Teratogenesis Flashcards
Which is the most famous teratogen?
Thalidomide
When is the critical period of using thalidomide?
34th and 50 day after last menstrual period
Children exposed to Thalidomide during the first trimester develop what?
Phocomelia (limb defects)
When in pregnancy is the ovum resistant to teratogenic agents
During 2 week period between conception and implantation
During development when does organogenesis occur?
Days 18-60
What is defined as the fetal phase?
From end of embryonic state to term
Characterized by growth of already developed organs
What are examples of CNS functions that are disrupted with Teratogenesis
cause intrauterine growth retardation, or cause dysfunction of a particular organ (e.g., renal failure)
MOA of Teratogenesis?
Antineoplastic agents often produce teratogenicity through cytotoxicity (depressed mitosis and promotion of cell death) of critical cell masses. Attempts at repair may lead to uncoordinated growth and exacerbation of the original malformation
What are other MOA of Teratogenesis
Directly affects DNA
Affects angiogenesis during developement
Inhibits enzymes needed for organ development
Deplete nutrient and vitamins
FDA Pregnancy Categories
What is Category A defined as?
Adequate and well-controlled studies have failed to demonstrate a risk to the fetus in the first trimester of pregnancy (and there is no evidence of risk in later trimesters)
- Folic acid
- levothyroxine
Category B and meds
Animal reproduction studies have failed to demonstrate a risk to the fetus and there are no adequate and well-controlled studies in pregnant women
- Amoxicillin
- Insulin R and N
Which grade pregnancy is absolutely contradindicated for treatments
Category X
Category C
Animal reproduction studies have shown an adverse effect on the fetus and there are no adequate and well-controlled studies in humans, but potential benefits may warrant use of the drug in pregnant women despite potential risks
- Sertraline, fluoxetine
- albuterol
Which teratogens have preconception risk factors and considered dangerous for pregnancy
Antiepileptic drugs
Carbamazepine
Phenytoin
Valproate
Isotertinoins
Oral anticoagulants (warfarin)
Slide 14 Potential adverse effects and Prevention
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What adverse effect can Carbamezapine have on babies
Neural tube defects
How can Valproate effect baby developement
Neural tube defects
Small mouth
Narrow forehead
Flat philtrum
Phenytoin and how it effects baby developement
Flat, broad nose
Shortened fingers
Isoretinoids and how it effects baby development
external ear defects/absence, congenital heart defects, hydrocephalus, mental retardation, clefts.
How does Warfarin effect baby development?
Produces fetal warfarin syndrome
- nasal hypoplasia
- calcific stippling of epiphyses
- short stubby fingers
What affects can alcohol have on fetal developement
IUGR and postnatal growth retardation
Microcephaly
Mental retardation
Facial abnormalities.
FAS is likely to develop with ingestion of how many drinks per week
2-14 weeks
How do ACE-I and ARBs affect fetal development
Congenital renal failure
Skull abnormalities,
Oligohydramnios (from impaired renal formation and function)
When are ACE-I and ARBS not considered teratogenic?
First trimester
MOA of Methotrexate?
Folic acid antagonist
It inhibits dihydrofolate reductase
What are teratogenic effects when taking Methotexate
Microcephaly
Short limbs
IUGR
Hypoplastic skull with wide fontanels and craniosynostosis
What teratogenic affect does Diethylstilbesterol (DES) have
Clear cell vaginal adenocarcinoma
Premature labor (as teenager or adult) in female offspring
Hypospadias in male offspring
What teratogenic affect does radiation have?
Microephaly and mental retardation
If intense enough can cause cancer
How can Tetracycline affect children?
Discoloration of teeth from deposition of antibiotic in calcifying teeth