Pregnancy Pharmacology

jmanderson's version from 2015-12-12 19:22

Tocolytics, Oxytocics, and Antenatal Drugs (Powerpoint)


Question Answer
Give the steroid that can be used to suppress pre-term labor and when and how often it is given.17-hydroxyprogesterone acetate 250mcg IM weekly from 16-36 weeks
Describe tocolytic and give three purposes for them.(1) To postpone delivery to allow max effect of antenatal steroid; (2) To allow time for transportation to equipped facility; (3) To prolong pregnancy when underlying self-limited conditions exist that can cause labor
Nifedipine MOAblocks voltage and primarily L-type Ca channels
Nifedipine physiological actionsSmooth muscle relaxation; tocolytic (unapproved); PTL 48-72 h
Mg-Sulfate MOAinhibits both L type and ligand gated voltage-gated Ca channel
Terbutaline MOAβ2-adrenergic receptor agonist
Terbutaline physiological actions(1) Causes bronchodilation and relaxation of the uterine smooth muscle; (2) Indicated in Intrauterine Fetal Distress (Unapproved) and Asthma
Give the mechanism of magnesium sulfate action and its one approved indication related to pregnancy.Inhibits Calcium channels; Relaxes uterine smooth muscle.; Indicated as a tocolytic (unapproved) and Eclampsia seizures (approved)
Give three physiological effects of betamethasone on the pre-term fetal lung.Increased development of pneumocytes; Increases gas exchange in the alveoli; Increases the production and secretion of surfactant; Increases production of surfactant binding proteins and enhance fetal lung antioxidant enzymes
betamethasone IndicationFetal lung maturation to prevent respiratory distress syndrome and reduction in intraventricular hemorrhage
gestational age and risk factor that makes treatment with betamethasone appropriateGive to mother between 26-34 weeks who are at risk of PTL within 7 days.
Give four specific oxytocic drugs.Oxytocin; Prostaglandins - Diniprostone and Misoprostol; Ergot Alkaloid – Methylergonovine
Give three organs that have oxytocin receptors and the effects of oxytocin stimulation at each.(1) Myometrium of Uterus where they found induce uterine contractions (Pitocin); (2) Mammary glands where it induces milk ejection; (3) Brain where they affect reproductive behaviors and social bonding
Give three indications for dinoprostoneCervical ripening; Induction; Postpartum Hemorrhage
How does dinoprostone differ from misoprostolDinoprostone works on PGE2, whereas Misoprostol is a PGE1 analog
receptor stimulated by methylergonovine5-HT2a receptor on myometrial cell

Tocolytics, Oxytocics, and Antenatal Drugs (Handout)


Question Answer
a natural steroid used for pre-term labor, as well as when and how it is givenProgesterone = given via IM shots weekly from 16-36 wk gestation
Give four pregnancy conditions in which tocolytics are either not indicated or not proven to be effective.Women having preterm contractions w/o cervical changes (esp. women whose cervix is dilated < 2 cm), no reduction in rates of respiratory distress syndrome, does not reduce adverse perinatal outcomes or improve pregnancy, does not reduce # of premature deliveries.
four conditions where tocolytics are contraindicated.Intrauterine demise, intrauterine infection, lethal fetal anomaly, significant vaginal bleeding, severe preeclampsia and maternal hemodynamic instability, cervix dilated > 4 cm
the black box warning to the use of IV terbutaline and whenUsing IV terbutaline for > 48-72 hours has potential for serious maternal heart problems or death
Give the condition for which magnesium sulfate is contraindicated.Myasthenia gravis
Give one tocolytic that cannot be used in combination with magnesium sulfate.Do not give Mg-sulfate with nifedipine (hypotension)
Give one tocolytic that can be used in combination with magnesium sulfate.Can give Mg-sulfate with Indomethacin (doesn’t cause hypotension)
the antibiotic given for Group B Streptococcus (GBS) in pregnant womenPCN
when PCN monitored in pregnant womenMonitor at 35-37 wk gestation with vaginal/rectal culture (if negative, you don’t need to treat)
when is PCN given prophylactically in pregnant womenwoman is in labor and no culture data is available, fever > 100.4, or membrane rupture at least 18 h prior to gestation < 37 wk
Give two conditions for which oxytocin is the drug of choice.Induction of Labor, Postpartum Hemorrhage
Give three contraindications to treatment with dinoprostone (PGE2 analog).asthma, glaucoma, or MI
Give three M drugs that are effective abortifacientsMifepristone (RU-486), Misoprostol (a prostaglandin), Methotrexate
Give the gestational age limits to use of mifepristone as abortifacientMifepristone = good up to day 63
Give the gestational age limits to use of methotrexate as abortifacientMethotrexate = good up to day 49

