lactation/pregnancy Flashcards
what 5 aspects must be considered in regards to pregnancy/lactation and medications?
- Drug safety during pregnancy and lactation
- Drug toxicity during pregnancy
- Physiological changes during pregnancy that may affect drug action and kinetics
- Cross-placental transfer of drug molecules and their metabolites
- Excretion in breast milk
__% of pregnant women are exposed to teratogenic medications with __% of children born with physical or mental birth defects. why is this important?
6%, 3%
risk of exposure to these meds is small but IMPACTFUL when there is exposure
FDA published the _____________to address the limitation of prescription drug labeling
Pregnancy and Lactation Labeling Rule (PLLR)
what was the previous FDA labeling for drugs with regards to pregnancy risk?
A–>X
this was misleading, those assumed A was safer than X but this wasn’t ENTIRELY true…
what are the old FDA labels for drugs? A-X? (weeds maybe)
A: studies have failed to demonstrate a risk to the fetus in the first trimester
B: animal studies FAILED to demonstrate risk to fetus. no adequate and well-controlled studies in pregnant women
C. animal studies showed adverse effect to fetus, no adequate and well-controlled studies in humans
D. positive evidence of HUMAN fetal risk, benefits MAY warrant use
X: positive evidence HUMAN fetal risk, risks outweigh benefits
what changed in the new FDA labeling?
more options with more information from pt taken into account… “ risk categories replaced with narrative sections”
best resource for information on drugs in pregnancy?
Briggs
when is the most dangerous exposure time for a teratogen?
first 8 weeks
teratogen effect in the first 2 weeks of fetal development?
“all or none”: if a drug is a teratogen will either terminate pregnancy or have no effect
teratogen effect in wks 3-8 wks of fetal development?
most devastating defects. this is the most critical time of development
weeks 9-40 of fetal development, what is happening?
growth and developmental function
what defect can aminoglycosides (GNATS) cause?
8th cranial nerve tox- vestibular dysfunction
what defect can Alkylating Agents (Cyclophosphamide) (chemo agents) cause?
Absence of digits, multiple anomalies
Antiepileptic Drugs (Valproate, carbamazepine, phenytoin, phenobarbital) defects?
neural tube defects and others
Isotretinoin (for acne) defects ?
multiple severe birth defects
warfarin defects?
Bone deformities, fetal hemorrhage
statin defects?
spina bifida
alcohol abuse defects?
fetal alc syndrome, microcephaly
cocaine and nicotine defects?
low birth weight, pre-term birth
what about the gut in pregnancy causes altered drug absorption?
INCREASED PH ( absorption of weak acids and bases altered) & N/V and DELAYED GASTRIC EMPTYING (general drug abs altered)
how can drug distribution change b.c of pregnancy?
Increased body fat increases volume of distribution of fat soluble medications
Fat soluble medications have a decrease in elimination due to the greater volume of distribution
how can metabolism of drugs change b/c of pregnancy?
Mixed effects with increases and decreases in CYP450 enzymes and changes in transport proteins
how can excretion of drugs change b/c of pregnancy?
Increases in maternal plasma volume, cardiac output, and GFR increase – subsequently decreases plasma concentrations of renally eliminated medications
5 PK properties that influence placental drug transfer?
- lipid solubility
- molecular size
- placental transporters
- protein binding
- placental & fetal drug metabolism
how does lipid solubility effect placental drug transfer?
Lipophilic and un-ionized drugs diffuse across placenta and enter fetal circulation
how does molecular size effect placental drug transfer?
smaller (low molecular weight) = crosses more easily
how do placental transporters effect placental drug transfer?
P-glycoprotein transporter pumps drug back into maternal circulation
how does protein binding effect placental drug transfer?
High maternal protein binding decreases transfer across placenta
for pregnancy, eliminate all ____ meds
non-essential
two vaccines for pregnant women
flu and Tdap (Tdap for each pregnancy a woman has)
what vitamin and dosage should pregnant women take?
folic acid: 400mcg daily for healthy women, 4-5mg daily for women at risk of neural tube defect of fetus
what are the top 3 drugs we use for symptomatic morning sickness?
Doxylamine/pyridoxine (Diclegis): first choice, $$$
Ondasetron (Zofran): if daily
Phenothiazines (promethazine, prochlorperazine): fine but causes drowsiness
what drugs can we use for heartburn? (4)
*Magnesium/aluminum (tums)
*Calcium (calcium carb- tums)
Ranitidine
Omeprazole
what drugs can we use for constipation? (3)
- Non absorbable bulk laxatives (Metamucil, Citrucel)
- Surfactants (stool softners)
what do we do for hemorrhoids?
Correct constipation
Sitz bath
treatment for HA? (2)
txt:
1. Rest, ice packs
2. Acetaminophen
what drugs can we give for coagulation disorders? (2)
- heparin
2. low molecular weight heparin: (Enoxaparin (Lovenox) preferred agent)
what coagulation drugs should we AVOID for pregnancy women?
warfarin
discontinue anti-coag drugs ____ hrs before ______
24, C-section or vaginal delivery
drug of choice for gestational DM? why?
Insulin
- Lower risk of neonatal hypoglycemia
- Less maternal weight gain
- Better glycemic control
what is our 1st line for HTN?
