Benzylisoquinolinium Muscle Relaxants Flashcards
What are the ED95s of atracurium, cisatracurium and mivacurium?
Atracurium - 0.23 mg/kg
Cisatracurium - 0.05 mg/kg
Mivacurium - 0.08 mg/kg
Intubating dose is 2 x ED95 dose. This is true also for the aminosteroid NMBAs.
What are the onset times for atracurium, cisatracurium and mivacurium after administration of 2x ED95 dose (normal intubating dose)?
Atracurium - 110 seconds
Cisatracurium - 150 seconds
Mivacurium - 170 seconds
What are the clinical durations of action for atracurium, cisatracurium and mivacurium after administration of 2x ED95 dose (normal intubating dose)?
Atracurium - 43 mins
Cisatracurium - 45 mins
Mivacurium - 16 mins
What is particular about elimination of atracurium?
It undergoes spontaneous decomposition by a chemical reaction that is dependent only upon the pH and temperature.
This is Hofmann elimination and it is not dependent on liver or kidney function. The drug is stable at 4ºC and pH 3.4, i.e. the conditions of storage. In vitro at 37ºC and pH 7.4 it has a half-life of 50 minutes.
Consequently, atracurium can be used in patients with deranged organ function in the absolute certainty that neuromuscular blockade will wear off.
Atracurium is also partially eliminated by ester hydrolysis catalysed by non-specific esterases.
Regarding the onset time and duration of action of the benzylisoquinolinium NMBAs available in the UK (true or false):
At equipotent doses, atracurium has the fastest onset time
True. 110 seconds, vs 150 seconds (cisatracurium) and 170 (mivacurium).
Regarding the onset time and duration of action of the benzylisoquinolinium NMBAs available in the UK (true or false):
Following a dose of 2 x ED95, the onset time of all available benzylisoquinolinium NMBAs is less than 3 minutes
True
Regarding the onset time and duration of action of the benzylisoquinolinium NMBAs available in the UK (true or false):
After equipotent doses, the duration of action of atracurium and cisatracurium is similar
True, around 45 mins
Regarding the onset time and duration of action of the benzylisoquinolinium NMBAs available in the UK (true or false):
After equipotent doses, the duration of action of mivacurium is approximately one-third that of cisatracurium
True, around 16 mins
Regarding the onset time and duration of action of the benzylisoquinolinium NMBAs available in the UK (true or false):
Mivacurium has a rapid onset of action and can be used for rapid sequence induction
False. Onset of action is relatively slow. None of the benzylisoquinolinium drugs are suitable for rapid sequence induction.
Regarding the elimination of atracurium (true or false):
The Hofmann elimination is only dependent on pH and temperature
True.
Regarding the elimination of atracurium (true or false):
Atracurium is stored at 4°C and a pH of 7.4
False. The drug is stable at 4°C and pH 3.4 - the conditions of storage.
Regarding the elimination of atracurium (true or false):
At a pH of 7.4 and 37°C the in vitro half-life of atracurium is 50 minutes
True. In vitro at 37°C and pH 7.4 it has a half-life of 50 minutes.
Regarding the elimination of atracurium (true or false):
Atracurium should be avoided in patients with hepatic and renal dysfunction
False. The unique feature of atracurium that is different from any previous neuromuscular blocking drug is that it undergoes spontaneous decomposition by a chemical reaction that is dependent only upon the pH and temperature. Consequently, atracurium can be used in patients with deranged organ function in the absolute certainty that neuromuscular blockade will wear off.
Regarding the elimination of atracurium (true or false):
In addition to Hofmann elimination, atracurium also undergoes breakdown by plasma cholinesterase
False. It also undergoes ester hydrolysis.
What are the volumes of distribution of atracurium and cisatracurium?
Atracurium - 0.16 L/kg
Cisatracurium - 0.14 L/kg
What are the elimination half-lives of atracurium and cisatracurium?
Atracurium - 20 mins
Cisatracurium - 25 mins
What are the clearance rates of atracurium and cisatracurium?
Atracurium - 5.5 ml/kg/min
Cisatracurium - 5.2 ml/kg/min
Would you reverse mivacurium?
Pharmacological antagonism with neostigmine is recommended, but when spontaneous recovery is underway it progresses rapidly, and pharmacological reversal of mivacurium gains relatively little.
Neostigmine tends to inhibit the activity of plasma cholinesterase which, like succinylcholine, are the main route of metabolism of mivacurium.
