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Spring 2018 Pharm Exam 2 > Lecture 4: Reproductive Toxicology > Flashcards

Lecture 4: Reproductive Toxicology Flashcards

1
Q

What is a repro toxicant (makeup/produced by)?

A

protein produced by organism as defense mechanism

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2
Q

3 main endpoints (harmful/AEs) for repro toxicants?

A
  1. Fertility
  2. Pregnancy outcome (birth defects, others)
  3. Lactation
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3
Q

What can Parvovirus B19 cause?

What does it not cause?

A

Can cause hydrops

Does not cause birth defects (structural malformation)

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4
Q

How does exposure level relate to repro toxicology?

A

EVERYTHING toxic at high enough dose level

NO reproductive toxicants only toxic exposure scenarios

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5
Q

Mutagenesis

Test for it?

A

changing genetic code (depends on dose)

AMES test - identifies chemicals mutagenic–> cause birth defects

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6
Q

How to do AMES test

A
  • bacteria (Salmonella) altered to be independent of AA nutrient
  • observed for back mutation to natural state
    (growth = back mutated)
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7
Q

Can mutagenesis or carcinogenesis predict reproductive toxicity?

A

NO

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8
Q

3 mechanisms for defining repro toxicant?

A
  1. Mutagenesis
  2. Carcinogenesis
  3. Endocrine activity

not good way to define it…cant predict repro toxicity and endo activ not spp

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9
Q

What is the radiation dose that is considered the counseling threshold?

A

5 rads

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10
Q

What does counseling threshold mean?

A

Abn outcome = same chance as general population

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11
Q

What is the radiation dose that definitely causes bad outcomes (microcephaly, retardation)

A

50 rads

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12
Q

What 2 circumstances is withholding Tx worse for fetus? (reason to give meds in preg)
Why?

A
  1. DM –> incr in fetal malformations

2. Asthma –> growth prob

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13
Q

What does category X in pregnancy mean?

Not mean?

A

Categ X = CI in pregnancy

DOES NOT MEAN CAUSES BIRTH DEFECTS

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14
Q

What is an example of 2 meds CI in preg (Categ X)

A
  1. Accutane

2. OCPs

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15
Q

Why is Accutane CI in preg (Categ X)?

A

causes malformation in high % of exposed embryos or other developmental abnormality

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16
Q

Why are OCPs CI in preg (Categ X)?

A

CI NOT b/c causes birth defects

CI b/c not effective/indicated in preg

17
Q

What med is in Categ D?

pt decides whether benefit > risk

A

Valproic acid

18
Q

What is included in new labels of drugs (3)?

A
  1. Risk summary (of human + animal studies)
  2. Clinical considerations (risk of untreated dz, dose adjustment in preg)
  3. Summary of data
19
Q

What type of study typically done before drug 1st marketed

A

Experimental animal studies `

20
Q

Why are monkeys worse than rats for experimental animal studies?

A

monkeys = less offspring per preg –> less opportunities for fetal malformations

21
Q

ACE inhibitor toxicity leads to what?

A

Absence of scalp/skill

poison fetal RAAS –> HoTN –> dont urinate–> absensce of amniotic fluid –> pressure necrosis of scalp

22
Q

When does the fetal RAAS develop?

A

fetal RAAS dev in 2nd trimester

23
Q

What does Diethylstilbestrol (DES) cause (2 things)?

A

Clear cell carcinoma & malformations of developing genital tract

24
Q

What are the 2 malformations of developing genital tract caused by Diethylstilbestrol?

A
  1. T shaped uterine cavity (instead of triangular)

2. Norm vaginal epithelium replaced by columnar epithelium –> more risk for CA as adolescent

25
Q

Why was Diethylstilbestrol prescribed originally?

A

Given to pregnant women to prevent miscarriage, premature labor, and related complications

26
Q

What drug causes Phocomelia?

what is Phocomelia?

A

Thalidomide

Malformations of the arms and legs

27
Q

What is selective embryotoxicity?

What drug exhibits this?

A

at certain doses the drug is selectively toxic to embryo (not mother)

Thalidomide

28
Q

What are 2 future types of testing for repro toxicity adverse outcome pathways?

A

In vitro/silico screening

29
Q

3 molecular initiating events in the adverse outcome pathway

A
  1. Receptor activation

2/3. protein or DNA binding

30
Q

3 key events in the adverse outcome pathway

A
  1. Gene activation, Protein production
  2. Altered signaling
  3. Altered tissue, disrupted homeostasis
31
Q

3 Adverse outcomes in the adverse outcome pathway

A
  1. malformations
  2. organ dysfxn
  3. lethality

Spring 2018 Pharm Exam 2 (6 decks)

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