Pharmacology in Pregnancy

Question 1

what changes occur in pregnancy that can affect absorption?

Answer 1

> morning sickness
> increased gastric emptying
> increased gut motility
> increased blood flow (increased absorption)
> increased cardiac output
> decreased tidal volume

Question 2

what changes occur in pregnancy that can affect distribution?

Answer 2

> increased plasma volume
increased fat
decreased amount if plasma proteins due to dilution

Question 3

what changes in pregnancy affect metabolism?

Answer 3

> oestrogen and progesterone can induce or inhibit liver p450 enzymes

Question 4

how does an increase in GFR in pregnancy effect drug secretion?

Answer 4

> there is increased secretion of many drugs

> there is a decrease in plasma concentration so a decrease in renally cleared drugs

Question 5

what pharmacodynamic changes can occur in pregnancy?

Answer 5

there may be a change in the site or action and the receptor response so efficacy and adverse effects may change

Question 6

what are the principles of prescribing in pregnancy?

Answer 6

> try non-pharma first
use for shortest time period and intermittently if possible
use lowest effective dose
don’t under treat the disease harmful to the fetus
consider stopping or reducing prior to the pregnancy
avoid in 1st 10 weeks
use drugs with best safety record

Question 7

what differences in the foetus affect pharmacokinetics?

Answer 7

> less protein binding so more drug available
little fat
relatively more blood flow to the brain
less enzyme activity
different izoenzymes
amniotic fluid allows accumulation and recirculation

Question 8

what drugs should be avoided in breast feeding?

Answer 8

> cytotoxics
> immunoosupressants
> anticonvulsants
> opiates
> amiodarone
> lithium
> radioidine

Question 9

what are the principles of prescribing in breast feeding?

Answer 9

> avoid unnecessary drug use
licenced safe for <2yrs probs. safe for breast feeding
choose drug with pharmacokinetic properties to reduce infant exposure (high protein bound)

Question 10

what materials pass form mother to foetus?

Answer 10

> glucose
> O2
> lipids
> ions
> viruses
>antibodies
> vitamins

Question 11

what affects the materials exchanged through the placenta?

Answer 11

> size
electrical charge (non-ionised cross more easily)
lipophilicity
protein binding

Question 12

what materials are passed from the foetus to the mother?

Answer 12

> urea

> CO2

Question 13

when is the biggest risk of teratogenicity?

Answer 13

in the first trimester during organogenesis

Question 14

what are the mechanisms of teratogenicity?

Answer 14

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

Question 15

name some teratogens

Answer 15

> anticonvulsants
> ACE inhibitors
> alcohol
> retinoids
> NSAIDS
> anticoagulants

Question 16

what teratogenic effect does valproate have?

Answer 16

neural tube defect

Question 17

what are the teratogenic effects of NSAIDS?

Answer 17

premature closure of the ductus arteriosus

Question 18

what are the teratogenic effects of warfarin?

Answer 18

> haemorrhage

> CNS and skeletal effects

Question 19

what is fetotoxicity?

Answer 19

drugs having toxic effects on the foetus later on

Question 20

what problems can arise in fetotoxicity?

Answer 20

> foetal death
> structural malformations
> growth retardation
> functional impairment
> carcinogenesis

Question 21

what are the different categories of fetotoxicity in drugs?

Answer 21

A. controlled studies show no risk
B. animal studies show no risk
C. no studies or data
D. evidence of risk but benefit may outweigh
X. no benefit and proven risk

Question 22

what is enzyme mediated teratogenesis?

Answer 22

drugs may interact with specific receptors and enzymes of foetal development

Question 23

what drug causes neural crest cell disruption?

Answer 23

retinoid drugs

Question 24

what problems arise from neural crest cell disruption?

Answer 24

> pharyngeal gland abnormalities
> oesophageal atresia
> ventricular septal defects
> craniofacial malformations
> aortic arch anomalies

Question 25

why does folate antagonism have such an impact?

Answer 25

because this pathway is a key process in DNA formation and new cell production

Question 26

what drugs block conversion of folate to TNF by binding to the enzyme irreversibly?

Answer 26

> methotrexate

> trimethoprim

Question 27

what drugs block the enzyme pathway?

Answer 27

> phenytoin
carbamazepine
valproate