asthma Flashcards
what is asthma?
an condition associated with: airway hyperresponsiveness reversible airflow limitation bronchial inflammation
what are the symptoms of asthma?
wheezing shortness of breath cough worse at night
what are the triggers for asthma?
intrinsic- emotion, diet, cold air/ exercise
extrinsic - exposure to allergens drugs (asiprin, beta blockers), pollutants (cigerette smoke, dust, fumes)
what are the long term aims of asthma treatment?
abolish symptoms maintain optimal lung function prevent permenant lung damage prevent death from acute attack avoid unnecessary side effects
what are the differences between reliever and preventer medication for asthma?
reliever - bronchodilator → relax smooth muscle / widens airway (works rapidly and directly to reverse bronchoconstriction)preventer - anti-inflammatory → stops response to allergen
name four types of bronchodilators used in asthma
beta 2 adrenergeric receptor agonists
theophylline
muscarinic receptor anatagonists
leukotriene receptor antagonists
give three examples of preventer medication used in asthma
beclometasone sodium cromoglicate montelukast
which target is most appropriate to treating asthma?
ß2 receptors as these are found in: lungs blood vessels muscle spindles
what does salbutamol have a similar structure to?
adrenaline
how can ß2 adrenergic receptor agonists be given?
inhaled or orally
name two short acting ß2 adrenergic receptor agonists and explain when they would be given
salbutamol
terbutaline*inhaled beefore exertion to reduce exercise induced asthma - duration of action 3-5hrs
name two long-acting ß2 adrenergic receptor agonists and explain when they would be given
salmeterol
formoterol* only used in patients taking inhaled steriods - can be taken 1-2 times daily - duration of actio 12hrs
what are the side effects of ß2 adrenergic receptor agonists? explain why these occur
tremor - ß2 receptors in muscles activated increased HR - stimulation of cells in SA node reduced K+ (hypokalaemia) - stimulation of sodium/potassium pump nervous tension/ headache - activation of ß2 receptors in CNS
how can the systemic effects of ß2 adrenergic receptor agonists be reduced?
by inhaling drug
when would a glucocorticosteroid be used in asthma?
as a preventer
name five glucovorticosteroids that are used via an inhaler to prevent asthma attacks
beclomethasone diproprionate budesonside fluticasone propionate prednisolone hydrocortisone
why are the systemic effects of inhaled glucocorticosteroids reduced?
poor bioavailablity
what can glucocorticosteroids often be administered in combination with?
ß2 adrenergic receptor agonists
describe the activation of ß2 adrenoceptors
ß2 adrenergic receptor agonists bind to ß2 receptor causing a conformational change to the molecule. This change in shape converts ATP to cAMP which activates PKA and muscle relaxation
describe the actions of glucocorticoids in asthma
reduces production of:
cytokines, spasmogens (LTC4, LTD4), leuocyte chemotaxins (LTB4, PAF)
therefore reduces:
bronchospasm, recruitment and activation of inflammatory cells
explain the mechanism of action of glucocorticosteroids (GCs)
GCs are synthesised from cholesterol allowing them to cross cell membrane
when inside the cell GCs bind to steroid receptors
the drug-receptor complex forms a dimer which can cross into nucleus
in nucleus the dimer binds to specific DNA sequence inducing or supressing genes
protein production influenced
GCs inhibit transcription of COX-2 gene - reducing protein production and inflammation
what are the side effects of glucocorticosteroids?
local immunosuppression - oral thrush local effects on vocal cords - dysphonia (hoarseness)
what is prednisolone used forn and how does it work?
treats acute asthma attack short course - 7 days (high dose) continue with high dose inhaled steroid in chronic/severe asthma
works by: suppressing immune system activity and release of inflammatory mediators
explain the danger of stopping glucocorticosteroids abruptly
results in acute adrenal insuffiency as patients ability to synthesise GCs has been suppressed → leads to patient being unable to maintain a stress response leading to addisonian crisis
what are antimuscarinic receptor antagonists and what are they used for?
short acting (reliever) - 3-5hrs used alonside high-dose inhaled glucocorticosteroids for severe asthma
what is the mechanism of action for antimuscarinic receptor antagonists?
block muscarinic receptors → blocks action of endogenous acetylcholine
inhibits elevated mucus secretion
given an example of an antimuscarinic receptor antagonists and explain its side effects
ipratropium - causes dry mouth and precipitates glaucoma
what are cromoglicates and how do they work?
cromones inhibit release of chemicals from inflammatory cells(mast cells) → prevents bronchospasm reduces allergen induced responses and bronchospasm during/after exercise
stops mast cell degranulation
name 2 cromoglicates
nedocromil sodium sodium cromoglicate
* stops mass cells releasing histamine and other chemicals - mainly used in children
what do leukotrienes cause?
bronchoconstriction release of inflammatory cells increase in secretions in airways
what do leukotriene receptors antagonists do?
relax airways and prevent inflammation
give two examples of leukotriene receptor antagonists and explain side effects
montelukast
zafirlukast*
causes GI disturbance
when is theophylline (aminophylline) used?
orally or IV in patients with persistant symptoms / severe acute asthma
can theophylline be used with other drugs?
yes - ß agonists and/or steroids
what are the drawbacks and side effects of theophylline?
drawbacks: narrow therapetic windowside effects: increased HR, palpitations, convulsions, headache
explain the mechanism of action of theophylline
blocks phosphodiesterase enzyme (PDE) which breaksdown into 5’AMP - therefore more cAMP is available to stimulate smooth muscle relaxation
what is omalizumab (xolair) used for and how it given?
an antibody (given subcutaneously) every 2-4 weeks reduces effect of allergen induced reactions used in adults with severe allergic asthma not controlled by ß agonists and glucocorticosteroids
what are the side effects of omalizumab?
bruising pain on injection small risk of anaphylaxis
what is the mechanism of action of omalizumab?
antibody inhibits binding of IgE to receptor surface of mast cell and basophils prevents release of pro-inflammatory mediators and reduces allergen induced airway reactions
describe the treatment strategy for asthma from mild to severe
inhaled short acting ß2 agonists (as needed)
inhaled steroids
add inhaled long acting ß2 agonists and increase dose ofinhaled steroids
short and long acting ß2 agonists and inhaled steroids and another drug (eg. LTR antagonist)
continuous or frequent use of oral steriods (and immunosuppressants
what can be substituted for inhaledß2 agonists in stage 1 of the asthma treatment strategy?
ipratropium
oral ß agonists
theophyllines
describe what therapy would be given in acute asthma attack
bronchodilators given via nebuliser glucocorticosteroids given (oral prednislone, IV hydrocortisone) - route depends on severity oxygen therapy needed if O2 saturation reduced (
in poor response aminophylline injection (severe, acute attacks)
what are the side effects of cromoglicates?
irritation of upper resp. tract
hypersensitivity reactions
what are the actions of leukotriene antagonists?
act on cystrinyl-leukotriene receptors
prevent actions of LTC4, LTD4 (which are brochial spasmogens and stimulate mucus secretion)
what are the side effects of leukotriene antagonists?
headache
GI disturbance
when would antimuscarinic receptor antagonists be used?
in asthma where there is evidence of overactive Ach production
describe the muscarinic system in normal airways and in some asthma airways
normal - Ach released from cholinergic nerves, few muscarinic receptors activated , smooth muscle relaxed airways open
asthma - Ach more active so more muscarinic receptors activated which causes contraction of smooth muscle
