Lec 19: Drug Induced Birth Defects

Question 1

what are the possible outcomes of pregnancy

Answer 1

healthy, healthy but with short term effects, spontaneous abortion, major birth defects, minor anomalies

Question 2

what is a teratogen

Answer 2

agent or factor causing congenital malformations or abnormal mental dev in fetus or after birth

Question 3

what is teratogenesis

Answer 3

initiation of bird defects

Question 4

what is chemical tertogenesis

Answer 4

birth defects caused by exposure to chemicals

Question 5

what is the incidence of teratogenesis

Answer 5

due to all causes, 1-3%. due to drugs, less than 2%

Question 6

why is assessing teratogenesis difficult

Answer 6

because of number of prenatal death, cant know whether it was bc of defect

Question 7

what is a major birth defect

Answer 7

affects child survival

Question 8

what is thalidomide teratogenesis

Answer 8

phocomelia: short limbs bc of thalidomide

Question 9

what is thalidomide

Answer 9

made in 53, on market in 57
used as tranquilers and anti vomiting medicine

Question 10

what happens in thalidomide tertogenecity

Answer 10

but: defects include limb reduction, facial hemangioma, smal; ears, eye abnomrlaities, kidney malformations, heart disease

Question 11

when is thalidomide terotegencity high risk period

Answer 11

20-36 days post fert

Question 12

what is the mechanism of teratogenecity

Answer 12

binds to crbn, then destabalizes cd147/mcti which leads to limb malformation

Question 13

was thalidomide taken off market after tertogenecity

Answer 13

no,

Question 14

relationship between thalidomide and inflammation

Answer 14

actually had other uses (imflammation reduction in leprosy)

Question 15

why is it challenging to identify human terotogens?

Question 16

what happens during embyotic phase?

Answer 16

day 0 to 56 where tissues and organs develop

Question 17

what happens during fetal phase?

Answer 17

56 until birth: rapid growth of tissues and organs

Question 18

what is the all or nothing period? what happens?

Answer 18

first two weeks post conception where, if too many cells are killed, the embryo cant survive.

Question 19

when is organogenesis? significance?

Answer 19

3-8 weeks post conception, where it is more sensitive to chemicals

Question 20

why is the first trimester so important?

Answer 20

thats when development is really getting initiated

Question 21

what are the consequences of teratogenesis

Answer 21

death, mutations (DES), structural anomalies (thalidomide), functional anomalies (alochol)

Question 22

what factors influence drug transfer to fetus

Answer 22

placenta
drug properties

Question 23

what characteristics of the placenta influence placental drug transfer?

Answer 23

blood flow
drug transport
drug met

Question 24

what properties of the drug influence placantal drug transfer? how?

Answer 24

weight
lipid solubility
protein binding
ionization

Question 25

how do drugs cross the maternal placental fetal unit?

Answer 25

1. admin to mom. some goes in receprtor, moms brain, moms tissues, moms liver. 2. free drug passes through placenta and goes to fetal parts , some comes back through umbilical artery

Question 26

what are the direct effects of drugs on the fetus?

Answer 26

receptor mediated tox reactive intermediate mediated tox ie: proteratogens -> electrophiles -> target dna proteins and lipids

Question 27

what are the indirect effect of drugs on the fetus?

Answer 27

poor nutrition disease states altereted blood supply

Question 28

human teratogen examples?

Answer 28

anticancer agents anticoags

Question 29

why are anticancer drugs dangerous during preg?

Answer 29

ie: cyclophose causes cns malformations

Question 30

why are anticoags dangerous during preg? specific examples?

Answer 30

ie: growth retardation and chondrodysplasia (abnormal cartilage growth), hypoplastic nasal bridge, cns malformations, heart defects

Question 31

what is fetal warfarin syndrome?

Answer 31

hypoplastic nose, flat face, low nasal bridge

Question 32

wjhy are antseizure agents during preg dangerous?

Answer 32

can cause dismorphic geatures ie: phenytoin: craniofacial dysmorphology, growth retardation, cns defecits,

Question 33

what is fetal hydantoin syndrome?

Answer 33

fetal dismorphia bc of phenytoin use

Question 34

what is a cleft lip or palate? when does it occur?

Answer 34

elft lip: lip and nostril formed together cleft palate: tissue on roof of mouth doesnt join properly occurs in fetal hydantoin syndrom

Question 35

what can phenytoin during preg lead to?

Answer 35

fetal hydantoin syndrom

Question 36

what can carmazepine and valproic acid during preg lead to?

Answer 36

neural tube defects

Question 37

what is late neurula? caused by which drug?

Answer 37

when the neural tube fails to close. carbamazepine, valproic acid

Question 38

what can late neurula lead so?

Answer 38

different defects anencephaly, craniorachischisis, oepn spina bifida, iniencephaly, encaphalocele, closed spina bifida

Question 39

what is the relationship between folic acid and neural tube defects?

Answer 39

can treat them

Question 40

what is diethylstilbestrol?

Answer 40

DES estrogen that causes vaginal/cervical cancer (clear cell adenocarcinoma), genital defects, effects not seen until puberty

Question 41

retinoids during preg can lead to

Answer 41

istretinoin can lead to cns, craniofacial, cvs, malformations

Question 42

what is retinoic acid embryopathy?

Answer 42

congenital condition caused by fetal exposure to retinoids

Question 43

what is fetal alcoholic spectrum disorder?

Answer 43

condition when fetus is exposed to alcohol growth retardation, microcephaly, mental retardation, neura defecits, facial dysmorphology

Question 44

chracteristics of fasd>

Answer 44

flat midface, smooth filtrum, thin lip, low nasal bridge, epicanthic folds, ear abnormalities, micrognathia

Question 45

brain changes of fasd babies?

Answer 45

smaller, malformed

Question 46

maternal smoking dangers/

Answer 46

less in women that stop smoking earlier, but low birth weight, abortion

Question 47

sedatives affect on neonates

Answer 47

may cause sedation in neonate

Question 48

when would neonatal withdrawl syndrome occur (NAS)

Answer 48

when mom exposed baby to drug, and now supply is cut off

Question 49

what is NAS

Answer 49

neonatal abstinance syndrome, happens within hours or days of delivery irritability, high pitched cry, tremor, rapid breathing, increased muscle tone, seizures

Question 50

drugs contributing to NAS