What is the teratogenic effect of valproic acid?
VPA has been associated with a variety of major and minor malformations, including a 20-fold increase in neural tube defects, cleft lip and palate, cardiovascular abnormalities, genitourinary defects, developmental delay, endocrinological disorders, limb defects, and autism.
Why is valproic acid teratogenic?
It is believed that VPA crosses the placenta and interferes with normal development causing developmental abnormalities in the fetus (teratogenesis). If a woman with epilepsy wishes to have children, the recommended treatment is to avoid VPA and use a single drug or a newer antiepileptic medication.
Why Valproic acid is contraindicated in pregnancy?
Valproic acid Pregnancy Warnings. Increased rates of fetal structural abnormalities, intrauterine growth retardation, and embryo-fetal death have occurred with valproate administration to pregnant animals at clinically relevant doses.
What is teratogenicity in pharmacology?
Teratogenicity is the ability of a drug to cause fetal abnormalities or deformities.
What is fetal anticonvulsant syndrome?
Foetal anticonvulsant syndrome is a group of malformations that can affect some babies if they are exposed to certain medicines, known as antiepileptic drugs (AEDs), while in the womb. Malformations include spina bifida, cleft palate, heart defects, learning problems and autism spectrum disorder.
How does valproic acid cause spina bifida?
Thus, VPA exposure prevents morphological and biomechanical conversion of the caudal extreme of the PNP during late spinal closure. Closure 5 facilitates neural fold apposition when completion of closure is imminent, such that its disruption in VPA-exposed embryos may lead to distal spina bifida.
What does valproic acid inhibit?
Valproic acid inhibits the activity of CYP2C9 at clinically relevant concentrations in human liver microsomes. Inhibition of CYP2C9 can explain some of the effects of valproic acid on the pharmacokinetics of other drugs, such as phenytoin.
What is Depakote mechanism of action?
Scientists do not know the mechanism of action of valproic acid. The most popular theory is that valproic acid exerts its effects by increasing the concentration of gamma-aminobutyric acid (GABA) in the brain. GABA is a neurotransmitter, a chemical that nerves use to communicate with one another.
What are the pregnancy precautions for valproate?
Dietary folic acid supplementation should be routinely recommended both prior to conception and during pregnancy for patients taking valproate because studies in the general population show that folic acid supplementation prior to conception and during early pregnancy reduces the risk of neural tube defects.
What is the maternal complication with sodium valproate AEDS )?
Maternal exposure to valproate was first linked to an increased risk of congenital spina bifida in the 1980s. Valproate has an increased risk of major congenital malformations and poor cognitive outcomes compared to other antiepileptic drugs.
What is the teratogenic action?
Teratogenic drugs: A teratogen is an agent that can disturb the development of the embryo or fetus. Teratogens halt the pregnancy or produce a congenital malformation (a birth defect). Classes of teratogens include radiation, maternal infections, chemicals, and drugs.
