CisatracuriumHave you ever been stuck doing a lame group project where everyone else in the group was slacking or goofing off while you were the only one doing most of the work? Did you think the project would turn out much better if you were allowed to work individually on it instead?
Meet cisatracurium, who was exactly the same way. |
Background
Cisatracurium is simply one of atracurium's 10 isomers, the 1R-cis, 1'R-cis isomer, that has been made into its own separate drug. In atracurium, this isomer only makes up about 15% of the total mixture, and the other 9 isomers are present too. In cisatracurium, on the other hand, the 1R-cis, 1'R-cis isomer is the only isomer. It was officially approved by the FDA on December 15th, 1995. It's the youngest NMB that they currently use. It's also called Nimbex, which stands for "excellent neuromuscular blocker," or if you would prefer the letters to be in the correct order, you could say "neuromuscular blocker of excellence."
The idea for cisatracurium was based on the desire to minimize the side effects caused by atracurium (namely histamine release). Since atracurium was technically 10 different molecules, there was the possibility that perhaps some of the 10 atracurium isomers would be more potent or cause less histamine release than others. So researchers began to study the individual atracurium isomers to see if they could find any that caused less side effects. It was found that one isomer, which we now know as cisatracurium, was more potent by itself than the overall atracurium mixture was, and it also did not cause histamine release like some of the other isomers. Therefore, it was made into its own separate drug.
To finish my analogy, atracurium with its mixture of 10 isomers is like being in a group project with yourself and 9 other people who may not be as hard-working as you are, goofing off, doing stuff they shouldn't be doing, and making the whole group less effective. Cisatracurium on the other hand is like you doing a group project except all your group members are clones of yourself so they're all more focused and efficient.
Pharmacology
Cisatracurium is classified as an intermediate onset and intermediate duration non-depolarizing neuromuscular blocking agent, although it still lasts a little bit longer than most intermediate duration NMBs. The ED95 for cisatracurium is 0.05 mg/kg, and a good intubating dose is 4x that, 0.2 mg/kg. Intubation conditions should be good to excellent within 90 seconds. Otherwise, a normal dose takes about 3 minutes to fully kick in and lasts about 45 minutes before it can be reversed.
It also has pretty much no side effects - it does not release histamine, and has no or very little effect on heart rate and blood pressure. It also undergoes Hofmann elimination, meaning it doesn't rely on the liver or kidneys to be broken down, making cisatracurium a truly excellent neuromuscular blocker indeed.
Cisatracurium vs. Atracurium
Cisatracurium is advantageous over atracurium because the cisatracurium isomer by itself does not cause histamine release. Also, because it is about four times as potent as atracurium with an ED95 of 0.05 mg/kg, it only takes 1/4 the amount of cisatracurium to produce the same effect as atracurium. One of other the problems with atracurium is that when it is broken down via Hofmann elimination, one of the products is laudanosine, which reduces the threshold for seizures (basically increases the likelihood of having one). Cisatracurium by itself also breaks down into laudanosine, but with cisatracurium, since you only have to give 1/4 as much to have the same effect as normal atracurium, then you only get 1/4 as much laudanosine.
The main disadvantage cisatracurium has over atracurium is that because it is more potent, it has a slower onset time. It also lasts a bit longer than regular atracurium. But that's seriously it. Plain and simple, cisatracurium is better.
Cisatracurium is simply one of atracurium's 10 isomers, the 1R-cis, 1'R-cis isomer, that has been made into its own separate drug. In atracurium, this isomer only makes up about 15% of the total mixture, and the other 9 isomers are present too. In cisatracurium, on the other hand, the 1R-cis, 1'R-cis isomer is the only isomer. It was officially approved by the FDA on December 15th, 1995. It's the youngest NMB that they currently use. It's also called Nimbex, which stands for "excellent neuromuscular blocker," or if you would prefer the letters to be in the correct order, you could say "neuromuscular blocker of excellence."
The idea for cisatracurium was based on the desire to minimize the side effects caused by atracurium (namely histamine release). Since atracurium was technically 10 different molecules, there was the possibility that perhaps some of the 10 atracurium isomers would be more potent or cause less histamine release than others. So researchers began to study the individual atracurium isomers to see if they could find any that caused less side effects. It was found that one isomer, which we now know as cisatracurium, was more potent by itself than the overall atracurium mixture was, and it also did not cause histamine release like some of the other isomers. Therefore, it was made into its own separate drug.
To finish my analogy, atracurium with its mixture of 10 isomers is like being in a group project with yourself and 9 other people who may not be as hard-working as you are, goofing off, doing stuff they shouldn't be doing, and making the whole group less effective. Cisatracurium on the other hand is like you doing a group project except all your group members are clones of yourself so they're all more focused and efficient.
Pharmacology
Cisatracurium is classified as an intermediate onset and intermediate duration non-depolarizing neuromuscular blocking agent, although it still lasts a little bit longer than most intermediate duration NMBs. The ED95 for cisatracurium is 0.05 mg/kg, and a good intubating dose is 4x that, 0.2 mg/kg. Intubation conditions should be good to excellent within 90 seconds. Otherwise, a normal dose takes about 3 minutes to fully kick in and lasts about 45 minutes before it can be reversed.
It also has pretty much no side effects - it does not release histamine, and has no or very little effect on heart rate and blood pressure. It also undergoes Hofmann elimination, meaning it doesn't rely on the liver or kidneys to be broken down, making cisatracurium a truly excellent neuromuscular blocker indeed.
Cisatracurium vs. Atracurium
Cisatracurium is advantageous over atracurium because the cisatracurium isomer by itself does not cause histamine release. Also, because it is about four times as potent as atracurium with an ED95 of 0.05 mg/kg, it only takes 1/4 the amount of cisatracurium to produce the same effect as atracurium. One of other the problems with atracurium is that when it is broken down via Hofmann elimination, one of the products is laudanosine, which reduces the threshold for seizures (basically increases the likelihood of having one). Cisatracurium by itself also breaks down into laudanosine, but with cisatracurium, since you only have to give 1/4 as much to have the same effect as normal atracurium, then you only get 1/4 as much laudanosine.
The main disadvantage cisatracurium has over atracurium is that because it is more potent, it has a slower onset time. It also lasts a bit longer than regular atracurium. But that's seriously it. Plain and simple, cisatracurium is better.