Asthma Flashcards
what is the definition of asthma?
a chronic inflammatory disorder of the airways in susceptible individuals, inflammatory symptoms are usually associated with widespread but variable airflow obstruction and an increase in airway response to a variety of stimuli. obstruction is often reversible, either spontaneously or with treatment
how many people in the uk die of asthma each year?
1200
how many people in the uk are admitted to hospital because of asthma each year?
80,000+ anually
what are the key pathophysiological features of asthma?
bronchoconstriction
muscosal oedema
excessive secretion of mucus
epithelial damage
what are the trigger factors of asthma?
house dust mites exercise air pollution occupational allergens food allergy drugs seasonal variation emotional disturbance cold, dry air
what are the classifications of asthma and what do they mean?
intrinsic (non-allergic)
extrinsic (allergic)
what age group does intrinsic asthma typically affect?
older patients
what age group does extrinsic asthma typically affect?
children (childhood)
what is the cause of intrinsic asthma?
hypersensitive airways (IgE normal) constrict to non-specific stimuli
what is the cause of extrinsic asthma?
type 1 hypersensitivity reaction
familial tendency
what are the triggers of intrinsic asthma?
aspirin, beta blockers
cold, dry air
exercise
respiratory infections
what are the triggers of extrinsic asthma?
pollen
food allergy
occupational allergens
house dust mites
what do you do to diagnose asthma?
lung function tests:
peak flow meter
or
spirometer
what does peak flow meter measure?
max rate of air flow on forced expiration
what does a spirometer measure?
FVC - forced vital capacity (total volume of expired air after full expiration)
FEV1 - air forcibly expired in 1 second
what do you do with FVC and FEV1 values?
FEV1/FVC should be 70-80%
asthma can be 20-30%
what do you give to a patient along with spirometer to diagnose asthma?
beta-2 agonist to reduce bronchoconstriction
then do spirometer again
should see an improvement
what happens if beta-2 agonist is given but the bronchoconstriction doesn’t improve?
COPD
what is COPD?
bronchitis and emphysema
how does early phase asthma work?
- trigger/ non-specific stimulus activates mast cells
- i) mast cells release LTC4 and LTD4, histamine and PGD2 which increase bronchospasm
ii) mast cells release chemotaxins and cytokines which lead to late phase asthma
how does late phase asthma work?
- infiltration of Th2 cells -> cytokine release
- infiltration of monocytes
- activation of eosinophils
i) these all lead to LTC4 and LTD4 and other mediators - these cause airway inflammation and airway hyperactivity which leads to bronchospasm, coughing and wheezing
ii) these all lead to EMBP and ECP - these lead to increase airway inflammation and airway hyperactivity which leads to bronchospasm, coughing and wheezing
what 3 ways of treating asthma are there?
relievers
controllers
preventers
what 3 kinds of relievers are there? (bronchodilators)
beta-2 agonists (short acting)
anti-cholinergics (short acting)
theophylline (short acting)
what 5 kinds of controllers are there?
beta-2 agonists (long acting) anti-cholinergics (long acting) theophylline (Slow Release) leukotriene modifiers omalizumab
what kinds of preventers are there?
corticosteroids - inhaled/oral
cromolyns
give 2 examples of an inhaled short-acting beta-2 adrenoreceptor agonist
salbutamol, terbutaline
give 2 examples of an inhaled long-acting beta-2 adrenoreceptor agonist
salmeterol, formoterol
what do inhaled beta-2 adrenoreceptor agonists do?
relax bronchiolar smooth muscle by stimulating beta-2 adrenoreceptors
fast acting
effects last hours
what are the side effects of inhaled beta-2 adrenoreceptor agonists?
tachycardia, fine tremor
what is the mechanism of action of inhaled beta-2 adrenoreceptor agonists?
- e.g. salbutamol stimulates beta-2 receptor
- adenylate cyclase is stimulated
- adenylate cyclase catalyses ATP -> cAMP
- cAMP causes relaxation
what do oral beta-2 adrenoreceptor agonists do? (bambuterol)
slower acting longer lasting additional symptom control (nocturnal) used only in addition to inhaled glucocorticoids patients with inhaler difficulty
what is an example of a beta-2 adrenoreceptor agonist?
bambuterol/salmeterol
what are the 2 theories of salmeterol function?
