Sun17October0644AM 3

A new neuromuscular blocking agent has been developed for intravenous use. It has a hepatic extraction ratio of 0.25 and has a structure containing three quaternary nitrogen atoms. In healthy volunteers it is found to have a half life of fifteen minutes.

Which of the following mechanisms of elimination is the single most likely explanation of this pharmacological behaviour?

(Please select 1 option)

It is eliminated through the lungs

It is an ester metabolised in the plasma and tissues

It is filtered and not reabsorbed by the renal tubules This is the correct answer

It is metabolised primarily in the liver Incorrect answer selected

It is rapidly redistributed

Explanation

By a process of exclusion the neuromuscular blocking agent is likely to be filtered and not reabsorbed by the renal tubules.

Neuromuscular blocking agents with one or more quaternary nitrogen atoms tend to be highly polar and ionised. The molecules therefore have low lipid solubility, reduced diffusion capacity across membranes and low volume of distribution.

A compound with three quaternary nitrogen atoms is not likely to be an ester. Its high polarity would prevent rapid transfer of the molecules into the tissues.

With drugs with a low hepatic extraction ratio (<0.3) the venous drug concentration is virtually identical to the arterial concentration. The drug is not primarily metabolised in the liver.

Therefore:

Clearance is insensitive to changes of liver blood flow

Clearance is very sensitive to alterations in protein binding, intrinsic metabolism and excretion

There is no first pass metabolism when given orally.

There is no reason why any neuromuscular blocking agent should be eliminated by the lungs.

Answer Statistics

1

4%

2

50%

3

9%

4

19%

5

20%

Times answered: 235