Aminosteroid Neuromuscular Blocking Agents Flashcards
Regarding the structure and function of the aminosteroid NMBAs (true or false):
Vecuronium is the bisquaternary analogue of pancuronium
False. It is the monoquaternary analogue.
Regarding the structure and function of the aminosteroid NMBAs (true or false):
Aminosteroid NMBAs compete with acetylcholine for binding to the alpha-subunit of the nicotinic receptor
True. The quaternary ammonium group binds to the alpha-subunit. These agents are competitive antagonists of acetylcholine.
Regarding the structure and function of the aminosteroid NMBAs (true or false):
Three minutes after the administration of rocuronium to a woman in the third trimester of pregnancy, the concentration of rocuronium in the umbilical vein is similar to that in the maternal plasma
False. The quaternary ammonium group is positively charged and therefore these agents are not lipid soluble and cross the placenta to a very limited extent.
Regarding the structure and function of the aminosteroid NMBAs (true or false):
Aminosteroid NMBAs are lipid soluble compounds that easily cross the blood-brain barrier
False. The quaternary ammonium group is positively charged and therefore these agents are not lipid soluble and do not cross the blood-brain barrier.
Regarding the structure and function of the aminosteroid NMBAs (true or false):
Monoquaternary aminosteroid NMBAs undergo greater biliary secretion than bisquaternary compounds
True. Monoquaternary ammoniums, having only one fixed positive charge, are slightly more lipid soluble than bisquaternary compounds and undergo greater biliary excretion.
With which groups of patients does caution on dose need to be exercised when administering aminosteroid NMBAs?
Because aminosteroid NMBAs depend upon renal and hepatic function for their elimination, they are more susceptible to pharmacokinetic drug interactions (eg CYP 450 inducers such as carbamazepine and inhibitors such as cimetidine) than the benzylisoquinolinium NMBAs.
Both renal and hepatic function decline with age. Reduced clearance of the aminosteroid NMBAs is evident in the elderly; a prolonged duration of action should be anticipated.
Enzyme function is temperature dependent; clearance of the aminosteroid NMBAs is reduced in hypothermic patients.
Liver cirrhosis and renal failure will also reduced clearance and hence prolong action.
What are the volumes of distribution of pancuronium, vecuronium and rocuronium?
Pancuronium - 260 ml/kg
Vecuronium - 270 ml/kg
Rocuronium - 220 ml/kg
What proportion of pancuronium, vecuronium and rocuronium are bound to plasma proteins?
Pancuronium - 20-60%
Vecuronium - <20%
Rocuronium - <20%
What are the clearance rates of pancuronium, vecuronium and rocuronium?
Pancuronium - 1.8 ml/min/kg
Vecuronium - 5.2 ml/min/kg
Rocuronium - 5.2 ml/min/kg
What are the elimination of half-lives of pancuronium, vecuronium and rocuronium?
Pancuronium - 140 mins
Vecuronium - 71 mins
Rocuronium - 69 mins
Regarding agents and their metabolite or route of elimination (true or false):
30% of pancuronium is excreted in the urine
False. 60% of pancuronium is excreted in the urine. It has two quaternary ammonium groups and is not lipid-soluble.
Regarding agents and their metabolite or route of elimination (true or false):
20% of vecuronium undergoes deacetylation in the liver
True. Although vecuronium undergoes predominantly biliary secretion, only 20% is deacetylated in the liver.
Regarding agents and their metabolite or route of elimination (true or false):
17-desacetyl metabolite of rocuronium has very little neuromuscular blocking activity
True. It is 20 times less potent than the parent compound.
Regarding agents and their metabolite or route of elimination (true or false):
3–hydroxypancuronium has half the potency of the parent compound
True. This may contribute to prolonged neuromuscular block or postoperative residual curarization in patients with renal impairment.
