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Therapeutics > Drug Use In Pregnancy > Flashcards

Drug Use In Pregnancy Flashcards

1
Q

Most drugs move from the maternal circulation into the fetal circulation by:

A

Diffusion

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2
Q

Maternal albumin ___(decreases/increases), while fetal albumin ___(decreases/increases) throughout pregnancy.

A

Decreases; Increases

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3
Q

High fetal albumin means:

A

High concentration of
protein-bound drugs

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4
Q

Are pregnant women eligible to participate in clinical trials?

A

NO

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5
Q

___ was found safe in animal studies, but teratogenic in humans.

A

Thalidomide

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6
Q

The available clinical studies in pregnancies suffer from which kind of bias?

A

Recall bias

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7
Q

The available clinical studies in pregnancies suffer from bias and require:

A

Large number of subjects

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8
Q

What are the reasons for drug therapy in pregnancy?

A

1) Pregnancy-induced conditions
2) Chronic conditions diagnosed before pregnancy
3) Acute conditions that may occur during pregnancy
4) Fetal therapy

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9
Q

What are some common pregnancy induced conditions?

A

1) Nausea
2) Vomiting
3) Preeclampsia
4) Eclampsia

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10
Q

Which drugs are used for fetal therapy?

A

1) Corticosteroids
2) Phenobarbital
3) Zidovudine

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11
Q

Why are corticosteroids given for fetal therapy?

A

To stimulate fetal lung maturation (surfactant) when preterm birth is expected

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12
Q

Why is Phenobarbital given for fetal therapy?

A

Induce fetal hepatic enzymes responsible for the glucuronidation of bilirubin

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13
Q

Giving Phenobarbital as fetal therapy lowers the risk of ___ in newborns.

A

Jaundice

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14
Q

Why is Zidovudine given for fetal therapy?

A

Decreases transmission of HIV from the mother to the fetus.

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15
Q

Combinations of __ antiretroviral agents can eliminate fetal HIV infection almost entirely.

A

Three

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16
Q

What factors affect placental drug transfer?

A

1) The physicochemical properties of the drug
2) The duration of exposure to the drug
3) Pharmacokinetics of the drug in fetal tissues

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17
Q

Drug passage across the
placenta is dependent on:

A

1) Lipid solubility
2) Degree of drug ionization

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18
Q

___(Lipophobic/Lipophilic) drugs tend to diffuse readily across the placenta and enter the fetal circulation.

A

Lipophilic

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19
Q

How long does Thiopental take to cross the placenta?

A

Immediately

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20
Q

What can Thiopental cause in newborn infants?

A

1) Sedation
2) Apnea

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21
Q

Should we use Thiopental as anesthesia in C-sections?

A

No

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22
Q

Tubocurarine is a ___(high/low) ionized drug.

A

High

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23
Q

Highly ionized drugs cross the placenta ___(rapidly/slowly) and achieve very ___(high/low) concentrations in the fetus.

A

Slowly; Low

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24
Q

Impermeability of the placenta to polar (or ionized) compounds is ___(relative/absolute).

A

Relative

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25
Q

What happens if high enough maternal-fetal concentration of highly ionized drug gradients are achieved?

A

Polar compounds can cross the placenta in measurable amounts

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26
Q

Which drug is almost completely ionized at physiologic pH?

A

Salicylate

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27
Q

Why does Salicylate cross the placenta rapidly?

A

Because the small amount of salicylate that is un-ionized is highly lipid-soluble.

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28
Q

Drugs with molecular weights of __–__ daltons can cross the placenta easily.

A

250-500

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29
Q

Drugs with molecular weights of __–__ daltons cross the placenta with difficulty.

A

500-1000

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30
Q

Drugs with molecular weights >__ daltons cross the placenta very poorly.

A

1000

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31
Q

Why is Heparin unable to cross the placenta?

A

1) Large size
2) Highly polar

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32
Q

Does insulin cross the placenta?

A

No

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33
Q

Maternal blood has a pH of ___ while fetal blood is __.

A

7.4; 7.3

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34
Q

Weakly basic drugs with pKa above 7.4 will be ___(more/less) ionized in the fetal compartment.

A

More

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35
Q

Weakly basic drugs with pKa above 7.4 will lead to:

A

Ion trapping = higher fetal blood levels

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36
Q

Many drug transporters have been identified in the placental ____ membrane.

A

Brush border

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37
Q

____ transporter pumps back a variety of drugs into the maternal circulation

A

P-glycoprotein

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38
Q

What drugs does P-glycoprotein transporter pump back?

