C H A P T E R 2 0
Anxiolytic and hypnotic agents
311
Contraindications and cautions
Contraindications to barbiturates include allergy to
any barbiturate and a previous history of addiction to
sedative/hypnotic drugs
because the barbiturates are
more addicting than most other anxiolytics.
Other con-
traindications are latent or manifest porphyria,
which
may be exacerbated
; marked hepatic impairment or
nephritis,
which may alter the metabolism and excre-
tion of these drugs
; and respiratory distress or severe
respiratory dysfunction,
which could be exacerbated
by the CNS depression caused by these drugs.
Preg-
nancy is a contraindication
because of potential adverse
effects on the fetus
; congenital abnormalities have been
reported with barbiturate use.
Use with caution in people with acute or chronic
pain
because barbiturates can cause paradoxical excite-
ment, masking other symptoms
; with seizure disorders
because abrupt withdrawal of a barbiturate can precipi-
tate status epilepticus
; and with chronic hepatic, cardiac
or respiratory diseases,
which could be exacerbated by
the depressive effects of these drugs.
Care should be
taken with breastfeeding women
because of the poten-
tial for adverse effects on the infant.
Adverse effects
As previously stated, the adverse effects caused by barbi-
turates are more severe than those associated with other,
newer sedatives/hypnotics. For this reason, barbiturates
are no longer considered the mainstay for the treatment
of anxiety. In addition, the development of physical tol-
erance and psychological dependence is more likely with
the barbiturates than with other anxiolytics.
The most common adverse effects are related to
general CNS depression. CNS effects may include drows-
iness, somnolence, lethargy, ataxia, vertigo, a feeling of a
“hangover”, thinking abnormalities, paradoxical excite-
ment, anxiety and hallucinations. GI signs and symptoms
such as nausea, vomiting, constipation, diarrhoea and
epigastric pain may occur. Associated cardiovascular
effects may include bradycardia, hypotension (par-
ticularly with IV administration) and syncope. Serious
hypoventilation may occur, and respiratory depression
and laryngospasm may also result, particularly with
IV administration. Hypersensitivity reactions, including
TABLE 20.2
DRUGS IN FOCUS Barbiturate used as anxiolytic-hypnotic
Drug name
Dosage/route
Usual indications
Phenobarbitone
sodium (generic)
Adult: 30–120 mg/day PO, slow IV or IM
Paediatric: 1–6 mg/kg PO b.d. or t.d.s. or
1–3 mg/kg/day by slow IV or IM
Sedative–hypnotic; control of seizures
Onset: 10–60 minutes
Duration: 4–16 hours
Special considerations: Taper gradually
after long-term use; give IV slowly;
monitor injection sites
Prototype summary: Phenobarbitone
Indications:
Sedation, short-term treatment of
insomnia, long-term treatment of tonic–clonic
seizures and cortical focal seizures, emergency
control of certain acute convulsive episodes,
preanaesthetic.
Actions:
Inhibits conduction in the ascending RAS;
depresses the cerebral cortex; alters cerebellar
function; depresses motor output; can produce
excitation, sedation, hypnosis, anaesthesia and deep
coma; and has anticonvulsant activity.
Pharmacokinetics:
Route Peak
Onset
Duration
Oral
15 mins
30–60 mins 10–16 hours
IM
10–30 mins 4–6 hours
IV up to 15 mins 5 mins
4–6 hours
T
1/2
:
79 hours; metabolised in the liver, excreted in
urine.
Adverse effects:
Somnolence, agitation, confusion,
hyperkinesias, ataxia, vertigo, CNS depression,
hallucinations, bradycardia, hypotension, syncope,
nausea, vomiting, constipation, diarrhoea,
hypoventilation, apnoea, withdrawal syndrome,
rash.
rash, serum sickness and Stevens–Johnson syndrome,
which is sometimes fatal, may also occur.
Clinically important drug–drug interactions
Increased CNS depression results if these agents are
taken with other CNS depressants, including alcohol,
antihistamines and other tranquillisers. If other CNS
depressants are used, dose adjustments are necessary.
There is often an altered response to phenytoin if
it is combined with barbiturates; evaluate the person
frequently if this combination cannot be avoided. If bar-
biturates are combined with monoamine oxidase (MAO)
inhibitors, increased serum levels and effects occur. If
the older sedatives/hypnotics are combined with MAO
inhibitors, people should be monitored closely and nec-
essary dose adjustments made.
