L7 Drugs in Pregnancy and Lactation

Teratogenesis - Pregnancy phases and risk" • Pre-embryonic (conception to 17 days) - All or nothing, i.e. if many cells damaged the pregnancy will spontaneously [blank_start]miscarry[blank_end] • Embryonic (Day 18-55) - Cells are differentiating and major organs forming, embryo is most [blank_start]vulnerable[blank_end] to teratogens • Foetal (day 56 to birth) - Some structures still developing (cerebral cortex, renal glomeruli) - prone to [blank_start]damage[blank_end]. Deafness can still occur in this period

Non-teratogenic harm to the foetus: • Anything that causes [blank_start]vasoconstriction[blank_end] of the placental vasculature may harm the foetus • Spontaneous abortions (e.g. [blank_start]isotretinoin[blank_end]) • Intra-uterine growth retardation • Prematurity and still-births ([blank_start]warfarin[blank_end]) • Neonatal CNS depression or withdrawal

Physiologic changes during pregnancy can affect the pharmacokinetics/pharmacodynamics of drugs: • Changes in total body [blank_start]weight[blank_end] and body [blank_start]fat[blank_end] composition • Prolonged gastrointestinal transit time which can affect the [blank_start]bioavailability[blank_end] of drugs • Expanded plasma volume, more extracellular fluid & total body water which may increase the [blank_start]volume[blank_end] of distribution for [blank_start]hydrophilic[blank_end] drugs

ADEC Pregnancy Categories (Australia) does not take into account [blank_start]rare idiosyncratic[blank_end] reactions in the neonate to a medicine that crosses the placenta, or in cases of [blank_start]overdose[blank_end], occupational exposure etc.

Folic acid should be started at least one month before conception occurs – and some conditions require higher doses, e.g. epilepsy

Factors that determine transfer into breast milk: • Drug concentrations in the maternal plasma; some drugs are poorly absorbed into the maternal [blank_start]circulation[blank_end] • Drug [blank_start]lipophilicity[blank_end] (Note that fat is a small proportion of milk) • Drug protein binding • Milk pH (Milk pH = 7.0–7.2. More acidic than plasma (pH = 7.4) some ion trapping) • Molecular size – drugs that are <500 Da. • Most drugs transfer into milk(rare exceptions: [blank_start]insulin, heparin[blank_end].) • Most drugs transfer by [blank_start]passive[blank_end] diffusion (unionised, unbound drug) • Extent of transfer depends on properties of the drug, blood and breast milk

• Decreased milk production = dopamine [blank_start]agonists[blank_end] e.g. bromocriptine, [blank_start]oestrogen[blank_end]-containing contraception • Increased milk production = dopamine [blank_start]antagonists[blank_end] e.g. domperidone, SSRIs, opioids

If WAMD <10% the drug will be safe for the baby to ingest through breast milk.