Pregnancy/Lactation CLASS 1

Define teratogen

any agent with the potential to produce abnormal development of the fetus

Most of the major anomalies can happen with exposure in what phase?

embryonic period (3-8 weeks)

How do you estimate a due date?

Add 1 week to the date of LMP and subtract 3 months

Based off last menstrual period

Define gravidity

How many times a woman has been pregnant

Define parity

How many children a woman has had

What does TPAL stand for?

T- term

P- pre-term

A- aborted/ectopic/miscarriage

L- living

The kinetics are influenced by what 2 major factors?

1. maternal physiologic changes

2. effects of placental-fetal compartment

What are some maternal physiologic changes affecting absorption?

• N/V

• delayed gastric emptying

• decreased gastric acidity

• increased blood flow to the maternal skin

What are some maternal physiologic changes affecting distribution?

• body fat increase

• plasma volume expansion

• total body water increase

• decreased protein binding, increased fraction (fu) of drugs

What are some maternal physiologic changes affecting metabolism?

• Increases in estrogen and/or progesterone stimulate or decrease hepatic enzymes of CYP450

• Increased total hepatic blood flow

What is hypoalbumenia?

dilution from increased plasma volume

Increased concentrations of what 2 things may decrease protein binding sites for drugs?

1. steroid

2. placental hormones

With metabolism, there are increases in what activity? (CYP__)

• 3A4

• 2D6

• phenytoin

With metabolism, there are decreases in what activity? (CYP__)

• 1A2

• 2C19

• xanthine oxidase

• NAC

• Reduced elimination of theophylline and caffeine

What are some maternal physiologic changes affecting elimination?

• eGFR begins to rise during 1st trimester and peaks at 50% increase in 2nd

• renal blood flow increases 25-50% early during gestation

• renal drug excretion may increase

Maternal and fetal rug concentrations are dependent on what factors?

• amount of drug that crosses the placenta

• The extent of metabolism by the placenta

• fetal drug distribution and elimination of the drug

What drugs cross the placenta readily?

• MW <500

• lipid soluble

• non-ionized

• long half life

What drugs are not likely to cross?

• MW > 1000

• Protein bound

True or false: fetal plasma is more basic than maternal

false; more acidic

Weak _____diffuse across placental barrier and become ionized

bases

What is ion trapping?

The weak bases diffuse across the placental barrier, become ionized, and a net movement of the drug from mom to the fetal compartment

Which stage of teratogen exposure will you likely see more anomalies involved with growth and functional aspects

fetal period (day 57-term)

The _____ is most susceptible to teratogens

embryo

What are the current pregnancy categories?

• 8.1 - pregnancy

• 8.2 - lactation

• 8.3 - females and males of reproductive potential (new)

During pregnancy, high estrogen and progestin levels (stimulate/inhibit) lactogenesis?

inhibit

There is a dramatic decrease in ______ at delivery which triggers milk secretion

progesterone

Movement from plasma to milk is generally _____ diffusion

passive

What drug properties tend to cross into milk?

• MW <500

• lipid soluble

• free drug

• non-ionized drug

• Maternal drug dose, frequency, and duration

What is the relative infant dose? (RID)

popular method for estimating exposure risk

estimate for how much medication the infant is exposed to on a weight-normalized basis

How do you calculate the RID?

divide infants dose via milk by mother’s dose

A RID of _____is typically considered safe

<10%

What % of pregnant women take at least 1 medication during pregnancy?

50%

Overall, approx. 1-3% of newborns in the U.S. are affected with congenital abnormalities. Of these, what % are thought to be due to medications?

3%

Recommendation of folic acid doses

04.-0.9mg daily and BEFORE pregnancy

What % of pregnant women experience N/V

70-80%

1st line pharm treatment for N/V

pyridoxine 10mg ± doxylamine 10mg po 3-4x/day

everyday, scheduled

N/V starts around _____ weeks and peaks severity during ______ weeks

6 weeks, 11-13 weeks

Why do women experience GERD while pregnant?

increased levels of progesterone and estrogen which relaxes lower esophageal sphincter

1st line treatment for GERD

antacids or sucralfate

True or false: sodium bicarbonate antacids are okay for GERD

false

2nd line for GERD

H2RA (famotidine)

3rd line for GERD

PPIs

What should you not use to help constipation?

• magnesium and sodium salts

• castor oil and mineral oil

What can you use for constipation?

• physical exercise, increase fiber and fluids

• supplemental fiber and/or stool softener

• bulk forming agents

• osmotic laxatives

• stimulant laxatives

Treatment for tension HA

APAP 1000mg

Treatment for migraine

• APAP 1000mg

• propranolol

• If refractory - triptans

PPD occurs up to ___ year after delivery

1

NSAIDS should be avoided in which trimester? (tension)

3rd

For migraine, NSAIDs are for use only in ___ trimester

2nd

ASA is not preferred in ____ trimester

3rd

What agents are contraindicated for migraines?

• ergotamine

• dihydroergotamine

Medication approved for PPD in someone that is medication naive

Zuranolone 50mg PO qhs x 14 days

What is the preferred ICS agent in asthma?

budesonide