Neuromuscular Junction – Phase II block

I wanted to clarify the phase II block that we discussed today at the tutorial (ok, the one that the 8 people who were at the tut discussed)

Some facts about Phase II block

  • It occurs exclusively with exposure to depolarising muscle relaxants
  • Prolonged exposure of the neuromuscular junction to scoline causes one of two events to occur – desensitisation block or phase II block
  • What I described to you today was desensitisation block – remember that the receptors fluctuate constantly between open, closed and desensitised states. Agonists (scoline) predispose to desensitisation as they have a higher affinity for the desensitised receptors and they promote transition to the desensitised state. It follows that prolonged exposure will result in an increase in the average number of receptors which are desensitised. Normally ACh is so rapidly inactivated that desensitisation does not occur. This may be a safety mechanism.
  • Phase II block differs from desensitisation block. It is characterised by fade, tetanic fade and post-tetanic facilitation. After initial depolarisation, the membrane potential gradually returns to normal even though the nAChRs are still exposed to drug and neurotransmission is blocked.
    • There is still debate about the actual process
    • It may be a presynaptic phenomenon (at another AchR where scoline can bind (not the alpha3Beta2))
    • It may result from some postjunctional receptor desensitisation
    • It may be due to activation of the NA/K ATPase pump by initial depolarisation of the postsynaptic membrane which repolarises it.

 

This probably doesn’t clarify this much, but to be honest, i’ve done a (very brief) literature review and most papers are pretty vague as to what causes phase II block.

What they are clear about is that treatment is controversial. If the pt is known to have NORMAL AChE then the recommendation is to give neostigmine. If the patient has ABNORMAL AChE then neostigmine will at best have no effect and at worst worsen the block.

I hope this helps somewhat.

Mike

 

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