Foetal Drug Exposure & The Placenta

Question 1

what is placenta

Answer 1

• placenta = organ that connects maternal and foetal circulation
• semi-permeable barrier
  > allows exchange of nutrients, gases, other compounds
  > allows elimination of wastes

Question 2

3 main mechanisms by which medications cross the placenta
Placental Drug Transfer

Answer 2

• passive diffusion
• facilitated diffusion
• active transport

Question 3

list factors that influence passive diffusion
(in brackets what is more likely to pass)

Answer 3

• molecular weight (lower)
• lipophilicity (more lipophilic)
• protein binding (unbound)
• ionisation (non-ionised)
• concentration gradient
• placental thickness (thinner)
• placental blood flow

Question 4

all drugs in circulation have an equilibrium of

which will cross the placenta

Answer 4

• protein bound and free drug
• ionised and non-ionised drug

only unbound / free crosses placenta
non-ionised

phenomenon can occur for both

Question 5

why cant highly ionised drugs cross placental barrier

Answer 5

too hydrophilic

Question 6

placental changes during gestation include increases in …. with the increasing _______ _______ of foetus
which have what affect on passive diffusion

Answer 6

increase in
- blood flow
- surface area
- placental permeability
which increase passive diffusion

with the increasing nutritional requirements of foetus

Question 7

what results in transport of the drug from maternal to foetal circulation and vice versa; into and out of foetal circulation (can pump drug out of foetal circulation and back into maternal circulation)

Answer 7

• facilitated diffusion
• active transport

Question 8

facilitated diffusion and active transport tends to occur with drugs that have structural similarities to _____ compounds

Answer 8

drug structure - endogenous compounds

Question 9

what does facilitated diffusion require (2)

Answer 9

• carrier substance - saturable
• concentration gradient

Question 10

what does active transport require (2)

Answer 10

• active transport proteins
• energy-dependent (=> don’t need gradient)

Question 11

what is active transport not dependent on

Answer 11

• concentration gradient (diffusions both are)
• electrochemical gradient

Question 12

list 3 active transport proteins

Answer 12

• P-glycoprotein
• multi-drug resistance protein
• breast cancer resistance protein

Question 13

what can presence of enzymes on placenta surface alter

Answer 13

drug exposure (drug levels in body)

Question 14

Placental Metabolism involves the

Answer 14

expression of metabolising enzymes (cytochrome P450) on surface of placenta

Question 15

when could placental metabolism be of clinical significance

Answer 15

• when treatment relies on foetal exposure to a drug
• since placental metabolism alters drug exposure and foetal exposure

Question 16

what does the placental metabolism alter foetal exposure to

Answer 16

• parent drug
• metabolites
• by-products