Teratogens Flashcards
What is the most famous teratogen
Thalidomide
List the abnormalities found with thalidomide
- Limb Defects: Phocomelia* (1st trimester)
- External ear defect
- Visceral anomalies
List te Thalidmodes
- Lenalidomide
2. Pomalidomide
what are thalidmodes currently FDA approved in the treatment of?
- Erythema nodosum leprosum
2. Multiple myeloma
When does organogenesis occur?
18-60 weeks gestation
When do most gross malformations occur?
Before day 36
How long does CNS sensitivity last for?
2 weeks-end of gestation
Palate sensitivity?
lasts about 3 weeks
Define fetal phase
End of embryonic state to term
What do teratogens usually affect?
- CNS growth
- Intrauterine growth
- Dysfunction of a particular organ: e.g. renal failure
List the MOA of teratogenesis
- Cytotoxicity: Depressed mitosis and promotion of cell death
- Directly interfere with DNA
- Affect angiogenesis (e.g. thalidomide)
- Inhibit enzymes (e.g. warfarin)
- Nutrient and Vitamin deficiencies (e.g. folate antagonist)
Carbamazepine teratogenic
Neural Tube Defect (1%)
Phenytoin Teratogenic
- Short Fingers
- Flat, broad bridge of nose
- Far apart eyes
Valporate teratogenic
- Neural Tube Defect: 1st trimester exposure
- Developmental delay
- Narrow forehead
- Flat Philtrum
Isotretinoin (retinoids) teratogenic
- External Ear defects/absence
- Congenital Heart Dz
- Hydrocephalus
- Mental Retardation
- Wide spacing of eyes (hypertelorism)
- Clefts
What is the % of miscarriages with the use of isotretinoin
40%
Warfarin effects during the 1st trimester (6-9 weeks)
Fetal Warfarin Syndrome:
- Nasal Hypoplasia
- Calcific Stippling of epiphyses
- Short stubby fingers
Warfarin effects AFTER 1st trimester
- CNS defects from in utero hemorrhage with scarring
2. Bone defects: Dwarfism, scoliosis, skull defects
Alcohol effects
- IUGR & Postnatal Growth Retardation
- Microcephaly (small head)
- Mental Retardation
- Facial Abn: low nasal bridge, small eye openings, shot nose, smooth phitrum
How many drinks a week is associated with FAS?
2-14 drink
ACE-I/ ARB effects
- Oligohydraminos
- Congenital renal failure
- Skull abn.
Methotexate MOA
Folic Acid antagonist: MTX inhibits dihydrofolate reductase
Methotexate embryopathy
- Microcephaly
- Short Limbs
- IUGR
- Hypoplastic skull w/ wide fontanels & craniosyntosis
What Methotexate dose is typically required to cause embryopathy
> 10 mg/wk