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Unit 2 Pharm III > L20: Drugs in Pregnancy > Flashcards

L20: Drugs in Pregnancy Flashcards

1
Q

Period of organogenesis

A

First trimester

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2
Q

2 main concerns when giving a drug in pregnancy

A

Whether the drug is teratogenic

Whether the drug can affect the fetus near term

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3
Q

Example of a drug that can cause hemolytic anemia if given to a fetus near term

A

UTI drugs

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4
Q

Teratogen:

A

agents that cause birth defects, congenital malformation, abnormal development in an exposed embryo or fetus:

Dose-dependent; selective for target organs
May exert effects at specific time in development
Caution in women of childbearing age
Contraception recommended or required→ not everyone realizes right away when pregnant

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5
Q

Thalidomide is super teratogenic, but most toxic during _____

A

Weeks 3-7

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6
Q

Example of a category A drug

A

Folic acid

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7
Q

Category A

A

Controlled studies show no risks

Adequate, well-controlled studies in pregnant women demonstrate no risk in any trimester of pregnancy

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8
Q

Category B

A

No evidence of risk in humans

ONE of the following:
Adequate, well-controlled studies in pregnant women have not shown and increased risk of fetal abnormalities despite adverse findings in animals,
In the absence of adequate human studies, animal studies indicate no fetal risk.

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9
Q

Category C

A

Risk cannot be ruled out

No adequate, well-controlled human studies; adverse effects shown in animal studies, or are lacking, possibility of fetal harm

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10
Q

Category D

A

Positive evidence of human fetal risk

Studies in humans have demonstrated fetal risk. “WARNING” statement about such drugs appeared on the package insert.

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11
Q

Category X

A

Contraindicated in pregnancy

Known teratogens
Use requires contraception
“Contraindication” section of the package insert.

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12
Q

8.1

A

Pregnancy

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13
Q

8.2

A

Lactation

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14
Q

8.3

A

Females and males of reproductive Potential

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15
Q

Drug absorption in pregnancy

A

Drug absorption: high circulating levels of progesterone slow gastric emptying and gut motility, resulting in slower drug absorption

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16
Q

Drug metabolism in pregnancy

A

Drug metabolism: hepatic drug metabolizing enzymes are induced during pregnancy – may lead to rapid metabolic degradation of drugs, particularly lipid soluble drugs.

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17
Q

Drug excretion in pregnancy

A

Drug excretion: renal plasma flow increased by 100% and glomerular filtration rate by 70%, drugs that are eliminated by the kidney are eliminated more rapidly than non-pregnant women.

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18
Q

Increases in total blood volume in pregnancy

A

Increase in total blood volume: change in cardiac output, blood pressure and glomerular filtration rate – leads to changes in volume of distribution of drug and metabolism, absorption, excretion, protein binding, placenta passage.

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19
Q

Always assume that ______

A

any drug taken during pregnancy will reach the fetus

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20
Q

Placenta:

A

semipermeable
barrier and site of metabolism
(oxidation reactions)

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21
Q

Placental and fetal metabolism

A

The placenta metabolizes some drugs but may also produce toxic metabolites (e.g., ethanol). Drugs that enter the fetal circulation may be metabolized by the fetal liver, and metabolites may be more toxic than the parent drugs.

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22
Q

Examples of conditions that SHOULD be treated in pregnant mothers

A

Thyroid disorders, the baby also needs T3 for development

Hypertension

Hyperglycemia

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23
Q

Drugs that may have beneficial effects in fetus

A

Avoiding preterm labor

Corticosteroids to mature lung

Antivirals to prevent transmission of herpes or HIV

Drugs for fetal heart problems

Folic acid (cat A) to prevent neural tube defects→ 400 ug/day → prevent development of neural tube defects

24
Q

Mechanisms for drugs not used in pregnancy

A

Damage or inhibit synthesis of DNA and/or RNA (i.e. Actinomycin D)

Antimetabolites and other cancer treatments: rapidly proliferating cells affected most

Radiation: therapeutic or accidental, free radicals can damage enzymes

Thalidomide: folic acid antagonist

Isotretinoin: affects cell differentiation/proliferation

Hormones may alter development

25
Q

Drugs that are ______ soluble cross the membrane, drugs that are _______ don’t

A

Cross: highly lipid soluble

Don’t cross: highly ionized

26
Q

Salicylate crosses the placenta by ____-

A

Salicylate is highly ionized BUT it has a small non-ionized highly lipid soluble fraction that crosses readily

27
Q

Why can heparin be used in pregnancy?

A

> 1000 molecular weight, can’t cross the placenta

28
Q

Why can warfarin cross the placenta?

A

Molecular weight <500

29
Q

What’s the exception to the molecular weight rule?

