Neuromuscular blocking drugs

Question 1

Where do the cell bodies of alpha motor neurons sit?

Answer 1

ventral horn of vertebrae

Question 2

neuromuscular synaptic terminal diagram.

6 stages.

Answer 2

Question 3

What kind of receptors are found at the neuromuscular junction?

Answer 3

nicotinic type 1 (ion channel) ACh receptors.

(2 alpha subunits)

Question 4

What is the relevance of nicotinic receptors at the neuromuscular junction being different to ganglionic nicotinic receptors

Answer 4

Neuromuscular specific drugs can be developed.

Question 5

How many ACh molcules are needed to bind to nAChR to stimulate a response? Which subunits do they bind to?

Answer 5

2, to the alpha subunits.

(NB other subunits are beta, delta and gamma)

Question 6

Name a drug type that acts on the central processes (generation of APs in the spinal cord) of the SNS. Give two examples.

Answer 6

spasmolytics.

diazepam, baclofen.

Question 7

What drug types target conduction of nerve AP in the motor neurone?

Answer 7

local anaesthetics.

Question 8

What types of drugs effect ACh release from the presynaptic neurone? Give an example.

Answer 8

Ca2+ entry blockers

neurotoxins - botulinum toxin.

hemicholinium (what is this)

Question 9

Name some drugs that effect the depolarisation of the motor end plate, inhibiting AP initiation.

Answer 9

tubocurarine

suxamethonium

Question 10

What category of drug effects propagation of AP along muscle fibre and so muscle contraction? GIve an example.

Answer 10

Spasmolytics - dantrolene.

Question 11

What are the two classes of neuromuscular blockers? Give some examples.

Answer 11

1. non-depolarising (competitive antagonists) - tubocurarine, atracurium.
2. depolarising (agonists) - sexamethonium.

Question 12

What effects do neuromuscular blockers have on consciousness, pain sensation and respiration?

Answer 12

consciousness - no effect.

pain sensation - no effect

assist respiration.

Question 13

Explain the mechanism of action of suxamethonium.

Answer 13

It produces an extended end-plate depolarisation –> depolarisation block.

i.e. receptor overstimulated and then response shuts down.

Question 14

What is the physiological response to suxamethonium.

Answer 14

fasciculations –> flaccid paralysis

Question 15

How is suxamethonium administered?

Answer 15

I.V.

Question 16

What is suxamethonium’s duration of effect?

Answer 16

approx. 5 mins.

Question 17

How is suxamethonium metabolised?

Answer 17

by pseudocholinesterase in liver and plasma

Question 18

What are the two main uses of suxamethinium?

Answer 18

• endotracheal intubation
• muscle relaxant for Electro convulsive therapy.

Question 19

Outline the unwanted effects of suxamethonium.

Answer 19

post operative muscle pains.

bradycardia - counteracted by simultaneous atropine administration.

hyperkalaemia - in patients with soft tissue injury/burns (due to increased nicotinic receptors to amplify response to damaged area). This can cause ventricular arrhythmias/cardiac effects.

increased intraocular pressure - avoid administration for eye injury/glaucoma patients.

Question 20

Outline the mechanism of action of tubocurarine (non-depolarising blocker)

Answer 20

competitive nAChR antagonist.

70-80% block necessary for effect.

Question 21

What is the effect of tubocurarine? What is the order of onset?

Answer 21

flaccid paralysis.

extrinsic eye muscles –> small muscles of face, limbs, pharynx, respiratory muscles.

Recover in opposite order.

Question 22

What are the uses of tubocurarine?

Answer 22

relaxation of skeletal muscles during surgical operations (less anaesthetic needed)

Permit artificial ventilation.

Question 23

How can the actions of non-depolaring blockers be reversed?

Answer 23

anticholinesterases

e.g. neostigmine + atropine.

Question 24

How is tubocurarine administered?

Answer 24

I.V.

Question 25

What is the duration of effect of tubocurarine?

Answer 25

1-2 hours (relatively long)

(atracurium = 15 mins)

Question 26

How is tubocurarine excreted? What must be considered when administering it?

Answer 26

not metabolised - excreted in urine (70%) and bile (30%)

dangerous if patient has impaired renal/hepatic function - atracurium used instead.

Question 27

What barriers is tubocurarine unable to cross?

Answer 27

BBB and placenta

Question 28

Outline potential unwanted effects of tubocurarine.

Answer 28

Ganglionic blockade and histamine release cause side effects -

hypotension (ganglion block - TPR reduces, histamine - vasodilation)

tachycardia (can lead to arrhythmias) - due to compensation for hypotension and blockade of vagal ganglia.

bronchospasm, excess bronchial/salivary secretions (due to histamine)

apnoea.