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育龄期女性癫痫的管理

Managing epilepsy in women of childbearing age.

作者信息

Crawford Pamela M

机构信息

The Special Center for Epilepsy, York District Hospital, York, UK.

出版信息

Drug Saf. 2009;32(4):293-307. doi: 10.2165/00002018-200932040-00004.

Abstract

Epilepsy affects the menstrual cycle, aspects of contraception, fertility, pregnancy and bone health in women. It is common for seizure frequency to vary throughout the menstrual cycle. In ovulatory cycles, two peaks can be seen around the time of ovulation and in the few days before menstruation. In anovulatory cycles, there is an increase in seizures during the second half of the menstrual cycle. There is also an increase in polycystic ovaries and hyperandrogenism associated with valproate therapy. There are no contraindications to the use of non-hormonal methods of contraception in women with epilepsy. Non-enzyme-inducing antiepileptic drugs (AEDs) [valproate, benzodiazepines, ethosuximide, levetiracetam, tiagabine and zonisamide] do not show any interactions with the combined oral contraceptive (OC). There are interactions between the combined OC and hepatic microsomal-inducing AEDs (phenytoin, barbiturates, carbamazepine, topiramate [dosages>200 mg/day], oxcarbazepine) and lamotrigine. Pre-conception counselling should be available to all women with epilepsy who are considering pregnancy. Women with epilepsy should be informed about issues relating to the future pregnancy, including methods and consequences of prenatal screening, fertility, genetics of their seizure disorder, teratogenicity of AEDs, folic acid and vitamin K supplements, labour, breast feeding and care of a child. During pregnancy, the lowest effective dose of the most appropriate AED should be used, aiming for monotherapy where possible. Recent pregnancy databases have suggested that valproate is significantly more teratogenic than carbamazepine, and the combination of valproate and lamotrigine is particularly teratogenic. Most pregnancies in women with epilepsy are without complications, and the majority of infants are delivered healthy with no increased risk of obstetric complications in women. There is no medical reason why a woman with epilepsy cannot breastfeed her child. The AED concentration profiled in breast milk follows the plasma concentration curve. The total amount of drug transferred to infants via breast milk is usually much smaller than the amount transferred via the placenta during pregnancy. However, as drug elimination mechanisms are not fully developed in early infancy, repeated administration of a drug such as lamotrigine via breast milk may lead to accumulation in the infant. Studies have suggested that women with epilepsy are at increased risk of fractures, osteoporosis and osteomalacia. No studies have been undertaken looking at preventative therapies for these co-morbidities.

摘要

癫痫会影响女性的月经周期、避孕、生育能力、妊娠及骨骼健康。癫痫发作频率在整个月经周期中变化很常见。在有排卵的周期中,排卵时及月经前几天可见两个发作高峰。在无排卵的周期中,月经周期后半期癫痫发作会增加。丙戊酸盐治疗还会使多囊卵巢及高雄激素血症增多。癫痫女性使用非激素避孕方法没有禁忌证。非酶诱导的抗癫痫药物(AEDs)[丙戊酸盐、苯二氮䓬类、乙琥胺、左乙拉西坦、噻加宾和唑尼沙胺]与复方口服避孕药(OC)之间无相互作用。复方OC与肝微粒体诱导型AEDs(苯妥英、巴比妥类、卡马西平、托吡酯[剂量>200mg/天]、奥卡西平)及拉莫三嗪之间存在相互作用。所有考虑妊娠的癫痫女性都应接受孕前咨询。癫痫女性应了解与未来妊娠相关的问题,包括产前筛查的方法及后果、生育能力、癫痫发作疾病的遗传学、AEDs的致畸性、叶酸和维生素K补充剂、分娩、母乳喂养及照顾孩子等。妊娠期间,应使用最合适的AED的最低有效剂量,尽可能采用单药治疗。最近的妊娠数据库表明,丙戊酸盐的致畸性明显高于卡马西平,丙戊酸盐与拉莫三嗪联合使用时致畸性尤其高。大多数癫痫女性的妊娠无并发症,大多数婴儿健康出生,女性发生产科并发症的风险没有增加。癫痫女性没有医学理由不能母乳喂养孩子。母乳中的AED浓度曲线与血浆浓度曲线一致。通过母乳转移到婴儿体内的药物总量通常远小于孕期通过胎盘转移的量。然而,由于婴儿早期药物消除机制尚未完全发育,通过母乳反复给予拉莫三嗪等药物可能导致婴儿体内药物蓄积。研究表明,癫痫女性发生骨折、骨质疏松和骨软化的风险增加。尚未开展针对这些合并症的预防性治疗研究。

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