Pharmacology in pregnancy and breastfeeding

Question 1

what % of women take a drug during pregnancy? (prescribed and OTC)

Answer 1

50-90%

60% prescribed and 90% OTC

Question 2

Why may a woman be on medication?

Answer 2

hypertension 
asthma
epilepsy 
migraine 
mental health 
anti-coagulant

Question 3

4 basic pharmacokinetic processes

Answer 3

absorption
distribution
metabolism
excretion

Question 4

Absorption changes - oral route

Answer 4

morning sickness, nausea and vomiting

increased gastric emptying and gut motility

Question 5

absorption changes - intramuscular

Answer 5

increased blood flow so increased absorption

Question 6

absorption changes - inhalation

Answer 6

increased CO and decreased tidal volume may cause increased absorption of inhaled drugs

Question 7

2 distribution changes

Answer 7

increase in plasma volume and fat –> increased Vd

Greater dilution of plasma will decrease relative amount of plasma protein –? increased free fraction of drug

Question 8

What changes can oestrogen and progesterone play in metabolism changes?

Answer 8

can induce or inhibit P450 liver enzymes

Question 9

2 examples of metabolism changes

Answer 9

phenytoin levels down due to induced metabolism

theophylline levels up due to inhibited metabolism

Question 10

Excretion changes and the consequences of this

Answer 10

GFR can increase by 50% so increased excretion of many drugs which means plasma conc reduced and need an increase in dose of renally cleared drugs

Question 11

Pharmacodynamic changes

Answer 11

concentration of drug, metabolites at sites of biological action –> due to blood flow
mechanism of action due to changes in receptors

Question 12

3 functions of placenta

Answer 12

1. attach fetus to uterine wall
2. provide nutrients to fetus
3. allow fetus to transfer waste products to the mother’s blood

Question 13

Mother –> fetus

Answer 13

oxygen - glucose - amino acids - vitamins - lipids, FA, glycerol - alcohol, nicotine, drugs - ions eg Na, Cl, Ca, Fe - antibodies - viruses

Question 14

fetus –> mother

Answer 14

CO2 - urea - other waste products

Question 15

Placental transfer depends on: -

Answer 15

a - molecular weight (smaller molecules <500Da)
b - polarity (non-polar)
c - lipid solubility (lipid soluble)
d - protein bound drugs can cross

Question 16

Fetal PK - distribution (4)

Answer 16

circulation different (umbilical vein –> liver)
less protein binding so more free drug
little fat
relatively more blood flow to the brain

Question 17

fetal PK - metabolism

Answer 17

less fetal enzyme activity - increases with gestation

different isoenzymes

Question 18

Excretion of fetus is into…

Answer 18

amniotic fluid and is swallowed and recirculated

Question 19

Can drugs and metabolites accumulate in amniotic fluid?

Answer 19

yes

Question 20

Teratogenicity - what trimester?

Answer 20

1

Question 21

fetotoxicity - what trimester?

Answer 21

2 and 3

Question 22

What % of fetal abnormalities are drugs responsible?

Answer 22

2

Question 23

When is the biggest risk of drugs in pregnancy?

Answer 23

organogenesis (3-8 weeks)

Question 24

Mechanism of teratogenicity (6)

Answer 24

1. folate antagonism
2. neural crest cell disruption
3. endocrine disruption - sex hormone
4. oxidative stress
5. vascular disruption
6. specific receptor on enzyme medicated teratogenesis

Question 25

Importance of folate

Answer 25

key roles in DNA formation and new cell production

Question 26

2 groups of drugs that antagonise folate and 1 example of each

Answer 26

1. block folate –> THF by binding irreversibly to enzyme
   - -> methotrexate, trimethoprim
2. block other enzymes in pathway eg phenytoin, valproate

Question 27

Folate antagonistic drugs tend to result in what?

Answer 27

neural tube, oro-facial or limb defects

Question 28

What group of drugs can cause neural crest cell disruption?

Answer 28

retinoid drugs eg isotretinoin

Question 29

5 problems with drugs causing neural crest cell disruption

Answer 29

1. aortic arch anomalies
2. ventricular septal defects
3. craniofacial malformations
4. oesophageal atresia
5. pharyngeal gland abnormalities

Question 30

Explain the basis of enzyme mediated teratogenesis and an example

Answer 30

Drugs inhibit/stimulate enzymes for therapeutic effects may also interact with specific receptors and enzymes damaging fetal development
Eg –> NSAIDS causing oro-facial cleft and cardiac septal defects

Question 31

Fetotoxicity

Answer 31

toxic effect on fetus later in pregnancy

Question 32

5 possible issues of fetotoxicity

Answer 32

1. growth retardation
2. structural malformations
3. fetal death
4. carcinogenesis
5. functional impairment

Question 33

examples of drugs that can cause fetotoxicity

Answer 33

ACEI/ARBs - renal dysfunction and growth retardation

Question 34

Category A-X of fetotoxicity and very brief description

Answer 34

A - controlled human studies show no fetal risks - safest
B - animal studies: no risk, human studies do
C : insufficient studies
D : evidence of risk exists but benefits outweigh risks
X: proven fetal risk outweigh any benefit

Question 35

List some known teratogenic drugs to avoid

Answer 35

valproate - NTD
warfarin - haemorrhage
ACEI, NSAIDS, alcohol, retinoids

Question 36

7 drugs to avoid in breastfeeding

Answer 36

1. cytotoxics 2. immunosuppressants 3. Lithium
2. amiodarone 5. Anti-convulsants 6. radio-iodine
3. drugs of abuse

Question 37

Basic principles of prescribing in pregnancy

Answer 37

try non-pharm first
drug with best safety record, lowest effective dose
shortest time/intermittent
avoid first 10 weeks pregnancy is possible
stop or reduce dose before delivery
do not under treat disease which may be harmful to fetus

Question 38

Basic principles of prescribing in breastfeeding

Answer 38

avoid unnecessary and check up to date info
licensed in paeds - safe
PK that reduce infant exposure eg protein bound