Pharmacology in Pregnancy

Question 1

What must be true for a substance to be classified as a teratogen?

Answer 1

• It must cause a pattern of birth defects
• These defects must be timing-/dose-specific
• They must cause defects in genetically susceptible individuals

Question 2

True or false: all teratogens always cause birth defects (elaborate/explain)

Answer 2

• False
• Some routes of administration (such as topical retinoids) or low enough doses do not cause birth defects

Question 3

How does timing of teratogen exposure affect the possible downstream effects? Why?

Answer 3

• During 1st trimester, organogenesis is occurring. Therefore, malformations are most likely to occur at this point in time.
• During second and third trimester, these structures are in place, and we’re more likely to see developmental (growth, neurobehavioural) delays

Question 4

Give some examples of drug classes that shouldn’t be used during pregnancy (or should be considered for removal)

Answer 4

• ACEis and ARBs
• Immunomodulators/suppressors like methotrexate
• Antiepileptics (valproate, carbimazole); although consider risk-benefit analysis of seizures»
• NSAIDs

Question 5

How does pregnancy affect drug absorption?

Answer 5

• Oral is usually less (nausea/vomiting, more alkaline gut environment, uterus getting in the way)
• IM/SC is usually greater

Question 6

How does pregnancy affect drug distribution?

Answer 6

• Increased plasma volume (more required for same conc)
• Increased body fat (↑ dispersion of lipophilic drugs)
• ↓ serum protein (can increase therapeutic effect)

Question 7

How does pregnancy affect drug metabolism?

Answer 7

• Pregnancy hormones (like P4 and E) can affect liver enzymes unpredictably
• Drug clearance can be increased or decreased

Question 8

How does pregnancy affect drug clearance (renal/hepatobiliary)?

Answer 8

• Increased GFR, but also increased resorption (variable effects)
• Reduced hepatobiliary clearance

Question 9

What factors influence a drug’s ability to passively diffuse across the placenta?

Answer 9

• Size
• Charge
• Lipid-solubiliuty
• Concentration gradient
• Placental perfusion/conc gradient

Question 10

What factors affect a drug’s ability to perform facilitated diffusion to/from a fetus?

Answer 10

• Same as diffusion (what are these?) plus:
• Carrier substance (?saturated)

Question 11

True or false: the placenta can metabolise drugs

Answer 11

• True (!!)
• It can express enzymes that affect the placenta
• This has clinical significance for determining toxicity, but also when the drug SHOULD be reaching the fetus for therapeutic purposes