Drugs in pregnancy and lactation Flashcards
Explain transfer of high molecular weight drugs across placenta
Insulin
Negligible transfer
Explain transfer of lipophilic un-ionised drugs across placenta
Cross placenta easier than polar drugs
Explain transfer of weakly basic dugs across placenta
Get stuck in foetal circulation from low PH compared to mother
Factors considered for pregnancy, foetus, and neonates
Teratogen
Pharmacological effect from time exposed to drug
Pharmacokinetic changes
Teratogen definition and examples
Drug interfering with normal growth and development of fetus
ACEi, androgens, carbamezpine, lithium, phenytoin, misoprostol, tetracycline, warfarin
Drug PK effect on neonates
- ACEi, antidepressants/opioids /benzos, NSAIDs
ACEi- renal dysfunction, intrauterine growth retardation
Antidepress- withdrawal
NSAIDs- premature closure of ductus arteriousus
Effects of drug exposure in pre-embryonic stage
First 17 days
Either death of embryo or complete recovery (all or nothing)
Malformation unlikely
Effects of drug exposure in embryonic stage
Days 18-56
Organogenesis
Greatest risk of major birth defects by interfering with organ function
Effect of drug exposure in late embryonic stage
Weeks 8-38
CNS damage from ethanol
Absorption changes in pregnancy
TBW increases
Plasma volume increases
Vd increases
Loading dose needed
Protein binding changes in pregnancy
Albumin binds acidic drugs
Plasma albumin drops
Increased fraction of unbound drugs
Metabolism changes in pregnancy
Hepatic drug metabolising enzymes are induced in pregnancy
More hepatic metabolism
Clearance changes in pregnancy
GFR increases until birth
Renally excreted drugs are excreted faster
Need higher maintance doses
Category A drugs
No proven increase of malformation or harm observed
Category B drugs
Limited number of studies
No increase in frequency o malformation or other harm
B1- animal safe
B2- animal studies inadequate/lacking
B3- animal studies show increased risk, uncertain in humans
Category C drugs
Cause/suspected cause of harm without malformation
May be reversible
Category D drugs
Cause/suspected cause of malformation
Adverse effects
Category X drugs
High risk of causing permanent damage they should not be used
Questions to consider when introducing a drug
Gestational age
How essential is drug
How much will pass to foetus
Is there an alternative
Factors influencing extent/rate of passive diffusion into breast milk
Maternal PK
Physiological nature of blood vs milk
Physiochemical properties of drug
pKa influences on drug transfer into breast milk
Measure of fraction of drug ionised at given pH
Basic drugs- greater pKa at acidic pH so milk will trap wek bases.
Acidic drugs- trap in maternal placenta
Protein binding influence of drug transfer
Highly bound drugs stay in placenta, low milk concentration
Lipophilic drug influence into breast milk
Highly lipophilic drugs dissolve into milk
Characteristics of drugs minimally transferring into breast milk
Acidic drugs
Highly protein bound
Low-to-moderate lipophilicity
High mik:plasma ratio indicates
Drug in milk (>1.5)
Unsafe because higher concentration in milk than plasma
Low milk:plasma ratio indicates
Safer
Only minimal levels are transferred to milk
Techniques used to reduce infant exposure to drugs
Give maternal dose immediately after feeding
Use topical treatments when possible
Avoid large immediate dose
Use long duration of lower dose
Drugs at high exposure for breast milk transfer
Amiodarone
Carbimazole
Lithium
Theophylline
Metronidazole
Isoniazid
