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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

Table 14-1 International Classification of Epileptic Seizures with Treatment Recommendations

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).

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, nausea, vomiting, ...

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