pregnancy and lactation Flashcards
What are some counseling tips for pregnant women?
balanced diet
prenatal vitamins
decreased caffeine
no raw meat/fish
eat fruits & veggies daily (washed)
what are some PK changes seen in pregnancy?
Maternal plasma volume, cardiac output, and glomerular filtration increase by 30% to 50% or higher
increased body fat > increased volume of distribution in fat soluble drugs
plasma albumin concentration decreases
How does a decrease in plasma albumin concentration effect drugs in pregnancy?
increases the volume of distribution of drugs that are highly protein bound
unbound drugs are more rapidly cleared by the liver and kidney during pregnancy, resulting in little change in concentration
Effect of pregnancy of hepatic perfusion?
perfusion increases
theoretically increases the hepatic extraction of drugs
PK changes due to nausea and vomiting?
delayed gastric emptying
alters the absorption of drugs
Effect of gastric pH in pregnancy?
increased gastric Ph
affects the absorption of weak acids and bases
Effect of higher levels of estrogen and progesterone?
alter liver enzyme activity and increases the elimination of some drugs but result in accumulation of others
What is important when dealing with drugs during pregnancy?
super important to look up dosing and monitoring recommendations for a given drug
Usual change in drug dosing during pregnancy?
usually lower maternal drug levels
on average, increased clearance wins out most of the time,
What are some factors that affect movement of drug from maternal > fetal circulation?
Lipophilicity
Protein binding
Molecular weight
Drug pKa
Placental CYP450
Describe lipophilicity in pregnancy.
Highly lipophilic drugs more easily cross placental cell membranes (endothelial, placental) to enter into the fetal circulation
When can hydrophilic agents cross the placenta?
if protein binding is low enough and molecular weight is small enough
Describe protein binding in pregnancy
Highly protein-bound drugs have a lower free fraction that is available to diffuse into the fetal circulation
Which reach higher concentrations in the fetus: least maternal protein bound drugs or highly protein bound drugs?
LEAST maternal protein bound drugs
During pregnancy, while there is a gradual lowering of maternal albumin, there is a ___ fetal albumin
gradual rise in
True or false, during pregnancy, the ratio of maternal-fetal albumin concentrations remains that same.
FALSE
different ratios of fetal: maternal concentrations occur
Drugs with molecular weights___ readily cross the placenta
less than 500 Da
Do larger molecules (600-1000Da) cross the placenta? What about those greater than 1000 Da?
YES: they just cross more slowly
NO: not in sig. amounts
Fetal pH compared to maternal pH?
fetal pH is slightly lower than maternal
So, some deg of ion trapping can concentration some drugs on the fetal side
If a pregnant women needs a corticosteroid, which one should you give? Why?
Prednisolone
the placenta converts prednisolone to the inactive prednisone - does not expose fetus to active corticosteroid
effects of drugs used for anesthesia/analgesia on fetus?
generally cross well and produce fetal effects that can be seen at delivery: respiratory depression from narcotics
(why we need to get baby out soon during c-section)
When do CYP450s begin to appear?
as early as 14 weeks and increase throughout pregnancy
What aspect of fetal drug metabolism remains immature until near or after birth?
glucuronidation
What antihypertensives are believed to be safe during pregnancy?
Beta blockers
Methyldopa
Hydralazine
Calcium blockers
Magnesium sulfate
When is magnesium sulfate used for HTN in preg?
for serious pregnancy-induced hypertension which is usually accompanied by proteinuria, peripheral edema and hyperreflexia
given IV
What HTN drugs are contraindicated in preg?
ACE-I
ARBs
What abx are safe during pregnancy?
UTIs are common
- Nitrofurantoin
- Penicillin and Derivatives
- Cephalosporins
Which abx are avoid in pregnancy? Why?
sulfonamides
mainly near term, because they displace bilirubin from albumin and may enhance kernicterus
What antiemetics are thought to be safe in pregnancy?
Promethazine (Phenergan)
Ondansetron
Drug class of Promethazine (Phenergan)? ADEs?
anticholinergic
dystonias, akathisia
what drug can be used to suppress lactation?
Bromocriptine was previously used but no longer used due to increased reports of stroke, MI, seizures and HTN
What effects whether a drug will enter breast milk?
Lipophilicity
Molecular weight
Pharmacokinetics (e.g., half-life)
Protein binding
Ionization
How do drugs move into breast milk?
by passive diffusion and carrier-mediated transporters
What is the milk-to-plasma drug concentration ratio?
Ratio of drug concentration in breast milk to that in plasma
generally meaningless, what matters is how much total drug is ingested and absorbed by the baby
usually small compared to oral therapeutic dose for the infant
What is the “safe” exposure index?
value of no more than 10% of a therapeutic dose for infants
used as a conservative cutoff
What drugs are exceptions to the “safe” exposure index value?
drugs that cause hemolysis in infants with G-6-PD deficiency
chemotherapeutic agents
Are ADEs from drugs in breast milk common?
No, but always use caution
What drugs should you use caution with when prescribing to pregnant women?
ACEs, alkylating agents, analgesics, abx, anti-epileptics, antidepressants, antihistamins, BB, mood stabilizers
What abx should you avoid in preg?
ciprofloxacin
Doxycycline
Use of oxycodone and Meperidine in pregnancy ?
Avoid in large doses
use of Methadone in pregnancy?
considered safe
What drugs should be avoided in breast feeding women?
methotrexate, lithium, Phenobarbital, Primidone and ethosuximide, chemo drugs, sedatives, Amiodarone, Atenolol, Betadine
What BBs are safe during pregnancy?
Propranolol
Labetelol
