Neuromuscular Blockers – Skeletal Muscle Relaxants

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.