pharmacology in pregnancy and breast feeding Flashcards
why may a woman be on medication during pregnancy, childbirth and lactation
htn asthma epilepsy migraine mental health anticoagulant use
pharmacokinetics of drugs
absorption
distribution
metabolism
excretion
pharmacokinetic changes in pregnancy: absorption - oral route
may be more difficult - morning sickness
decrease in gastric emptying and gut motility - unlikely to be prob with regular dosing but may affect single dose medication
pharmacokinetic changes in pregnancy: absorption - intramuscular route
blood flow increases during pregnancy so absorption for SC/IM routes may be enhanced
pharmacokinetic changes in pregnancy: absorption - inhalation
increased cardiac output and decreased tidal volume during pregnancy which may cause increased absorption
pharmacokinetic changes in pregnancy: distribution changes
increase in plasma volume and fat will change distribution of drugs - increase volume of distribution
greater dilution of plasma will decrease relative amount of plasma proteins - increase fraction of free drug (–> pharmacodynamically active)
pharmacokinetic changes in pregnancy: metabolism changes
oestrogens and progestogens can induce or inhibit liver P450 enzymes, increasing or reducing drug metabolism
pharmacokinetic changes in pregnancy: excretion changes
GFR increased in pregnancy leading to increased excretion of many drugs and reduction in circulating drug level
can reduce plasma conc
pharmacodynamic changes in pregnancy
less well understood
pregnancy may affect site of drug action and receptor response to drugs - conc. of drug, metabolites at sites of biological action, mechanism of action (changes in receptors)
efficacy and adverse effects may be diffferent
factors which affect placental drug transfer and drug effects on foetus
drug physiochemical properties
rate at which drug crosses placenta and amount reaching foetus
duration drug exposure
distribution in different foetal tissues
stages of placental and foetal development
effects of drugs when used in combination
placental transfer of medication depends on
molecular weight of drug (smaller crosses easier)
polarity (unpolarised cross easier)
lipid solubility (lipid soluble will cross)
understanding of foetal pharmacokinetics
not well understood
foetal pharmacokinetics: distribution
circulation different to adult
less protein binding than adult so more free drug available
less fat in foetus so diff distrubution
relatively more blood flow to brain and less-well developed blood-brain barrier
foetal pharmacokinetics: metabolism
reduced enzyme activity, increases with gestation
foetus exhibits different P450 isoenzymes to adults
foetal pharmacokinetics: excretion
excretion into amniotic fluid which foetus swallows leading to recirculation
drugs and metabolites can accumulate in amniotic fluid, can cause significant toxicity
what trimester does teratogenicity affect
first
what trimester does fetotoxicity affect
second and third
principles of prescribing for women childbearing age
always consider possibility pregnanyc
warn of potential risks
when treating medical conditions, advise women to attend before getting pregnanct
discuss contraception if prescribed medications are teratogenic
principles of prescribing in pregnancy
try non-pharma Rx first
use drug with best safety record
check SPC for most up to date info
use lowest effective dose
use drug for shortest time and intermittently if can
avoid first 10wks preg if can
consider stopping/reducing dose before delivery
never undertreat a disease which may be harmful to baby/mum
mechanisms of teratogenic drugs
folate antagonism endocrine disruption - sex hormones neural crest cell disruption oxidative stress vascular disruption specific receptor or enzyme mediated teratogenesis
folate metabolism
folate metabolism is key process in DNA formation and new cell production
folate antagonism
two groups of drugs affect this:
- block conversion of folate to THF by binding irreversibly to enzyme - methotrexate, trimethoprim
- block other enzymes in folate pathway e.g. phenytoin, carbamazepine, valoprate
what does folate antagonism do to baby
tends to result in neural tube, oro-facial or limb defects
neural crest cell disruption
assoc with retinoid drugs e.g. isotretinoin
aortic arch anomalies ventricular septal defects craniofacial malformations oesophageal atresia pharyngeal gland anomalies
enzyme-mediated teratogenesis
drugs which inhibit or stimulate enzymes to produce therpeutic effects may also interact with specific receptors and enzymes damaging foetal developement
e.g. NSAIDs causing orofacial clefts and cardio-septal defects
possible issues of fetotoxicity
growth retardation structural malformations foetal death functional impairment carcinogenesis
examples of foetotoxic drugs
ACE-I/ARBs –> renal dysfunction and growth retardation
ACEI effect on foetus and which trimester(s)
all trimesters
renal damage
warfarin effect on foetus and which trimester(s)
1st - resp tract formation
2- CNS malformation
3rd - risk bleeding: IC haemorrhage
issues with drugs and lactation
almost all drugs mother takes will be present in breast milk
remember, pharmacokinetics different in neonate compared to foetus
drugs to be avoided in breastfeeding
cytotoxics immunosuppresants anti-convulsants (not all) amiodarone lithium radio-iodine
herbal medicines and breast feeding
should be avoided
