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REPRO > PHARM-neonatal > Flashcards

PHARM-neonatal Flashcards

1
Q

Why might you prescribe corticosteroids to a pregnant mother?

A

to stimulate lung maturation of fetus

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2
Q

why would you prescribe digoxin or flecanide to a pregnant mother?

A

treat a fetal arrhythmia

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3
Q

why would you give NSAIDs to a pregnant mother?

A

to close the ductus arteriosus

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4
Q

why would you give anti-HIV drugs to a pregnant mother?

A

to prevent the fetus from getting HIV from mom

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5
Q

Do most drugs cross the placenta?

A

YES

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6
Q

what are the 2 factors that determine the effects of drug therapy on the fetus?

A

timing and duration of exposure

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7
Q

what is the most common drug class taken during pregnancy?

A

antibiotics

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8
Q

about what percentage of pregnant women have depression?

A

20%

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9
Q

what percentage of pregnant women with depression take an antidepressant during the pregnancy?

A

~10%

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10
Q

what are the PK properties that determine whether a drug will cross the placental barrier?

A
  • lipid solubility
  • degree of ionization at physiologic pH
  • MW <600 traverse
  • duration and timing of exposure (most important)
  • maternal plasma protein drug binding
  • placental development and blood flow
  • energy dependent drug transporter proteins (P-gp, MRP, BCRP)
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11
Q

drugs that have a molecular weight greater than _____________ do not pass the placental barrier?

A

1000 (rationale for heparin use in pregnancy)

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12
Q

what are the 2 most important factors regarding trans-placental drug passage?

A

duration and timing (short term unlikely to have AE vs. chronic)

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13
Q

what are the energy dependent drug transporter proteins that may affect trans-placental drug passage?

A

P-gp
MRP
BCRP

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14
Q

what kind of changes to the energy dependent drug transporter proteins could influence the extent of fetal drug exposure?

A

polymorphisms

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15
Q

what role does the placenta play in placental drug metabolism?

A

has limited drug metabolic activity

  • aromatic oxidation (hydryoxylation, N-dealkylation, demethylation)
  • can decrease fetal exposure, decrease toxicity
  • can increase exposure to carcinogens (benzpyrene)
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16
Q

placental drug metabolism can increase the exposure to which notable carcinogen?

A

benzpyrene

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17
Q

what is phocomelia?

A

seal-limbs

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18
Q

why wasnt the thalidomide disaster quickly resolved?

A

negative animal tests delayed drug withdrawal despite increasing evidence of human tragedy

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19
Q

what is the name of the protein that thalidomide binds to?

A

cerebion

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20
Q

how does thalidomide cause phocomelia?

A

prevents expression of critical genes involved in limb development

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21
Q

what are two modern uses of thalidomide therapy?

A

leprosy and multiple myeloma

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22
Q

if a drug is going to cause an adverse effect on the developing fetus the pregnant mother must take it on a _____________basis

A

chronic

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23
Q

what are the 3 things that show that a particular drug is teratogenic?

A
  • characteristic set of malformations
  • exert effects at a particular stage of development
  • show dose-dependent incidence
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24
Q

why do many pregnant mothers expose their baby to potentially dangerous drugs?

A

about 50% of pregnancies are unplanned so the mom may be not even realize she is pregnant until about 2 weeks

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25
Q

what are the 2 types of species that are used to evaluate teratogenic potential?

A

rodent (rats) and non-rodent (rabbits)

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26
Q

what are the 6 mechanisms of teratogenicity?

A
  1. folate antagonism
  2. neural crest disruption
  3. endocrine disruption
  4. oxidative stress
  5. vascular disruption
  6. specific receptor or enzyme-mediated effects
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27
Q

which drug causes a folate antagonism?

A

lamotrigene

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28
Q

which drug causes depletion of Vit. B12; DHFR co-factor

A

cholestyramine

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29
Q

which 2 drugs are folate antimetabolites?

A

valproic acid and MTX

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30
Q

which 2 drugs cause interference with neural crest migration?

A

bosentan (pax3, cadhereins)

isotretinoin (RA & RX receptors)

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31
Q

which 2 drugs are teratogenic by having effects on sex hormone agonists/antagonists (androgen-estrogen) balance?

A

DES

environmentals

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32
Q

which drug is teratogenic by having effects on ROS generated by fetal metabolism (PG synthetases & lipoxygenases)

A

thalidomide

33
Q

which 2 drugs cause problems with placental obstruction & spasm leading to fetal hypoxia?

A

misoprostol

ergotamine

34
Q

which 2 classes of drugs cause problems in renal bloodflow & development?

A

ACEis & ARBs

35
Q

which class of drugs is teratogenic by causing cholesterol depletion?

A

statins

36
Q

are the COX inhibitors teratogens?

A

yes

37
Q

which 2 drugs have teratogenic effects by acting on serotonin receptors & transporters?

A

sumatriptan

fluoxetine

38
Q

Explain the effect of early SSRI exposure on congenital malformations?

A
  • increase risk of anencephaly, craniosynostosis, omphalocele, septal defects
  • increase risk of cardiac abnormalities
39
Q

explain the effect of early SSRI exposure on persistent PAH?

A

increased risk in infants

40
Q

can depression in a pregnant mother cause AE in the fetus?

A

YES

41
Q

what are some of the pregnancy complications of early SSRI exposure?

A

increased spontaneous abortion, increased risk of preeclampsia

42
Q

what are the effects of early SSRI exposure on pregnancy outcome?

