C H A P T E R 2 3
Antiseizure agents
361
It is indicated for the control of absence seizures (see
Table 23.2).
Pharmacokinetics
Ethosuximide is available for oral use. This drug crosses
the placenta and enters breast milk (see Contraindica
tions and cautions). Ethosuximide is readily absorbed
from the GI tract, reaching peak levels in 1 to 7 hours.
It is metabolised in the liver and excreted in the urine.
The half-life of ethosuximide is 30 hours in children and
60 hours in adults. The established therapeutic serum
level for ethosuximide is 40 to 100 mcg/mL.
Contraindications and cautions
Ethosuximide is contraindicated in the presence of
allergy
to avoid hypersensitivity reactions
. Caution
should be used with ethosuximide in people with inter
mittent porphyria,
which could be exacerbated by the
adverse effects of the drug
, and those with renal or
hepatic disease,
which could interfere with the metab-
olism and excretion of the drug and lead to toxic
levels.
Use during pregnancy should be discussed with
the woman because of the potential for adverse effects
on the fetus. Another method of feeding the baby
should be used if one of these drugs is needed during
breastfeeding.
Blood dyscrasias, including some with a fatal
outcome, have been reported to be associated with
use of ethosuximide; therefore, periodic blood counts
should be performed. Should signs and/or symptoms of
infection (e.g. sore throat, fever) develop, blood count
determinations should be considered at that point.
Adverse effects
Ethosuximide has relatively few adverse effects
compared with many other antiepileptic drugs. Many
of the adverse effects associated with the succinimides
are related to their depressant effects in the CNS. These
may include depression, drowsiness, fatigue, ataxia,
insomnia, headache and blurred vision. Decreased
GI activity with nausea, vomiting, anorexia, weight
loss, GI pain and constipation or diarrhoea may also
occur. Bone marrow suppression, including potentially
fatal pancytopenia, and dermatological reactions such
as pruritus, urticaria, alopecia and Stevens–Johnson
syndrome may occur as a result of direct chemical irrita
tion of the skin and bone marrow.
Clinically important drug–drug interactions
Use of ethosuximide with primidone may cause a
decrease in serum levels of primidone. People should be
monitored and appropriate dose adjustments made if
these two agents are used together.
O
ther drugs
for treating absence
seizures
Three other drugs that are used in the treatment of
absence seizures do not fit into a specific drug class
(Table 23.2). These include acetazolamide (
Diamox
,
Glaumox
), sodium valproate (
Epilim
) and zonisamide
(
Zonegran
) (not available in New Zealand).
Therapeutic actions and indications
Sodium valproate reduces abnormal electrical activity in
the brain and may also increase GABA activity at inhibi
tory receptors. Acetazolamide—a sulfonamide—alters
electrolyte movement, stabilising nerve cell membranes.
Another sulfonamide—zonisamide—is a newer agent
that inhibits voltage-sensitive sodium and calcium
channels, thus stabilising nerve cell membranes and
modulating calcium-dependent presynaptic release of
excitatory neurotransmitters. See Table 23.2 for usual
indications related to these drugs.
Pharmacokinetics
Sodium valproate, available for oral and IV use, is
readily absorbed from the GI tract, reaching peak levels
in 1 to 4 hours. It is metabolised in the liver and excreted
in the urine with a half-life of 6 to 16 hours.
Acetazolamide, which can be given orally, IM or
IV, is readily absorbed from the GI tract and is excreted
unchanged in the urine with a half-life of 2.5 to 6 hours.
Zonisamide, an oral drug, is well absorbed from the
GI tract, reaching peak levels in 2 to 6 hours. It is prim
arily excreted unchanged in the urine, with a half-life of
63 hours.
Prototype summary: Ethosuximide
Indications:
Control of absence seizures.
Actions:
May act in inhibitory neuronal systems;
suppresses the electroencephalographic pattern
associated with absence seizures; reduces frequency
of attacks.
Pharmacokinetics:
Route
Peak
Oral
3–7 hours
T
1/2
:
30 hours (children), 60 hours (adults);
metabolised in the liver, excreted in the urine and
bile.
Adverse effects:
Drowsiness, ataxia, dizziness,
irritability, nervousness, headache, blurred vision,
pruritus, Stevens–Johnson syndrome, nausea,
vomiting, epigastric pain, anorexia, diarrhoea and
pancytopenia.
