PHRD5935 Pharm/Tox Lecture 13 - Developmental Toxicology

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daynuhmay
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PHRD5935 Pharm/Tox Lecture 13 - Developmental Toxicology
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2014-05-19 07:33:57
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Developmental Toxicology
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Developmental Toxicology
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  1. any structural or functional alteration, reversible or irreversible, caused by environmental insule, which interferes w/ homeostasis, normal growth, differentiation, development, and/or behavior
    developmental toxicity
  2. fetotoxicity
    altered growth
  3. malformation & fcnal deficit
    teratogenicity
  4. 4 outcomes resulting from developmental toxins
    • 1) lethality
    • 2) malformation
    • 3) fcnal disorder
    • 4) growth retardation
  5. most important concept in dev tox
    stage-specific sensitivity to toxins
  6. how do chemicals produce teratogenic effects?
    disrupt the developmental program
  7. what teratogenecity is governed by
    dose-effect relations
  8. why does Vd vary so much during pregnancy
    buildup of fat & water is not uniform throughout gestation
  9. change in oral absorption due to pregnancy
    • dec in GI motility
    • delayed stomach emptying
  10. change in elimination during pregnancy
    • inc GFR 
    • more rapid renal excretion
  11. drugs MW >____ do not easily cross the placental membrane
    1000
  12. drugs MW <____ DO cross the placental membrane
    600
  13. most chemical drugs have a MW of...
    250-400
  14. pregnancy category of beta blockers
    Category C
  15. pregnancy category of ASA
    Category C
  16. pregnancy category of alcohol
    Category D
  17. sensitive period of exposure to thalidomide
    20-40days
  18. thalidomide mech of teratogenic action
    prevents angiogenic outgrowth during early limb formation
  19. non-steroidal estrogen responsible for genital tract anomalies in offspring
    DES (diethylstilbestrol)
  20. anticonvulsant mood-stabilizing drug linked to malformed children exposed in utero (eg: spina bifida, prominent forehead)
    valproic acid (Depakote)
  21. valproic acid mech of teratogenesis
    deregulation of retinoic acid homeostasis
  22. manic-depressive psychosis tx assoc'd w/ cardiovascular anomalies & cleft palate
    lithium
  23. anticoagulant of choice in pregnancy
    heparin (doesn't cross placenta)
  24. teratogenic effect of warfarin if exposed during the FIRST trimester
    axial & appendicular skeleton effects
  25. teratogenic effect of warfarin if exposed during SECOND & THIRD trimesters
    CNS disorders (mental retardation)
  26. drug assoc'd w/ significant adverse effects on the fetal kidney
    ACE inhibitors
  27. critical exposure time to retinoic acid during pregnancy
    3-5 weeks
  28. drug that induces birth defects by disrupting the vasculature in the placenta, thereby inducing intrauterine hypoxia & malnutrition
    cocaine
  29. even brief periods of decreased ____ concentrations are teratogenic
    glucose
  30. protozoan parasite able to cross the placenta
    toxoplasma gondii
  31. 5 drugs thought to be teratogenic but are safe
    • 1) diazepam
    • 2) OC's
    • 3) spermicides
    • 4) salicylates
    • 5) bendectin
  32. drug that is a combination of doxylamine & vit B6 thought to be teratogenic but is safe
    bendectin
  33. agents to be avoided during breast feeding (5)
    • 1) cancer chemotherapy drugs
    • 2) abx
    • 3) narcotics
    • 4) androgens
    • 5) cimetidine
  34. estimation of infant's dose while breastfeeding
    [conc in milk] x [vol milk consumed]
  35. important value during breastfeeding
    milk:plasma ratio of drug (if >1, concentrated into milk & not rec'd to use during breastfeeding)
  36. time required to eliminate 90-95% of an agent (equally dist'd in the plasma & milk)
    3-5 plasma elimination half-lives

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