Neuromuscular Blocking Drugs Flashcards

1
Q

Describe how impulses are transmitted across synapses.

A

Action potential propagates along the presynaptic neurone -> depolarisation of presynaptic membrane -> opening of voltage gated calcium channels -> calcium influx -> vesicle exocytosis

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2
Q

What type of receptor is found at the neuromuscular junction?

A

Nicotinic acetylcholine receptors

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3
Q

Where are these receptors found on the muscle fibre?

A

Motor end plate (usually in the middle of the muscle fibres)

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4
Q

What does depolarisation of this membrane cause? Describe the character of this depolarisation.

A

This causes a change in end plate potential
This is a graded potential meaning that it is dependent on the amount of acetylcholine released and the number of receptors stimulated
Once the end plate potential reaches a threshold, it generates an action potential that propagates in both directions along the muscle fibre

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5
Q

Where is acetylcholinesterase found?

A

It is bound to the basement membrane in the synaptic cleft

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6
Q

State the three main neuromuscule blockers.

A

Tubocurarine
Atracurium
Suxamethonium

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7
Q

State the two main types of nicotinic acetylcholine receptor.

A

Ganglionic

Muscle

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8
Q

Describe the structure of nicotinic acetylcholine receptors.

A

They consist of 5 subunits (subunits can be alpha, beta, gamma, delta, epsilon)
There are always 2 alpha subunits, which bind to acetylcholine and activate the receptor

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9
Q

How many molecules of acetylcholine are required to activate one nicotinic acetylcholine receptor?

A

2

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10
Q

Name two drugs that are used as spasmolytics and describe theiraction.

A

Diazepam
Baclofen (GABA receptor agonist)
They both facilitate GABA transmission

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11
Q

Give some examples of conditions in which spasmolytics may be used.

A

They are both useful in some forms of cerebral palsy and spasticity following strokes

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12
Q

What do local anaesthetics have their effect on?

A

Conduction of action potentials in motor neurones (so if you inject local anaesthetic to a motor neurone then you may see some muscle weakness)

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13
Q

Describe the action of neurotoxins.

A

Neurotoxins inhibit the release of acetylcholine and hence block the contraction of respiratory skeletal muscle causing death

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14
Q

What are the two types of neuromuscular blocker?

A

Depolarising

Non-depolarising

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15
Q

Name another spasmolytic that has a different action to create the same effect.

A

Dantrolene – it works in the muscle fibres themselves by inhibiting calcium release in the muscle fibre

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16
Q

Describe the difference in mechanism of action between depolarising and non-depolarising NM blockers. Which NM blockers fall into each category?

A
Depolarising = suxamethonium = nicotinic acetylcholine receptor AGONIST  
Non-depolarising = tubocurarine + atracurium = nicotinic acetylcholine receptor antagonist
17
Q

How do NM blockers affect consciousness and pain sensation?

A

They do NOT

18
Q

What must you always do when giving NM blockers?

A

Assist respiration because of their effect on respiratory muscle action

19
Q

Describe the difference in structure between non-depolarising and depolarising NM blockers?

A
Non-depolarising = big, bulky molecules with limited movement around their bonds  
Suxamethonium = made up of two acetylcholine molecules that are linked together. This is more flexible and allows rotation. As it is madeup of two acetylcholine molecules it can binds to the two alpha subunits and activate the receptor.
20
Q

Describe the mechanism of action suxamethonium.

A

Suxamethonium is a nicotinic receptor agonist.
It causes an extended end plate depolarisation leading to a depolarising block of the NMJ
This is a phase 1 block
NOTE: it is not metabolised as rapidly as acetylcholine so it will remain bound to the nicotinic receptors making them switch off due to overstimulation
It eventually results in FLACCID PARALYSIS

21
Q

What does suxamethonium normally cause before causing the flaccid paralysis?

A

Fasciculations – individual fibre twitches as the suxamethonium begins to stimulate the nicotinic receptor (remember it is an agonist)

22
Q

What is the duration of paralysis of suxamethonium?

A

5 mins

23
Q

How is suxamethonium metabolised?

A

It is metabolised by pseudocholinesterase (butyrylcholinesterase) in the liver and plasma

24
Q

What are some uses of suxamethonium?

A

Endotracheal intubation – relaxes the muscles of the airways
Muscle relaxant for electroconvulsive therapy – treatment for severe clinical depression

25
Q

State and explain four unwanted effects of suxamethonium.

A

Post-operative muscle pains
 Due to initial fasciculations
Hyperkalaemia
 If there is soft tissue injury or burns you will lose some neurones innervating the tissuea
 Then you will get upregulation of receptors in the skeletal muscle – deinnervation supersensitivity
 So if you give suxamethonium you get an exaggerated response with a bigger influx of sodium and bigger efflux of potassium
Bradycardia
 This is due to the direct muscarinic action on the heart
 This effects tends to be prevented because suxamethonium is usually given after GA and hence following administration of atropine (muscarinic antagonist) in the pre-med
Raised intraocular pressure
 AVOID for eye injuries and glaucoma

26
Q

Describe the mechanism of action of tubocurarine.

A

Tubocurarine is a competitive nicotinic acetylcholine receptor antagonist.
You only need 70-80% block to achieve full relaxation of the muscles
If you block this proportion of the receptors then the end-plate potential generated will NOT reach the threshold

27
Q

Describe the order of relaxation of skeletal muscles and the orderin which they return back to normal when given tubocurarine.

A

This also causes flaccid paralysis.
Order:
 Extrinsic eye muscles (first to relax, last to go back to normal)
 Small muscles of the face, limbs and pharynx
 Respiratory muscles

28
Q

State two uses of tubocurarine.

A

Relaxation of muscles during surgical operations (this means that less general anaesthetic is needed)
Permit artificial ventilation

29
Q

How can the actions of NM blockers be reversed?

A

Give an anti-cholinesterase (e.g. physostigmine)

30
Q

What else must you give with this drug when trying to reverse theactions of NM blockers?

A

Atropine
Giving physostigmine will raise the synaptic concentration of acetylcholine at ALL cholinergic synapses (not just the neuromuscular junctions) so you need some atropine to block these unwanted effects

31
Q

How are all NM blockers administered?

A

Intravenously

32
Q

What is the duration of paralysis of tubocurarine?

A

40 mins

33
Q

Describe the metabolism and excretion of tubocurarine?

A

It is NOT metabolised at all

It is excreted in the urine (70%) and bile (30%)

34
Q

Under which conditions would you get an increased duration of action of tubocurarine? What would you change under these conditions?

A

Impairment of hepatic or renal function increases the duration of action of tubocurarine
Under these conditions you would use ATRACURIUM (15 min duration) and is NOT affected by liver or kidney function

35
Q

State some unwanted effects of tubocurarine.

A

MAIN EFFECTS: ganglion block + histamine release from mast cells cause most of the unwanted effects
 HYPOTENSION – histamine can act on H1 receptors and cause vasodilation
 TACHYCARDIA – reflex tachycardia in response to hypotension
 BRONCHOSPASM – caused by histamine release
 EXCESSIVE SECRETIONS (bronchial and salivary) – histamine release
 APNOEA – which is why you assist respiration