L8 - drugs affecting neuromuscular transmission Flashcards
what is motor unit
myelinated motor nerve and the fibres it innervates
how big is the synaptic cleft
60nm
what do schwann cells do at the neuromuscular junction
form lids over synaptic cleft
what is the end plate
the section of muscle membrane in ‘contact’ with the synapse
what processes can drugs act of to modify neuromuscular synaptic transmission
synthesis
storage
release
receptors the NT acts on
uptake of the NT from cleft
how is ACh synthesised
from choline & acetyl CoA via the CAT enzyme
what is the CAT enzyme
choline acetyl transferase
why is ACh packaged into vesicles?
- because it can only be released once in vesicles
2. will be broken down if not in vesicles
what drug blocks uptake of choline
hemicholinium
what drug blocks ACh uptake into vesicles?
vesamicol
how can Ca2+ channels be blocked?
with a bigger ion eg Mg2+
what can block ACh exocytosis
botulinum toxin
role of acetylcholinesterase’s? (AChE)
rapidly break down ACh in cleft
structurally how does ACh activate the nicotinic receptor
1 ACh binds to each of the a subunits
the channel opens up
this opening of channel causes depolarisation of end plate
what is an end plate potential?
depolarisation of the muscle membrane after the cleft due to activation of the nicotinic receptors
what does tubocurarine do
drug that causes skeletal muscle relaxation
what is suxamethonium
muscle relaxant
Nicotinic ACh agonist
describe suxamethonium structure
dimer of ACh
how does suxmethonium work
produces muscle depolarisation but isn’t broken down by AChE’s so depolarisation is prolonged
how does suxamethonium cause muscle relaxation?
- binds to NAChR and causes prolonged depolarisation
- Na channels are stuck in inactive state and cant repolarise
- no new action potentials can be generated
refractory period doesn’t end
why use suxamethonium?
- less general anaesthetic needed
- rapid onset of action (60s)
- short duration
clinical use for suxamethonium
to release trachea for endo-tracheal intubation
what breaks down suxamethonium?
butyryl
what inhibits AChE’s
neostigmine
what does neostigmine do
inhibits the breakdown of ACh in NMJ to reverse effects of reversible competitive antagonists
(reverses effects of muscle relaxation)
does neostigmine reverse the effects of suxamethonium ?
no
what is myasthenia gravis
autoimmune disease where antibodies bind to a subunits of NAChR leading to their destruction
what can be used to diagnose Myasthenia gravis
edrophonium
what can be used to treat myasthenia gravis and how
neostigmine
- it increases [ACh] in cleft by decreasing its breakdown by AChE’s
- this increases the likelihood of ACh binding to remaining NAChR’s
- helps transmission
