Uteroplacental & Fetal Physiology Pt. 2 (Exam 2) Flashcards
What variables change the rate and amount of transfer of (drugs, toxins, O₂, CO₂, etc.) in the intervillous space?
- Concentration gradient
- Permeability
- Restriction of movement (some substances are bound to in the placental tissue to prevent fetal uptake)
What is passive diffusion and what are some substances/drugs move via passive diffusion? (examples)
Movement along a concentration gradient
- O₂
- CO₂
- Most anesthetic drugs
In regards to facilitated diffusion, a higher temperature will ______ rate of diffusion.
increase
What is facilitated diffusion and what’s an example of a molecule that moves via facilitated diffusion?
Movement with the help of carrier proteins still following a concentration gradient
- Ex: Glucose
What is Active transport?
What is required for active transport?
What are examples of ions that utilize active transport?
Movement against a concentration gradient, requiring ATP
Also Requires:
- Protein membrane carrier
- Saturation kinetics
- Competitive inhibition
Ex. Na⁺, K⁺, Ca⁺⁺
What transfer mechanism is characterized by membrane rearrangement, vesicle formation, and the movement of large macromolecules? What does it require?
Pinocytosis: cellular engulfment
- requires energy
What is an example of pinocytosis transfer in pregnancy?
Transfer of IgG from mother to fetus
What are the major factors that impact drug transfer across the placenta?
- Blood flow
- Lipid solubility
- Protein binding
- pKa & pH/charge
- Molecular size
(Also, gestational age, maternal factors, and placental drug metabolism).
What is the primary factor affecting anesthetic drug delivery across the placenta? Why?
Blood flow because most drugs are passively transferred.
High lipid solubility results in _______ bilayer penetration.
more bilayer penetration
can lead to drug trapping in placental tissue
What drug is an example of high lipid solubility resulting in placental tissue trapping of the drug?
Sufentanil
Why are bupivacaine and ropivacaine less likely to cross the placenta?
Both are highly protein-bound.
(free unbound fraction of drug equilibrates across placenta)
Albumin binds to _____ and ________ compounds.
α-1 acid glycoprotein binds to ______ compounds.
- Albumin binds acidic & lipophillic compounds
- α-1 acid glycoprotein binds basic compounds
What is pKa?
The pH at which 50% of a drug is ionized & 50% is non-ionized
Do ionized or non-ionized drugs tend to cross the placenta more easily?
non-ionized
What is ion-trapping?
When the fetus has a lower pH than the mother resulting in drugs being trapped in fetal circulation via H⁺ binding to non-ionized drug.
What is an example of a highly ionized drug that doesn’t cross the placenta easily?
- Succinylcholine
prevents crossing of the drug in the first place
Drugs with a molecular weight of ________ typically cross the placenta.
< 500 Da (Daltons)
Most drugs with a molecular weight of _______ do not cross the placenta.
> 1000 Da (Daltons)
What are examples of drugs that don’t cross the placenta due to their high molecular weight?
- NDNMB’s
- Heparin
- Protamine
What anticholinergics readily cross the placenta?
- Atropine
- Scopolamine
What anti-hypertensives readily cross the placenta?
- β blockers
- Nitroprusside
- Nitroglycerin
What local anesthetic can readily cross the placenta? (in contrast to other LA’s)
Lidocaine
What drug classes typically are able to readily cross the placenta?
- Anticholinergics
- Anti-hypertensives
- VAA’s
- Benzo’s
- Ephedrine
- Induction agents
- Tylenol
- Neostigmine
- Warfarin
What drugs DO NOT readily cross the placenta?
- Glycopyrrolate
- Heparin
- Succinylcholine
- NDNMBD’s
- Sugammadex*
- Phenylephrine
What drugs should be used to reverse paralysis in pregnant patients? Why?
Neostigmine & Atropine
Glyco does not cross the placenta, thus neostigmine will cause severe fetal bradycardia with neostigmine administration. Use atropine to avoid this.
What is a teratogen?
Substance that increases the risk of a fetal defect
When during development are teratogens most likely to cause fetal defect?
~15 - 60 days gestational age
Which anesthetics drugs are proven teratogens?
None
However, we like to minimize or eliminate fetal exposure to anesthesia in the 15 - 60 days gestational period.
What drug that we commonly use is not regulated by the FDA?
N₂O (medical gas, not drug), so it is not classified
What is the teratogenicity profile of benzodiazepines?
Class D FDA Rating (positive evidence of risk)
- Probable cleft palate formation from GABA activity
- Chronic exposure (not a one time low dose)
Especially Diazepam.
How does meperidine affect the fetus?
- Neonatal CNS depression
- Can cause seizures due to normeperidine (metabolite) accumulation
How does morphine affect the fetus?
- ↓ maternal respirations = ↓ fetus O₂
- fewer fetal heart rate accelerations (not a good sign)
What opioid can be really useful for maternal sedation? Why?
Remifentanil
Maternal sedation without significant neonatal effects
Rapid metabolism = minimal fetal exposure.
What is P50 ?
The partial pressure of O₂ at which Hgb is 50% saturated with O₂
- quantifies the affinity of hemoglobin for oxygen
At ____ mmHg of partial pressure of oxygen, 50% of fetal hgb are saturated.
19mmHg
What is the P50 of vadult Hgb?
27 mmHg PO2
How does the P50 of HbF compare to that of HbA?
HbF = 19 mmHg
HbA = 27 mmHg
HbF will preferentially pick up O₂ from the mother’s blood.
A lower P50 will result in a ________ oxygen affinity.
higher
What concept is linked with the increase of CO₂ and decrease of pH (acidity) resulting in a _______ affinity of Hgb for oxygen.
Bohr Effect
- decreased affinity = increased unloading
(Right shift in curve)
The presence of CO₂ and blood acidity in fetal blood will _______ the release of O₂ from maternal hemoglobin.
enhance
Right shift = Release
What happens as the CO₂ content of fetal blood decreases?
CO₂ diffuses down concentration gradient into maternal blood → Fetal blood becomes alkaline → curve shifts left → facilitates more O₂ uptake (↑O₂ affinity) by HbF.
Left shift = Lock
How will maternal hyperventilation affect fetal oxygenation?
Hyperventilation = hypocapnia/maternal alkalosis → maternal oxyhemoglobin curve shifts left and prevents as much O₂ from getting to the baby (decreased unloading)
What are examples of drugs that are non-ionized and can become ion-trapped when becoming more ionized in fetal circulation?
- Local anesthetics
- opioids
these weak bases are more non-ionized in maternal blood and become more ionized in more acidic fetal blood leading to inability to easily cross back into maternal blood
Do benzodiazepines readily cross the placenta or not?
BZDs readily cross the placenta
Do opioids readily cross the placenta or not?
opioids readily cross the placenta
Is sugammadex a good choice for paralytic reversal in the pregnant patient?
sugammadex has not been widely studied in the pregnant population and is not recommended
What specific opioid agonist-antagonist is discussed to be useful for pain relief in the pregnant patient?
Butorphanol (stadol)
- blocks and activates pain receptors
- provides pain relief with less fetal side effects
