So the reversal agents that
we most commonly use are
Neostigmine, Edrophonium, and Pyridostigmine.
And all of these drugs are Acetylcholinesterase
inhibitors. They prevent the breakdown
of Acetylcholine in the neuromuscular space.
We'll talk about Suggamadex in a moment,
which is a newer drug,
which forms a new compound with Rocuronium,
thus taking Rocuronium out of the system,
and rapidly reversing its effect.
Acetylcholinesterase inhibitors act upon nicotinic
receptors (skeletal muscle)
and muscarinic receptors, which produce
all the effects from the vagus nerves. So,
gut activity, salivation, bronchomotor smooth
muscle tone, all those sorts of effects that the vagus produces.
And unfortunately, Acetylcholinesterase inhibitors
aren't smart enough to only reverse nicotinic receptors,
they also reverse muscarinic receptors.
So that we always add an anti-muscarinic
drug along with the reversal
agent to prevent some of those side effects. So, those drugs
are usually Atropine, which is very rapidly acting,
and Glycopyrrolate, which is actually a better match
with Neostigmine. And these help
avoid excessive airway and salivary secretions,
severe bradycardia which can be caused
by excessive vagal stimulation, and induction
of an asthma attack. So we're going
to talk a little bit about Suggamadex now.
It's a new agent that works by combining irreversibly
with Rocuronium. It has a very rapid
onset, and it can be given at any
time Rocuronium has been given.
So there's no delay in its responsiveness.
Whereas with the Acetylcholinesterase inhibitors,
you usually have to wait with Rocuronium
about 20 minutes before they have any effect. With Suggamadex,
you can give it right after you give the Rocuronium,
and it'll rapidly reverse the effect of the Rocuronium.
It's not available in North America,
but it's available in Europe, and in Japan, and in parts
of South America. Unfortunately, its cost may limit
its use by anesthesiologists.
And this is the chemical structure of
Suggamadex, and think
of it more as a doughnut,
with an outer ring that is polarized,
and a central hole in the doughnut,
which is very lipophilic, so it sucks
lipids in. And this is kind of what
it looks like. On the far right
is an imaginary representation
of Rocuronium. The middle slide is the Suggamadex.
See the hole in the middle is the lipophilic portion.
And the slide to the far right is the combination
of Suggamadex and Rocuronium,
where the lipophilic entity
of Rocuronium, which is a steroid
nucleus, is sucked into
the Suggamadex core, and
the outer rim of the Suggamadex has been modified,
so that it is polar, and has arms
that are opposite and equal to the polar arms
on the Rocuronium. So the total effect
is just to lock this Rocuronium
into an irreversible combination.
So it's an irreversible combination as I mentioned.
Very rapid onset, around a minute,
whereas Neostigmine as I mentioned, the peak effect
of Neostigmine even in somebody who can be reversed,
is around 8 minutes, and it lasts as long,
it takes as long as 18 minutes to actually reverse
the effect of Rocuronium. Suggamadex has
no effect on muscarinic receptors,
it appears to have a very clean side effect
profile. It'll reverse even very large
doses of Rocuronium in about 75 seconds
or less. But it's not available everywhere
in the world and it's expensive. So let's just review
this presentation. We talked
about vapours. We talked about induction drugs.
We talked about gases and nitrous oxide.
We talked about muscle relaxants and reversal agents.
And we ultimately talked about Suggamadex
and its effect on relaxation of Rocuronium,
but only Rocuronium.
As you can see from this presentation,
there are many drugs in anesthesiology
and they are complex. And they often interact
in ways that are unexpected
and can cause, you know, side effects that
are unpleasant and have to be dealt with
and anticipated. So, one of the duties
of an anesthesiologist
is to use these drugs in a safe fashion,
with full knowledge of how they work, in those cases
where we really know how they work, and what
to expect in terms of side effects, and to do the best in his
or her ability to reduce those side effects.