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.
What is a teratogenic response?
On exposure to a toxic agent, a developing embryo will exhibit a response that ranges from none to severe (i.e. death or malformation). This response at a given dosage is sometimes defined as teratogenic (or developmental toxic) severity and is dependent on exposure conditions.
What is the teratogenic effect of thalidomide?
Teratogenicity is the most severe and well-known adverse effect associated with thalidomide. Babies born with malformations such as amelia, phocomelia, bone hypoplasia and absence of bones resulted from the thalidomide tragedy.
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.
Is Lamotrigine a teratogenic drug?
It is recognised that some, particularly valproate, carbamazepine and lamotrigine, are human teratogens, while others including topiramate require further investigation.
What stage of pregnancy is at most risk for teratogenic effects?
Treatment of common illnesses in early pregnancy is complicated because of the risk of teratogenic effects of drugs on the fetus. The period of greatest risk is between the first and eighth week of pregnancy.
What is the most common teratogenic effect associated with thalidomide?
Thalidomide is a teratogenic drug, meaning that when taken while pregnant, it can have terrible impacts on fetal development and cause irreversible damages. Phocomelia, a limb atrophy, is the most common malformation linked to thalidomide, but all phocomelia cases aren’t caused by thalidomide.
Which form of thalidomide is teratogenic?
Thalidomide exists in two mirror-image forms: it is a racemic mixture of (R)- and (S)-enantiomers. The (R)-enantiomer, shown in the figure, has sedative effects, whereas the (S)-isomer is teratogenic.
Why Valproate is contraindicated in pregnancy?
The use of Sodium valproate (Epilim) is contraindicated in pregnancy due to the risk to the unborn baby (fetus). Congenital malformations have been estimated to affect between 6.7%1 and 12.4%2 of children exposed to Epilim in the womb.
Can valproic acid be given in pregnancy?
FDA previously warned pregnant women and women of childbearing age about valproate use during pregnancy due to the known risk of birth defects (teratogenic effects) of these products. A teratogen is anything known to cause birth defects during development of an embryo or fetus.
What are the characteristics of a human teratogen?
CHARACTERISTICS OF A HUMAN TERATOGEN. 1. An increase in the frequency of an abnormal fetal effect; 2. A dose-response relationship; there is a threshold below which the exposure is not teratogenic; 3. Period of greatest sensitivity; 4. Established mechanism of action, which often requires animal model; 5.
How are malformations induced in a teratogen dam?
Malformations induced by teratogens are the end result of morphogenetic interactions between the genes of the embryo which confer the potentialities for normal or abnormal development and the environment of the embryo which includes the dam’s genotype and environment, in addition to the teratogen.
When does the susceptibility to teratogen exposure begin?
Thus, susceptibility to teratogen exposure for a given conceptus actually begins even prior to when it is conceived. Figure 1. Timeline of important events during pregnancy that may be disrupted by a teratogenic exposure.
How does an agent become a teratogenic agent?
In order for an agent to be teratogenic it must show some specificity in regard to the tissues affected. The damage produced must be differential so that certain structures can be malformed without, at the same time, destroying the entire conceptus.