asthma drugs

Question 1

what is asthma characterised by

Answer 1

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

Question 2

what are triggers for asthma

Answer 2

many types which are triggered by different stimuli e.g

allergens, viral infections, air pollution, aspirin, exercise

Question 3

what is mechanism of asthma

Answer 3

stimuli lead to generation of inflammatory mediators which lead to symptoms and features of asthma

Question 4

what is mechanism of allergic asthma

Answer 4

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

Question 5

what are mediators in asthma

Answer 5

histamine, leukotrienes, PAF, cytokines etc

Question 6

how is asthma treated

Answer 6

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)

Question 7

how are cromoglycate and nedocromil used in asthma treatment

Answer 7

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

Question 8

how are beta 2 agonists used in asthma treatment

Answer 8

increase cAMP causing relaxationof bronchial smooth muscle

prevent release of mediators from mast cells

e.g salbutamol

Question 9

how are muscarinic antagonists used in asthma treatment

Answer 9

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

Question 10

what is mechanism of methylxanthines

Answer 10

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

Question 11

how does asthma treatment differ in mild treatment to severe treatment

Answer 11

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