L8 - drugs affecting neuromuscular transmission

Question 1

what is motor unit

Answer 1

myelinated motor nerve and the fibres it innervates

Question 2

how big is the synaptic cleft

Answer 2

60nm

Question 3

what do schwann cells do at the neuromuscular junction

Answer 3

form lids over synaptic cleft

Question 4

what is the end plate

Answer 4

the section of muscle membrane in ‘contact’ with the synapse

Question 5

what processes can drugs act of to modify neuromuscular synaptic transmission

Answer 5

synthesis
storage
release

receptors the NT acts on
uptake of the NT from cleft

Question 6

how is ACh synthesised

Answer 6

from choline & acetyl CoA via the CAT enzyme

Question 7

what is the CAT enzyme

Answer 7

choline acetyl transferase

Question 8

why is ACh packaged into vesicles?

Answer 8

1. because it can only be released once in vesicles

2. will be broken down if not in vesicles

Question 9

what drug blocks uptake of choline

Answer 9

hemicholinium

Question 10

what drug blocks ACh uptake into vesicles?

Answer 10

vesamicol

Question 11

how can Ca2+ channels be blocked?

Answer 11

with a bigger ion eg Mg2+

Question 12

what can block ACh exocytosis

Answer 12

botulinum toxin

Question 13

role of acetylcholinesterase’s? (AChE)

Answer 13

rapidly break down ACh in cleft

Question 14

structurally how does ACh activate the nicotinic receptor

Answer 14

1 ACh binds to each of the a subunits
the channel opens up

this opening of channel causes depolarisation of end plate

Question 15

what is an end plate potential?

Answer 15

depolarisation of the muscle membrane after the cleft due to activation of the nicotinic receptors

Question 16

what does tubocurarine do

Answer 16

drug that causes skeletal muscle relaxation

Question 17

what is suxamethonium

Answer 17

muscle relaxant

Nicotinic ACh agonist

Question 18

describe suxamethonium structure

Answer 18

dimer of ACh

Question 19

how does suxmethonium work

Answer 19

produces muscle depolarisation but isn’t broken down by AChE’s so depolarisation is prolonged

Question 20

how does suxamethonium cause muscle relaxation?

Answer 20

1. binds to NAChR and causes prolonged depolarisation
2. Na channels are stuck in inactive state and cant repolarise
3. no new action potentials can be generated

refractory period doesn’t end

Question 21

why use suxamethonium?

Answer 21

1. less general anaesthetic needed
2. rapid onset of action (60s)
3. short duration

Question 22

clinical use for suxamethonium

Answer 22

to release trachea for endo-tracheal intubation

Question 23

what breaks down suxamethonium?

Answer 23

butyryl

Question 24

what inhibits AChE’s

Answer 24

neostigmine

Question 25

what does neostigmine do

Answer 25

inhibits the breakdown of ACh in NMJ to reverse effects of reversible competitive antagonists
(reverses effects of muscle relaxation)

Question 26

does neostigmine reverse the effects of suxamethonium ?

Answer 26

no

Question 27

what is myasthenia gravis

Answer 27

autoimmune disease where antibodies bind to a subunits of NAChR leading to their destruction

Question 28

what can be used to diagnose Myasthenia gravis

Answer 28

edrophonium

Question 29

what can be used to treat myasthenia gravis and how

Answer 29

neostigmine

1. it increases [ACh] in cleft by decreasing its breakdown by AChE’s
2. this increases the likelihood of ACh binding to remaining NAChR’s
3. helps transmission