PT3: Mechanisms of Asthma Hyperactivity

Question 1

what is asthma

Answer 1

chronic inflammatory disorder of the airways

Question 2

what is asthma associated with

Answer 2

variable airflow obstruction; increase in airway response to a variety of stimuli

Question 3

what are two lung function tests

Answer 3

PEFR, FEV1

Question 4

what does PEFR stand for

Answer 4

peak expiratory flow rate

Question 5

what does FEV1 stand for

Answer 5

forced expiratory volume in 1 second

Question 6

what is the mechanism of hyperresponsiveness

Answer 6

increased smooth muscle contractility
cell growth stimulated by inflammation
increased excitatory nerve activity
decreased bronchodilator activity

Question 7

what is hyperplasia

Answer 7

more muscle cells

Question 8

what is hypertrophy

Answer 8

bigger muscle cells

Question 9

how does the ANS cause bronchoconstriction

Answer 9

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

Question 10

what category of drug is ipratropium

Answer 10

muscarinic antagonist

Question 11

what is ipratropium

Answer 11

quaternary ammonium compound, poorly absorbed with few CNS effects

Question 12

how is ipratropium used as asthma treatment

Answer 12

used in irritant induced bronchospasm
by inhalation/nebuliser
used in asthma/bronchitis/COPD

Question 13

how does tiotropium compare to ipratropium

Answer 13

improved pharmacokinetics

Question 14

what happens when presynaptic receptors are blocked

Answer 14

undesirable effect
enhanced ACh production; ACh competes with ipratropium at M3 receptor
increasing
ACh can overcome the effects of ipratropium

Question 15

what receptors does tiotropium work on

Answer 15

blocks M3 receptors but allows ACh to exert negative feedback to limit further release

Question 16

what is tiotropium

Answer 16

has kinetic selectivity

binds all receptors but fast dissociation at M2; so the negative feedback system is preserved

Question 17

what are the bronchodilating mechanisms of the ANS

Answer 17

circulating adrenaline - acts on beta-adrenoreceptors on airway smooth muscle
inhibitory non-adrenic non-cholinergic tansmitters (dilatory neuropeptides, neuronally derived NO)

Question 18

what bronchodilators are used therapeutically

Answer 18

beta-adrenoreceptor agonists

PDE inhibitors

Question 19

what is the bronchodilator activity of beta2-adrenoreceptor agonists

Answer 19

activates MLC phosphate, opens K+ channels, inactivated MLCK, calcium sequesteration

Question 20

what beta-agonists are short acting

Answer 20

isoprenaline, salbutamol, salmeretol

Question 21

what beta-agonist is long acting

Answer 21

formoterol

Question 22

what is the order of lipophilicity of beta2-agonists

Answer 22

salmeretol>formoterol>salbutamol

Question 23

how does formoterol work

Answer 23

forms depot in lipid membrane and ‘leaks’ out to interact with receptor

Question 24

what does salmeretol work

Answer 24

interacts with the membrane and diffuses laterally to bind receptor

Question 25

what is the long duration of action of salmeretol

Answer 25

nerve stimulation causes contraction of airway smooth muscle

inhibited by beta agonists

Question 26

what is an example of a PDE inhibitor

Answer 26

theophylline

Question 27

what is theophylline

Answer 27

phosphodiesterase inhibitor (PDE III & IV in airway smooth muscle; inhibition of PDE leads to increased cAMP causing bronchodilation)
narrow therapeutic window

Question 28

what are the excitatory neurotransmitters causing bronchoconstriction

Answer 28

ACh (M3 receptors)

eNANC

Question 29

what are the inhibitory neurotransmitters causing bronchodilation

Answer 29

adrenaline
iNANC
NO
ACh (M2 receptors)