pharmacology in pregnancy

Question 1

what are absorption changes in pregnancy ?

Answer 1

oral may be more difficult due to morning sickness
IM route - blood flow increase so absorption may also increase
inhalation - increased CO so increase absorption

Question 2

what are distribution changes in pregnancy ?

Answer 2

increased plasma volume so more diluted

increased free drugs as protein diluted

Question 3

what are metabolic changes in pregnancy ?

Answer 3

oestrogen and progesterone can induce live P450 enzymes which increase metabolism

Question 4

what are excretion changes in pregnancy ?

Answer 4

GFR increased by 50% leading to increased excretion

reduced concentration

Question 5

what substances are favoured to transfer across the placenta ?

Answer 5

smaller size
non-polar
lipid soluble

Question 6

what is different about fetal drug ADME ?

Answer 6

less protein binding so more free drugs
less metabolism
recirculation of excreted drugs through amniotic fluid

Question 7

what are teratogenic drugs ?

Answer 7

do damage in first trimester

Question 8

what are fetotoxic drugs ?

Answer 8

do damage in second and third trimester

Question 9

what are mechanisms for teratogenicity ?

Answer 9

folate antagonism
neural crest cell disruption
endocrine disruption
oxidative stress
vascular disruption

Question 10

what drugs affect folate antagonism ?

Answer 10

methotrexate
trimethoprim
phenytoin
carbamazepine
valproate

Question 11

what defects do drugs that affect folate antagonism produce ?

Answer 11

neural tube defect
oro-facial defect
limb defects

Question 12

what drugs cause neural crest disruption ?

Answer 12

retinoid drugs

Question 13

what problems are seen in drugs that cause neural crest cell disruption ?

Answer 13

aortic arch anomalies
VSD
craniofacial malformations
oesophageal atresia
pharyngeal gland abnormalities

Question 14

what drugs interact with enzymes to cause fetal damage ?

Answer 14

NSAIDs

Question 15

what defects are seen in NSAID use during pregnancy ?

Answer 15

orofacial clefts

cardiac septal defects

Question 16

what drugs are fetotoxic ?

Answer 16

ACE inhibitors

ARBs

Question 17

what are possible issues from using fetotoxic drugs ?

Answer 17

growth retardation
structural malformations
fetal death
functional impairment
carcinogenesis

Question 18

what are the different grades assigned to drugs based on their potential to damage pregnancy ?

Answer 18

A - human studies, no fetal risk
B - animal studies, no fetal risk
C - no adequate studies
D - evidence of human fetal risk, benefits outweigh
X - proven fetal risks outweigh benefits

Question 19

what is warfarin associated with in pregnancy ?

Answer 19

haemorrhage in fetus

malformations in CNS and skeletal systems

Question 20

what drugs should be avoided in breast feeding ?

Answer 20

cytotoxics
immunosuppressants
anti-convulsants
drugs of abuse
amiodarone
lithium
radio-iodine

Question 21

what are key principles of prescribing in pregnancy ?

Answer 21

non-pharma first
drug with best safety record
lowest effective dose
shortest time possible
avoid in first 10 weeks if possible
stop/reduce before delivery