72 Section 2/ Drugs Acting on CNSTherapeutic Uses
- As antianxiety agent.
- As hypnotic.
- As anticonvulsant.
- As preanaesthetic medication.
DIAZEPAM
Being highly lipophilic it is quickly ab-
sorbed from the gastrointestinal tract. The
kinetics of redistribution of diazepam is
complicated by enterohepatic circulation.
Initially there is high concentration in CNS
after intravenous injection, then due to redis-
tribution of drug the concentration starts fall-
ing in brain. It has a plasma half life of more
than 20 hours. Diazepam is metabolised in
liver to pharmacologically active metabolite,
desmethyldiazepam which has a long
plasma half life (80 hrs). It crosses the pla-
cental barrier and when given before labour
may cause hypotonia and mild respiratory
depression in neonates.
It is indicated as hypnotic, in anxiety,
tension, muscle spasm, psychosomatic and
behaviour disorders, dysmenorrhoea, cere-
bral palsy, upper motor neuron spasticity,
sedative for surgical procedures, labour,
tetanus, eclampsia and epilepsy.
LORAZEPAM
It provides prompt relief from a variety
of symptoms associated with anxiety and in
anxiety associated with depression.
It is readily absorbed when given orally.
Peak concentrations in plasma occur ap-
proximately 2 hours following administra-
tion. The halflife of unconjugated lorazepam
in human plasma is approximately 12 to 16
hours. At clinically relevant concentration,
lorazepam is approximately 90 percent
bound to plasma proteins. It is conjugated
to inactive glucuronide metabolite and is
excreted in urine.
The most frequent adverse reactions
reported are sedation, followed by
dizziness, weakness and unsteadiness. Less
frequent adverse reactions include
disorientation, depression, nausea, change
in appetite, headache, sleep disturbance,
agitation, dermatological symptoms
including very serious reactions, eye-
function disturbance, together with various
gastrointestinal symptoms and autonomic
manifestations. The incidence of sedation
and unsteadiness increases with age.
It is used in anxiety disorders or anxiety
associated with depressive symptoms, as
pre-surgical medication.OXAZEPAM
It is used in tension, anxiety disorders,
anxiety associated with alcohol withdrawal,
agitation and irritability in older patients
and psychoneurosis.
Adverse effects include sedation, ver-
tigo, dizziness, disorientation, blurred vision
and dependence.MIDAZOLAM
Midazolam is a new, short acting ben-
zodiazepine with sedative properties, twice
as potent as diazepam. It is also used as an
anaesthetic inducing agent.
The mechanism of action of midazolam
though not clearly understood is probably
similar to other benzodiazepines i.e. through
interference with GABA reuptake. It has a
relatively high affinity for benzodiazepine
receptors.