Precautions for antiepileptic drug therapy in women of childbearing age with epilepsy

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1 the dynamic changes of estrogen and progesterone in the period of ovulation or non ovulation or menstrual period will change the excitabil


1 the dynamic changes of estrogen and progesterone in the period of ovulation or non ovulation or menstrual period will change the excitability of neurons and the frequency of epileptic seizures. You can take acetazolamide, clobazam (CLB) or the use of hormone therapy (anti estrogen or progesterone). Acetazolamide is weak carbonic anhydrase inhibitors, a mild diuretic effect and anti epileptic effect, but may cause transient mild metabolic acidosis. The usual daily dose of 250-1000mg is divided into 2 doses, the use of intermittent therapy, that is, the seizure prone period of 10-14 days, but not for pregnant women. 2 polycystic ovary syndrome (polycystic ovary syndrome, PCOS) seizures interfere with the release of hormones in the hypothalamus and pituitary, and antiepileptic drugs can also cause the disorder of sex hormones. About 30% of the women with epilepsy had polycystic ovary and the control group was about 15%. Sodium valproate (VPA) and polycystic ovary, androgen increased, hyperinsulinemia and obesity, VPA treated epilepsy 60% women with polycystic ovary, and accept other antiepileptic drugs the incidence rate of 20%-30% before the age of 20 in those taking VPA had the highest incidence. After stopping the drug, VPA related symptoms and signs are reversible. 3 seizures during pregnancy according to observation, in pregnant women with previous epilepsy, seizure frequency was increased about 20%-33%, 7%-25% number of attacks, 50%-83% had no significant changes, the influencing factors of sexual hormone concentration, AED metabolism, changes in sleep habits, patients on drug compliance and there is no new stress the event (such as a failed marriage, economic distress etc.). During pregnancy tonic clonic seizures can lead to maternal and fetal hypoxia and acidosis, increased maternal and fetal mortality. According to reports, the mother of all types of seizures in the first years of pregnancy, the fetal malformation rate of up to 12.3%, while the incidence of non epileptic seizures of fetal malformation rate was only about 4%. Therefore, before and after pregnancy, every March, the last 4 weeks before delivery should be monitored in time to adjust the plasma concentration of AED, the protein binding rate of high or moderate AED should be measured at its free level. 4 fetal antiepileptic drug syndrome fetal antiepileptic drug syndrome refers to the combination of different clinical manifestations associated with chronic antiepileptic drug toxicity, including intrauterine fetal growth is slow and the severe congenital malformation, mild dysplasia, microcephaly, cognitive dysfunction, infant death. Minor anomaly refers to the development of health is not a threat or offset variation, the incidence rate was 6%-20%, showed distal finger (toe) and nail bed hypoplasia, facial deformities, such as hypertelorism, wide nose, short Alice nose, epicanthus, ear abnormalities and low hairline. Severe deformity refers to abnormal birth important anatomic structure, significantly interferes with the organ function need to intervene and correct, the incidence rate was 1.25%-11.5%, including cleft lip, cleft palate, congenital heart disease (such as atrial septal defect, tetralogy of Fallot, ventricular septal defect, aortic coarctation, patent ductus arteriosus, pulmonary valve (stenosis) and neural tube defects such as spina bifida and anencephaly). Urogenital defects (such as hypospadias) the incidence rate was 4%-6%.

Many traditional drugs such as benzene two nitrogen Zhuo, phenytoin (PHT), C Masi Bing (CBZ), phenobarbital (PB) and VPA teratogenicity. The incidence of neural tube defects in the CBZ treatment group was first in the VPA group and l%-2% in the treatment group (0.5%-1%) in the treatment group (), which was about 10 times that of the general population. A comprehensive analysis of 5 prospective studies showed that the absolute risk of neural tube defects caused by VPA monotherapy can be as high as 3.8%, especially in the VPA daily dose of more than 1000mg of the increased risk of mothers.

More collaborative studies highlight the importance of VPA dose. The critical dose of VPA should be controlled at 1000mg / D, and the plasma concentration should be 70ug / ml. Except for VPA and CBZ, the teratogenicity of other AED was not significantly different. But very clear is that fetal antiepileptic drug syndrome with antiepileptic drug species increase and increase the risk of exposure to multiple drugs, and high doses of the greatest risk of fetal malformation, occurs in the first 3 months of pregnancy. The incidence of severe malformations in infants treated with more than 4 AED was about 25%. The teratogenic mechanism of AED is presumed to be due to the production of free radical intermediates produced by drugs, which is associated with the development of DNA. High concentrations of oxidative metabolites are associated with a high risk of fetal malformations, and the susceptibility to oxidative susceptibility is determined by genes. Folate deficiency is also a possible mechanism of PHT, CBZ, PB and VPA teratogenicity.

Take AED of childbearing age women should pay attention to: (1) should take 0.4-5mg folic acid every day; (2) in the pre pregnancy should be as far as possible the use of the type of attack for the lowest effective dose, the best curative effect, the best tolerated monotherapy. If there is a past history or family history of neural tube defects, the use of VPA, CBZ, or early consideration should be avoided for the use of antiepileptic drugs other than CBZ and VPA. (3) maternal serum alpha fetoprotein (AFP) and amniotic fluid alpha fetoprotein and acetylcholinesterase were detected at 15-22 weeks of gestation, and the detection rate of neural tube defects was more than 95% weeks (16-20 weeks). (4) the final month of daily oral vitamin K1 10mg of pregnancy, childbirth neonatal intramuscular injection or intravenous injection of vitamin K LMG, in order to avoid anti epileptic drugs Vit K and Vit K the lack of correlation between the dependent clotting factors to reduce bleeding.

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