Aminosteroid Neuromuscular Blocking Agents

Question 1

Regarding the structure and function of the aminosteroid NMBAs (true or false):

Vecuronium is the bisquaternary analogue of pancuronium

Answer 1

False. It is the monoquaternary analogue.

Question 2

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

Answer 2

True. The quaternary ammonium group binds to the alpha-subunit. These agents are competitive antagonists of acetylcholine.

Question 3

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

Answer 3

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.

Question 4

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

Answer 4

False. The quaternary ammonium group is positively charged and therefore these agents are not lipid soluble and do not cross the blood-brain barrier.

Question 5

Regarding the structure and function of the aminosteroid NMBAs (true or false):

Monoquaternary aminosteroid NMBAs undergo greater biliary secretion than bisquaternary compounds

Answer 5

True. Monoquaternary ammoniums, having only one fixed positive charge, are slightly more lipid soluble than bisquaternary compounds and undergo greater biliary excretion.

Question 6

With which groups of patients does caution on dose need to be exercised when administering aminosteroid NMBAs?

Answer 6

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.

Question 7

What are the volumes of distribution of pancuronium, vecuronium and rocuronium?

Answer 7

Pancuronium - 260 ml/kg
Vecuronium - 270 ml/kg
Rocuronium - 220 ml/kg

Question 7

What proportion of pancuronium, vecuronium and rocuronium are bound to plasma proteins?

Answer 7

Pancuronium - 20-60%
Vecuronium - <20%
Rocuronium - <20%

Question 8

What are the clearance rates of pancuronium, vecuronium and rocuronium?

Answer 8

Pancuronium - 1.8 ml/min/kg
Vecuronium - 5.2 ml/min/kg
Rocuronium - 5.2 ml/min/kg

Question 9

What are the elimination of half-lives of pancuronium, vecuronium and rocuronium?

Answer 9

Pancuronium - 140 mins
Vecuronium - 71 mins
Rocuronium - 69 mins

Question 10

Regarding agents and their metabolite or route of elimination (true or false):

30% of pancuronium is excreted in the urine

Answer 10

False. 60% of pancuronium is excreted in the urine. It has two quaternary ammonium groups and is not lipid-soluble.

Question 11

Regarding agents and their metabolite or route of elimination (true or false):

20% of vecuronium undergoes deacetylation in the liver

Answer 11

True. Although vecuronium undergoes predominantly biliary secretion, only 20% is deacetylated in the liver.

Question 12

Regarding agents and their metabolite or route of elimination (true or false):

17-desacetyl metabolite of rocuronium has very little neuromuscular blocking activity

Answer 12

True. It is 20 times less potent than the parent compound.

Question 13

Regarding agents and their metabolite or route of elimination (true or false):

3–hydroxypancuronium has half the potency of the parent compound

Answer 13

True. This may contribute to prolonged neuromuscular block or postoperative residual curarization in patients with renal impairment.

Question 14

Regarding agents and their metabolite or route of elimination (true or false):

Up to 33% of rocuronium is excreted in the urine

Answer 14

True. It undergoes predominantly biliary excretion.

Question 15

What are the ED95s of pancuronium, vecuronium and rocuronium?

Answer 15

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.

Question 16

What are the onset times for pancuronium, vecuronium and rocuronium?

Answer 16

Pancuronium - 220 secs
Vecuronium - 180 secs
Rocuronium - 75 secs

Question 17

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

Answer 17

C. ED95 is the dose required for 95% depression of twitch response, where ED stands for effective dose.

Question 18

Which is the agent with the greatest potency?

A. Pancuronium
B. Vecuronium
C. Rocuronium
D. Pipecuronium
E. Rapacuronium

Answer 18

D.Pipecuronium is the most potent aminosteroid NMBA with an ED95 of 0.045 mg/kg.

Question 19

Which is the agent with the most potent active metabolite?
A. Vecuronium
B. Rocuronium
C. Pancuronium

Answer 19

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.

Question 20

Which of the following is a bisquaternary ammonium compound?

A. Vecuronium
B. Rocuronium
C. Pancuronium

Answer 20

Pancuronium is bisquaternery

Question 21

Regarding pancuronium (true or false):

Is a bisquaternary amine

Answer 21

True. The two nitrogen atoms each have four substituent groups (and is permanently charged).

Question 22

Regarding pancuronium (true or false):

Is lipid-soluble

Answer 22

False. The quaternary ammonium groups are ionized and therefore the compound is not lipid-soluble.

Question 23

Regarding pancuronium (true or false):

Undergoes predominantly biliary excretion

Answer 23

False. It is mainly excreted unchanged in the urine.

Question 24

Regarding pancuronium (true or false):

The 17-hydroxy metabolite is half as potent as the parent compound

Answer 24

False. 3-hydroxypancuronium has half the neuromuscular blocking potency of the parent compound.

Question 25

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

Answer 25

True. Neuromuscular block only becomes evident when 70–80% of the receptors are blocked.

Question 26

Regarding non-depolarising NMBAs (true or false):

There is an inverse relationship between the potency of a non-depolarising NMBA and its onset time

Answer 26

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.

Question 27

Regarding non-depolarising NMBAs (true or false):

Vecuronium is the most potent aminosteroid NMBA

Answer 27

False. Pipecuronium is the most potent aminosteroid NMBA.

Question 28

Regarding non-depolarising NMBAs (true or false):

ED50 is a measure of potency

Answer 28

True. The dose required for 50% depression of twitch response is an indicator of potency.

Question 29

Regarding non-depolarising NMBAs (true or false):

The potency of a monoquaternary non-depolarising NMBA may be increased in acidotic conditions

Answer 29

True. The tertiary amine becomes protonated and therefore positively charged, this increases the potency.