pregnancy physiology


Question Answer
Absorption changesN/V, delayed gastric emptying, increase in gastric pH
Distribution changesplasma volume increase, albumin concentration decrease, body fat increase
Metabolism changeshepatic perfusion increases, estrogen/progesterone alter liver enzymes
Elimination changesGFR increase, renal blood flow increases
Placenta Drug Transfer Lipid Solubilitylipophilic drugs diffuse easier across placenta to fetus (opioids, ABX)
Placenta Drug Transfer Molecular Sizelow molecular weight drugs cross easily, big molecules don’t (heparin, insulin)
Placenta Drug Transfer pHmaternal 7.4/fetal 7.3 – weak bases cross easier
Placenta Drug Transfer Transportersp-gp pumps drugs to maternal circulation
Placenta Drug Transfer Protein Bindingmaternal albumin increases, fetal albumin decreases



Question Answer
Teratogenicity depends onembryonic stage, dose, specificity of agent, simultaneous exposure to other teratogens, timing of exposure
Old FDA teratogen system labeling(A, B, C, D, or X) Does not specify nature, severity, timing, incidence rate or treatability; teratogenic v. fetotoxic effects not specified
New system of labelingmuch more detailed
ACEIrenal damage in 2nd – 3rd trimester
amphetaminessuspected abnormal development patterns
androgensmasculinization of female fetus
TCAsfetal withdrawal sx
barbituratesfetal dependence
cocainerisk of spontaneous abortion, abruption placenta, premature labor, cerebral infarction, abnormal development
diazepamneonatal dependence
etOHfetal alcohol syndrome and related neurodevelopmental defects (e.g., retardation)
heroineneonatal dependence
lithiumEBSTEIN’S ANOMALY (R ventricular hypoplasia, tricuspid valve insufficiency), neonatal toxicity after 3rd trimester
methotrexatemultiple congenital malformations
misoprostolMOBIUS SEQUENCE (clubfoot, muscle hypoplasia of face/eyes, facial paralysis)
phenytoinFETAL HYDANTOIN SYNDROME (cleft lip/palate, microcephaly, strabismus, cardiac def., mental def.)
PTUcongenital goiter
smokingintrauterine growth retardation, prematurity, sudden infant death syndrome
SSRIsneonatal abstinence syndrome, persistent pulm. hypertension of newborn
Tamoxifenrisk of spontaneous abortion or fetal damage
thalidomidephocomelia (shortened/absent long bones of limb)
valproic acidNEURAL TUBE DEFECTS; cardiac and limb malformations
warfarin1st tri (hypoplastic nasal bridge, chondrodysplasia); 2nd tri (CNS malformations); 3rd tri (risk of bleeding, discontinue 1 mo before delivery

