Ethosuximide arid other succimides

Pharmacology

Ethosuximide is only effective with petit-mal seizures. It seems to facilitate the transfer of glucose in the brain and, under experimental conditions, it raises the seizure threshold.

Ethosuximide is well-absorbed when taken orally, and reaches a maximum concentration in the blood after 3-4 hours. It binds to protein plasma only to a limited extent. Plasma concentrations of 40-100|ig/ml are required to prevent petit-mal seizures.

Toxicology

There are only a few reports of ethosuximide therapy during pregnancy. No typical pattern of birth defects has been observed in the infants of 57 treated women (Lindhout 1992). In a series of 18 fetuses exposed during the first trimester, there were no birth defects (Rosa 1993, cited in Briggs 2005). No adverse effect was detected either among 13 exposures (Samrén 1997). Although the available reports are in no way sufficient for a differentiated risk assessment, there does not seem to be a teratogenic risk comparable to the other anticonvulsants. There is a report of neonatal hemorrhage following in utero exposure to ethosuximide, indicating a vitamin K antagonistic potential (Speidel 1974).

There is insufficient experience with the other succinimides, mesux-imide and phensuccimide, to assess their risks in pregnancy.

Recommendation. Ethosuximide belongs to the drug of choice for petitmal seizures in pregnancy. Mesuximide and phensuccimide are less well-studied, and are therefore not recommended.

Exposure to succimide derivatives does not require a termination of pregnancy. However, detailed ultrasound diagnosis around week 20 should confirm normal development of the fetus.

To decrease the risk of coagulation disturbances in the fetus and newborn, the newborn should receive 1 mg of vitamin K (preferably intramuscularly) at birth and 1 mg orally every 3 days in the first 2 weeks of life (see also section 2.10.6).

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