PT3: Mechanisms of Asthma Hyperactivity Flashcards
what is asthma
chronic inflammatory disorder of the airways
what is asthma associated with
variable airflow obstruction; increase in airway response to a variety of stimuli
what are two lung function tests
PEFR, FEV1
what does PEFR stand for
peak expiratory flow rate
what does FEV1 stand for
forced expiratory volume in 1 second
what is the mechanism of hyperresponsiveness
increased smooth muscle contractility
cell growth stimulated by inflammation
increased excitatory nerve activity
decreased bronchodilator activity
what is hyperplasia
more muscle cells
what is hypertrophy
bigger muscle cells
how does the ANS cause bronchoconstriction
airway innervated by the vagus nerve - cholinergic nerves (ACh on M3 receptors), excitatory non-adrenic non-cholinergic transmitters (neurokinin A, B, P)
all stimulate GPCR leading to elevation of intracellular free calcium
what category of drug is ipratropium
muscarinic antagonist
what is ipratropium
quaternary ammonium compound, poorly absorbed with few CNS effects
how is ipratropium used as asthma treatment
used in irritant induced bronchospasm
by inhalation/nebuliser
used in asthma/bronchitis/COPD
how does tiotropium compare to ipratropium
improved pharmacokinetics
what happens when presynaptic receptors are blocked
undesirable effect
enhanced ACh production; ACh competes with ipratropium at M3 receptor
increasing
ACh can overcome the effects of ipratropium
what receptors does tiotropium work on
blocks M3 receptors but allows ACh to exert negative feedback to limit further release
what is tiotropium
has kinetic selectivity
binds all receptors but fast dissociation at M2; so the negative feedback system is preserved
what are the bronchodilating mechanisms of the ANS
circulating adrenaline - acts on beta-adrenoreceptors on airway smooth muscle
inhibitory non-adrenic non-cholinergic tansmitters (dilatory neuropeptides, neuronally derived NO)
what bronchodilators are used therapeutically
beta-adrenoreceptor agonists
PDE inhibitors
what is the bronchodilator activity of beta2-adrenoreceptor agonists
activates MLC phosphate, opens K+ channels, inactivated MLCK, calcium sequesteration
what beta-agonists are short acting
isoprenaline, salbutamol, salmeretol
what beta-agonist is long acting
formoterol
what is the order of lipophilicity of beta2-agonists
salmeretol>formoterol>salbutamol
how does formoterol work
forms depot in lipid membrane and ‘leaks’ out to interact with receptor
what does salmeretol work
interacts with the membrane and diffuses laterally to bind receptor
what is the long duration of action of salmeretol
nerve stimulation causes contraction of airway smooth muscle
inhibited by beta agonists
what is an example of a PDE inhibitor
theophylline
what is theophylline
phosphodiesterase inhibitor (PDE III & IV in airway smooth muscle; inhibition of PDE leads to increased cAMP causing bronchodilation) narrow therapeutic window
what are the excitatory neurotransmitters causing bronchoconstriction
ACh (M3 receptors)
eNANC
what are the inhibitory neurotransmitters causing bronchodilation
adrenaline
iNANC
NO
ACh (M2 receptors)
