Drugs in pregnancy and lactation

Question 1

Explain transfer of high molecular weight drugs across placenta

Answer 1

Insulin
Negligible transfer

Question 2

Explain transfer of lipophilic un-ionised drugs across placenta

Answer 2

Cross placenta easier than polar drugs

Question 3

Explain transfer of weakly basic dugs across placenta

Answer 3

Get stuck in foetal circulation from low PH compared to mother

Question 4

Factors considered for pregnancy, foetus, and neonates

Answer 4

Teratogen
Pharmacological effect from time exposed to drug
Pharmacokinetic changes

Question 5

Teratogen definition and examples

Answer 5

Drug interfering with normal growth and development of fetus

ACEi, androgens, carbamezpine, lithium, phenytoin, misoprostol, tetracycline, warfarin

Question 6

Drug PK effect on neonates
- ACEi, antidepressants/opioids /benzos, NSAIDs

Answer 6

ACEi- renal dysfunction, intrauterine growth retardation
Antidepress- withdrawal
NSAIDs- premature closure of ductus arteriousus

Question 7

Effects of drug exposure in pre-embryonic stage

Answer 7

First 17 days
Either death of embryo or complete recovery (all or nothing)
Malformation unlikely

Question 8

Effects of drug exposure in embryonic stage

Answer 8

Days 18-56
Organogenesis
Greatest risk of major birth defects by interfering with organ function

Question 9

Effect of drug exposure in late embryonic stage

Answer 9

Weeks 8-38
CNS damage from ethanol

Question 10

Absorption changes in pregnancy

Answer 10

TBW increases
Plasma volume increases
Vd increases
Loading dose needed

Question 11

Protein binding changes in pregnancy

Answer 11

Albumin binds acidic drugs
Plasma albumin drops
Increased fraction of unbound drugs

Question 12

Metabolism changes in pregnancy

Answer 12

Hepatic drug metabolising enzymes are induced in pregnancy
More hepatic metabolism

Question 13

Clearance changes in pregnancy

Answer 13

GFR increases until birth
Renally excreted drugs are excreted faster
Need higher maintance doses

Question 14

Category A drugs

Answer 14

No proven increase of malformation or harm observed

Question 15

Category B drugs

Answer 15

Limited number of studies
No increase in frequency o malformation or other harm
B1- animal safe
B2- animal studies inadequate/lacking
B3- animal studies show increased risk, uncertain in humans

Question 16

Category C drugs

Answer 16

Cause/suspected cause of harm without malformation
May be reversible

Question 17

Category D drugs

Answer 17

Cause/suspected cause of malformation
Adverse effects

Question 18

Category X drugs

Answer 18

High risk of causing permanent damage they should not be used

Question 19

Questions to consider when introducing a drug

Answer 19

Gestational age
How essential is drug
How much will pass to foetus
Is there an alternative

Question 20

Factors influencing extent/rate of passive diffusion into breast milk

Answer 20

Maternal PK
Physiological nature of blood vs milk
Physiochemical properties of drug

Question 21

pKa influences on drug transfer into breast milk

Answer 21

Measure of fraction of drug ionised at given pH
Basic drugs- greater pKa at acidic pH so milk will trap wek bases.
Acidic drugs- trap in maternal placenta

Question 22

Protein binding influence of drug transfer

Answer 22

Highly bound drugs stay in placenta, low milk concentration

Question 23

Lipophilic drug influence into breast milk

Answer 23

Highly lipophilic drugs dissolve into milk

Question 24

Characteristics of drugs minimally transferring into breast milk

Answer 24

Acidic drugs
Highly protein bound
Low-to-moderate lipophilicity

Question 25

High mik:plasma ratio indicates

Answer 25

Drug in milk (>1.5)
Unsafe because higher concentration in milk than plasma

Question 26

Low milk:plasma ratio indicates

Answer 26

Safer
Only minimal levels are transferred to milk

Question 27

Techniques used to reduce infant exposure to drugs

Answer 27

Give maternal dose immediately after feeding
Use topical treatments when possible
Avoid large immediate dose
Use long duration of lower dose

Question 28

Drugs at high exposure for breast milk transfer

Answer 28

Amiodarone
Carbimazole
Lithium
Theophylline
Metronidazole
Isoniazid