Maternal - Fetal Pharmacokinetics • Define Pharmacokinetics • Understand how pregnancy changes...

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

Thank You!

Contact Information: 541-706-2665 NICU Educator

rjbates@stcharleshealthcare.org