this drug about 3 times in the last year.
The non-depolarizing muscle relaxants are all
relatives of the early arrow poison curare,
from the Amazon area, where the Amazon
natives used curare to shoot monkeys.
And the monkeys were then taken, and they were
part of the food supply. And curare works
by causing generalized paralysis in the monkeys.
And because they couldn't breathe, they couldn't survive.
Subsequent to curare, a number of drugs
have been developed. And the slide
here, kind of shows the order in which they came
on the scene. So Curare, Gallamine,
Pancuronium, Vecuronium, Atracurium,
Cisatracurium, Mivacurium, Rocuronium
are the kind of sequence
with which these drugs were marketed.
They all compete with Acetylcholine,
so the concentration of the drug
relative to the concentration of Acetylcholine,
determines the degree of paralysis of voluntary
muscles. Each of these drugs has
its own characteristics, so that they
vary on speed of onset, duration of action,
and effects upon the cardiovascular system,
and whether or not they release histamine.
When first injected, they cause complete paralysis
because the competitive balance with Acetylcholine
favors the muscle relaxant. We inject
a lot of muscle relaxant. As the surgery progresses,
the muscle relaxants are washed away, become
diluted in normal body fluids,
and are excreted primarily
unchanged in the urine, and Acetylcholine
takes over. Therefore, it is often
necessary to repeatedly inject muscle relaxants,
non-depolarizing muscle relaxants, to maintain surgical paralysis.
And believe me, the surgeons tell us when they think more paralysis
is necessary. The balance between Acetylcholine
and muscle relaxant can be changed
by giving an Acetylcholinesterase
inhibitor. These agents prevent the metabolism
of Acetylcholine by locally
produced Acetylcholinesterase, thus shifting
the competitive balance towards recovery
of muscle activity. So normally,
Acetylcholine is released at
the nerve ending, passes across the neuromuscular
junction to the neuro, to the muscle end-plate,
causes depolarization, and then is rapidly
broken down by Acetylcholinesterase.
What we do as anesthesiologists,
is we block the effect of Acetylcholinesterase,
thus blocking metabolism
of Acetylcholine, increasing
the concentration of Acetylcholine, and overcoming
the effect of the non-depolarizing muscle relaxant.
This is Rocuronium, which is the newest
of the non-depolarizing muscle relaxants.
It has a rapid onset of action,
about 75 seconds in higher doses,
which isn't quite as fast as big doses
of Succinylcholine, which usually work
in anywhere from 45 seconds to 60 seconds.
Rocuronium has a short duration
of action, around 20 minutes in regular doses,
but as high as an hour when we give
large doses. It produces no histamine release.
It produces no fasciculations
or myalgia. It has no effect
on the cardiovascular system.
But it does have side effects. Now, the most
important of these is residual paralysis. So this
is the patient who wakes up at the end of his
or her surgery, and continues to have weak muscles.
The other problem with Rocuronium is that,
it requires normal or near normal renal
function for it to be excreted.
And in patients with abnormal renal function,
it tends to accumulate and then it's very
difficult to reverse. The relaxation
we get with Rocuronium is not quite as profound
as with Succinylcholine. So that, if you're
in a hurry or if you need really profound
relaxation, most anesthesiologists favour
Succinylcholine. It does not however,
trigger malignant hyperthermia.
So the reversal agents that
we most commonly use are