A

Large antibodies are transferred across the membrane

30
Q

How does the placenta keep out drugs?

A

Drug transporters:
The P-glycoprotein transporter (MDR) pumps many drugs and toxic compounds back into the maternal circulation, keeping them from crossing the placenta

31
Q

Which drugs are pumped out of the placenta by P-glycoprotein transporter?

A

Vincristine
Doxorubicin
Protease inhibitors for HIV.

32
Q

Protein binding in the fetus

A

The binding affinity of fetal proteins is lower, so drugs that may be highly bound in the maternal blood may be less so in the fetus.

Highly lipid soluble drugs like anesthetics are more influenced by rate of blood flow.

33
Q

Placental and fetal metabolism

A

the placenta metabolizes some drugs but may also produce toxic metabolites (e.g., ethanol).

Drugs that enter the fetal circulation may be metabolized by the fetal liver, and metabolites may be more toxic than the parent drugs.

34
Q

What’s the big lesson from DES use?

A

Teratogenic effects are not always seen immediately

35
Q

Diethylstilbestrol

A

1940-1971 treatment of threatened abortion

Dosage was equivalent to estrogenic effect of 55,666 birth control pills

36
Q

Diethylstilbestrol

abnormalities

A

1st trimester→ Multiple abnormalities of the vagina, cervix, and uterus consisting of vaginal and/or cervical ridges

Adenocarcinoma of the vagina or cervix has developed in some of these daughters as they entered their 20s

37
Q

Warfarin is a _____

A

Oral vitamin K antagonist that causes embryofetopathy

38
Q

Warfarin syndrome abnormalities

A 
Saddle nose, Depressed nasal bridge
Epiphyseal stippling
Vertebral calcifications
Intellectual disability
Short neck
Fetal death
39
Q

Thalidomide was used to _______

A

Sedative, combat nausea in pregnant women

40
Q

Thalidomide causes _______

A

Damage DNA through oxidative stress→ limb deformities

41
Q

Thalidomide has ______ and is subject to strict controls

A

Orphan drug status

42
Q

Isotretinoin use and MOA

A

Systemic tx of severe acne:
activate retinoic acid receptors that bind to specific DNA sequences and affect cellular differentiation and
proliferation, or induce apoptosis.

43
Q

Isotretinoin abnormalities

A

Extremely teratogenic: even 1 exposure in first 3 weeks
Birth defects : hydrocephaly; microcephaly; intellectual disability;
ear and eye abnormalities; cleft lip and palate and heart defects,
Increased the risk of miscarriage, premature delivery, infant deaths.

44
Q

iPLEDGE program for use in women:

A

For isotrentinoin

(-) pregnancy test
2 forms of birth control→ on surgical or hormonal→ start 1 month before + continue 1 month after therapy

45
Q

Ribavirin is used to treat

A

HCV

RSV

46
Q

Ribavirin causes

A

malformations of skull, palate, eye, jaw, limbs, skeleton, and GI tract

Intrauterine fetal death

Male and female-mediated teratogenicity

Aerosolized exposure problematic

47
Q

Avoiding ribavirin teratogenicity

A

hCG: before use, q month while using and 6 months after
Both men and women of
childbearing potential must use 2 forms of effective
contraception during treatment and for 6 months after
discontinuation

48
Q

Anticonvulsants

A

Very common teratogen in women of childbearing age

Safety concerns: mother, developing fetus, neonate/infant

Seizure control correlates with plasma drug concentrations: Metabolism concerns: steady state plasma concentrations of antiepileptic drugs tend to fall unless the drug doses are increased – increased maternal glomerular filtration and renal clearance (gabapentin); increased biotransformation (induction of p450s) increase elimination; dilutional effect from increased maternal fluid.

49
Q

Anticonvulsants treat

A

Epilepsy
psychiatric disorders
pain management

50
Q

Lowest risk anticonvulsants

A

levetiracetam
lamotrigine
***

gabapentin
clonazepam

51
Q

Never give this anticonvulsant

A

Valproate

52
Q

Medium risk anticonvulsants, avoid

A

Phenytoin
Phenobarbitone
Carbamazepine
Topiramate

53
Q

Feta hydantoin syndrome

A

cleft lip, cleft palate, congenital heart disease, slowed growth, mental deficiency: phenytoin, phenobarbitone

54
Q

Carbamazepine

Topiramate abnormalities

A

Craniofacial abnormalities, developmental delay, mental retardation

55
Q

Valproate abnormalities

A

1st trimester→ major and minor malformations:

Neural tube defects→ spina bifida, cleft lip/palate

Cardiovascular abnormalities, endocrine disorders, genitourinary defect, limb defects, facial abnormalities

Developmental delay, autism/autism spectrum disorder

Unit 2 Pharm III (8 decks)

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