306
P A R T 4
Drugs acting on the central and peripheral nervous systems
The benzodiazepines used as anxiolytics include alpra-
zolam (
Xanax
), bromazepam (
Lexotan
) (not available in
New Zealand), clobazam (
Frisium
), diazepam (
Valium
),
lorazepam (
Ativan
), oxazepam (
Serepax
), temazepam
(
Normison
,
Temaze
) and triazolam (
Halcion
). Box 20.2
provides an exercise in calculating the dose for a child
receiving a sedative/hypnotic.
Therapeutic actions and indications
The benzodiazepines are indicated for the treatment
of the following conditions: anxiety disorders, alcohol
withdrawal, hyperexcitability and agitation, and pre
operative relief of anxiety and tension to aid in balanced
anaesthesia. These drugs act in the limbic system and the
RAS to make gamma-aminobutyric acid (GABA) more
effective, causing interference with neuron firing (Figure
20.1). GABA stabilises the postsynaptic cell. This leads
to an anxiolytic effect at doses lower than those required
to induce sedation and hypnosis. The exact mechanism
of action is not clearly understood. Benzodiazapines
reduce muscle spasm by a central action that is inde-
pendent of their sedative effect. As increased muscle
tone is a common feature of anxiety states and may
contribute to the aches and pains, including headaches
that often trouble anxious people, the relaxant effect of
benzodiazepines may, therefore, be clinically useful.
Pharmacokinetics
The benzodiazepines are well absorbed from the
gastrointestinal (GI) tract, with peak levels achieved in
30 minutes to 2 hours. They bind strongly to plasma
protein and their high lipid solubility causes the drug to
accumulate gradually in body fat, crossing the placenta
and entering breast milk. The benzodiazepines are
metabolised extensively in the liver and are eventually
excreted as glucoronide conjugates in the urine. Several
benzodiazepines are converted into active metabolites,
such as
N
-desmthyldiazepam, which can have a half-
life of as long as 60 hours and which accounts for the
tendency of many benzodiazepines to produce cumula-
tive effects and long hangovers when given at regular
intervals. People with liver disease must receive a smaller
dose and be monitored closely. Excretion is primarily
through the urine.
Contraindications and cautions
Contraindications to benzodiazepines include allergy to
any benzodiazepine; psychosis,
which could be exacer-
bated by sedation
; and acute narrow-angle glaucoma,
shock, coma or acute alcoholic intoxication,
all of which
could be exacerbated by the depressant effects of these
drugs.
A 3-year-old boy, weighing 25 kg, is prescribed chloral
hydrate as a hypnotic at bedtime.The order reads:
50 mg/kg/day PO at bedtime.The drug comes in a syrup
form as 1 g/10 mL. How much syrup would you give as
the bedtime dose?
First, figure out what the correct dose would be:
50 mg/kg × 25 kg = 1250 mg
Set up the equation using the available form and
prescribed dose, remembering to convert grams to
milligrams
1250
1000
×
10
1
= 12.5 mL
Because this is a child, it is good practice to ask another
nurse to calculate the correct dosage and then compare
your work, so you can double-check the accuracy of your
calculations.
Calculations
BOX 20.2
Barbituates generally
depress cortex, RAS
and cerebellum
Cortex
Limbic
system
RAS
Cerebellum
GABA
Benzodiazepines,
zopiclone
GABA effects
Zolpidem
affects serotonin
levels in RAS
Mechanisms
not understood:
buspirone
chloral hydrate
dexmedetomidine
promethazine
Cell firing inhibited,
leading to stabilisation
FIGURE 20.1
Sites of action of the benzodiazepines, barbiturates and
other anxiolytics.
