Drugs in Pregnancy

Question 1

Why are the stages of embryogenesis and fetal development uniquely susceptible to exogenous compounds?

Answer 1

1. There is rapid cellular growth and division
2. Many tissues are in the process of differentiation

Question 2

What are the criterion for taratogens?

Answer 2

1. Results in a characteristic set of malformations and is organ-selective
2. Exerts its affects at a specific stage of fetal development
3. Is dose dependant

Question 3

What is the name for a substance that would cause fetal abnormalities, distress and negative outcomes that ISN’T a teratogen?

Answer 3

Fetopathic

Question 4

What are the mechanisms of teratogenisis?

Answer 4

• DNA mutations
• Chromosome breaks
• Impaired mitosis
• Macro and Micro nutrient deficiency
• Specific protein interactions/inhibition

Question 5

What are some of the maternal factors that could play into adverse effects for the fetus?

Answer 5

• Maternal genetics (cleft lip occurs more frequently in caucasians)
• Maternal disease (HTN, diabetes, infection)
• Maternal nutrition (macro/micro nutrient deficiency like folic acid)
• Maternal stress

Question 6

What are the FDA risk categories and what does each mean?

Answer 6

A → controlled studies in human women fail to demonstrate risk in the first trimester (no evidence in third), possibility of fetal harm appears remote

B → animal studies have not demonstrated risk but there are no controlled studies in women OR animal studies have demonstrated risk but it hasn’t been shown to effect humans

C → studies in animals have adverse effects for the fetus and there are no controlled studies in women OR studies in women or animals are unavailable

D → positive evidence of fetal risk but there may be more harm done by getting the mother to stop therapy

X → absolute contraindication

Question 7

What is Thalidomide?

Answer 7

A drug that was used to treat N/V in pregnant women but it is a teratogen during the 16 week period where fetal limbs are being developed

Resulted in malformations of limbs in the 1960s

Relatively safe except for those 16 weeks and was taken from the market

10-20% were effected with the deformed limbs

Question 8

What is Diethylstilbestrol?

Answer 8

Non-steroidal estrogen used to prevent miscarriage by stimulating hormonal production in the placenta

Maternal use of DES prior to 18 weeks of age was correlated to the development of vaginal cancer in the female offspring and males ended up with lower sperm counts or sperm quality (long taking toxic effect)

Question 9

What are retinoids and why are they contraindicated in pregnancy?

Answer 9

Retinoids are acid-related compounds that bind the hormone retinoid acid receptor which can dimerize with other hormonal receptors

Retinoic acid maps are used to tell the fetal cells where to go and when, when Retinoids are administered, this is changed

Retinoid receptors heterodimerize with thyroid receptors which are crucial for development

May cause other problems including vitamin A deficiency, knocking out retinaldehyde dehydrogenase in mice, knocking out retinoic acid receptors in mice → all causing malformations

Question 10

What is the adverse fetal effect most strongly associated with maternal smoking or exposure to smoke?

Answer 10

Low birth weights

Strongest association with both tobacco and cannabis smoke

Suggests causative factor for lower birth weights are the aromatic hydrocarbons instead of nicotine/cannabinoids

Question 11

What is the adverse fetal effect from drinking alcohol while pregnant?

Answer 11

Fetal Alcohol Syndrome (FAS) → triad of abnormalities; craniofacial abnormalities, CNS dysfunction and pre/post-natal stunting of growth

~5% estimated incidence in children of “heavy drinkers”

Question 12

Why are anticonvulsants contraindicated in pregnancy?

Answer 12

Many drugs used to treat seizures are associated with fetal malformations and other adverse effects

Phenytoin, carbamazepine, topiramate and valproic acid are human teratogens

Question 13

What are the changes in pregnancy toxicokinetics throughout pregnancy?

Answer 13

• changes in body fat and water content
• changes in GI tract function
• changes in CV function
• changes in blood volume and extravascular compartment volume
• changes in metabolism and excretion

Question 14

What effects the ability of a drug to cross the placental barrier?

Answer 14

• lipid/water solubility
• ionization
• molecular weight (anything >500 won’t cross easily)
• placental transporters
• plasma protein binding ability
• metabolism in the placenta
• pH differences between fetal and maternal blood