How is atracurium metabolised?
45% of atracurium undergoes Hofmann elimination to laudanosine and a mono-quaternary acrylate.
The remainder of the drug is metabolised by non-specific ester hydrolysis to a mono-quaternary alcohol and a mono-quaternary acid.
Up to 10% of atracurium is excreted unchanged in the urine.
Is the elimination of atracurium affected by changes in pH?
Variation of pH in the clinical range does not significantly affect atracurium elimination.
How is cisatracurium metabolised?
77% of cisatracurium undergoes Hofmann elimination to laudanosine and a mono-quaternary acrylate.
The mono-quaternary acrylate is hydrolysed to a mono-quaternary alcohol that undergoes further Hofmann elimination to laudanosine.
Cisatracurium undergoes minimal ester hydrolysis and up to 15% of the drug is excreted unchanged via the kidneys.
Which drug produces more laudanosine: atracurium or cisatracurium?
Atracurium produces more laudanosine. Because cisatracurium is more potent than atracurium, fewer molecules are given and less laudanosine is produced. Laudanosine levels after a bolus dose of cisatracurium are about 10% of those after an equipotent dose of atracurium.
Regarding histamine release and benzylisoquinoliniums (true or false):
Histamine release is more likely with benzylisoquinolinium NMBAs than with aminosteroid NMBAs
True
Regarding histamine release and benzylisoquinoliniums (true or false):
Histamine release is likely when the benzylisoquinolinium NMBA is injected slowly
False. These changes are related to the dose and the rate of injection. Slow injection minimises histamine release.
Regarding histamine release and benzylisoquinoliniums (true or false):
Histamine release is less of a problem with cisatracurium than with atracurium
True. The histamine-releasing tendency of cisatracurium is less than that of atracurium.
Regarding histamine release and benzylisoquinoliniums (true or false):
Mivacurium administration does not result in hypotension, but may cause facial erythema and bronchospasm
False. Hypotension, erythema and bronchospasm may all occur.
Regarding histamine release and benzylisoquinoliniums (true or false):
A patient who has had an anaphylactic reaction to atracurium may safely be given cisatracurium
False. Either drug can cause anaphylaxis, and there is cross-reactivity between atracurium and cisatracurium. A patient who has had an anaphylactic reaction to atracurium should not be given cisatracurium.
Which of these statements regarding the benzylisoquinoliniums NMBAs is true?
A. Atracurium may be useful for rapid sequence induction
B. Mivacurium has a rapid onset of action
C. Cisatracurium is safe to use in patients with malignant hyperthermia
D. Fasciculations are seen after a bolus of atracurium
E. The benzylisoquinolinium NMBAs are dependent upon renal excretion for elimination
C. Cisatracurium is safe to use in patients with malignant hyperthermia
Onset of action is relatively slow. None of these drugs is suitable for rapid sequence induction. Giving two to three times the ED95 may shorten the onset time. No fasciculations are seen as they are all non-depolarising. The benzylisoquinolinium NMBAs are independent of renal excretion.
Regarding atracurium and isomerism (true or false):
Atracurium displays geometric isomerism, but not stereoisomerism
False. It displays both geometric and stereoisomerism.
Regarding atracurium and isomerism (true or false):
Atracurium has four chiral centres
True
Regarding atracurium and isomerism (true or false):
The commercial preparation includes 16 isomers
False. The commercial preparation includes 10 isomers.
Regarding atracurium and isomerism (true or false):
Cisatracurium is the C1-R-cis isomer of atracurium
True
Regarding atracurium and isomerism (true or false):
15% of an ampoule of atracurium is cisatracurium
True
Regarding the isomers of mivacurium (true or false):
Mivacurium consists of three isomers
True. Trans-trans, which comprises 58% of the mixture; cis-trans, which is 36% of the mixture; and cis-cis, which is 6% of mivacurium.
Regarding the isomers of mivacurium (true or false):
All three isomers of mivacurium are of equal potency
False. The minority isomer (cis-cis) is metabolised much more slowly and half-life is over 30 minutes, but it is also less potent than the other two isomers.
Regarding the isomers of mivacurium (true or false):
In the commercial preparation, each isomer of mivacurium makes up an equal proportion of the mass of drug
False. Trans-trans, which comprises 58% of the mixture; cis-trans, which is 36% of the mixture; and cis-cis, which is 6% of mivacurium.
