Neonatal & Fetal Pharm Flashcards
What is the most used class of drugs during pregnancy?
Antibiotics
So is this really important? Do most drugs cross the placenta?
YES! They do! Es muy importante!
What drugs can be given to the mother to stimulate fetal lung maturation?
Corticosteroids
What drugs can be given to the mother to close a patent ductus arteriosus?
NSAIDs (not sure if these are given to the mother or to the baby once it is born) Cuz u want the ductus to be open until birth right?
Do free drugs or bound drugs cross the placenta?
Free
What is the most important factor that crossing of the placenta is dependent on?
Duration & timing of exposure to drug
What are some other factors that crossing the placenta is dependent on? List 6
- Lipid solubility
- Degree of ionization at normal pH
- Molecular weight (1000 will not)
- Maternal plasma protein binding
- Placental development & blood flow
- Energy dependent drug transporter proteins
What metabolic powers does the placenta have that may reduce fetal exposure & toxicity to a drug?
The placenta can metabolize drugs via aromatic oxidation (hydroxylation, methylation, alkylation)
What is another metabolic baracade that a drug must surpass to be toxic to the fetus?
Fetal hepatic metabolism! (Recall that 40-60% of placental blood enters directly into the fetal liver)
What is the classic teratogenic drug that caused devastating effects on babies?
Thalidomide
What was thalidomide used for?
Morning sickness in pregnancy (this was an off-label use; it was developed as an OTC sedative)
What was the effect of thalidomide on babies?
Phocomelia (seal limbs)
Thalidomide interacts with multiple biological pathways but what was specifically mentioned?
Cereblon protein
What was the result of the thalidomide tragedy?
All new drugs are now tested for teratogenicity
What are the parameters a drug must meet to be classified as a teratogen? There are 3
- Drug must show a characteristic set of malformations
- Drug must exert those effects at a particular stage of fetal development
- Drug must show dose-dependent incidence
What percentage of US pregnancies are unplanned? Why does this matter?
50% are unplanned; it matters because these people are on drugs when they get pregnant. If they delay the OB/GYN visit, they will be taking the drugs while the fetus develops! Thats bad, mkay.
What percentage of births have some sort of defect?
4%.. Not necessarily from drugs
When does a drug have the most potential for serious morphological effects?
While the organs are developing (weeks 3-9). Later drug exposure leads to less morphologic and more physiologic effects
In regards to regulatory standards of drugs, how are they tested for teratogenicity? Meaning, what animals are they tested on?
Drugs are tested on rodent & non-rodent (typically rat & rabbit)
600 compounds have shown to be teratogenic in animal models. What percentage of those have proven to be teratogenic in humans?
10%
What kinds of compounds do you worry about when it comes to teratogenicity? Name 7
FNRdeltaCNS
- Folate inhibitors
- Drugs that interact w/ nuclear receptors or androgen receptors
- Drugs that increase ROS
- Alter blood flow (especially kidneys)
- Cholesterol drugs
- NSAIDs
- SSRI’s
Whats peculiar about SSRI’s and birth defects?
SSRI’s mech of being a teratogen is unknown. Depression can cause birth defects.. So is it the drug or the disease?? Nobody knows..
Tell me about pregnancy exposure registries
Women enroll in them when they become pregnant. They then go about their business like they normally would. The mom and the baby are followed up. More people –> more power for the registry –> it will soon invade and enslave us all
Describe a retrospective cohort study and list a couple limitations of this kind of study
It may detect assc between drug & outcome but CANNOT establish causality. Also, you have some recall bias and time elapsed problems
Describe a case control study and list a limitation
Starts by identifying the outcome (useful for rare ones). then ask mothers if they had exposure to such and such. Recall bias is a limitation
What did the 2007 FDA ammendments act do?
Established post-marketing studies if drug was questionable. Basically, you market the drug then monitor everyone who is taking it
Isotretinoin (accutane) is a known teratogen. What must a patient do to obtain a prescription to isotretinoin?
- Full informed consent
- 2 negative pregnancy tests
- Monthly pregnancy tests
- Counseling on birth control methods (use 2 of them)
- Register with nationwide survey
- No blood donation
Every tablet of isotretinoin has a picture of a pregnant woman with a red X over it. What does the picture mean and what do some patients think it means?
What it means: DONT GET PREGNANT WHILE TAKING THIS DRUG!!
What patients can think it means: “You cannot get pregnant while taking this drug” (as in “it cant physically happen”)
Short and sweet, what does category A mean?
No worries
Category B?
Neg animal studies & no studies in humans.. Or animal studies positive & human studies negative
Category C?
Animal studies positive & no human studies.. Or no animal/human studies at all
Category D?
Definitely risk to fetus, but maternal benefit may outweigh fetal risk
Category X?
Risk for fetus outweighs maternal benefit
What are the 8 differences in neonatal pharmacokinetics?
- Slower GI and faster IM absorption
- More body water than lipid
- Less protein binding
- Immature hepatic enzymes (less CYP function)
- BBB is more permeable
- Immature renal fx
- Longer drug half life
- Pediatric dosing should be based on body surface area, NOT weight like in adults
Breast feeding: milk is acidic and has high fat content. This means that what kinds of drugs “get trapped” in breast milk?
Basic & lipid soluble drugs
All things being equal, do u want a breastfeeding woman to take a short half life drug or a long half life drug?
Short!
What class of drugs must you be most cautious with when breastfeeding?
Psychoactive drugs
What drugs are you worried about with paternal teratogenicity?
VCR: Anti-virals, anti-cancer, & retinoids
