asthma drugs Flashcards
what is asthma characterised by
increased bronchial hyperresponsiveness to a variety of stimuli
airway obstruction that is reversible
inflammation of bronchial mucosa
loss of bronchial epithelium
mucus plugging of airway
what are triggers for asthma
many types which are triggered by different stimuli e.g
allergens, viral infections, air pollution, aspirin, exercise
what is mechanism of asthma
stimuli lead to generation of inflammatory mediators which lead to symptoms and features of asthma
what is mechanism of allergic asthma
allergen such as pollen triggers an IgE antibody response
this leads to cell fixation of IgE which leads to allergen/IgE interaction
this leads to mast cell activation which leads to mediator production leading to inflammation of airways
what are mediators in asthma
histamine, leukotrienes, PAF, cytokines etc
how is asthma treated
inhibition of mediator release/formation
antagonism of effects of mediators via neurotransmitters
drugs used:
cromoglycate and nedocromil (inhaled prophylactics)
beta2 agonists (inhaled or oral)
muscarinic antagonists (inhaled)
methylxanthines (oral)
anti-inflammatory glucocorticoids (inhaled or oral)
H1 antagonists (oral) (little value in asthma, will reduce acute airway obstruction partially)
how are cromoglycate and nedocromil used in asthma treatment
anti-allergens
mechanism unknown but 2 hypotheses;
inhibition of release of mediators of inflammation from cells involved in pathogenesis (mast cells, eosinophils, neutrophils)
inhibition of sensory nerve activity in reflexes which promote bronchoconstriction and neurogenic inflammation of airways
cromoglycate is not active orally, nedocromil is
they are given regularly to prevent attacks, not useful to treat an established attack
how are beta 2 agonists used in asthma treatment
increase cAMP causing relaxationof bronchial smooth muscle
prevent release of mediators from mast cells
e.g salbutamol
how are muscarinic antagonists used in asthma treatment
oral or parenteral use is not used due to side effects of muscarinic blockade
given by inhilation which is poorly absorbed into circulation
most effective in types of asthma in which reflex bronchoconstriction predominates, used to inhibit acetylcholine bronchoconstriction
does not effect histamine leukotiene mediated constriction
what is mechanism of methylxanthines
e.g theophylline
inhibitor of phosphodiesterase
prevent cAMP breakdown via phosphodiesterase
at high conc can release calcium from intracellular pools
cAMP activates protein kinase A which leads to bronchodilation
how does asthma treatment differ in mild treatment to severe treatment
short acting beta2 agonists are use for relief in all
mild patients are given inhaled low doses of glucocorticoids
as it gets more severe a leuktriene modifier is added
if more severe leukotriene modifier is replaced with long lasting beta 2 agonist and GC dose is increased
if very severe GCs are taken orally instead of inhaled, and an Anti-IgE is given on top of beta 2 agonist