A

1) Anticancer drugs (Vinblastine, Doxorubicin)
2) Anti-HIV drugs

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39
Q

Binding of drugs to plasma proteins (particularly albumin) may reduce:

A

1) Rate of transfer
2) Amount transferred

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40
Q

The transfer of highly lipid soluble drugs will depend on:

A

Placental blood flow

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41
Q

Which drug is highly lipid soluble?

A

Thiopental

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42
Q

Fetal proteins have __(higher/lower) binding affinity than maternal proteins.

A

Lower

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43
Q

Very high maternal protein binding of ___ is associated with lower fetal blood levels. Why?

A

Glyburide;
1) It does not cross the placenta
2) Effluxed from the fetal circulation

44
Q

The placenta plays a role as a site of ___ of some drugs passing through it.

A

Metabolism

45
Q

___ is oxidized by the placenta.

A

Pentobarbital

46
Q

Very high maternal protein binding of glyburide is associated with:

A

Lower fetal blood levels

47
Q

The metabolic capacity of the placenta may lead to formation of:

A

Toxic metabolites (ethanol,
benz(a)pyrenes)

48
Q

Some drugs that enter the fetal ___ may be partially metabolized before reaching the fetal circulation.

A

Liver

49
Q

What are the possible effects of drugs on the fetus?

A

1) No Effect
2) Restricted growth
3) Impairment of functional development
4) Placental damage, Abortion & Death
5) Neonatal problems
6) Congenital malformations (Teratogenicity)

50
Q

The baseline risk of congenital malformations is:

A

3-6%

51
Q

< _% of congenital malformations are due to drugs.

A

1

52
Q

65-75% of congenital malformations are:

A

Idiopathic

53
Q

What are the causes of Congenital Malformations?

A

1) X-Radiation
2) UV radiation (skin cancer).
3) Viral Infections
4) Drugs and chemicals (Thalidomide and limb
deformities)

54
Q

Which maternal viral infection can cause congenital malformations?

A

Rubella

55
Q

For >90% of available drugs, the human teratogenic risk is NOT determined. Why?

A

1) Drug experiments during human pregnancy to test for teratogenicity is unethical and
prohibited.

2) Evidence to support teratogenesis is derived from animal studies. (Not accurate)

56
Q

Types of congenital anomalies are determined by:

A

The time of exposure during pregnancy

57
Q

What is phocomelia?

A

Congenital anomaly where the proximal aspect of an extremity is absent with the hand or foot attached directly to the trunk. (no arm or leg, just hand or foot)

58
Q

Which drug causes phocomelia?

A

Thalidomide

59
Q

The thalidomide phocomelia risk occurs during which weeks of gestation?

A

4th-7th (when the arms & legs develop)

60
Q

What are the possible teratogenic mechanisms?

A

1) Folic acid deficiency, or use of folic acid antagonists
2) Neural crest cells disruption
3) Drugs may disrupt the normal processes of cell differentiation
4) Endocrine disruptions
5) Oxidative stress
6) Vascular disruption
7) Chronic high consumption of ethanol
8) Smoking

61
Q

What congenital anomaly is caused by folic acid deficiency?

A

Neural tube defects (spina bifida)

62
Q

Neural crest cells disruption can be caused by:

A

1) Endothelin receptor blockers
2) Folic acid antagonists
3) Retinoic acid

63
Q

What drug is an endothelin receptor blocker?

A

Bosentan

64
Q

Which drugs may disrupt the normal processes of cell differentiation?

A

Vitamin A analogs (isotretinoin,
etretinate)

65
Q

______ increased the risk of vaginal adenocarcinoma in daughters, and hypospadias and cryptorchidism in sons of mothers taking it during pregnancy

A

Diethylstilbesterol

66
Q

Oxidative stress (reactive oxygen species) causes:

A

Irreversible damage of DNA, proteins, and lipids = inactivation of many enzymes and cell
death + alteration of gene expression.

67
Q

Diethylstilbesterol increased the risk of ___ in daughters, and hypospadias and cryptorchidism in sons of mothers taking it during pregnancy

A

Vaginal adenocarcinoma

68
Q

Vascular disruption includes:

A

1) Hypoperfusion
2) Hyperperfusion
3) Hypoxia
4) Obstruction

69
Q

Which trimesters are the worst for alcohol drinking?

A

First and second

70
Q

What can alcohol drinking during pregnancy cause?

A

Fetal Alcohol Syndrome

71
Q

Fetal Alcohol Syndrome affects:

A

1) CNS
2) Growth
3) Facial development

72
Q

Craniosynostosis is caused by:

A

Maternal smoking

73
Q

To be considered teratogenic, a drug should:

A

1) Result in a characteristic set of malformations, indicating selectivity for certain target organs.

