Asthma Flashcards
asthma is worse at
night
airway narrowing in asmtha is due to
increased thickness of airway wall
increased mucus
increased constriction of airway smooth muscle
increased mucus is due to
activation of larger submucosal glands
more goblet cells
reliever/rescue medications
beta 2 adrenoceptor agonists
rapidly reverse/prevent bronchoconstriction
controller medications
inhaled corticosteroids
suppression of airway inflammation
substances released within the airway wall during an ASM
leukotrienes and histamine
acetylcholine
neuropeptides
endothelin-1
leukotrienes and histamines are released from
activated mast cells
salbutamol and efermoterol
given by aerosol
rapidly activate beta 2 adrenoceptors located on the surface of airway smooth muscle cells, causing relaxation irrespective of the substances causing bronchoconstriction
short acting beta 2 adrenoceptor agonists
bind to and stimulate beta 2 adrenoceptors on airway smooth muscle inducing bronchodilation irrespective of the mediator causing bronchoconstriction do nto inhibit inflammation rapid onset of action salbutamol, terbutaline SABAs
long acting beta 2 adrenoceptor agonists
salmeterol and formoterol long-lasting bronchodilator actions structure is similar to salbutamol, but has an additional lipophilic tail that binds to a second binding site on beta 2 adrenoceptors salmeterol and femoterol LABAs
2 SABAs
salbutamol and terbatuline
2 LABAs
salmeterol and formooterol
difference between salmeterol and formoterol
salmeterol is delayed onset of action and not a useful reliever
formoterol is a rapid onset of action - can be used as a reliever
muscarinic cholinoceptor antagonists
not effective relievers
eg. ipratropium bromide, tiotropium
only reverse acetyl choline induced constriction
delayed onset of action
leukotriene receptor antagonists
not effective releievers
eg. m montelukast
only reverse leukotriene induced constriction
delayed onset of action due to being given orally
what are salmeterol (LABA), muscarinic cholinoceptor antagonists and leukotriene receptor antagonists used for
add-on therapy to Beta 2 adrenoceptor agonists and inhaled corticosteroids to improve asthma control
controller medications
suppress airway inflammation and provide better long term control of asthma symptoms
SABA only treatment
inhibit contraction of smooth muscle but not other factors contributing to airway narrowing
associated with increased risk of asthma
inhaled corticosteroids
do not relieve acute bronchoconstriction
front line therapy
reduces expression of genes and proteins that drive driive Th2/eosinophilic inflammatory response often seen in asthma
adverse effects of ICS
osteoporosis, hypertension, diabetes, airway and systemic infections caused by long term use
given by inhalation to avoid side effects
ICS example
fluticasone
must be given prophylactically to be effective
clinical benefits of ICS
decreased airway inflammation
decreased sputum and decreased exhaled NO (marker of inflammation)
less airway narrowing
improved lung function
more symptom free days
reduction in morbidity and mortality
less hospital drugs and reduced asthma medication usage
why is asthma sub optimally controlled
irregular use of inhaler medications (poor or non adherence)
incorrect inhaler technique - most patients do not use effectively
inadequate treatment of comorbidities
asthma heterogeneity - different phenotypes, some respond less well to ICS
true glucocorticoid resistance - rare
asthma phenotype responding poorly to inhaled corticosteroids
neutrophilic asthma
combination inhalers
combines two Classes of medicine in one inhaler
- most commonly ICS and LABA
advantages of combination inhalers over individual inhalers
- improved adherence
- reduce iver reliance on SABA only bronchodilators
- reduced frequency of asthma attacks
leukotrienes
potent mediators of inflammation, whose production by mast cells and eosinophils is unregulated in asthma
cysteinyl leukotrienes
LTC4, LTD4, LTE4
all contain cycteine residue within their structure
leukotrienes bind to
CysLT1 receptors in the airways and induce airway narrowing
LT receptor antagonists
block interaction of cysteine leukotrienes with CusLT1 receptor
decrease airway narrowing
LT receptor antagonists example
zafirlukast, montelukast, Singulair
monoclonal antibodies
to target IgE
omalizumab
humanised monoclonal antibody that targets free IgE preventing binding to the IgE receptor
used to treat uncontrolled severe allergic asthma
limitations of omalizumab
expensive and given by subcutaneous injection
other biologicals
mepolizumab - targets free IL-5
benralizumab - targets IL-5 receptor on eosinophil
IL-5 cytokine
key cytokine in proliferation, activation and survival of eosinophils and 50% of patients with severe asthma have elevated levels of blood/sputum eosinophils
anti IL-5/IL-5R antibodies are useful for
asthmatics with high blood/sputum eosinophils that continue to have asthma attacks despite high doses of ICS
in allergic asthma, air way narrowing is due to three things
increased thickness of the airway wall - Th2/eosinophillic inflammation
increased mucus due to activation of larger mucus glands and more goblet cells
increased airway smooth muscle constriction
