15) Muscle Relaxants - Reversal of block

The effect of non-depolarizing neuromuscular-blocking drugs may be reversed

with acetylcholinesterase inhibitors, neostigmine, and edrophonium, as commonly used examples.
Of these, edrophonium has a faster onset of action than neostigmine, but it is unreliable when used
to antagonize deep neuromuscular block. Acetylcholinesterase inhibitors increase the amount of
acetylcholine in the neuromuscular junction, so a prerequisite for their effect is that the
neuromuscular block is not complete, because in case every acetylcholine receptor is blocked then it
does not matter how much acetylcholine is present. It is given by injection either into a vein, muscle,
or under the skin. After injection effects are generally greatest within 30 minutes and last up to 4
hours.
Sugammadex is a newer drug for reversing neuromuscular block by rocuronium in general
anaesthesia. It is the first selective relaxant binding agent (SRBA).
By interfering with the breakdown of acetylcholine, neostigmine
indirectly stimulates both nicotinic and muscarinic receptors. Unlike physostigmine, neostigmine has
a quaternary nitrogen; hence, it is more polar and does not enter the CNS, but it does cross
the placenta. Its effect on skeletal muscle is greater than that of physostigmine. Neostigmine has
moderate duration of action – usually two to four hours. Neostigmine binds to the anionic and
esteric site of cholinesterase. The drug blocks the active site of acetylcholinesterase so
the enzyme can no longer break down the acetylcholine molecules before they reach
the postsynaptic membrane receptors. This allows for the threshold to be reached so a new impulse
can be triggered in the next neuron. In myasthenia gravis there are too few acetylcholine receptors
so with the acetylcholinesterase blocked, acetylcholine can bind to the few receptors and trigger a
muscular contraction.