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Reproductive > Sweatman Drugs in Pregnancy > Flashcards

Flashcards in Sweatman Drugs in Pregnancy Deck (89):
1

name some indications when we are directly giving the fetus drugs

1. lung maturation-corticosteroids
2. fetal arrhythmias-digoxin
3. patent ductus arteriosus-NSAIDS promote closure
4. anti HIV to prevent maternal infection of fetus

2

drugs that cross placenta

nearly all dude
*short term and long term effects possible
*effect depends on timing and duration of exposure and how that drug affects fetal growth

3

number of women who are pregnant and taking drugs is

declining

4

most common drugs given to pregnant women

antibiotics (10-14 days), antifungals, analgesics

5

opioid drugs of abuse

morphine, codeine, hydrocodone, naloxene, buprenorphine

6

stimulant drugs of abuse

amphetamines, cocaine, phencylidine, nicotine

7

depressant drugs of abuse

alcohol, barbiturates, cannabis, marijuana, hashish

8

hallucinogen drugs of abuse

LSD, psilocybin, mescaline, inhalants, nitirtes

9

major signs that alert of of dependency withdrawl of abused substance

autonomic hyper reactivity, irritability, excessive crying, poor feeding, and abnormal reflexes

10

rate of onset of symptoms from these abused substances depends on...

varies by drug from immediate to delayed. dependent on how much of the drug has accumulated in the CNS and the relative rate of release from the tissue (rate of decline)

11

duration of adversity

not short term--> weeks to months

12

how, in rare cases is the adversity counteracted...

by subjecting the infant to lower and tapering doses of the prescription drug

13

opiate receptors are located priminently in the

brain and enteric nervous system of the GI tract

14

in the CNS and opiate would be...
and thus, absence/withdrawal would lead to .....

sedating


CNS hyperreactivity and associated autonomic hyperactivity upon withdrawal

15

in the GI tract and opiate would be...thus, withdrawal would manifest as

consitpation---> withdrawal=diarrhea

16

neonatal narcotis abstienence syndrome varies with

opiate and time of exposure and exposure amount

17

if withdrawal symptoms are severe enough, and not responding to non-pharm (environemental measures) nor milder pharm support
what should you give

low, tapering doses of morphine or methadone

*phenobarbitol if first line agents not effective

18

fetus has an extra compartment for ciruclating drug that the mother does not have

amniotic fluid

19

placental involvement

can conduct some metabolic processed and therefore convert materials from maternal to fetal tissues

20

what determines the amount of drug that crosses the placenta

LIPID, MW, Ionization
>duration and timing (small duration less likely to cause harm)
>Maternal plasma protein binding
>Placental development and blood
>energy dependent drug trannys (pgp and MRP and BCRP)

21

rationale for heparin in pregnancy rather than warfarin

lower molecular weight
*dont wage WARFARin on baby keep the baby HEPPY

22

polymorphisms in energy dependent drug pumps can affect drug passage on an individual basis are present where

1. placenta
2. GI
3. BBB
4. Kidney

23

polymorphisms in ___, ____, _____ can determine fetal drug exposure on an individual basis (must be accounted for and different in everyone)

PGP, BCRP, MDR1

24

metabolic capabilities of placenta

hydroxylation, n-dealkylation, demethylation

25

can fetal liver metabolize drugs

yes, 40-60%, but not all the placental blood travels thru the fetal liver...there some metabolism takes place
*hepatic metabolism alters toxicity profile acting at the location of the fetus

26

placenta increases or decreased fetal exposure or toxicty

decreases exposures usually and decreaeses toxicity (placenta is kinda protective)

27

one bad thing placental metabolism does

may increase exposure to carcinogens--> benpyrene

28

use off-label for monring sickness and caused tertogenic effects in the 1950s in england

thalidomide

29

effect of thalidomide

phocomelia-seal limbs (weird stubby arms)

30

prenatal death in weeks

1 and 2

31

major morphologic abnormalitis

week 3-7

32

physiologic defects and minor morphologic defects seen in

week 8-term

33

single exposure to teratogen is unlikely to

produce adverse effects on the fetus
*expectant mother must take it on a more chronic basis, although not necessarily the entire pregnancy

34

to be a proven teratogen..must show (3)

>characteristic set of malformations
>exert effects at a particular stage of fetal development
>dose dependent incidence

35

what percentage of pregnancies are unplanned

50%

36

how many births have some sort of defect

4%
genetic or unidentified environmental factors

37

many women may go____days before they realize theya re pregnant

14--> giving time for toxic drug exposure during this critical phase of implantation and initial development

38

all candidate drugs must be tested in ____ _____. one ____ and one ____

two species
one rodent
one non-rodent

39

PERHAPS THE MODELS BEING INDICATED TO SHOW TOXICITY ARE OVERSENSITVE BECAUSE

OF THE THOUSANDS OF DRUGS OUT THERE...600 HAVE BEEN SHOWN TO BE TOXIC IN ANIMAL MODELS...LESS THAN 10% OF WHICH ARE PROVEN HUMAN TERATOGEN/TOXIC

40

6 MECHS OF RECOGNIZED TERATOGENICITY

>FOLATE ANTAGONISM
>NEURAL CREST DISRUPTION
>OXIDATIVE STRESS
>ENDOCRINE DISRUPTION
>VASCULAR DISRUPTION, >SPECIFIC RECEPTOR OR ENZYME MEDIATED EVENTS

41

folate antagonism also affects

DNA and RNA-protein synthesis

42

nuclear receptor targetting drugs such as______, can lead to up or down regulation of critical genes durining