Regarding the isomers of mivacurium (true or false):
In the commercial preparation, the most abundant of the isomers is the cis-cis isomer
False. Trans-trans, which comprises 58% of the mixture; cis-trans, which is 36% of the mixture; and cis-cis, which is 6% of mivacurium.
Regarding the isomers of mivacurium (true or false):
All three isomers are equally susceptible to breakdown by plasma cholinesterase
False.
Regarding the distribution of the benzylisoquinolinium NMBAs (true or false):
The benzylisoquinoliniums are highly water-soluble
True
Regarding the distribution of the benzylisoquinolinium NMBAs (true or false):
The volume of distribution of the benzylisoquinoliniums is similar to that of the extracellular fluid volume
True
Regarding the distribution of the benzylisoquinolinium NMBAs (true or false):
Accidental oral ingestion of the benzylisoquinolinium NMBAs would not be expected to have any effect on neuromuscular function
True
Regarding the distribution of the benzylisoquinolinium NMBAs (true or false):
The benzylisoquinolinium NMBAs are dependent on renal excretion for elimination
False. The unique property of atracurium, Hofmann elimination, means that the anaesthetist can rely on recovery even in patients with no renal function.
Regarding the distribution of the benzylisoquinolinium NMBAs (true or false):
The quaternary ammonium cations remain ionized irrespective of the pH of the solution
True
Regarding the elimination of mivacurium (true or false):
Mivacurium undergoes limited Hofmann elimination
False.
Regarding the elimination of mivacurium (true or false):
Mivacurium elimination is not altered in patients with succinylcholine apnoea
False. Mivacurium is eliminated by plasma cholinesterase. This is the key route of elimination and, like succinylcholine duration, is very prolonged in patients with plasma cholinesterase deficiency, either inherited or acquired. A patient with succinylcholine apnoea also has mivacurium apnoea.
Regarding the elimination of mivacurium (true or false):
Patients with Child’s Class C liver disease have reduced mivacurium elimination
True. Because plasma cholinesterase is synthesised in the liver, patients with liver disease have reduced levels.
Regarding the elimination of mivacurium (true or false):
All three isomers of mivacurium are equally susceptible to breakdown by plasma cholinesterase
False.
Regarding the elimination of mivacurium (true or false):
Elimination of the cis-cis isomer is reduced in renal failure
True.
Regarding the elimination of atracurium and cisatracurium (true or false):
77% of a dose of atracurium is eliminated by Hofmann elimination
False. 45% of atracurium undergoes Hofmann elimination to laudanosine and a mono-quaternary acrylate.
Regarding the elimination of atracurium and cisatracurium (true or false):
77% of a dose of cisatracurium is eliminated by Hofmann elimination
True.
Regarding the elimination of atracurium and cisatracurium (true or false):
10% of atracurium is eliminated unchanged in the urine.
True.
Regarding the elimination of atracurium and cisatracurium (true or false):
A greater proportion of atracurium is eliminated in the urine than cisatracurium
False.
Regarding the elimination of atracurium and cisatracurium (true or false):
A greater proportion of cisatracurium undergoes ester hydrolysis, by non-specific plasma esterases, than atracurium
False. 77% of a dose of cisatracurium is eliminated by Hofmann elimination as versus the 45% of atracurium. The remaining percentage is eliminated by ester hydrolysis.
Regarding laudanosine (true or false):
It is active at the neuromuscular junction, but has only 1/100 the potency of the parent drug
False. Laudanosine has no activity at the neuromuscular junction.
Regarding laudanosine (true or false):
It is epileptogenic in animals
True
Regarding laudanosine (true or false):
Levels are elevated in patients with renal failure
True
Regarding laudanosine (true or false):
It is a product of the ester hydrolysis of atracurium and cisatracurium
False. It is a product of the Hofmann elimination. 77% of cisatracurium undergoes Hofmann elimination to laudanosine and a mono-quaternary acrylate. The mono-quaternary acrylate is hydrolysed to a mono-quaternary alcohol that undergoes further Hofmann elimination to laudanosine.
Regarding laudanosine (true or false):
Plasma levels are greater following 2 x ED95 of cisatracurium than 2 x ED95 of atracurium
False. Because cisatracurium is more potent than atracurium, fewer molecules are given and less laudanosine is produced. Laudanosine levels after a bolus dose are about 10% of those after an equipotent dose of atracurium.
