Neuromuscular Blocking Drugs

Question 1

What neurotransmitter do motor neurones use?

Answer 1

ACh

Question 2

What is the target site of neurotransmitters from motor neurones?

Answer 2

Nicotinic ACh receptors (different to ganglionic) on the End Plate - usually in the middle of the fibres

Question 3

What type of potential is generated in the muscle?

Answer 3

a Graded end-plate potential

• it depends on how much ACh is released and how many receptors are stimulated

Question 4

When is an action potential generated in a muscle?

Answer 4

When the end-plate potential reaches a threshold. The action potential then propagates in both directions

Question 5

How is ACh broken down once it has exerted its effect on the end-plate?

Answer 5

By Acetylcholinesterase which is bound to the basement membrane in the synaptic cleft

Question 6

What are the three main neuromuscular blockers?

Answer 6

Tubocurarine

Atracurium

Suxamethonium

Question 7

What are Diazepam and Baclofen?

Answer 7

Diazepam - Sapsmolytic that facilitates GABA transmission

Baclofen - GABA receptor agonist

Both potentiate the actions of GABA

Question 8

What are the five sites that drugs can interact with to effect movement?

(Give the type of drug for each site)

Answer 8

Central processes - Spasmolytics

Conduction of AP in motor neurone - Local Anaesthetics

ACh release - Hemicholinium, Ca²⁺ entry blockers, Neurotoxins

Depolarisation of End-plate - Tubocurarine, Suxamethonium

Propagation of AP along fibre/muscle contraction - Spasmolytics

Question 9

Where do neuromuscular blocking drugs act?

Answer 9

The nicotinic receptors on the motor end-plate

Question 10

What type of drugs are Tubocurarine and Atracurium?

Answer 10

Competitive nicotinic receptor antagonists

Question 11

What type of drug is Suxamethonium?

Answer 11

Nicotinic receptor agonist

Question 12

What is the structure of Suxamethonium?

Answer 12

Made up of two ACh molecules that are linked together - can bind to two alpha subunits; is much more flexible and allows rotation

Question 13

How does Suxamethonium cause neuromuscular blocking?

Answer 13

Causes extended end-plate depolarisation leading to a depolarisation block of the NMJ (phase 1)

It isn’t metabolised as rapidly as ACh so remains bound to the receptors and these will very quickly switch off

Question 14

What type of paralysis does Suxamethonium cause?

Answer 14

Flaccid paralysis - there is no muscle tone

Question 15

What are two uses of Suxamethonium?

Answer 15

Endotracheal intubation - relaxes the skeletal muscle of the airways

Muscle relaxant for Electroconvulsive therapy

Question 16

What are three unwanted effects of Suxamethonium?

Answer 16

Post-op muscle pains due to initial fasciculations (fibre twitches as the drug begins to stimulate the receptors)

Hyperkalemia after soft tissue injury or burns - loss of innovating neurones leading to upregulation of receptors = deinnervation supersensitivity. Suxa will then give an exaggerated response and you will get a bigger influx of Na and efflux of K. This can lead to Ventricular arrhythmias/cardiac arrest

Raised intraocular pressure - avoid for eye injuries and glaucoma

Question 17

What is the effect of Suxamethonium on the heart?

Why are the effects usually prevented?

Answer 17

Bradycardia due to muscarinic action on the heart

Effects generally prevented as Atropine (muscarinic antagonist) is usually given in anaesthetic pre-med

Question 18

What is the route of administration for Suxamethonium and how long is its duration of paralysis?

Answer 18

Intravenous

5 minutes

Question 19

What is the mechanism of action of Tubocurarine?

Answer 19

It is a competitive nicotinic ACh receptor antagonist

If 70-80% of receptors are blocked, then full relaxation of muscles is achieved as the threshold is not reached

Question 20

What is the effect of Tubocurarine?

Answer 20

Flaccid paralysis

Question 21

What is the main use of Tubocurarine?

Answer 21

Relaxation of the skeletal muscles during operations

This allows lower doses of GA as the role of making the muscles relax has been taken over by the Tubocurarine

It also permits artificial ventilation

Question 22

How can the effects of Tubocurarine be reversed?

What drug is given with it and why?

Answer 22

With an anticholinesterase like Neostigmine

Atropine is also coadministered to prevent muscarinic receptor overstimulation

Question 23

What is the route of administration for Tubocurarine and how long does the paralysis last?

Answer 23

Intravenously (does not cross BBB or placenta)

40-60 mins

Question 24

What drug would you give instead of Tubocurarine in patients with impaired hepatic or renal function?

Answer 24

Atracurium (15 min duration)

Not affected by liver or kidney function unlike Tubocurarine

Question 25

What two ways can Tubocurarine cause unwanted effects and what are they?

Answer 25

Ganglion Block:

• Hypotension, Tachycardia

Histamine release:

• Hypotension, bronchospasm, excessive secretions, apnoea