Sat27November0445PM 49

A benzodiazepine is chosen for clinical use because it has a half-life of 2-4 hours.

Which of the following properties is unique to this benzodiazepine?

(Please select 1 option)

It is the drug of choice for status epilepticus Incorrect answer selected

It is a ligand gated ion channel agonist for the chloride ion

It can be reversed using an inverse agonist

It has receptors at high density in the limbic system

It is water soluble at a pH of 3.5 and lipid soluble at a pH of 7.4 This is the correct answer

Explanation

The benzodiazepine in question is midazolam. It is the only benzodiazepine that exhibits tautomeric change (dynamic isomerism). At a pH of 3.5 the molecule is ionised and water soluble, however when injected into the body at a pH of 7.4 it becomes unionised and lipid soluble, easily capable of crossing the blood brain barrier.

Midazolam has a short half life of 2-4 hours.

As a benzodiazepine it is an agonist for the GABAA receptors. The GABAA receptors are widely distributed in the central nervous system and are found in high density in the cerebral cortex, hippocampus, thalamus, basal ganglia and limbic system. GABAA receptors are ligand gated ion channels, the endogenous agonist being the inhibitory neurotransmitter gamma-aminobutyric acid. It is a pentameric protein (2a, 2ß and one subunit) that spans the cell membrane and the interaction of agonist with the alpha subunit results in a conformational change resulting in the influx of chloride ions culminating in neuronal hyperpolarisation.

Whilst having an anticonvulsant action, midazolam is not the agent of choice for status epilepticus. The benzodiazepine of choice for status epilepticus is lorazepam.

All benzodiazepines can be reversed with the inverse agonist flumazenil.

Answer Statistics

1

36%

2

8%

3

10%

4

2%

5

46%

Times answered: 238