Regarding agents and their metabolite or route of elimination (true or false):
Up to 33% of rocuronium is excreted in the urine
True. It undergoes predominantly biliary excretion.
What are the ED95s of pancuronium, vecuronium and rocuronium?
The dose required for 95% depression of twitch response is the ED95, where ED stands for effective dose. Quoted ED95 values are the mean ED95 values from a representative sample of the population. Following the administration of ED95 of a NMBA, the twitch height would be expected to be 5% of the control response.
Pancuronium - 0.06 mg/kg
Vecuronium - 0.05 mg/kg
Rocuronium - 0.3 mg/kg
The recommended intubating dose is 2 x ED95.
What are the onset times for pancuronium, vecuronium and rocuronium?
Pancuronium - 220 secs
Vecuronium - 180 secs
Rocuronium - 75 secs
What is the ED95?
A. The dose that blocks neuromuscular transmission in 95% of the population
B. The dose that blocks 95% of the nicotinic receptors at the NMJ
C. The dose that suppresses the twitch response by 95%
D. The same for all aminosteroid NMBAs
E. The dose that provides the best conditions for intubation
C. ED95 is the dose required for 95% depression of twitch response, where ED stands for effective dose.
Which is the agent with the greatest potency?
A. Pancuronium
B. Vecuronium
C. Rocuronium
D. Pipecuronium
E. Rapacuronium
D.Pipecuronium is the most potent aminosteroid NMBA with an ED95 of 0.045 mg/kg.
Which is the agent with the most potent active metabolite?
A. Vecuronium
B. Rocuronium
C. Pancuronium
A. A small fraction of vecuronium is metabolised to 3-hydroxyvecuronium which is active at the NMJ and nearly as potent as the parent drug, i.e. ~80% as potent.
A small fraction of rocuronium is metabolised to 17-desacetylrocuronium, which is 20 times less potent than the parent compound and has very little neuromuscular blocking activity.
Five to ten percent of the injected dose of pancuronium is metabolised to 3-hydroxypancuronium which has half the neuromuscular blocking potency of the parent compound.
Which of the following is a bisquaternary ammonium compound?
A. Vecuronium
B. Rocuronium
C. Pancuronium
Pancuronium is bisquaternery
Regarding pancuronium (true or false):
Is a bisquaternary amine
True. The two nitrogen atoms each have four substituent groups (and is permanently charged).
Regarding pancuronium (true or false):
Is lipid-soluble
False. The quaternary ammonium groups are ionized and therefore the compound is not lipid-soluble.
Regarding pancuronium (true or false):
Undergoes predominantly biliary excretion
False. It is mainly excreted unchanged in the urine.
Regarding pancuronium (true or false):
The 17-hydroxy metabolite is half as potent as the parent compound
False. 3-hydroxypancuronium has half the neuromuscular blocking potency of the parent compound.
Regarding non-depolarising NMBAs (true or false):
When 50% of the nicotinic acetylcholine receptors in the neuromuscular junction are occupied by an aminosteroid NMBA, there is no demonstrable reduction in twitch height
True. Neuromuscular block only becomes evident when 70–80% of the receptors are blocked.
Regarding non-depolarising NMBAs (true or false):
There is an inverse relationship between the potency of a non-depolarising NMBA and its onset time
True. For an agent of lower potency a greater mass of drug is administered generating a greater concentration gradient from the plasma to the NMJ and a more rapid onset.
Regarding non-depolarising NMBAs (true or false):
Vecuronium is the most potent aminosteroid NMBA
False. Pipecuronium is the most potent aminosteroid NMBA.
Regarding non-depolarising NMBAs (true or false):
ED50 is a measure of potency
True. The dose required for 50% depression of twitch response is an indicator of potency.
Regarding non-depolarising NMBAs (true or false):
The potency of a monoquaternary non-depolarising NMBA may be increased in acidotic conditions
True. The tertiary amine becomes protonated and therefore positively charged, this increases the potency.