A 
increase preterm birth
decrease gestational length
decreased birth weight
increase small for gestational age
 (smaller babies earlier)
43
Q

explain the effect of monoamines w/ early SSRI exposure?

A

decrease serotonin
decrease NE
decrease metabolites

44
Q

explain the neuro-developmental defects related to early SSRI exposure?

A
  • decreased response to acute pain
  • increased tremulousness (motor & psychomotor develop. changes)
  • increased risk of autism
45
Q

what are pregnancy exposure registries?

A
  • enroll women exposed to drug before pregn. outcomes are known
  • collect outcome data on maternal fetal & infant health
  • may focus on 1 or several drugs in same class
  • may be sponsored by drug maker or academic centers
  • size and duration limited by study objectives
  • UNLESS the registry is large, these have limited ability to detect risk, esp. for rare malformations
46
Q

how are retrospective cohort studies used in discovering drug teratogens?

A

they can reveal an association b/w maternal exposure & pregnancy outcome, but CANNOT establish a causal relationship

47
Q

how are case-control studies used in discovery drug teratogens?

A

offers ability to detect a rare event

  • may be convincing enough to establish causality
  • begins w/ outcome of interest
48
Q

what is the point of the 2007 FDA amendments act?

A

requires post-marketing studies when there is question of safety or possibility of teratogen, or when additional data are needed for safe use of an approved drug.

49
Q

what are some of the results of the use of isotretinoin during pregnancy?

A 
CNS malformations
hydrocephalus
skull & head abnormalities
IQ <85
thymus deficiency
50
Q

what do we make women do if they want to take isotretinoin?

A

sign full informed consent before prescription

  • 2 neg. pregn. tests + monthly tests
  • abstain from sex or use 2 methods of BC
  • register w/ nationwide survey
  • avoid blood donation-sharing meds
51
Q

describe the GI PK differences in neonates

A

slower GI, but faster IM absorption

52
Q

describe the body water PK differences in neonates:

A

more body water than lipid in early life

53
Q

describe the protein binding PK differences in neonates

A

limited protein binding in infants

54
Q

describe the liver PK differences in neonates:

A

larger Liver/body wt ratio in infants

55
Q

describe the enzymes PK differences in neonates:

A

immature enzymes in neonates

56
Q

describe the brain/body wt ratio in neonates:

A

larger brain/body-wt ratio

57
Q

describe the BBB PK differences in neonates:

A

higher BBB permeability

58
Q

describe the renal function in neonates:

A

immature renal function

59
Q

how does the half life of drugs typically change in babies?

A

drugs have much longer half lives (dose adjustment may be needed to account for continual maturation of various neonatal systems)

60
Q

what is a more accurate way than body wt to calculate pediatric dosing?

A

surface area

61
Q

what do you need to think carefully consider if you are going to use certain agents in a breastfeeding mom?

A

individual risk/benefit ratio

62
Q

caution is advised for drugs and agents with unproven benefits, long half-lives (which may lead to accumulation) and what 3rd category?

A

drugs having known toxicity to the mother or infant

63
Q

describe the pH and fat content of breast milk?

A

pH~7 and high fat content

  • will concentrate bases
  • will concentrate lipid soluble drugs
64
Q

if you are prescribing a drug to a breastfeeding mother do you want it to have a long or a short half life?

A

short half life

65
Q

when would you tell the breastfeeding mother to take her dose?

A

after breastfeeding

66
Q

when do you want to be most cautious with treating a mom who is breastfeeding?

A

be most cautious in early post-partum

-as breast milk buds mature they let in fewer drugs through the breast milk

67
Q

if a mom is breastfeeding and taking chloral hydrate what is the effect on the baby?

A

drowsiness if fed at peak concentrations

68
Q

if a mom is breastfeeding and taking chloramphenicol what is the effect on the baby?

A

too low for grey baby syndrome

-bone marrow suppression, blood dyscrasias

69
Q

if a mom is breastfeeding and taking diazepam what is the effect on the baby?

A

sedation; accumulation in neonates

70
Q

if a mom is breastfeeding and taking heroin what is the effect on the baby?

A

can produce narcotic dependence

71
Q

if a mom is breastfeeding and taking iodine (labeled) what is the effect on the baby?

A

thyroid suppression

72
Q

should a breastfeeding mom take lithium?

A

avoid unless levels quantitated

73
Q

what happens to the baby if a breastfeeding mom is taking methadone and then stops?

A

the baby will have withdrawal

74
Q

if a mom is breastfeeding and taking PTU what is the effect on the baby?

A

thyroid suppressed

75
Q

what are the 3 main categories of drugs that have effects on babies of breastfeeding moms?

A
  1. drugs acting on CNS (sedation or dependence)
  2. drugs that suppress thyroid function
  3. chloramphenicol (BMS, blood dyscrasias)
76
Q

what class of drugs should make pediatricians extra vigilant in monitoring infant growth and neurologic development?

A

psychoactive drugs (w/ infant serum concentrations exceeding 10% of mom’s)

77
Q

explain how a drug can cause paternal teratogenicity?

A

drug could lead to:

  • mutation in DNA or altered gene expression
  • direct contact w/ fetus via seminal fluid
78
Q

what are some of the results of paternal teratogenicity?

A

early pregnancy loss, stillbirth, preterm delivery, growth restriction

79
Q

what are the 4 major categories of drugs that cause paternal teratogenicity?

A
  1. antivirals
  2. anticancer
  3. mAbs
  4. retinoids

Also: androgen receptor antagonist, DMARD, & antiepileptic agent

REPRO (13 decks)

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