L8: drugs affecting neuromuscular junction Flashcards
How many processes can drug affect to modify chemical synaptic transmission?
5
What processes pre-synaptically can affect the synaptic transmission?
- Synthesis
- Storage
- Release
of the neurotransmitter
What processes post-synaptically can affect the synaptic transmission?
- Receptors
- Removal mechanism
for the neurotransmitter
First stage of events in pre-synaptic ‘cholinergic’ transmission
Acetylcholine is synthesised from choline + acetylcoenzyme A by action of enzyme Choline Acetyl Transferase (CAT)
Second stage of events in pre-synaptic ‘cholinergic’ transmission
Choline is taken into nerve terminal by a transporter protein
Synthesis
What does Hemicholinium block the uptake of?
Uptake of choline into nerve terminal
Storage
What does **AH5184 **block the uptake of?
Uptake of ACh into synaptic vesicle
Release
What does **Conotoxins **block?
Blocks voltage-gated Ca2+ channels
Release
What does Botulinum block?
Blocks process of exocytosis
Third stage of events in pre-synaptic ‘cholinergic’ transmission
ACh is stored by synaptic vesicles that are released by exocytosis
First stage of post-synaptic events in cholinergic transmission
After being released, ACh diffuses across synaptic gap & activates receptors on post-synaptic membrane
Two types of ACh receptors
1) Nicotinic Receptors
2) Muscarinic Receptors
What are nicotinic receptors activated by?
Nicotine from tobacco plant
What are muscarinic receptors activated by?
Muscarine from poisonous Fly Agaric mushroom
What is ACh broken down by during the removal from the synapse?
Enzyme acetylcholinesterase (AChE), found in the synaptic gap
Name the enzyme involved in the synthesis of acetylcholine (ACh)
Choline Acetyl Transferase (CAT)
Name the enzyme involved in the destruction of ACh
Acetylcholinesterase (AChE)
What happens to the choline produced following the destruction of ACh?
Being recycled, taken back into nerve terminal for synthesis of new ACh
What are the FIVE key processes that drugs can interfere with at any chemical synapse
1) Synthesis
2) Removal
3) Release
4) Receptors
5) Removal
What is the motor unit?
Motor nerve + muscle fibre it controls
Why is the muscle membrane thrown into folds?
Increasing SA
What is the specialised area of the muscle membrane called?
Muscle “end plate”
What is the neurotransmitter released in skeletal neuromuscular junction?
Acetylcholine
What is the receptor present on the muscle in skeletal neuromuscular junction?
Nicotinic acetylcholine receptors
Define agonist
Substance that mimics the actions of a neurotransmitter to produce a response when it binds to a specific receptor
How many protein subunits form the nicotinic ACh receptor?
5
Structure of nicotinic ACh receptor
5 protein subunit surrounding a non-selective cation channel which is permeable to Na+ & K+
When does the non-selective cation channel on the nicotinic ACh receptor open?
2 molecules of ACh bind to the protein complex, 1 to each alpha-subunit
What does opening of the channel of nicotinic ACh receptor leads?
Leads to depolarisation of the end-plate region of muscle membrane
Where is botulinum toxin found?
Uncooked foods
What is blepharospasm?
Involuntary tight closure of eyelids
What does botulin target in blepharospasm?
Inappropriate contraction of the skeletal muscle
Does botulinum toxin given locally or systemically?
Locally
Role of botulin in presynaptic transmission
Inhibits the release of ACh
Define antagonist
Substance that stops the action/effect of another substance
What are at the nicotinic ACh receptor to post- synaptically inhibit neuromuscular transmission?
Reversible competitive antagonists
Are reversible competitive antagonists GENERAL ANAESTHETICS?
NOOO, used alongside to stop contraction
How can effects of muscle relaxants during surgery be reversed?
Acetylcholinesterase inhibitor, neostigmine
