teratogens Flashcards
Thalidomide original use
originally used for tx of influenza, became used as anti-emetic and sleep aid
Thalidomide critical period
between 34th and 50th day after last menstrual period
20-30% of children exposed to thalidomide during critical period in 1st trimester developed…
limb defects aka phocomelia
Other abnormalities produced include external ear defects, visceral anomalies (agenesis of organs)
what are the 3 stages of development involved w/teratogenesis
- The ovum prior to fertilization is resistant to teratogenic agents
- During approximate 2wk period between conception and implantation (preimplantation stage)
- Organogenesis occurs from days 18 – 60 gestation
what teratogenic changes can occur during
fertilized ovum is generally resistant to teratogenic insults
relatively isolated from the maternal circulation
what teratogenic changes can occur during Organogenesis occurs from days 18 – 60 gestation
most gross malformations are determined before day 36
genitourinary and craniofacial anomalies can occur later
period of susceptibility (“critical period”) varies for each organ system
palate has period of sensitivity lasting about 3 weeks
CNS sensitivity lasts from about 2wks to near the end of gestation
teratogenesis and fetal phase
From end of embryonic state to term characterized by growth of already developed organs
Teratogens usually don’t cause gross structural abnormalities, but may cause…
CNS dysfunction, intrauterine growth retardation, or dysfunction of a particular organ (e.g., renal failure
when do effects of teratogenesis occur more frequently??
at higher doses rather than lower doses
Possible MOA of teratogenesis?
cytotoxicity of critical cell masses
directly interact w/DNA
angiogenesis during critical periods of development
inhibit enzymes
nutrient and vitamin deficiences
FDA pregnancy category A?
Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (no evidence of risk in later trimesters)
2 examples of FDA category A
Folic acid
levothyroxine
FDA pregnancy category B?
Animal reproduction studies have failed to demonstrate a risk to the fetus
2 examples of category B
Amoxicillin
Insulin R and N
FDA pregnancy Category C?
Animal reproduction studies have shown an adverse effect on the fetus
examples of category C?
Sertraline, fluoxetine
albuterol
T or F: Not all know animal teratogens have been found to be teratogenic in humans
True.
almost all known human teratogens have also been found to be teratogenic in animals
potential adverse pregnancy outcomes of anti-epileptic drugs? ie. Carbamazepine, phenytoin, valproate
causes craniofacial, cardiac, and limb defects
NTD 1%-10x background rate
Fetal hydantoin syndrome
management or prevention options for using anti-epileptic drugs in pregnancy
Use lowest possible dose to maintain control
Folic acid 4 mg daily
potential adverse pregnancy outcomes of isotretinoins?
Miscarriage
Known teratogen; causes CNS, craniofacial, and cardiac defects
management or prevention options for using isotretinoins?
Use effective pregnancy prevention
potential adverse pregnancy outcomes of oral anticoagulants?
fetal warfarin syndrome
management or prevention options for using oral anticoagulants?
Switch to nonteratogenic anticoagulant (e.g., LMWH) before becoming pregnant
Carbamazepine has a 1% risk of…
neural tube defects
possibly similar effects to phenytoin embryopathy
Valproate teratogenic effects during pregnancy
Neural tube defects from 1st trimester exposure, small mouth, developmental delay, narrow forehead, flat philtrum
Isotretinoin (retinoids) teratogenic effects
Abnormalities include external ear defects/absence, congenital heart defects, hydrocephalus, mental retardation, hypertelorism, and clefts.
~40% Miscarriag
Warfarin teratogenic effects during 1st trimester exposure (6-9wks)
produces fetal warfarin syndrome:
nasal hypoplasia,
calcific stippling of epiphyses, short stubby fingers
Warfarin teratogenic effects after first trimester
CNS defects from in utero hemorrhage with scarring
Bone defects–including dwarfism, scoliosis, skull defects
Alcohol misuse teratogenic effects? management?
Fetal alcohol syndrome –> cease alcohol intake before conception
teratogenic effects and obesity? management?
NTD
Preterm delivery
Diabetes, HTN, VTE
Cesarean section
wt. loss w/approp. nutritional intake
characteristics of fetal alcohol syndrome?
IUGR and postnatal growth retardation, Microcephaly, Mental retardation, Facial abnormalities
facial abnormalities seen in fetal alcohol syndrome?
small head, low nasal bridge, small eye openings, short nose, thin upper lip, smooth philtrum, underdeveloped jaw
ACE’s and ARB’s can result in…
Congenital renal failure, skull abnormalities, Oligohydramnios –> deformities (limb contractures, skull, facial)
Methtrexate MOA
Folic acid antagonist
MTX inhibits dihydrofolate reductase
embryopathy caused from methotrexate
Microcephaly
Short limbs
IUGR
Hypoplastic skull with wide fontanels and craniosynostosis
Typically requires doses > 10 mg/wk
adverse outcomes w/tobacco use during pregnancy
Preterm birth
Low birth weight
Spontaneous abortion
Increased perinatal mortality
management for tobacco use and pregnancy
cease tobacco use before conception
Nonpharmacologic therapies (CBT)
No consensus for NRT product, dosing, or frequency
what is DES causes
Clear cell vaginal adenocarcinoma
Premature labor (as teenager or adult) in female offspring
Hypospadias in male offspring
radiation and pregnancy
Microcephaly and mental retardation
If intense enough, concern for cancer
Tetracycline?
Bacteriostatic drug that inhibits protein synthesis
tetracycline ADE’s
Discolored teeth (yellow-brown staining) from deposition of antibiotic in calcifying teeth
Risk only after 17 weeks of gestation
