Lecture 32: Neuromuscular blockers

Question 1

What are the 3 aims of Anaesthesia : balanced approach says 3 different substances for so less side effects

Answer 1

1. Hypnosis/amnesia: through volatile/IV agents
2. Autonomic areflexia: through opioids
3. Immobility: through neuromuscular agents

Question 2

What type of receptors allow depolarisation of muscle fibres at their one NMJ: structure and function

Answer 2

Nicotinic pentamer ligand gated ion channel (ionophore) on the Post synaptic membrane

1. 2 AcH must be bound simultaneously to alpha sites to cause a conformational change
2. therefore Na+ can cross and cause depolarisation which is propagated by adjacent v-gated ion channels.

Question 3

What is the function of prejunctional (pre synaptic membrane) and extrajunctional: not at NMJ Ach receptors

Answer 3

1. Activation of pre facilitates mobilisation of vesicles towards the presynaptic membrane (positive feedback)
2. Normally present in small numbers they are upregulated in denervated muscle due to spinal injury and dystrophy

Question 4

What are the two types of neuromuscular blockers

Answer 4

Non depolarising and Depolarising

Question 5

What is the mechanism of action of non depolarising NM blocker

Answer 5

Competitive antagonism by mimic quaternary nitrogen atom of ACh which binds to alpha site with high affinity:

preventing access by ACh and prevents conformation change by rigidity and bulk.

It can be outcompeted by increased amounts of ACh / reduced conc of NMb due to elimination

Question 6

What are the notable features of mivacurium, Atracurium, Vecuronium, Rocuronium and Pancuronium - NDNMB

Answer 6

Short acting: Miva bc of plasma esterase metab- can be long acting if genetic defect tho

Medium acting:

• Atra: good in hep and renal failure bc of spontaneous degradation,
• Vecu: least likely for histamine release
• and Rocu: Fastest onset but anaphylaxis likely

Long acting;
-Pan: some effect at muscarinic receptors so tachycardia

Question 7

How can NDNMB use be reversed and when: what is used

Answer 7

Can be reversed after 1-2 twitches on train of 4.

Reversed using anticholinesterase eg. Neostigmine which inhibits breakdown of ACh at NMJ.

However it is also active at parasympathetic synapses (muscarinic) outside of the CNS so co-administered with Atropine (block muscarinic) to avoid bradycardia.

Question 8

How is the level of NDNM blockade measured and what does it look like at different stages of administering the NDNMB

Answer 8

1. four consecutive stimuli are delivered along the path of the nerve and the response measured.

In a normal patient there will be 4 big twitches all the same height

If profound block then all twitches gone

If coming back there will be first 1/4 then 2/4. All 4 will come back but with fading of height.

this is because of blocking the prejunctional receptors bc there is less AcH released upon successive stimuli

The ratio of height of last twitch/ first twitch should be 80% for acceptable patient recovery

Question 9

What is the mechanism of action for depolarising NM blockade and what agent is used.

Answer 9

1. Suxamethonium: 2 Ach molecules together binds to the two a subunits to agonise the receptor, producing one twitch= fasciculations.
2. However the ionophore remains open because the ACH esterase can’t breakdown Sux fast so the membrane is unable to repolarise= paralysis all over the body

Question 10

What are the dangers of Suxamethonium and what are the good things

Answer 10

• it causes K+ to rise in blood due to a prolonged leak- especially in patients with more extra-junctional receptors.
• It raises ICP
• Can cause bradycardia
• strong trigger for malignant hyperthermia, anaphylaxis
• some people have genetic defect in plasma cholinesterase which increases its duration to hours.

However
because of fast onset: 30s and fast offset-3-5min (AChesterase and plasma cholinesterase) good for intubation for patients at risk of aspiration