1) side chain binds to exoreceptor site near beta-2 adrenoreceptor, keeping it in close proximity to the receptor
2) durg enters lipid bilayer and attaches to receptor from within the membrane
what are 2 examples of anti-cholinergic drugs?
ipratropium bromide
tiotropium bromide
what do anti-cholinergic drugs do?
prevent vagally-mediated bronchoconstriction by blocking muscarinic ACh receptors of bronchial smooth muscle cells
alternative to inhaled beta-2 agonists if they have side effects
slower onset of inhaled beta-2 agonists, less effective but last longer
how do anti-cholinergic drugs work?
block muscarinic ACh receptor
what are 3 examples of methylxanthines?
theophylline, theobromine, caffeine
how does theophylline work?
oral bronchodilator
slow release form available
added for additional nocturnal symptoms
what are the side effects of theophylline?
serious!
tachycardia, persistant vomiting
indicate toxicity
methylxanthines: what is the mechanism of phosphodiesterase (PDE) inhibition?
“normally” adrenaline/noradrenaline activates beta-2 receptor which activates adenylate cyclase. adenylate cyclase catalyses ATP -> cAMP.
cAMP causes relaxation, and is also turned into 5’-AMP by PDE THEOPHYLLINE INHIBITS THIS
So leads to cAMP build up in smooth muscle to cause bronchodilation
methylxanthines: what is the mechanism of adenosine receptor antagonism?
theophylline acts as inhibitor of adenosine A1 and A2 receptors
antagonism of these receptors leads to bronchoconstriction and inflammation
inhibition of adenosine receptors could cause bronchodilation and reduce histamine reduced from mast cells
what kinds of purine receptors are there and what are their subtypes?
P1 and P2
P1: A1, A2, A3 all respond to adenosine
P2: P2x and P2y respond to ATP and/or ADP
what happens when adenosine acts on P1 receptors?
decreased heart rate
decreased blood pressure
decreased GI function
lethargy
how is the effects of P1 receptor stimulation by adenosine reversed?
caffeine
what is the summary mechanism of action of bronchodilatiors?
acetylcholine causes bronchoconstriction, but muscarinic antagonists decrease this
adenosine causes bronchoconstriction, but theophylline decrease this
cAMP causes bronchodilation, beta agonists increase ATP -> cAMP
cAMP causes bronchodilation, theophylline decreases the conversion of cAMP -> AMP to increase cAMP levels
what cortiosteroids can be used to treat asthma?
inhaled- beclomethasone
oral- hydrocortisone and prednisolone
what is the mechanism of action of corticosteroids of asthma?
suppression of inflammation by various mechanisms (revise steroid pathways)
reduce circulating immunocompetant cells and macrophages
inhibition of inflammatory mediators i.e. prostaglandins, leukotrienes and platelet activating factor
what is sodium cromoglycate?
mast cell stabilizer
what does sodium cromoglycate do?
inhibits early and late phases of asthma
prophylactic use only (not for asthma attacks)
what is the mechanism of action of sodium cromoglycate?
reduce influx of calcium into antigen-sensitised mast cells -> inhibits release of histamine and other mediators
what are the 4 theories about the mechanism of action of sodium cromoglycate?
1) inhibit mast cell degranulation and eosinophils
2) inhibit nerve stimulation (e.g. by irritants) that causes bronchoconstriction
3) inhibit action of platelet activating factor
4) inhibit release of cytokines from T-cells
how can asthma be treated by leukotriene synthesis inhibitor?
5-lipooxygenase inhibitors
immediate lung function improvement
what is an example of a leukotriene inhibitor?
Zileuton
how can asthma be treated by a leukotriene receptor antagonist?
inhibits inflammation, mucosal oedema and bronchoconstriction
used in adults and children
oral
patients with aspirin-sensitive asthma which involves LT production
what is an example of a leukotriene receptor antagonist?
Zafirlukast
how can you treat asthma with omalizumab?
humanised monoclonal antibody, selectively binds to IgE, preventing binding of IgE to FCepsilonRI antibody
limits release of inflammatory mediators
when do you use omalizumab?
add on with severe allergic asthma with usual treatment