Pax 3, cadherin, RAR, and RXR

neural crest embryologic development

43

where a drug interrupts hormonal dependent organs development

agonists or antagonist will disrupt hromonally dependent organ development

44

drugs that cuase oxidative stress do so by

teratogen stimulate prostaglandins and lipoxygenases

45

fetal hypoxia and fetal damage can be insuduced by drugs that

interrupt adequate oxygenation of developing fetus thru placental obstruction or spasm

46

ace and arb's cause

permanent renal dysfunction in the developing fetla kidney

47

widespread fetal dysfunction from lack of cholesterol for membrane production induced by

statins

48

chronic NSAIDS in pregnancy-->teratogenic on the basis that

developing body needs PG's and lipoxygenases for proper development

49

conundrum with depressed mothers

depression itself has bad outcomes for the fetus, while the SSRI's cause ahrm to the fetus to

50

SSRI's and pregnancy complications

incr. SA risk and risk of pre-eclampsia

51

SSRI's have what unique side effect in the infants

persistane PAH

52

paint the pciture of what a SSRI's teratogenized baby would look like

preterm, long, low BW, SfGA, anencephaly, omphalocele, cardiac defects, unresponsive to pain, tremors, psychomotor abn, autism

53

class A indicates

adequate studies in pregnant women-->no defects in first trimester, no increase risk in 2nd or 3rd

54

class B indicates

animal studies do not indicate risk, inadequate studies in humans,

or

animal studies show adverse effects and trials in pregnant women have been safe in first and no inc risk in 2nd or 3rd

55

class c indicates

animal studies=adverse, but no adequate studies in humans, or-no animal repro studies or human studies

56

class d

*maybe indicated if benefite>>>>risk and no other alternative
evidence of human fetal risk, but benefits might be acceptable despite potential risk

57

class x indicates

studies in animals or humans DEMONSTRATE fetal abnormalities, report indicate evidence of fetal risk, risk >>>>>>benefit in pregnant women

58

limitation for pregnancy exposure registries

unles very veyr large they will be unable to detect increased risk especially for rare malformations

59

three tools useful in determining causality

1. registry
2. case-controlled (probably able to determine causality)-->some bis
2. retrospective cohort study-->recall bias, can reveal associated but not causality

60

describe body composition and drug distribution in the newborn-first year

less body fat-lipophillic drugs distribute worse
*more body water-better distribution of hydrophillic agents

61

plasma binding in the neonate

exxagerated organ effect and greater potential distribution per dose

reduced capacity for plasma ptoetin binding in the newborn
*for drugs tat are significantly protein bound this greatly increases the free fraction-especially if another drug is even more affinity for protein

62

elimination in the neonate

immature kidney function compromises a major elimination foute for some drugs

63

skin of newborn

more easily perfused--> transdermal mroe sensitive route in the newborn

64

newborn and subcutaenous dosing

immature regulation of vascular perfusion lends to erradic absorption

65

liver/body wt for infants

larger liver/body weight in infants

66

enzyme profiles in infant

immature-->slower to break down/activate drug

67

brain/body wt ratio

larger in infants

68

blood brain barrier in infants

more permeable in infants

69

renal function in infants

immature

70

protein binding in infants

limited

71

absorption profiles in infants

slower GI
faster IM

72

neonatal changes in half life of drugs

1. in general, all drugs have longer half lives than in the adult
2. pehnytoin-dose adjustment may be necessary in an ongoing basis to account for continual organal maturation of the fetus

73

calculate dosing based on weight ratio to adult

Adults dose x (weight in kg/70)
*however, more accurately based upon Surface Area

74

breastfeeding and risk of drug exposure

the benefits of breastfeeding outweigh the risk of exposure to therapeutic agents via human breast milk

75

which ones desevere SPECIAL consideration

tose that are CONCENTRATED in the human breast milk or those that result in clinically significant on the basis of relative infant dose or detectable serum concentrations

76

caution is also advised for drugs with

unproven benefits, with long half lives that may lead to drug accumulation, or with known toxicity to the mother or infant

77

what types of drugs will be in breastmilk with greater concentrations

lipid soluble drugs
drugs with pH greater than 7 (bases)
*pH of breast milk is 7 (blood 7.4)

78

drugs that will not transfer into the breast milk as well

highly protein bound drugs

79

preferred drugs/timing during breast feeding

give dose after feeding
drugs with short half like preferred

80

time of greatest concern for drug in breast feeding

early post partum
*as the breast bud alveolar cells mature they transmit drug less and less

81

Drugs problematic in breast feeding: act in CNS: produce sedation/drowsiness/dependence

>Chloral Hydrate-drowsiness
>Methadone-withdrawal
>Diazepam-sedation
>Heroine-narcotic dependence
Lithium-avoid

82

antimicrobial problematic in breast feeding--causes grey baby syndrome

Chloramphenicol-Blood dyscrasia, bone Marrow Supress., grey baby
*if given directly or via breast milk

83

Drugs problematic in breast feeding: supress thyroid function

>iodine-thyroid supression
>Propothiouracil-thyroid supressed

84

Name some major SSRI's the pediatrician should be extra vigilant of when mother taking

Citalopram, Fluoxetine, Lamotrigene, Nortriptyline, Venlafaxine
*can exceed 10% of materanl plasmaconcentration in the infant

85

how long does it take for a functional spermatogonia to make a spermatozoon

64 days

86

paternal toxicity could cause

>mutation in the DNA or altered gene expression
>direct contact with the fetus via seminal fluid

87

paternal teratogens could lead to

early preganancy loss, still birth, preterm delivery, growth restriction

88

name some known paternal teratogens

heavy metals
solvents
pesticides
anesthetic gases, hydrocarbons
*workplace exposures

89

major drug classes represented for male teratogenicity

antivirals
anticancer
mab's
retinoids
DMARDS
AED
Androgen receptor antagonist