Drugs in Pregnancy and Lactation Flashcards
Discuss the transfer of high molecular weight drugs across the placenta
e.g. insulin
Negligible transfer
Discuss the transfer of lipophilic, un-ionised, polar, and weakly basic drugs across placenta
Lipophilic un-ionised drugs = cross placenta easier than polar drugs
Weakly basic drugs = may be trapped in foetal circulation due to their lower pH compared to mum
What factors about a drug should be considered if it was to be used in pregnancy, foetus, or neonate?
Teratogenicity
Pharmacological effect
timing of drug exposure
Pharmacokinetic changes
What are tetrataogens?
An agent that interfere with normal growth and development of foetus = some obvious, others take time to develop
What are some examples of teratogenic drugs?
ACE inhibitors
Androgens
Carbamazepine
Lithium
Misoprostol
Phenytoin
Tetracycline
Warfarin
When are signs of foetal stress due to drug development observed usually?
Generally only at birth
Outline some drugs and their pharmacokinetic effect on neonate (ACEi, antidepressants/benzos/opioids, anti-HTN, NSAIDs)
ACEi = renal dysfunction, intrauterine growth retardation
Antidepressants/ Benzos/ Opiods = w/drawal reaction
Anti-HTN = foetal hypoxia
NSAIDs = premature closure of ductus arteriosus
Explain the effects of drug exposure during the pre-embryonic stage
(first 17 days)
All-or-nothing response = either death of embryo or complete recovery and normal development
Malformation unlikely
Explain the effects of drug exposure during the embryonic stage
(days 18-56)
Organogenesis (except CNS, eyes, teeth, external genitals, ears)
Exposure to drugs = greatest risk of major birth defects by interfere with organ function
Explain the effects of drug exposure during the embryonic stage
(Weeks 8-38)
CNS can be damaged by some drugs (e.g. ethanol)
How does absorption change in pregnancy?
High circulating progesterone = delay gastric emptying, inc intestinal transit time
How does distribution change in pregnancy?
Inc in total body water, 30% inc in plasma volume = Inc Vd of drug
Loading dose may be required
How does protein binding change in pregnancy?
Albumin binds acidic drugs
Plasma albumin drops sig in preg = inc fraction of unbound drugs
How does metabolism change in pregnancy?
Hepatic drug metabolising enzymes are induced during preg
More hepatic metabolism
How does clearance change in pregnancy?
Inc GFR by approx 50% and remains high until after delivery
renally excreted drugs = more excretion, higher maintenance doses are required
Explain category A drugs in pregnancy
Taken by large number of preg women + women of child-bearing age
No proven inc in freq of malformation or direct/indirect harmful effect observed on foetus
Explain category B drugs in pregnancy
Drugs been taken by limited no. preg women/child-bearing age = no inc in freq of malformation or direct/indirect effect on foetus
B1 = animal studies showed no evidence
B2= studies in animals lacking or inadequate, available data show no effect
B3 = animal studies show evidence of inc occurrence of foetal damage, sig in human uncertain
Explain category C drugs in pregnancy
Drugs, due to pharm effect, suspected to/have caused harmful effects in foetus or neonate w/out malformation
Effects may be reversible, consult specialised texts
Explain category D drugs in pregnancy
Drugs have caused or suspected to have caused or may be expected to cause inc risk of foetal malformation or irreversible damage
May have ADRs
Consult specialised texts
Explain category X drugs in pregnancy
High risk of permanent damage
Should not be used in preg or possibility of preg
What questions should be considered when introducing a drug to pregnant mother/neonate/foetus?
Gestational age
How essential is drug
How much will pass to foetus
Safer alternatives?
How severe is illness?
What will happen if not treated?
What is ADEC category for drug?
What factors influence extent/rate of passive diffusion into breast milk?
Maternal pharmacokinetics
Physiological nature of blood vs milk
physiochemical properties of drug
How does drug pKa influence drug transfer into breast milk?
basic drugs = more ionised at acidic pH –> trap weak bases
Acidic drugs = more ionised at higher pH values –> trapped in maternal plasma
*more acidic drug stays in maternal plasma
How does drug protein binding influence drug transfer into breast milk?
*The higher the percentage the better
Highly bound drugs = retain in maternal plasma due to lower protein content in milk
How does drug lipophilicity influence drug transfer into breast milk?
highly lipophilic = dissolve into lipid content of milk –> inc extent of transfer into milk from maternal plasma
Summarise the characteristics of drugs that minimally transfer into breast milk
Acidic drug that is highly protein bound and has low to moderate lipophilicity
What does a high milk:plasma ratio indicate?
> 1.5 = drug may sequester into milk
What does a low milk:plasma ratio indicate?
<1 = minimal levels are transferred into milk
Highlight the techniques used reduce infant exposure to drugs
Give maternal dose directly after infant has fed = avoid maximal drug exposure
What drugs are at high exposure to infant from breast milk?
Amiodarone
carbimazole
isoniazid
lithium
theophylline
metronidazole
