Hi and welcome back to this introductory series on the neuromuscular junction. In part 2 we'll
be focusing on neuromuscular blocking agents, their basic interaction in the neuromuscular
junction and how it produces temporary muscle paralysis when administered to a patient.
A neuromuscular blocking agent or simply an NMBA or blocking agent for short, is a class of drug
that creates a communication block between a motor neuron and a muscle fiber, in the neuromuscular
junction which then results in temporary muscle paralysis, also known as a neuromuscular block.
Blocking agents are divided into two categories: depolarizing and non-depolarizing blocking agents.
Each have their own mechanism of function and therefore have different applications
in a clinical setting. Depolarizing agents have a short lasting mechanism of action
whilst non-depolarizing agents have a much longer lasting mechanism of action.
When taking a closer look we can see they function as follows. A blocking agent is
intravenously introduced into the bloodstream and enters the neuromuscular junction.
Depolarizing agents act predominantly on the post-synaptic receptor sites. The agent mimics
the action of the neurotransmitter acetylcholine by binding to the post-synaptic receptors on
the muscle fiber, causing the sodium gates to open and a sodium influx to occur resulting in
persistent muscle cell depolarization of the muscle fiber. This persistent depolarization
makes the muscle fiber resistant to any further stimulation by the acetylcholine.
Note that the acetylcholine reserve pool is constantly replenished and is not reduced
over time. The short duration of action of the depolarizing agent is due to a rapid hydrolysis
by pseudocholinesterase, therefore inducing a short-lasting block after which the agent
is then quickly worked out of the junction and returns back to normal functionality.
The depolarizing agent has a rapid onset of effect and a short mechanism of action,
therefore making it the preferred blocking agent for use in emergency cases where immediate
airway management is required. An example of depolarizing blocking agent is succinylcholine.
Succinylcholine is a short-acting agent where the mechanism of action is already apparent
within 60 seconds of intravenous administration and can continue to last for up to six minutes.
Non-depolarizing agents act on both the pre- and post-synaptic receptor sites.
The agent binds to the post-synaptic receptors on the muscle fiber,
thereby blocking the acetylcholine from binding to the same receptor sites.
The more receptors the blocking agent occupies the less opportunity the acetylcholine has to bind to
those same receptor sites, therefore decreasing the amount of sodium that
can enter the sodium gates, minimizing the ability for a muscle contraction to occur.
The non-depolarizing agent also binds to the presynaptic receptors on the motor neuron
thereby also blocking the positive feedback loop where choline from the neuromuscular junction is
recycled back into the end bulb of the neuron, thus reducing the overall acetylcholine reserve
pool as the overall acetylcholine reserve pool is reduced. Subsequent action potentials result in
lower and lower intensity muscle contractions. Non-depolarizing blocking agents are not
significantly metabolized by pseudocholinesterase therefore resulting in a longer lasting block.
Non-depolarizing agents also have a rapid onset of effect but however,
have a longer lasting mechanism of action and is therefore the preferred blocking agent for
longer duration indications such as endotracheal intubation, improving the surgical environment
and for mechanical ventilation. An example of non-depolarizing blocking agent is rocuronium.
Rocuronium is a longer-acting agent where the mechanism of action is already apparent within a
minute or two of intravenous administration and can continue to last between 30 to 90 minutes.
Due to its longer-lasting mechanism of action non-depolarizing blocking agents are more likely
to have NMT monitoring performed in order to determine when it is safe to extubate a patient
compared to shorter lasting depolarizing blocking agents. This covers the primary function of
neuromuscular blocking agents and how they serve to create a block in the neuromuscular junction.
Thank you for watching part 2 in our 3 part introductory series on the neuromuscular junction.
Please continue on to part 3 where we explore reversal agents and how
they are used to reverse a block in the neuromuscular junction.