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Maternal - Fetal
Pharmacokinetics Randa Bates, BSN, CNPT RN
Objectives • Define Pharmacokinetics
• Understand how pregnancy
changes pharmacokinetics
• Understand how drugs effect the
fetus
Pharmacokinetics
Physiologic Changes of Pregnancy
Total Blood Volume Increases
CO, SV, HR Increases
BP Initially decreases,
Increase in 3rd trimester
SVR Decreased
RBC **Decreased
Albumin Decreased
Intravascular Volume Increased
GFR Increased
Absorption, Pregnancy and
Fetus Maternal Fetal
Increased Progesterone level =
decreased GI motility and empting time
Only free unbound drugs cross
placental barrier
Decreased Acid and mucus =
decreased pH
Non ionized lipid soluble drugs move
across membranes more quickly
Increased CO and Minute Ventilation =
increased pulmonary absorption
pH (Maternal and Fetal) determine
placental transfer of drugs
Distribution, Pregnancy, and
Fetus Mother Fetus
50% plasma volume increase =
Altered volume of distributed drug
½ fetal circulation (thru UV) by passes
fetal liver
Average body water increases by 8 L 60% of fluid fetus, placenta, AF
Protein Binding, Pregnancy
and Fetus
Maternal Fetal
Reduced Number of
protein binding sites d/t
placental and steroid
hormones
Fetal plasma may have
higher or lower drug
affinity than maternal
Dilution Hypo-
albuminiema =
Decreased protein
binding
More free drug for fetal
absorption
Pregnancy related Dx
that affect Protein
Binding
Decreased placental
profusion, increased
free drug
Elimination, Pregnancy, and
Fetus
Maternal Fetal
Increased Hepatic
Metabolism via CYP450
pathway
Primarily via passive
diffusion thru placenta –
limited placental and fetal
metabolism
50% Increase in GFR =
substantial decrease in ½
life of most drugs
Fetal excretion of drugs into
amniotic fluid
Fetal Pharmacokinetics Maternal drug concentrations are higher
Passive Transfer Across placenta
Fetal Circulation – Renal
excretion = Amniotic fluid
Amniotic fluid traps
Fetus swallows fluid
Prolonged exposure
Effects higher
Placental Role
Drug Use in Pregnancy
HTN during pregnancy Chronic
Gestational
PIH
Pre-Eclampsia
Eclampsia
HELLP
Antihypertensive Therapy Drug Mode of Action Adverse
Maternal
Adverse Fetal Other
Nifedipine - C CCB
**Bioavail.
Route
dependant
Hypotension
HA, Flushing,
inhibition of
Labor
R/T decreased
uterine and
MCA perfusion
Preferred d/t BP
decrease w/o
tachycardia
Labetelol - C BB
Alpha effect
Highly Meta
Heart block
Low Glucose
NV
IUGR
Low glucose
Decreased
Neonatal
Respiratory
distress
Hydralazine -C Vasodilator,
Decreases SVR
–
Hard to predict
concentration
Tachycardia
HypoTN,
NV, HA, Flush
R/T precipitous
lowering of BP
Mag Sulfate – A
D
Blocks Calcium
Receptors
Arrhythmia
HypoTN
Resp Depress
Lethargy, RR
Depression
Neuroprotective
under 32 wks
gestation
Antihypertensive Monitoring Drug Monitoring
Nifedipine ECG, Blood Pressure, Pulse, - Fetal
monitoring of HR with loading and increased
doses, contractions
Labetalol BP, ECG, Fetal Heart Rate
Hydralazine BP, ECG, Fetal Heart Rate
Magnesium Sulfate ECG, BP, RR (if less than 16, discontinue),
DTR, Fetal HR, Contractions, monitor for
seizures, DECREASE STIMULATION!!!
Tocolytics Drug Maternal Fetal
Magnesium
Sulfate
Cannot use with
Nifedipine!!
Nifedipine
Terbutaline - B Beta-Mimetic
(causes a
cascade of
events with
outcome of
decreased CA)
tachycardia,
hypoglycemia
Increase in IVH
Increased risk
of
ASD
Glycemic Control Sulfonylureas –stimulate insulin release (Class b/c)
Insulin (Class B)
SSRI’s in
Pregnancy Fluoxetine and active
metabolite, nor fluoxetine (Class
C)
Maternal levels decreased by
50%, requiring increase dose
Newborn ½ life 5 days
Poor neonatal adaptation
Neurotransmitters
Opiates All substance that act on
opiate receptors (Class C)
Fentanyl, Morphine, Heroine, Codeine, methadone **, Rx drugs, suboxone
Opiates and metabolites cross placenta
PTL, poor nutrition, delay/arrested brain development
NAS- Abnormal EEG = to sleep deprivation
Nicotine Clearance 60-140% faster in
pregnancy, ½ life 50% less
Easily crosses placenta
Fetal levels higher
Binds to Neurotransmitter receptors
Effect timing of brain development
Neonatal Abstinence Syndrome
THC Crosses Placenta
Delayed excretion
Decreases
Cortical Neurons
Various Neurotransmitters
Dopamine Receptors
Result:
Learning deficits, delayed
male maturation, impaired
emotional reactivity
Marij baby costume image
Alcohol Dual insults related to
circulatory insufficiency
Depressant effects
neurotransmitter receptors
Decreases brain activity
Disrupts growth on many levels
FAS
Psychostimulants Cocaine, Meth and other
amphetamines
Enhanced release of
dopamine, norepinephrine,
and serotonin into cleft
Blocks re-uptake and
degradation of
neurotransmitters =
concentration in cleft
Vasoconstrictive effects
Take Homes Drug Classification
ADME
Optimization thru titration
Code/Trauma – SAVE THE
MOM
