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Copy of Perinatal Pharmacology

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Kristen Ostrem-Niemcewicz

on 16 March 2016

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Transcript of Copy of Perinatal Pharmacology

Background
2/3 of pregnant women need drug treatment for a variety of reasons
Pregnancy anatomy and physiologic changes influence drug absorption, distribution and elimination
Unethical to study medication use in pregnant women, most information from case reports, epidemiological studies & animal studies
CDC presentation on medication use in pregnancy
http://www.medscape.com/viewarticle/738087
Perinatal Pharmacology
Kristen Ostrem CNM, FNP-BC
Objectives
1. Review pharmacodynamic and pharmacokinetic factors for a pregnant woman, her placenta and fetus
2. List basic principles influencing exposure to the fetus
4. Compare and contrast pharmacology resources
5. Review changes in FDA drug labeling for pregnancy, lactation & reproductive potential
Placental Drug Transfer
Physiochemical properties
Rate and amount
Exposure duration
Fetal tissue distribution
Fetal developmental stage
Combined drug effects
Organogenesis week 3-8
Perinatal Pharmacology
Drug effects on the fetus wks 8-40
Direct
Alter placental function
Uterine stimulation
Placental drug transfer
Crosses by diffusion
Free unbound drugs pass to fetus
Molecular weight- low < 500g/mol cross freely
higher less easy to cross (500-1K g/mol), > 100g/mol do not cross
Examples: Heparin is higher molecular weight

Example: fetal blood is lower pH and higher albumen so those drugs will pass over to area of lower concentration
Drugs in Pregnancy Labeling Changes from
A,B,C,D,X
Drug Distribution
Four Compartments:
Fetus
Placenta
The mother
Amniotic Fluid
Placental Transfer
Active
Passive
Higher to lower concentration (eg: fetus can have higher valium concentrations than mother)
Depakote and Digoxin are
actively transported across the placenta
Drug transfer is facilitated by
Molecular size
Lipid solubility
Plasma protein binding
Acid/base properties
Most medications are low molecular weight (under 500 daltons) & easily transferred across the placenta
Large molecular wt medications like insulin and heparin transfer slowly
Fetal circulation is more acidic than moms

Leads to ion trapping of certain medications in the fetal compartment
Lipophyllic drugs cross placenta more readily than hydrophyllic
Most common medications used during pregnancy
Antibiotics
Antidepressants
Anxiolytics
NSAIDS
Asthma medications
65 medication fact sheets with up to date evidenc-based information on medication riks & known effects during pregancy
http://www.mothertobaby.org/otis-fact-sheets-s13037
Companies are required to provide information on pregnancy registries if available
Information on new FDA labeling to include:
Risk Summary
Clinical Considerations
Data
Lactation information includes:
Amount of drug in breastmilk
Potential effects on the baby

Reproductive Potenial
includes pregnancy testing, contraception recommendations and infertility information
Mom's physiology/pharmacokinetic changes
Circulatory volume increases
Lower plasma protein
higher levels of free unbound drugs
GI absorption and rate
Increased absorption of hydrophilic drugs. No change in absorption of lipophilic drugs
Varied metabolism of some drugs from estrogen and progesterone effects on hepatic enzymes (slower-caffeine)
Renal- GFR rate increases through third trimester, drugs excreted by kidneys clear more rapidly
Respiratory rate increased- rapid excretion of drugs
separated from mom's circulation by syncytiotrophoblast
Placenta has enzymes that metabolize some drugs
Epocrates App for Phone
Medication example
Metronidazole Category B found under safety & monitoring, trimester specific. Lactation: safety "Conditional"
References
Katzung B.G., Trevor A.J. (Eds), Basic & Clinical Pharmacology, 13e. Retrieved August 31, 2015 from http://accessmedicine.mhmedical.com/content.aspx?bookid=1193&Sectionid=69109136. Chapter 59
King, T & Brucker, M. (2011) Pharmacology for Women's Health. Boston: Jones & Bartlett * New edition out fall of 2015- recommended for midwifery students
King, T et al., (2015) Varney's Midwifery 5th ed. Chapter 5

Metronidazo0le Fact Sheet
Provides current evidence
on known risks for
pregnancy and lactation

http://www.mothertobaby.org/files/Metronidazole.pdf
Assignment:
Off label use of medications in pregnancy
1. Misoprostol
2. Magnesium Sulfate
3. Terbutaline
Full transcript