neuromuscular junction - pharmacology Flashcards

1
Q

describe the events that take place in a synapse

A
  1. Action potential propagated in motor neuron -
  2. voltage gated calcium channels open
  3. acetylcholine released into cleft
  4. acetyl choline binds receptor
  5. receptor’s ion channel opens
  6. acetylcholine destroyed by acetylcholinesterase
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2
Q

describe how an aciton potential activates a muscle fiber contraction

A

acetyl choline binds to sodium channels, they open and allow depolarizaiton of cell and the action potential continues in both directions

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3
Q

what sort of drug blocks the neuromuscular junction ?

A

neurotoxins

  • including agonists and antagonists of the nAChR

inhibitors of the AChE - acetyl choline esterase breaks down ACh so if you block this enzyme you’ll build up on ACh

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4
Q

what are the sites of pharmacologic effects in neurotransmission at the skeletal neuromuscular junction?

A

post synaptic (mainly used clinically)

  • nicotinic acetylcholine receptor -agonists/antagonists
  • acetylcholinesterase-block enzyme from breaking down ACh

pre-synaptic

  • machinery of exocytosis - block vesicle releases ACh
  • presynaptic Ca2+ channel
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5
Q

what drugs activate the ACh receptor?

A

Acetylcholine

Nicotine

Carbachol

Suxamethonium (succinylcholine)

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6
Q

what drugs block the ACh receptor?

A

D- Tubocurare

Pancuronium

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7
Q

What is the use of D-Tubocurarine?

A

it is a non-depolarizing agent so it blocks the ACh at the receptor region - by inhibiting binding

used during surgical anaesthesia to paralyse skeletal muscle

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8
Q

What is Pancuronium used for?

A

more potent than tubocurarine - synthetic substance also used for relaxing muscles during surgery -

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9
Q

What is alpha-bungarotoxin used for?

A

synthesized from cobra toxin - bind essentially irreversibly to nAChR and block neuromuscular junction function

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10
Q

What does succinylcholine do?

A

it is an AChR agonist - that depolarizes the NM blocker - causes initial muscle twitches then relaxation/paralysis

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11
Q

explain how acetylcholine receptor agonists work

A

voltage gated ion channels have an inactivation gate - so shortly after a depolarization, an internal portion swings in and blocks the sodium channel

the agonists of the receptor inhibit the ACh esterase - so more of the nuerotransmitter remains in the junction maintaining the signal for longer - so the inactivation gate stays disengaged for longer -

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12
Q

how do antagonists of the neuromuscular junction work?

A

they are blockers of the pre-synaptic Ca2+ channel -

Mg2+ ions - compete with Ca2+ entry to reduce ACh release - magnesium salts once used as anaesthetics

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13
Q

how do anaesthetists decide which anesthesia to use?

A

they chose the right drug with a half-life closest to the time of the surgery

*different muscles repond differently to the blockers

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14
Q

what do m-conotoxins do?

A

they block the particular voltage gated Na+ channel on skeletal muscles - cause paralysis but ACh still released in response to nerve stimulation

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15
Q

what does w-conotoxin do (omega) ?

A

blocks the Ca2+ channel at the presynaptic junction inhibiting ACh release

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16
Q

what is the reversal agent for ingestion of a nueromuscular blocking agent ?

A

mechanical ventilation - wait it out with the help of respiratory devices

17
Q

what does Botulinum toxin do? (botox)

A

it blocks release of ACh -prevents muscles reponding to nerve impulses - comprises endopeptidases which work by cleaving synaptic proteins required for vesicle release

18
Q

what is tetanus?

A

from the neurotoxin from Clostridium Tetani - organism gains entry to body via cuts and inhibits synaptic vesicle release into interneurons in the spinal cord - since these interneruons normally inhibit firing of motorneurons whcih activate skeletal muscle contraciton, this leads ot profound spasms - leading to rib fractures, respiratory arrest

avoid via immunization

19
Q

how does physostigmine work?

A
  • it is a prototypic anticholinesterase - plant alkaloid - increase the amplitude and prolong duration of the response to ACh
20
Q

how do neostigmine and pyridostigmine work?

A

they are synthetic anticholinesterases - increase the amplitude and prolong duration of reponse to ACh

21
Q

what is diisopropylfuorophosphate (DFP)?

A

it is an irreversible inhibitor of acetylcholinesterase - irreversible AChE inhibitor used as nerve gas and insecticide - cause paralysis and suffocation by inhibition of respiratory muscles

22
Q

what is Myasthenia Gravis?

A

common pirmary disorder of neuromuscular transmission - mainly in adulthood

ACh release is normal but size of EPP reduced due to immune respone against the nicotinicacetylcholine receptor in skeletal muscular junction - these antibodies will directly block receptor and compete for acetylcholine -

insufficient ACh “effect” - leads to extreme muscle contraction weakness and fatigue

( symptom= ptosis - eyelids want to shut )

diagnose with IgG autoantibodies against AChR -

treatment: boost acetylcholine amount by reducing AChE response - suppress immune system or thymectomy

23
Q

what is Lambert Eaton Myasthenic Myopathic syndrome?

A

also characterized by progressive muscle weakness and fatigue - antibodies attack presynaptic Ca2+ channel - lead to decreased ACh release - distinguished from myathenia gravis by disease affecting limb muscles (vs ocular, bulbar in MG) and repetitive stimulation of muscle improves condition but worsens MG