00:01
The depolarizing agent that we use in human
is succinylcholine. Now what is succinylcholine?
Succinylcholine is two acetylcholine molecules
linked together end-to-end.
00:14
Now, the duration of action of succinylcholine
is fairly short, only 100 seconds or so.
00:20
It does have side effect though. It can cause post op
muscle pain. It can cause hyperkalemia because you're
spilling potassium into interstitial tissues. And it can
cause gastroesophageal reflux disease and aspiration
because the muscles in the smooth muscles
in stomach will contract.
00:41
Important drug interactions. Succinylcholine can interact
with inhaled anesthetics to cause malignant hyperthermia.
00:49
Remember, I discussed this in a previous lecture,
the antidote to malignant hyperthermia is dantrolene.
00:56
And I've said this before, malignant hyperthermia,
dantrolene, under one minute.
01:02
Isoflurane and other inhaled anesthetics can also
potentiate neuromuscular blockade.
01:08
So this is something that we have to keep in mind,
when we're administrating anesthetic drugs.
01:13
Now, aminoglycoside antibiotics will
also interact with succinylcholine.
01:19
Gentamycin, tobramycin, these may potentiate
skeletal muscles relaxants.
01:26
Remember that succinylcholine is not reversed with the
cholinesterase inhibitors like pyridostigmine.
01:34
Now, let's think about that, why?
Well, pyridostigmine is a cholinesterase inhibitor.
01:41
What it does is it leaves more acetylcholine in
the synaptic cleft. When you have succinylcholine,
that acetylcholine is going through the channel,
and the muscle is already depolarized.
01:53
Adding more acetylcholine is not going to solve the problem.
01:59
You have to be cautious with these agents. We want to be
careful with succinylcholine in our older patients.
02:06
We want to be careful with patients who have had previous
myastenia gravis because their acetylcholine receptors
are a bit damaged. And you have to be careful of people
who have genetic variants that metabolize succinylcholine
very slowly. They will have a prolonged response.
02:22
The other caution that I'm going to put out there
is hyperkalemia.
02:26
Remember that when you have succinylcholine administered
to a patient, you're going to depolarize the muscle
and you may release potassium. It's particularly bad in
burn victims because they have been burned,
they have lots of cellular damage, and all of those cells
have released potassium into the blood.
02:45
In upper motor neuron disease, remember that these are
muscles that are not normally contracting,
or spinal cord injury, it's the same thing, so when you
contract those muscles or you depolarize those muscles,
you will release a lot of potassium. And finally, patients
who have intra-abdominal infection also are hyperkalemic
in response to succinylcholine.
We believe that this may be due to damage to cells as well,
but we're not entirely sure of the mechanism in this case.
03:13
Let's take a look now at the non-depolarizing agents.
Now, we have got a large list there,
let's just separate them out in terms of how long they act,
or how quickly they act.
03:25
Let's start with rocuronium. Rocuronium is used as a very
important neuromuscular blocker in anesthesia
and we sometimes use it in the intensive care unit as well
when we want to paralyze patients as we have them on ventilators.
03:40
It is eliminated through the bile.
The onset of action is about 10 seconds.
03:46
I personally have more experience with pancuronium.
This is something that is used in the ICU.
03:51
It has an onset of action of about 60 seconds,
and lasts for about 35 minutes.
03:58
And it is more used in the ICU than in the operating room.
Remember that pancuronium is the only agent here
that does not need a muscarinic
receptor antagonist for reversal.
04:13
Finally, there is tubocurarine. Tubocurarine has
an onset of about 2 minutes, and lasts about 60.
04:20
It is eliminated through the kidney.
It's a prototypical drug, but it is derived from curare
which is a naturally occuring paralytic
that was first found on Amazon tribes
who used to tip their arrows with this deadly agent.
04:37
Okay. With respect to these agents,
they can be reversed with cholinesterase inhibitors
that is different from succinylcholine.
There is a chemical antagonist of rocuronium.
04:50
There you have the neuromuscular blockers.