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Reproductive > PHARM: Fetal-Neonatal Pharmacology > Flashcards

PHARM: Fetal-Neonatal Pharmacology Flashcards

1
Q

What is the most commonly used drug class in pregnant women?

A

antibiotics

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2
Q

What are the two most important factors in the transmission of a teratogen across the placenta?

A

duration (chronic use) and timing (early in pregnancy is worse for organ malformations)

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3
Q

What is the absolute size restriction for drugs passing through the placenta?

A

molecular weight >1000

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4
Q

True or False: The placenta has the capacity to conduct metabolic processes?

A

TRUE: (ex. aromatic oxidation—hydroxylation, N-dealkylation, demethylation) can convert drug materials passing from maternal to fetal tissue (may reduce OR increase toxicity).

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5
Q

What is the major concern of energy dependent drug transporter proteins (can push drug against its concentration gradient) in the placenta?

A

polymorphisms that make them overactive

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6
Q

True or False: the liver of the fetus is too immature to take part in maternal drug metabolism.

A

FALSE: fetus can also alter the toxicity profile!

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7
Q

Why is drug binding important in pregnant women?

A

Limited plasma protein binding of drugs in the neonate is important clinically, because free drug can disperse better and is more quickly metabolized.
• Neonate has worse plasma protein binding (need to crank dose down)

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8
Q

What drugs lead to folate antagonism?

A

Lamotrigene, cholestyramine, valproic acid

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9
Q

How do Lamotrigene, cholestyramine, and valproic acid lead to teratogenicity?

A

Interference with folate causes interruption of RNA, DNA, and protein synthesis

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10
Q

What drugs lead to neural crest disruption?

A

Bosentan

Isotretinoin

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11
Q

How do Bosentan and Isotretinoin lead to teratogenicitiy?

A

Nuclear receptor target (Pax 3, RAR, RXR, cadherin) disruption can lead to down regulation of critical genes during neural crest embryologic development

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12
Q

What drugs lead to fetal endocrine disruption?

A

DES, environmentals

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13
Q

How do DES and environmentals casue teratogenicity?

A

If an organ is hormonally dependent, drugs that are hormonal agonists or antagonists can disrupt development

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14
Q

What drugs lead to oxidative stress in fetuses?

A

Thalidomide (not in EVERY neonate exposed, only in the 14 day period when limbs form)

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15
Q

How did thalidomide cause teratogenicity?

A

Prostaglandins and lipoxygenases are stimulated by teratogens and can lead to ROS that cause cellular dysfunction

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16
Q

What drugs lead to vascular disruption in fetuses?

A

Misoprostol and ergotamine

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17
Q

How do misoprostol and ergotamine cause teratogenicity?

A

interrupt adequate oxygenation of developing fetus though production of placental obstruction or spasm can lead to fetal hypoxia/damage

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18
Q

What effects do ACEIs and ARBs have on the fetus?

A

Functional impairment of kidney

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19
Q

What effects do SSRIs (ex. sumatriptan, fluoxetine) have on the fetus?

A

SSRIs act in unknown mechanism to cause congenital malformations, PAH, physical and developmental adversities (need to ask if depression is also playing a role in these).

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20
Q

What effects do statins have on the fetus?

A

decrease availability of cholesterol for membrane structure and function in the fetus

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21
Q

What effects do NSAIDs have on the fetus?

A

produce dysfunction by decreasing COX products in the cell (can lead to failure of DA closure if given in utero)

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22
Q

What effects does warfarin have on the fetus?

A

Early, can cause fetal bleeding. Later it can cause other problems (scarring of organs).

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23
Q

What may occur in newly delivered infants who have been acutely withdrawn from continued trans-placental drug transfer?

A

physical dependence manifests as withdrawal

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24
Q

What are the most common symptoms of drug withdrawal in infants?

A

autonomic hyperactivity with irritability, excessive crying, poor feeding and abnormal reflexes

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25
Q

What factors alter the onset of withdrawal symptoms in the infant?

A

drug type
how much of the drug has accumulated in the CNS
relative rate of release from tissue (rate of decline)

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26
Q

How might you reduce the duration of adverse withdrawal symptoms?

A

re-exposing neonate to lower drug doses and tapering them down.

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27
Q

What are the major receptor locations of opiates?

A

CNS depressant and GI (constipation

28
Q

What are CNS symptoms of opiate withdrawal?

A 
CNS hyperactivity (ex. tremors, seizures, increased wakefulness, high-pitched cry, frequent yawning/sneezing, etc.)
associated autonomic hyperactivity (ex. sweating, fever, nasal stuffiness)
29
Q

What are the GI symptoms of opiate withdrawal?

A

diarrhea, dehydration, vomiting, poor weight gain

30
Q

True or false: all drugs are tested for teratogenicity in at least 4 species.

A

FALSE: in two (rodent and non-rodent)

31
Q

What must a drug show to be classified as a teratogen?

