pharmacology in pregnancy Flashcards
what are absorption changes in pregnancy ?
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
what are distribution changes in pregnancy ?
increased plasma volume so more diluted
increased free drugs as protein diluted
what are metabolic changes in pregnancy ?
oestrogen and progesterone can induce live P450 enzymes which increase metabolism
what are excretion changes in pregnancy ?
GFR increased by 50% leading to increased excretion
reduced concentration
what substances are favoured to transfer across the placenta ?
smaller size
non-polar
lipid soluble
what is different about fetal drug ADME ?
less protein binding so more free drugs
less metabolism
recirculation of excreted drugs through amniotic fluid
what are teratogenic drugs ?
do damage in first trimester
what are fetotoxic drugs ?
do damage in second and third trimester
what are mechanisms for teratogenicity ?
folate antagonism neural crest cell disruption endocrine disruption oxidative stress vascular disruption
what drugs affect folate antagonism ?
methotrexate trimethoprim phenytoin carbamazepine valproate
what defects do drugs that affect folate antagonism produce ?
neural tube defect
oro-facial defect
limb defects
what drugs cause neural crest disruption ?
retinoid drugs
what problems are seen in drugs that cause neural crest cell disruption ?
aortic arch anomalies VSD craniofacial malformations oesophageal atresia pharyngeal gland abnormalities
what drugs interact with enzymes to cause fetal damage ?
NSAIDs
what defects are seen in NSAID use during pregnancy ?
orofacial clefts
cardiac septal defects
what drugs are fetotoxic ?
ACE inhibitors
ARBs
what are possible issues from using fetotoxic drugs ?
growth retardation structural malformations fetal death functional impairment carcinogenesis
what are the different grades assigned to drugs based on their potential to damage pregnancy ?
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
what is warfarin associated with in pregnancy ?
haemorrhage in fetus
malformations in CNS and skeletal systems
what drugs should be avoided in breast feeding ?
cytotoxics immunosuppressants anti-convulsants drugs of abuse amiodarone lithium radio-iodine
what are key principles of prescribing in pregnancy ?
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
