Pregnancy and Lactation Flashcards
Counseling tips for lactating women include
Eat a balanced diet
Take prenatal vitamins (do not take if not specified for pregnant women!)
Intake should be no more than 0-1 cups of coffee, tea, or caffeinated beverage daily
Avoid raw meat (listeria) or fish with high mercury levels
Eat plenty of fruits and veggies, wash before eating!
What pharmacokinetics change with pregnancy (specifics)
- Maternal plasma volume increases
- Cardiac output increases
- Glomerular filtration increases (drug excretion decreases)
- Body fat increases (VoD increases)
- Plasma albumin decreases (VoD increases; unbound drugs cleared faster)
- Hepatic perfusion increases
- Delayed gastric emptying (N/V)
- Gastric pH increases
- Estrogen and progesterone increase
Overall, PK changes in pregnancy lead to
Increased volume of distribution
**Increased clearance
decreased protein binding
shorten or lengthen elimination half life
What factors affect movement of drug from maternal to fetal circulation
Lipophilicity protein binding molecular weight drug pKa placental CYP450
Highly lipophilic drugs…
more easily cross the placental barrier to enter fetal circulation
What conditions must be present to allow hydrophilic drugs (like lithium) to cross the placental barrier
Protein binding low enough
Molecular weight low enough
Highly protein bound drugs have a
lower free fraction available to diffuse into fetal circulation (AKA less crosses over)
-UNLESS you keep levels of the drug high enough, in which it may cross over solely due to the amount of drug present
How do least and most maternally protein bound drugs differ
Least protein bound reach higher concentrations in fetus than highly protein bound drugs
If a drug is more highly bound in the fetus rather than maternal, it will concentrate on
the fetal side
What happens to albumin in mom and baby
Lowers in mom but increases in baby!
But as pregnancy progresses, the ratio may change despite consistent maternal dosing
How does molecular weight affect drug movement
Low molecular weights (<500 Da) easily cross the placenta Larger molecules (600-1000 Da) cross more slowly >1000 Da do NOT cross the placental barrier
How do fetal and maternal pH compare
Fetal pH is slightly lower (7.3) than maternal pH (7.4)
So, some degree of ion trapping can concentrate drugs on the fetal side
What is pKa
a measure of acid strength
What were we made aware that the fetal CYP450 system does
Placenta converts prednisolone to the INactive prednisone
So, prednisolone can be used in pregnant patients without the risk of fetal exposure to an active corticosteroid!
Can anesthesia and analgesia drugs be used in pregnancy?
Not usually; they cross the placental barrier well and fetal effects can be noted at birth (respiratory depression 2/2 mom on narcotics)
Why do we get baby out ASAP after C-Section
because mom is given analgesics and anesthetics! We dont want to harm baby
Fetal CYP450 appears when
as early as 14 weeks, and increases throughout pregnancy
Glucuronidation is immature until
near or after birth
So, fetus can metabolize drugs that cross the placenta, and toxic agents can be found in the fetus
These anti-HTN are believed to be safe during pregnancy
CCB, Nifedipine Beta blockers Methyldopa Hydralazine CCB Magnesium Sulfate (IV infusion as inpatient)
These anti-HTN are contraindicated in pregnancy
ACE
ARB
-can both lead to fetal renal failure
These antibiotics are safe in pregnancy
Nitrofurantoin (macrobid, macrodantin)
Penicillins, cephalosporins
These antibiotics are NOT safe in pregnancy
Sulfonamides (displace bilirubin from albumin and enhance kernicterus
These antiemetics are safe in pregnancy
Promethazine (phenergan)
Ondansetron (zofran) if unrefractory
Vitamin B6!
A side effect of antiemetics in pregnancy are
Phenergan: anticholinergic, acute dystonia, akathisia
Zofran: headache
Bromocriptine previously was used in pregnancy to
Suppress lactation (TRH stimulates PRL secretion; Dopamine activates D2 to stop PRL) No longer recommended 2/2 reports of stroke, MI, Sz, and HTN in postpartum women
Bromocriptine is an
ergot derivative that activates D2 receptors and inhibits prolactin release= stop lactating!
Resources to check for drugs used in pregnancy include
Lactmed
motherisk.org
How do drugs move into breast milk
passive diffusion and carrier mediated transporters (similar to organic cation transporters found in liver and gut)
Explain different milk:plasma drug concentrations
>1: drug is concentrated in breast milk MC: 1 or less 25%: >1 15%: >2 BUT: ratio reported is meaningless
If the ratio doesnt matter, what DOES matter?
how much total drug is ingested and absorbed by the baby
-Total amount of a drug in a day’s volume of breast milk is usually small compared to an oral therapeutic dose for the infant
What exposure is used as a conservative cutoff for concern
Index value of no more than 10% of a therapeutic dose for infants
EXCEPT: drugs that cause hemolysis in infants with G6P deficiency, and chemotherapeutic drugs
Use caution with these drugs in breastfeeding women
Codeine Ciprofloxacin Doxycycline Fluoxetine Diphenhydramine Lithium -Lisinopril, Cyclophosphamide, Valporic acid
Absolutely avoid these drugs in pregnant women
Oxycodone Meperidine Methotrexate Lithium Phenobarbital Primidone (metabolized to phernobarb) Ethosuxamide Chemotherapeutic drugs Amiodarone Atenolol Nadolol Cocaine Iodine (betadine)
Instead of oxycodone and meperidine, use
- Use low dose morphine instead, or methadone
- intermittent LOW doses of oxycodone are considered safe
What BB can be used in breast feeding
Propranolol and labetalol
Can you use sedatives or hypnotics in breast feeding women
Intermittent use is fine, prolonged use has allegedly been shown to cause withdrawal symptoms in infant
How can you treat BV in pregnancy
Metronidazole
OR 2: clindamycin
How can you treat chlamydia in pregnancy
Azithromycin
OR: amoxicillin, erythromycin
How can you treat herpes in pregnant women
Acyclovir, started at 36 weeks gestation
How can you treat gonorrhea in pregnancy
Ceftriaxine (IM) PLUS Azithromycin
How can you treat syphilis in pregnancy
Primary, secondary, tertiary: Benzathine penicillin
Neurosyph: Aqueous penicillin G
How can you treat Trichomoniasis in pregnancy
Metronidazole
How can you treat allergic rhinitis in pregnancy
Intranasal corticosteroids (Budesonide)
Intranasal Cromolyn
First gen antihistamines (benadryl)
How can you treat asthma in pregnancy
Albuterol alone if intermittent
Albuterol + ICS (Budesonide) and LABA if persistent
How can you treat epilepsy in pregnancy
Safest AED: carbamazepine, lamotrigine, levetiracetam, phenytoin, gabapentin, henobarbital, topiramate, VPA
polytherapy has higher risk of malformations than monotherapy
How can you treat HIV in pregnancy
If currently on ART: continue regimen if viral load is suppressed Dual NRTI Ritonavir NNRTI Integrase inhibitor
How can you treat thyroid disorders in pregnancy
- Hyper: PTU (first trimester), Methamizole (after first trimester)
- Hypo: Levothyroxine