Methyldopa is 1st line therapy
Hypothyroidism txt in pregnancy?
levothyroxine
hyperthyroidism in pregnancy, what do we recommend for the 1st trimester vs the 2nd/3rd?
1st trimester – propylthiouracil (PTU)
2nd & 3rd trimester - methimazole
why do we only recommend PTU used for hyperthyroidism in the 1st trimester?
possibility of liver toxicity
Drugs for UTI? (4)
Penicillins (augmentin usually), Cephalosporin (keflex), sulfonamides (except 2rd trimester) , nitrofurantoin
what drugs are contraindicated for UTI in pregnancy? what is the reason to avoid each?
- tetracycline & doxycycline (teeth/bone development)
- fluoroquinolones (tendon developments)
- no sulfas in third trimester (jaundice of newborn)
what are the two preferred asthma drugs?
SABA (abluterol sulfate : proair, proventil, ventolin)
ICS (budesonide: Qvar, pulmicort) or (Fluticasone: Flovent, Ellipta)
two drug groups for allergic rhinitis in pregnancy?
- Inhaled Nasal Corticosteroids
- 2nd generation antihistamines : Cetirazine (Zyrtec) and loratadine (Claritin)
what is the #1 choice for depression in pregnancy?
SSRI: sertraline
.. also fluoxetine, citalopram
Antidepressants taken throughout and/or during last trimester may cause _____ ______ in the baby
discontinuation symptoms (Jitters or irritability) in baby
Reducing dose of antidepressant near end of pregnancy not recommended b/c …
it doesn’t minimize withdrawal symptoms and it may increase depression during post-partum period
what is preterm labor?
Defined as uterine contractions with cervical changes before 37 weeks
what do you do for a patient who has history of preterm labor?
17-hydroxyprogesterone acetate IM weekly from 16-37 weeks
3 agents to inhibit uterine contractions?
- Beta-agonist (terbutaline)
- Magnesium sulfate
- CCB (nifedipine)
how does MgSulfate help inhibit uterine contractions?
antagonizes effect of calcium decreasing contractions
how does CCBs (nifidepine) help inhibit uterine contractions?
blocks calcium necessary for muscle contraction
2 agents to induce pregnancy?
- oxytocin
- prostaglandin (dinoprostone & misoprostol)
2 ADRs of oxytocin
uterine rupter, fetal distress from hypoxia
MOA of prostaglandins?
relax smooth muscle of the cervix allowing dilation and passage of fetus through birth canal
MOA of oxytocin
stimulates receptor to increase calcium influx resulting in smooth muscle contraction
During lactation, drugs may pass from bloodstream to the breast milk if they are… (4)
- Lipid soluble
- Low molecular weight
- Low serum protein binding
- Drugs with longer ½ lives
2 ways to help decrease exposure of baby to a medication when breastfeeding
- Administer single daily dose meds around the longest sleep interval for the infant, usually after bedtime feeding
- Nurse immediately before dose when multiple doses are needed
drugs for allergic rhinitis when breastfeeding? which are preferred and which for long-term?
2nd generation antihistamines are preferred
Long Term use: use nasal steroids or cromoyln (mast cell stabilizer)
which asthma med is best when breastfeeding?
ICS- fluticasone
6 cardiovascular drugs safe for breastfeeding (maybe weeds)
Labetalol, atenolol, metoprolol, nifedipine, enalapril and captopril
All ___ drugs come out in breastmilk
All anti-depressants in breast milk
3 preferred agents for depression & breastfeeding?
SSRI (Sertraline, paroxetine) TCAs
6 safe agents during lactation (weeds)
Analgesics (ibuprofen, acetaminophen)
Antibiotics (penicillins, cephalosporins)
Anticonvulsants (phenytoin, carbamazepine)
Caffeine (moderation)
Insulin
Laxatives
effect on breastfeeding infant: alcohol ?
Impaired motor development, decreased milk consumption, sleep disturbances
effect on breastfeeding infant: amphetamines ?
Hypertension, tachycardia, seizures
effect on breastfeeding infant: benzos ?
Metabolite accumulation, prolonged ½ life in preterm infants
Apnea, cyanosis, withdrawal, sedation, cyanosis, seizures
effect on breastfeeding infant: cocaine?
Seizures, irritability, vomiting, diarrhea
effect on breastfeeding infant: heroine ?
Withdrawal symptoms, tremors, poor feeding
effect on breastfeeding infant: methamphetamines ?
Infant death, remains in breast milk 48 hours
effect on breastfeeding infant: marijuana?
Delayed motor development at 1 year, lethargy, decreased feedings
teratogen effect of ACE/ARB ?
Renal Damage, fetal lung hypoplasia, skeletal malformations, and fetal death (LOTS)
teratogen effect of lithium?
Ebstein anomaly (displacement of tricuspid valve), hypoglycemia, diabetes insipidus, thyroid dysfunction
teratogen effect of methimazole (hyperthyroidism drug) ?
GI, respirator, and skin anomalies
teratogen effect of (Tetracycline, minocycline, doxycycline)?
Discolored teeth, inhibited bone growth
teratogen effect of Thalidomide (cancer drug)?
limb defects
5 body systems whose changes in function during pregnancy lead to kinetic variations for drugs?
Cardiovascular, pulmonary, gastrointestinal, renal, hepatic function
