Failure of epoxide formation to influence carbamazepine‐induced teratogenesis in a mouse model

Finnell, Richard H.; Mohl, Virginia K.; Bennett, Gregg; Taylor, Stephen M.

doi:10.1002/tcm.1770060506

Cited by 13 publications

(5 citation statements)

References 16 publications

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“…Similar findings were found in study after the exposure to higher doses (1.000, 1.500 and 2.000 mg/kg). In those doses no specific pattern of malformation and no correlation between detected anomalies and dose were found (Finnel et al, 1986). The finding was supported also by following studies (Wray et al, 1982;Fritz et al, 1976).…”

Section: Carbamazepine (Cbz)supporting

confidence: 78%

Epilepsy and Anticonvulsant Therapy During Pregnancy

Maňáková¹,

Hubickova²

2011

Novel Treatment of Epilepsy

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Section: Carbamazepine (Cbz)supporting

confidence: 78%

Epilepsy and Anticonvulsant Therapy During Pregnancy

Maňáková¹,

Hubickova²

2011

Novel Treatment of Epilepsy

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“…Further studies showed small increases in the rate of cleft palate, dilated cerebral ventricles and growth retardation in mouse foetuses that were similarly treated during the period of organogenesis [Eluma et al, 1981; Eluma, 1984; Paulson et al, 1979; Sullivan et al, 1977]. When mice were chronically exposed to CBZ in their diet prior to and throughout gestation, a significant number of fetuses with congenital defects of the central nervous system or urogenital system were observed [Finnell et al, 1986a]. In experiments comparing teratogenicity of CBZ with other anticonvulsant drugs, it was consistently less teratogenic than phenytoin or primidone [El-Sayed et al 1983; Eluma et al, 1984; Sullivan et al, 1977].…”

Section: Antiepileptic Drugsmentioning

confidence: 99%

Antiepileptic drugs and pregnancy outcomes

Wlodarczyk

Palacios

George

et al. 2012

American J of Med Genetics Pt A

Self Cite

112

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The treatment of epilepsy in women of reproductive age remains a clinical challenge. While most women with epilepsy require anticonvulsant drugs for adequate control of their seizures, the teratogenicity associated with some antiepileptic drugs is a risk that needs to be carefully addressed. Antiepileptic medications are also used to treat an ever broadening range of medical conditions such as bipolar disorder, migraine prophylaxis, cancer and neuropathic pain. Despite the fact that the majority of pregnancies of women with epilepsy who are receiving pharmacological treatment are normal, studies have demonstrated that the risk of having a pregnancy complicated by a major congenital malformation is doubled when comparing the risk of untreated pregnancies. Furthermore, when antiepileptic drugs (AEDs) are used in polytherapy regimens, the risk is tripled, especially when valproic acid (VPA) is included. However, it should be noted that the risks are specific for each anticonvulsant drug. Some investigations have suggested that the risk of teratogenicity is increased in a dose-dependent manner. More recent studies have reported that in utero exposure to AEDs can have detrimental effects on the cognitive functions and language skills in later stages of life. In fact, the FDA just issued a safety announcement on the impact of VPA on cognition (Safety Announcement 6-30-2011). The purpose of this document is to review the most commonly used compounds in the treatment of women with epilepsy, and to provide information on the latest experimental and human epidemiological studies of the effects of antiepileptic drugs in the exposed embryos.

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“…Small increases in the rate of cleft palate, dilated cerebral ventricles and growth retardation were observed in mouse fetuses that were similarly treated during the period of organogenesis [72–75]. In mice chronically exposed to CBZ in their diet prior to and throughout gestation, a significant number of fetuses were observed with congenital defects of the CNS or urogenital system [76]. In experiments comparing teratogenicity of CBZ with other anticonvulsant drugs, it was consistently less teratogenic than PHT or primidone [72,74,77].…”

Section: Mechanisms Of Aed Teratogenicitymentioning

confidence: 99%

Teratogenic effects of antiepileptic drugs

Hill

Wlodarczyk

Palacios

et al. 2010

Expert Review of Neurotherapeutics

127

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Many antiepileptic drugs (AEDs) have therapeutic applications that extend beyond epilepsy to include neuropathic pain, migraine headaches and psychiatric disorders. The risk of some AEDs has been clearly established, but for newer drugs, small sample sizes and polytherapy exposures preclude a conclusive determination of their teratogenic potential. Most women with epilepsy will require AED therapy throughout their entire pregnancy to control seizures; the vast majority of pregnancies in women with epilepsy have positive outcomes. A conservative estimate suggests that AED monotherapy doubles, and polytherapy triples, the risk for major congenital malformations. Furthermore, while evidence is still accruing, recent investigations suggest that exposure to select AEDs results in altered cognitive function later in development. There is no evidence to suggest that additional folic acid supplementation ameliorates the increased risk of congenital malformations conferred by in utero AED exposure.

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Failure of epoxide formation to influence carbamazepine‐induced teratogenesis in a mouse model

Cited by 13 publications

References 16 publications

Epilepsy and Anticonvulsant Therapy During Pregnancy

Epilepsy and Anticonvulsant Therapy During Pregnancy

Antiepileptic drugs and pregnancy outcomes

Teratogenic effects of antiepileptic drugs

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