Drugs in Pregnancy Flashcards
What are the gastrointestinal absorption changes in pregnancy?
increased plasma progesterone –> decreased intestinal motility, prolonged gastric emptying
decreased gastric acid secretions –> increased pH (weak acids are ionized, less diffusion; weak bases primarily unionized, more diffusion)
increased mucous secretions which reduces membrane permeability
nausea and vomiting
?clinically significant as increased CO and intestinal blood flow allow for overall increased absorption
What are the pulmonary absorption changes in pregnancy?
increased tidal volume –> increased pulmonary blood flow, increased alveolar uptake
What are the changes in distribution in pregnancy?
Vd:
-increased body water –> may see decreased Cmax
protein binding:
-dilutional hypoalbuminemia
-steroid/placental hormones binding to proteins may decrease drug binding
What are the hepatic metabolism changes in pregnancy?
increased estrogen and progesterone –>
-increased 3A4 and 2D6
-decreased 1A2
-increased UGT
What are the renal function changes in pregnancy?
increased GFR –> increased elimination but generally not clinically significant
Describe fetoplacental absorption.
mostly passive absorption
-solubility, molecular size, ionization
Describe fetoplacental distribution.
fetal protein binding affinity different from maternal protein binding
fetal albumin concentration progressively increases while maternal decreases
Describe fetoplacental metabolism.
placenta and fetus capable of metabolism
more polar metabolites may accumulate
Describe fetoplacental elimination.
mainly diffusion to maternal compartment
efflux transporters present
What are the 3 key considerations for drug use in pregnancy?
effect of condition on pregnancy
effect of pregnancy on condition
effect of drug therapy on pregnancy
What is the baseline risk of a birth defect?
~ 3%
What percentage of birth defects are thought to be associated with drug treatment?
2-3%
What is the definition of teratogen?
agents that are capable of producing structural or functional abnormalities in the embryo or fetus
What might teratogens cause?
spontaneous abortion
congenital malformations
intrauterine growth restriction
cognitive/behavioral effects
carcinogenesis
mutations
When considering the potential effect of a teratogen, what are three considerations to keep in mind?
timing of exposure
dose, frequency of exposure
amount and quality of reproductive data
What are the effects of teratogens near time of conception?
all or none effect
-exposure in ~ 15 days postconception = spontaneous abortion
What are the effects of teratogens in the first trimester?
teratogen exposure during this stage more likely to cause physical malformations
-most critical time for organogenesis and physical formation
What are the effects of paternal teratogen exposure during the preconception period?
uncertain; no evidence that paternal exposure increases risk of birth defects
What are the effects of teratogens in 2nd and 3rd trimester?
functional and behavioral effects if exposure later in gestation
growth
CNS development - IQ, language development, behavior
What are the effects of teratogens at term?
premature labour - cigarette smoking, illicit drug use
neonatal withdrawal - opioids, SSRIs
constriction of ductus arteriosus - NSAIDs
What is the relationship between dose and teratogen effect?
dose-dependent relationship
-threshold dose is not known for many teratogens
-as a general rule, use the lowest effective dose for the shortest amount of time
Why do we know so little about reproductive data?
animal reproductive studies may provide direction but cannot be extrapolated to human use
most birth defects are rare, even if a pattern occurs
lack RCTs (ethical reasons)
What do we have for reproductive data?
case reports
case-control studies
-pregnant women who took drug and differentiate among pregnancies with defect vs those without
cohort studies
-pregnant women who took the drug vs those that didnt
registries
What are the problems with epidemiological studies?
recall bias - participants dont recall accurately, omit details
selection bias - proper randomization not achieved
no control of confounding factors
sample size
What are some key considerations in drug selection in pregnancy?
single entity
published data
-most effective and most reassuring safety data
local application if possible
lowest effective dose, shortest duration
shorter t1/2 when possible?
What are some important topics to discuss when counselling on drug use in pregnancy?
preconception planning
sharing info to help weigh risk vs benefit
risk
-baseline risk, risk vs benefit, minimizing risk
What are some factors besides drugs that can affect pregnancy outcomes?
age
underlying medical conditions
genetic conditions
obstetrical history
other exposures
socioeconomic status