2) Exert its effects at a particular stage of fetal development, during the limited time period of
organogenesis of the target organs.

3) Show a dose-dependent incidence.

74
Q

What factors affect the production of congenital malformations?

A

1) The dose of the teratogen (dose-dependent)
2) The developmental stage of the embryo
3) The Genetic Susceptibility of the Embryo
4) The physiological and pathological status of the mother

75
Q

To prevent congenital malformations give the mother the __(highest/lowest) effective dose for the ___(shortest/longest) duration.

A

Lowest; Shortest

76
Q

What is the timeline for blastogenesis?

A

Time of fertilization - Implantation (1-8 days)

77
Q

Normal human development first begins with:

A

Blastogenesis

78
Q

Up to which day after fertilization are the cells still totipotent and damaged cells replaced?

A

15th day

79
Q

What is the timeline for embryogenesis?

A

Time of implantation - the end of 8th week (2nd– 8th week).

80
Q

What happens if the blastocyst is exposed to teratogens?

A

Death. It WONT survive to show any malformations.

81
Q

When is the vulnerability of the developing embryo to teratogens greatest?

A

During embryogenesis (2nd-8th week)

82
Q

Why is embryogenesis the most vulnerable time?

A

Because this is the critical period for organogenesis

83
Q

What happens if the embryo is exposed to teratogens?

A

1) Gross malformations
OR
2) Fetal death

84
Q

What is the timeline for fetogenesis?

A

End of 8th week - End of pregnancy

85
Q

The most important events of fetogenesis are:

A

1) Differentiation of external genitalia
2) Histogenesis of CNS

86
Q

What happens if the fetus is exposed to teratogens?

A

1) Impairment of differentiation of external genitalia
2) Behavioral changes or impairment of mental development

87
Q

Is there a known teratogen that can cause congenital malformation in ALL fetuses?

A

No

88
Q

Which maternal physiological and pathological statuses can cause congenital malformations?

A

1) Age
2) Nutritional status (malnutrition)
3) Disease states (DM)

89
Q

What maternal ages have higher risk of congenital malformations?

A

1) <18 years
2) >35 years

90
Q

What happens if you give teratogenic drugs LATE or VERY NEAR DELIVERY in pregnancy?

A

NO congenital malformations, but adverse effects will occur.

91
Q

What happens if you give salicylates late in pregnancy?

A

May increase bleeding or delay
labor = low birth weight

92
Q

What happens if you give ACEis late in pregnancy?

A

Irreversible fetal renal damage

93
Q

What happens if you give opioids late in pregnancy?

A

Dependence in the fetus

94
Q

What happens if you give Thiopental very near delivery?

A

Sedation and apnea in the newborn

95
Q

What happens if you give opioids very near delivery?

A

Apnea in the newborn

96
Q

The risk of a neonatal abnormality in the absence of any known teratogenic exposure is about __.

A

3%

97
Q

What are some drugs associated with congenital anomalies during organogenesis?

A

1) Methotrexate
2) Cyclophosphamide
3) Sex hormones (androgens,
estrogens and progestins)
4) Lithium
5) Retinoids
6) Thalidomide
7) Certain antiepileptic drugs
8) Coumarins (ex. Warfarin)

98
Q

Which two drugs are likely to produce adverse effects during the second and third
trimesters?

A

1) NSAIDs
2) Tetracycline

99
Q

A drug that is categorized by the FDA as Category A is:

A

Safe to use during in pregnancy (No evidence of fetal risk)

100
Q

A drug that is categorized by the FDA as Category B is:

A

Relatively safe

101
Q

A drug that is categorized by the FDA as Category C:

A

Information about fetal risk is not available but risk can NOT be ruled out

102
Q

A drug that is categorized by the FDA as Category D:

A

Positive evidence of fetal risk

103
Q

A drug that is categorized by the FDA as Category X:

A

Definite fetal risk and the drug is contraindicated during pregnancy

104
Q

Which are better? Effective old drugs or new alternative drugs?

A

Effective old drugs

105
Q

Which drug is absolutely safe during pregnancy at high doses?

A

NONE

106
Q

What are some strategies to optimize the health of the mother while minimizing the risk to the fetus?

A

1) Identification of the pattern of medication use before conception

2) Eliminating nonessential medications

3) Discouraging self medication

4) Minimizing exposure to medications known to be harmful

5) Adjusting medication dosing

Therapeutics (23 decks)

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