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Ethosuximide is succinimide compound that is effective in the
treatment of absence (petit mal) seizures (Table 14-1).1,2 It
is the product of an intense structure-activity research effort
to find an specific agent to suppress absence seizures with a relatively
low side effect profile. While the exact mechanism of action is
not known, the antiepileptic effect of ethosuximide is thought to
result from its ability to decrease low-threshold calcium currents
in thalamic neurons.3 The thalamus has a key role in the
production of 3-Hz spike-wave rhythms that are a hallmark of absence
seizures. Ethosuximide may also inhibit the sodium-potassium ATPase
system and NADPH-linked aldehyde reductase.4
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The therapeutic range for ethosuximide is defined by most laboratories
as 40–100 μg/mL, although some
clinicians suggest drug concentrations as high as 150 μg/mL
with appropriate monitoring of serum concentrations and possible
side effects.5 The most common adverse effects of ethosuximide
are gastric distress, nausea, vomiting, and anorexia, but these gastrointestinal
problems appear to be caused by local irritation of gastric mucosa.
Generally, administration of smaller doses and more frequent dosing
of the drug produce relief from these side effects. In the upper
end of the therapeutic range (> 70 μg/mL)
some patients will begin to experience the concentration-dependent
adverse effects of ethosuximide treatment: drowsiness, fatigue,
lethargy, dizziness, ataxia, hiccups, euphoria, and headaches. Idiosyncratic
side effects that are independent of concentration include rash,
systemic lupus-like syndromes, and blood dyscrasias (leukopenia,
pancytopenia).
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The goal of therapy with anticonvulsants is to reduce seizure
frequency and maximize quality of life with a minimum of adverse
drug effects. While it is desirable to entirely abolish all seizure
episodes, it may not be possible to accomplish this in many patients.
Patients should be monitored for concentration-related side effects
(drowsiness, fatigue, lethargy, dizziness, ataxia, hiccups, euphoria,
headaches) as well as gastrointestinal upset associated with local
irritation of gastric mucosa (gastric distress, ...