A

1) must have characteristic set of malformations
2) must exert effects at a particular stage of fetal development
3) must show dose-dependent incidence

32
Q

Name the category of teratogenicity:
Animal studies have shown adverse effects on fetus but there are no adequate studies in humans OR no adequate animal or human studies

A

C

33
Q

Name the category of teratogenicity:
Studies in animals of humans demonstrate fetal abnormalities or adverse reaction—reports indicate evidence of fetal risk. Risk of use in pregnant woman clearly outweighs any possible benefit

A

X

34
Q

Name the category of teratogenicity:
Animal studies have not demonstrated risk to fetus but no adequate studies in pregnant women OR animal studies show adverse effect but no risk to fetus during human studies

A

B

35
Q

Name the category of teratogenicity:

Studies have not demonstrated risk to fetus in first trimester; no evidence for later effects.

A

A

36
Q

Name the category of teratogenicity:
Evidence of human fetal risk. Physician may encounter situations in which a drug of this category might be necessary during pregnancy if no alternative agent is available. Under these circumstances a careful analysis of the drugs known adverse effects, the patient’s clinical condition, and significantly, the stage of pregnancy, should all be considered when making a decision as to whether or not a drug should be used.

A

D

37
Q

When does paternal teratogenicity occur?

A

Major toxicant exposure during spermatogenesis can lead to mutation in DNA or altered gene expression and toxic exposure of developing fetus to seminal fluid can also occur.

38
Q

Name the 3 “weird” drugs that lead to male teratogenicity.

A

enzalutamide
leflunomide (DMARD)
pregabalin (antiepileptic)

39
Q

What drugs are better dispersed in new-borns: lipophillic or hydrophillic agents?

A

little body fat for lipophilic drugs and a higher percentage of total body water and extracellular water for districution of hydrophilic agents

40
Q

Why do newborns have a significant increases in free drug fraction?

A

a reduced capacity for plasma protein binding by drugs in the neonate

41
Q

What is the problem with subcutaneous treatment of newborns?

A

good skin perfusion but immature regulation of vascular perfusion so subcutaneous administration may be absorbed in an erratic manner

42
Q

How do you best dose pediatric patients?

A

Pediatric dosing is most accurately based upon surface area, but you can calculate based upon (adult dose X (weight in kg/70).

43
Q

What drugs are best transmitted by breast milk? Why?

A

acidic with high fat content—so breast milk will concentrate basic drugs and lipid soluble drugs

44
Q

What drugs are not transmitted well by breast milk?

A

drugs that are highly protein bound

45
Q

What is preferred in pregnant patients: drugs with long or short half-lives? Why?

A

drugs with shorter half-lives are preferred so that you can dose the patient after they breast-feed their neonate so that the levels can decline before the next feeding

46
Q

What are the changes in the content of breast milk early v. later in the day? What implications does this have for maternal therapy?

A

higher fat in morning (so take water-soluble drugs in the morning), lower fat in afternoon

47
Q

What drug can RARELY can kill a baby by causing respiratory arrest if transported through the breastmilk ?

A

Codeine

48
Q

Are monoclonal antibodies a risk in infants?

A

contraversial, IgA is the major antibody absorbed from breast milk for the development of passive immunity as a means of early protection before developing a fully responsive immune system, but IgG antibodies can also be transported (FcRn)

49
Q

What adverse effects does chloral hydrate cause in the infant?

A

drowsiness if fed at peak concentrations

50
Q

What adverse effects does chloramphenicol cause in the infant?

A

too low for Grey baby syndrome; bone marrow suppression

51
Q

What adverse effects does diazepam cause in the infant?

A

sedation and accumulation in neonates

52
Q

What adverse effects does heroin cause in the infant?

A

narcotic dependence

53
Q

What adverse effects does iodine (labeled) cause in the infant?

A

thyroid suppression

54
Q

What adverse effects does methadone cause in the infant?

A

withdrawal if drug is interrupted

55
Q

What adverse effects does propylthiouracil cause in the infant?

A

thyroid suppression

56
Q

What drugs cause: 20% spontaneous aborption, 20% teratogenic craniofacial, cardiac and CNS defects?

A

Retin-A

Oral isotretinoin

57
Q

What drugs have CV abnormality 4X risk, CNS defects 3X risk in the 1st trimester?

A

ACEIs and ARBs (captopril)

58
Q

What effects do ACEIs and ARBs have int he 2nd/3rd trimesters?

A

oligohydramnios with fetal renal function due to low angiotensin in mother and baby that decreases placental blood flow and decreases vascularization of retina and kidney

59
Q

What drug causes yellow teeth in infants?

A

tetracycline

60
Q

What drug causes hypoplasia of the nose and extremities with mental retardation in infants?

A

coumadin (fetal warfarin syndrome)

61
Q

What drugs lead to facial, limb hypoplasia/mental retardation in infants?

A

Phenytoin; Valproate; Carbamazepine (anti-seizure medications)

62
Q

What drug leads to cardiac abnormalities (Ebstein anomaly—atrialized right ventricle) in infants?

A

Lithium

63
Q

What drug leads to phocomelia in infants?

A

Thalidomide

64
Q

What drug leads to cervical uterine abnormalities in babies; vaginal clear cell adenocarcinoma in infants?

A

DES

65
Q

What drug leads to abnormal fetal growth and fetal addiction; preterm birth; placental abruption in infants?

A

cocaine

Reproductive (21 decks)

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