C H A P T E R 2 0
Anxiolytic and hypnotic agents
307
In addition, these sedative/hypnotics are contra
indicated in pregnancy
because a predictable syndrome
of cleft lip or palate, inguinal hernia, cardiac defects,
microcephaly or pyloric stenosis occurs when they
are taken in the first trimester.
Neonatal withdrawal
syndrome may also result. Breastfeeding is also a contra
indication
because of potential adverse effects on the
neonate (e.g. sedation).
Use with caution in elderly or debilitated people
because of the possibility of unpredictable reactions
and in cases of renal or hepatic dysfunction,
which
may alter the metabolism and excretion of these drugs,
resulting in direct toxicity. If possible, hypnotics should
be avoided in the elderly, because they are at greater
risk of becoming ataxic and confused, leading to falls
and injury.
Dose adjustments usually are needed for
such people. See the NZ Formulary
nzf_1997.html.
Dependence and tolerance (i.e. a gradual escala-
tion of dose needed to produce the required effect)
occurs with chronic use of all benzodiazepines there-
fore stopping treatment after weeks or months causes
increased symptoms of anxiety, together with tremor
and dizziness. Addiction (i.e. severe psychological
dependence which outlasts the physical withdrawal
syndrome) which can occur with many drugs of abuse is
not a major problem with benzodiazepines.
Adverse effects
The adverse effects of benzodiazepines are associated
with the impact of these drugs on the central and
peripheral nervous systems. Nervous system effects
include sedation, drowsiness, depression, lethargy,
blurred vision, headaches, apathy, light-headedness
and confusion. In addition, mild paradoxical excitatory
reactions may occur during the first 2 weeks of therapy.
Benzodiazepines may occasionally cause marked
respiratory depression and facilities for its treatment
are therefore essential. The drug flumazenil is used
to antagonise the effects of benzodiazepines (refer to
Box 20.3).
Several other kinds of adverse effects may occur.
GI conditions such as dry mouth, constipation, nausea,
vomiting and elevated liver enzymes may result.
Cardiovascular problems may include hypotension,
hypertension, arrhythmias, palpitations and respiratory
difficulties. Haematological conditions such as blood
dyscrasias and anaemia are possible. Genitourinary
(GU) effects include urinary retention and hesitancy,
loss of libido and changes in sexual functioning. Because
phlebitis, local reactions and thrombosis may occur
at local injection sites, such sites should be monitored.
Abrupt cessation of these drugs may lead to a with-
drawal syndrome characterised by nausea, headache,
vertigo, malaise and nightmares.
Clinically important drug–drug interactions
The risk of CNS depression increases if benzodiazepines
are taken with alcohol or other CNS depressants, so
such combinations should be avoided. In addition, the
effects of benzodiazepines increase if they are taken
with cimetidine, oral contraceptives or disulfiram. If any
one of these drugs is used with benzodiazepines, people
should be monitored and the appropriate dose adjust-
ments made.
Finally, the impact of benzodiazepines may be
decreased if they are given with theophyllines or ran-
itidine. If either of these drugs is used, dose adjustment
may be necessary.
Prototype summary: Diazepam
Indications:
Management of anxiety disorders, acute
alcohol withdrawal, muscle relaxation, treatment of
tetanus, antiepileptic adjunct in status epilepticus,
preoperative relief of anxiety and tension.
Actions:
Acts in the limbic system and reticular
formation to potentiate the effects of GABA, an
inhibitory neurotransmitter; may act in spinal cord
and supraspinal sites to produce muscle relaxation.
Pharmacokinetics:
Route Onset
Peak
Duration
Oral
30–60 mins 1–2 hours
3 hours
IM 15–30 mins 30–45 mins 3 hours
IV 1–5 mins
30 mins
15–60 mins
Rectal Rapid
1.5 hours
3 hours
T
1/2
:
20 to 80 hours, metabolised in the liver,
excreted in urine.
Adverse effects:
Mild drowsiness, depression,
lethargy, apathy, fatigue, restlessness, bradycardia,
tachycardia, constipation, diarrhoea, incontinence,
urinary retention, changes in libido, drug
dependence with withdrawal syndrome.
Care considerations for
people receiving benzodiazepines
Assessment: History and examination
■
■
Assess for contraindications or cautions:
known allergies to benzodiazepines
to prevent
hypersensitivity reactions
; impaired liver or kidney
function,
which could alter the metabolism and
excretion of a particular drug
; any condition that
might be exacerbated by the depressant effects of
the drugs (e.g. glaucoma, coma, psychoses, shock,
acute alcohol intoxication); and pregnancy and
breastfeeding.
