences respiration > 25/m pulse >110bpm
life-threatening asthma
PEF <33% oxygen sats <92% silent chest cyanosis poor respiratory effort arrhythmia hypotension exhaustion altered consciousness
treatment goals
minimise or eliminate symptoms maximise lung function prevent exacerbations minimise need for medication minimise adverse effects of treatment promote adherence with medication provide enough information and support to facilitate self-management
non-pharmacological measures for treating asthma
avoidance of triggers desensitisation to specific allergen house dust mite control measures smoking cessation weight reduction
pharmacological treatment of asthma
- relievers
2. preventers
what are relievers
beta 2 agonists
antimuscarinics
methylxanthines
what are preventers
corticosteroids
leukotriene receptor antagonists
cromones
methylxanthines
e.g. theophylline
additive effect when used in conjunction with small doses of beta 2 agonists
what do Short-acting beta 2 agonists do?
relaxes smooth muscles - bronchodilation by stimulation of beta 2 receotors on airway smooth muscle
example of short-acting beta 2 agonist
salbutamol and terbutaline
adverse effects of short-acting beta 2 agonist
fine tremor in hands nervous tension headache tachycardia hypokalaemia at high doses - modification of ATPase at Na+/K+
what is the mechanism of beta 2 agonists
stimulates GalphaS receptor
activates adenylate cyclase
lots of cAMP produced
cAMP inhibits myosin light chain kinase by inhibiting calcium elease
inhibits contraction - causing bronchodilation
what are antimuscarinics
2 classes
example of antimuscarinics
ipratropium
how do antimuscarinics work?
blocks muscarinic receptors as they cause bronchoconstriction
how are antimuscarinics administered?
by inhalation
maximal effect occurs 30-60 mins after use and lasts 3-6 hours
what are the adverse effects of antimuscarinics?
dry mouth constipation diarrhoea cough headache caution needed in prostatic hyperplasia, bladder outflow, obstruction, angle closure glaucoma - blocks tubes
examples of corticosteroids
beclomethasone
budesonide
fluticasone
how do corticosteroids work?
reduce bronchial inflammatory reactions - reduce oedema and mucous hypersecretion
inhibit production of inflammatory mediators acting as transcription factor
administration of corticosteroids
metered inhalation
must be used regularly for maximum benefit
what are the adverse effects of inhaled corticosteroids?
fewer systemic effects
hoarse voice
reflex coughing after inhalation
oral candidiasis
use of oral corticosteroids
more severe, less controlled asthma treated by oral corticosteroids
for acute attacks and chronic asthma
administration of oral corticosteroids
associated with many serious adverse effects
taken as a single dose in the morning
enough cannot be inhaled to be beneficial
examples of oral corticosteroids
hydrocortisone IV injection in emergency treatment of severe acute asthma
e.g. prednisolone
example of long-acting beta 2 agonists
salmeterol and formoterol
what are long-acting beta 2 agonists used for?
use with regularly inhaled corticosteroids
role in long-term control of chronic asthma
not for relief of asthma attack
administration of long-acting beta 2 agonists
combination inhalers available with corticosteroids and long-acting beta 2 agonists
e.g. symbicort
examples of leukotriene receptor antagonists
montelukast and zafirlukast
use of leukotriene receptor antagonists
blocks the effects of cysteinyl leukotrienes in airways
effective late on in late phase response
effective alone or with inhaled corticosteroids
well-tolerated with no common side effects
examples of Cromones
sodium cromoglicate
nedocromil sodium
use of cromones
no longer in guidelines
question over the effectiveness but still available
mechanism of action is unclear
may be of value in allergic asthma
prophylactic drug - no value in acute attacks
has side effects
must be withdrawn gradually over 1 week otherwise adverse effects
omalizumab
recombinant humanised monoclonal antibody
selectively binds to IgE forming a complex
recommended by NICE for use in adults and young people over 12 with severe persistent allergic (IgE mediated) asthma who meet specific criteria
well-controlled asthma
no daytime symptoms
no night time awakening due to asthma
no need for rescue medication
no limitations on activity, including exercise
normal lung function with minimal side effects
FEV1 and PEF greater than 80% of predicted
patient counselling
knowledge of disease state
knowledge of medicines
knowledge of how to monitor condition
monitoring of asthma
compliance
pulmonary function
theophylline
mechanism of action of methylxanthines?
Inhibits phosphodiesterase
phosphodiesterase breaks down cAMP, so by inhibiting phosphodiesterase it increases cAMP concentration
Administration of methyxanthines
given orally or very slow IV infusion - needs to be monitored as risk of toxicity
watch for interactions - hepatically metabolised
adverse effects - narrow therapeutic range, nausea, headaches, insomnia, abdominal discomfort, toxic effects above 25mg/L - seizures
