Perinatal Pharmacology

Question 1

define teratogen

Answer 1

an agent that induces congenital anomalies during embryo- or fetogenesis

Question 2

Rank the 4 most common causes of congenital malformation from most –> least

Answer 2

1. Unknown causes
2. Genetic causes
3. Maternal conditions
4. Drugs

Question 3

What are the 3 critical time periods during embryo and fetal growth? What are the possible consequences of drug effects at these stages?

Answer 3

1. Pre-implantation
   - low risk due to lack of interface between blastocyst and mother. Pluripotent cells can compensate or blastocyst will simply fail to implant and no viable pregnancy will occur.
2. Embryonic development (implantation to 60 days)
   - most high risk due to major organogenesis occurring
3. Fetal development
   - moderate risk, growth retardation and functional anomalies possible, significant brain effects possible.

Question 4

What % of women take at least 1 drug during pregnancy?

Answer 4

90% take at least 1

Question 5

What chemical properties make drugs favoured for transplacental diffusion?

Answer 5

small, lipophilic, uncharged, and non-protein bound drugs

Question 6

What is the relative pH of the breast milk compared to the plasma

Answer 6

Lower (ie. more acidic)

Question 7

What is the milk/plasma ratio and what does it tell you about the behaviour of a drug?

Answer 7

The higher the MP ratio, the more drug will be concentrated in the breast milk. MP>1 = more drug in the breast milk than the plasma

Question 8

What types of drugs (WA or WB) tend to accumulate in the breast milk? give some examples

Answer 8

weak base drugs tend to get trapped more because in an acidic environment, the protonated weak base form is favoured and because of the charge will be unable to cross back into the plasma.

Question 9

What are the differences between neonatal and adult oral absorption of drugs?

Answer 9

1. infants have higher gastric pH –> this will generally decrease the bioavailability of drugs that are degraded by stomach acid.
2. infants have erratic gastric emptying times and reduced intestinal surface area.

Question 10

How does topical absorption differ between infants and adults?

Answer 10

1. infants have a thinner stratum corneum which increases absorption.
2. greater relative SA on an infant than adult (13% body weight = skin vs only 3%).

Question 11

What is TBW like in an infant at birth? How does this affect pharmacodynamics?

Answer 11

TBW is highest at birth and decreases with age.

Water soluble drugs will have higher volumes of distribution in children and therefore higher mg/kg doses required for loading and maintenance.

Question 12

What is the concentration/ avidity of plasma proteins like in a newborn?

Answer 12

Concentration and avidity of plasma proteins are both lower in an infant.

This means lower doses of a protein bound drug need to be used to attain therapeutic concentrations of free, unbound drug.

Question 13

What is a risk of using drugs with normally high plasma protein avidity in neonates?

Answer 13

There’s an increased risk of drug interactions/toxicity as the neonatal proteins don’t bind as tightly and the drug can become more easily displaced, leading to higher free, active concentrations of the drug.

Question 14

How is neonatal metabolism different from that of an adult?

Answer 14

Neonates are not born wit a full complement of metabolic enzymes
- this affects oral bioavailability, drug clearance, and half lives

Question 15

How is excretion of drugs different between a newborn and an adult?

Answer 15

GFR and renal tubular secretion are at only ~20% maturity for the first year of life (in a term baby)

Need to adjust dose and/or doing interval to prevent drug accumulation and toxicity.