Pregnancy primidone

The answer is d. (Katzung, pp 411, 1029.) An increased incidence of spina bifida may occur with the use of valproic acid during pregnancy Cardiovascular, orofacial, and digital abnormalities may also occur. The main issue with the use of phenobarbital or primidone (metabolite is phe-nobarbital) for the fetus is neonatal dependence on barbiturates. 

Folate (pteroylglutamic acid) is essential for the synthesis and methylation of DNA during fetal and early postnatal development (Nunn et al., 1986). Folate deficiency may result from poor diet, malabsorption, from treatment with anticonvulsant drugs such as phenytoin or primidone, as well as from antifolate drugs such as methotrexate. Folate deficiency during pregnancy leads to an increased prevalence of fetal malformations such as spina bifida and related neural tube defects. Findings... 

Transient elevations of the serum transaminases occur in 12% to 15% of patients receiving isoniazid and usually occur within the first 8 to 12 weeks of therapy. Overt hep ato toxicity, however, occurs in only 1% of cases. Risk factors for hepatotoxicity include patient age, preexisting liver disease, excessive alcohol intake, pregnancy, and the postpartum state. Isoniazid also may result in neurotoxicity, most frequently presenting as peripheral neuropathy or, in overdose, as seizures and coma. Patients with pyridox-ine deficiency, such as pregnant women, alcoholics, children, and the malnourished, are at increased risk. Isoniazid may inhibit the metabolism of phenytoin, carbamazepine, primidone, and warfarin." Patients who are being treated with these agents should be monitored closely, and appropriate dose adjustments should be made when necessary. 

Hormonal contraceptives are less reliable during the use of phenytoin and barbiturates such as phenobarbital and primidone. Intermenstrual breakthrough bleeding and spotting can take place, and pregnancies have occurred. Controlled studies have shown that phenytoin and phenobarbital can reduce contraceptive steroid levels. 

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