Asthma Flashcards
what is acute asthma?
airway obstruction/constriction due to inflammation
2 phases of reaction of asthma ?
immediate phase and late phase
what happens in the immediate phase?
bronchospasm
increased mucus production
vasodilation
release of inflammatory mediators
what happens in the late phase?
recruitment of leukocytes and t cells
further release of inflammatory mediators
what is chronic asthma?
pathological change to bronchioles long standing inflammtion
drugs with adverse effects in patients with respiratory disease?
non-selective beta blockers (propranolol)
NSAIDs
what do the release of inflammatory mediators (MBP and cytokines) in the late phase cause?
eosinophil major basic protein MBP causes epithelial damage
cytokines - amplify inflammation
what cells are released in sensitisation to asthma (1st exposure)?
activated Th2 cells release cytokines IL-4,13,5
what does IL-4 stimulate in sensitisation?
stimulates IgE release from B cells, activates mast cells
what does IL-13 do in sensitisation?
stimulates IgE mucus secretion
what does IL-5 do in sensitisation?
activates locally recruited eosinophils
what is the immediate response when re-exposed to antigen?
antigen binds to IgE-IgE receptor complex
cross-links IgE receptor
stimulates Ca2+ entry into mast cells
what does the entry of Ca2+ cause?
release of secretory granules containing histamine
release of leukotrienes LTC4 LTD4 - muscle contraction
release of chemotaxins LTB4 causing inflammation
the airway remodelling in chronic asthma?
1- increased mass of smooth muscle
2 - accumulation of fluid (oedema)
3 - increased mucus secretion
4 - exposed sensory nerve endings casue bronchial hyperresponsiveness
5 - airway narrowing increases resistance
what can be tested in diagnosis of asthma?
demonstration of obstruction with spirometry and peak flow test
eosinophil count blood test
allergy test
Drugs to target immediate phase bronchospasm of asthma?
bronchodilators
- beta2 agonists
- muscarinic antagonists
- xanthines
how do b2 agonists work?
act directly on beta2 adrenoreceptor (Gs) to increase cAMP and induce muscle relaxation
decreases mucus secretion
types and examples of b2 agonists?
short acting (SABA) - salbutamol 4-6hr
long acting (LABA) salmeterol 12hr
how do muscurinic antagonists work?
block M3 receptor, block Gq signalling, decrease Ca2+ to dilate bronchi
block M3 mucus secretion
types and examples of muscarinic agonists?
short acting (SAMA) - ipratropium
long-acting (LAMA) - tiotropium
how do xanthines work?
block phosphodiesterase enzymes to increase cAMP causing muscle relaxation and bronchodilation
example of a xanthine?
theophylline
what drugs target the late phase?
glucocorticoids
how do glucocorticoids work in asthma?
inhibit transcription of phospholipase A2 to decrease production of inflammatory mediators
example of glucocorticoids?
beclomethasone - inhaler
prednisolone - oral short term
hydrocortisone - injection
drugs to target both phases?
chromolyn
cysteinil leukptrien1 receptor(cys-LT1) antagonist - montelukast
how does cromolyn work?
mast cell stabiliser prevents release of histamine and mediators
depresses neuronal reflexes to inhibit hyper responsiveness
how does CysLT1 antagonist work?
block leukotriene induced bronchospasm
effective for mild persistent asthma
example of CysLT1 anatagonist?
montelukast
what makes salmeterol longer acting?
2 binding sites
binds to active site and a specific exo-site that prolongs stimulation
where are the 2 beta receptors found?
B1 - heart
B2 - bronchial smooth muscle
difference between noradrenaline/adrenaline and isoprenaline binding?
adrenaline - non-selective
iso - only beta-adrenoreceptors
which isomer of salbutamol is more active?
R isomer
S isomer associated with toxicity
