Teratogens Flashcards
Thalidomide: intended use
- anti-emetic
- sleep aid
Thalidomide: teratogenic effect (3)
-limb defects **(phocomelia)
- external ear defects
- visceral organ abnormalities (ex. agenesis of organs)
Thalidomide: mechanism of teratogenesis
inhibits angiogenesis during limb bud formation (1st trimester)
What organ system is affected usually during the fetal phase?
CNS function
Name the mechanisms of teratogenesis
- Cytotoxicity
- DNA interaction
- Angiogenesis (ex. thalidomide)
- Enzyme inhibition (ex. warfarin)
- Nutrient and Vitamin Deficiency (ex. folate antagonists)
FDA: category A
studies have not shown risk in 1st trimester
Ex. Folic Acid, Levothyroxine
FDA: category B
Animal reproduction studies haven’t shown risk.
Ex. Amoxicillin, Insulin R and N
FDA: category C
Animal studies have shown adverse effect
Ex. Sertraline, Fluoxetine, Albuterol
FDA: category D
positive evidence of human fetal risk
FDA: category X
positive evidence for risk to human fetus
Antiepileptic drugs (Ex. Carbamazepine, Phenytoin, Valproate) adverse outcome
-craniofacial, cardiac, and limb defects
How do you prevent adverse effect with antiepileptic drugs?
- use lowest dose possible to maintain control
2. Folic acid 4mg daily
Isoretinoins (Ex. Accutane): adverse pregancy effects
- Miscarriage
- CNS, craniofacial, and cardiac defects
How do you protect against the ADE of Isotretinoins?
use effective pregnancy
Oral anticoagulants: Pregnancy ADEs
fetal warfarin syndrome
Carbamazepine: Pregnancy ADE
neural tube defect
Phenytoin: baby birth defects
- flat broad nose bridge
- Far apart eyes
- Crossed eyes (strabismus)
- Ptosis
- Underdeveloped fingers and toes*
Valproate: Pregnancy ADE
neural tube defects (from 1st trimester exposure)
- small mouth**
- narrow forehead
- flat philtrum
Isotretinoin (Retinoids): ADE of pregnancy
- External ear defects/absence
- congenital heart defects
- hydrocephalus*
Warfarin: Pregnancy ADEs of 1st trimester
First trimester (6-9 weeks)
- nasal hypoplasia
- calcific stippling of epiphyses
- short stubby fingers
Warfarin: Pregnancy ADEs after 1st trimester
- CNS defects
- Bone defects (ex. dwarfism, scoliosis, skull defects)
Alcohol: Pregnancy ADEs
- microcephaly
- mental retardation
- facial abnormalities
**one drink a day doesn’t change risk
ACE/ARBs: ADEs of pregnancy
- congenital renal failure
- skull abnormalities
(concern in all trimesters)
Methotrexate: ADEs of pregnancy
Folic acid antagonist
- Microcephaly
- short limbs
- hypoplastic skull with wide fontanels
(typically requires doses higher than 10mg/week
Smoking: ADEs in pregnacy
- preterm birth
- low birth weight
- spontaneous abortion
- increased perinatal mortality
Diethylstilbestrol (DES): ADE in pregnancy
- clear cell vaginal adenocarcinoma
- Premature labor
- Hypospadias in male
Radiation: ADE in pregnancy
microcephaly
Tetracycline: ADE in pregnancy
-discolored yellow-brown teeth
Cocaine: ADE in pregnancy
- increased risk of spontaneous abortion
- abruptio placentae
