- Non-depolarising block can be "reversed" using an anti-cholinesterase drug such as neostigmine
- By inhibiting acetylcholinesterase at the NMJ from breaking down the ACh that is released into the synaptic cleft, the concentration of ACh that reaches the post-synaptic ACh receptors
is greatly increased
- NDMRs are competitive antagonists to ACh, so by increasing the ACh concentration, this shifts the balance of binding to the nic ACh receptor in favour of ACh
- If the balance is shifted enough, then enough nic ACh receptors can be activated to depolarise the motor end plate to threshold and re-establish signal transmission across the NMJ
Why do we need to add an anti-muscarinic?
- The anti-cholinesterase drugs not only affect the NMJ, but also affect the autonomic system synapses that use ACh as the neurotransmitter - mainly the post-ganglionic parasympathetic fibres that release ACh that acts on muscarinic ACh receptors
- If an anti-muscarinic drug were not given in combination with the anti-cholinesterase, it would cause unopposed
parasympathetic stimulation resulting in bradycardia, ↑
secretions, miosis, ↑
Neostigmine/Atropine or Neostigmine /Glycopyrrolate?
- Neo/atropine used to be the common combo because glyco was expensive, but neo/glyco has now become the routine choice because of 2 advantages
- Onset and duration of action
- neo and glyco have similar times to onset and durations of action, hence "cancel out" each other better
- atropine has a faster onset and shorter duration than neo, potentially resulting in early tachycardia then late bradycardia
- Central anticholinergic syndrome
- glyco is a quaternary amine and cannot cross the blood-brain barrier, while atropine is a tertiary amine and can cross the BBB and potentially cause central anticholinergic syndrome, particularly in elderly patients
Why can't a deep block be reversed?
- To reliably reverse a block, a TOFC of at least 2 - preferably 4 - is advisable before attempting reversal
- This is because of the ceiling effect of neostigmine
- There is a finite amount of ACh at the NMJ
- Once all the AChE has been inhibited, further increasing the dose of neostigmine will not result in higher ACh concentration
- Hence a deep level of block cannot be antagonised using this method. Contrast this with sugammadex, which can be used to reverse a deep block