bronchodilators

Question 1

SNS on the smooth muscle does what and how

Answer 1

it releases adrenergic compounds onto the beta 2 adrenoreceptors of the lungs. this leads to adenylate cyclase activation as they are GPCRs this leads to cAMP activation which then acts to block smooth muscle contraction

Question 2

how do the muscarinic receptors act on smooth muscle

Answer 2

binding to M2 causes a gene-inhibitory response which inhibits adenylate cyclase resulting in decrease in cAMP so more contraction
M3 binding leads to a pathway that increases levels of calcium within the cell directly causing increased contraction of the smooth muscle cell.

Question 3

how do beta 2 agonists work

Answer 3

example is salbutamol. these increase cAMP in the smooth muscle cell, this results in increased PKA activity. this PKA increases conductance of Ca2+-sensitive K+ channels. this results in increased hyperpolarisation of the smooth muscle cell, resulting in smooth muscle relaxation.

Question 4

PKs of salbutamol

Answer 4

it is a rescue inhaler as it is able to reverse bronchoconstriction, it is delivered by inhalation and has a fast onset of effect in 5-15 minutes. this is good for treating exercise-induced asthma.

Question 5

what do we never use at the same time as salbutamol

Answer 5

beta blockers like metoprolol. as these beta blockers will block the beta 2 receptors, meaning that any bronchospasm cannot be treated by beta agonists

Question 6

what are ADRs

Answer 6

of SABAs, tremor of skeletal muscle due to activation of B2 receptors, increased heart rate and force of contraction due to activation of beta 1s.
hypokalemia possibly causing myocardium hyperexcitability

Question 7

whats the difference between LABA and SABA

Answer 7

LABA have a lipophilic side chain which acts to resist breakdown of the drug, increasing duration of effects.
LABAs are not rescue inhalers as their effects do take longer to kick in.

Question 8

whats in symbicort

Answer 8

there is a ICS - budesonide
then there is formoterol which replaces need for salbutamol as it can act as a rescue inhaler and a LABA

Question 9

why can we not just use a LABA

Answer 9

these can not provide relief during acute bronchospasm. and they do not address the underlying inflammation

Question 10

why do we more want to aim to antagonise the M2 receptors

Answer 10

Normally the ACh released at the muscarinic receptors feedsback to inhibit itself. But if we block the M2 receptors this doesn’t occur and instead there is constant activation of the M3 receptors. Hence we want to more just antagonise the M3 receptors.

Question 11

what is an example of a SAMA

Answer 11

– Ipratropium, these antagonise the M3 and prevent the effects of the PNS there

Question 12

ADRs of SAMA and how do we get around this

Answer 12

we get around it through inhalation. Dry mouth, headache, GI motility disorders, urinary retention, tachycardia, palpitations. Doesn’t have CNS effects as it cannot cross the blood brain barrier.

Question 13

example of a LAMA

Answer 13

tiotropium

Question 14

what are the preferred bronchodilators for COPD

Answer 14

the muscarinic antagonists

Question 15

what receptor do the SAMAs and LAMAs antagonise

Answer 15

the M3 muscarinic receptors