pregnancy problems and Rx


Question Answer
Constipation Rxfiber, fluids, stool softeners, osmotic laxitives, topical anesthetics
GERD Rxsmall frequent meals, avoid etOH/tobacco, avoid food at bedtime, Al/Ca/Mg antacids, sucralfate, H2RAs, reserve PPIs
Nausea/Vomiting Natural Rxginger
Gestational DMrisk of fetal loss, major malformations (macrosomia), screen high risk women at prenatal visit
Gestational DB Rxdietary modification, INSULIN (DOC), glyburide (doesn’t cross placenta), Metformin, maintain FPG < 90-99
Severe HTN Rxsupplement Ca, labetalol (alpha-beta blocker), hydralazine (vasodilator), nifedipine (CCB that vasodilates)
Gestational or chronic HTN Rx (goal BP 150-100)labetalol, methyldopa, !!!DHP-CCBs (-ipine)!!!!
Gestational transient thyroxicosisusually resolves by 20 wk from decreased hCG (recall hCG and TSH have the same alpha-subunits)
Gestational transient thyroxicosis Rxantithyroid usually not needed
Post-partum thyroiditis Rxbeta-blockers, levothyroxine
Acute VTE RxLMWH (enoxaparin sodium) throughout pregnancy and for 6 wk after delivery
Single episode VTE Rxantepartum monitoring
Intermediate risk and high VTE risk Rxantepartum prophylaxis w/ LMWH plus 6 wk postpartum prophylaxis w/ LMWH or warfarin (very low milk levels w/ warfarin doses up to 12 mg/d)
UTIs RxCan use Amoxicillin-clavulanate, cephalosporin, TMP-SMX
Chlamydia Rxuse Azithromycin/Amoxicillin
Lymphagranuloma venereum Rxuse erythromycin base
Trichomoniasis & Bacterial Vaginosis Rxuse Metronidazole
HA Rxcan use sx improvement for migraines, relaxation, biofeedback, stress management, sumatriptan for unresponsive migraine/antiemetics
Allergic rhinitisnasal congestion caused by pregnancy (vascular engorgement and hormone-caused mucus)
Allergic rhinitis Rxavoid allergens, INTRANASAL CORTICOSTEROIDS (most effective w/ low systemic effects), nasal cromolyn, antihistamines, avoid PO decongestants
Asthmaif it is inadequately controlled in mom, it is bad for the baby (preterm, preeclamsia, LBW, still birth); Rx same as non-pregnant
Diabetes mellitusfrequent dose adjustment needed, INSULIN is DOC
EPILEPSYfrequency of SZ doesn’t change in women during pregnancy (but serum concentration of antiepileptic drugs may change)  MONITOR “free” serum concentrations (risk of untreated epilepsy is considered higher than risks of drug therapy)
All pregnant pts on anti-epileptic meds supplementfolic acid
Postpartum depressionsx develop during pregnancy or up to 6 mo after delivery, screen for this in all pts
Postpartum depression Rxpsychotherapy,, cognitive behavioral therapy, group/family therapy, drugs (Sertraline – SSRI)
Hypothyroidismincrease risk of preeclampsia, premature birth, miscarriage, growth restriction, have to monitor TSH more often q4wk for 1st half of pregnancy
Hypothyroidism Rxlevothyroxine
Hyperthyroidismless common, assoc. w/ fetal death, LBW, IUGR, preeclampsia
Hyperthyroidism RxPTU 1st trimester, methimazole 2nd-3rd trimesters

risky pregnancy meds


Question Answer
Contraindicated for pregnant HTNACEs, ARBs, direct renin inhibitors (neonatal renal failure and cardiac defects)!!!!!!
Acute VTE contraindicatedWARFARIN - 1st trimester (nasal hypoplasia, stippled epiphyses, limb hypoplasia, eye abnormalities); 2nd-3rd trimesters (CNS abnormalities)
Avoid in pregnant UTIsFLUOROQUINOLONES (inhibits cartilage & bone development in newborn) and TMP-SMX during 3rd trimester (kernicterus & hyperbilirubinemia)
Avoid in STIs and pregnancyTetracyclines (e.g., Doxycycline) due to teeth discoloration
Avoid in pregnancy HA RxACETAMETOPHIN/IBUPROFEN in 3rd trimester (premature closure of DUCTUS ARTERIOSIS); opioids
SSRIsparoxetine (risk of CARDIAC MALFORMATIONS); causes neonatal abstinence syndrome (tremor, GI problems, increased muscle tone, sleep distrubances, high-pitched cries)
LithiumEBSTEIN’S ANOMALY (R ventricular hypoplasia, tricuspid valve insufficiency), floppy baby syndrome, nephrogenic DI, thyroid dysfunction, cardiac arrhythmias
Valproate and carbamazepineNTD/spina bifida; monitor for apnea, rash, drowsiness or poor sucking; unusual bruising or bleeding; jaundice
Antipsychoticstypical (old generation) --> no teratogenicity; atypical (new generation) --> higher rate of LBW infants
Benzodiazepinesfloppy baby syndrome, withdrawal syndrome