Card Set Information

2012-11-10 11:03:44

Pharm from Caldwell and Gopman's lecture, drugs for pregnancy, OCPs, labor induction, abortifacents
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  1. What are the drugs used to tx htn, pregnancy-induced htx, and pre-eclampsia
    Methyldopa, labetalol, nifedipine, hydralazine, magnesium sulfate
  2. Methyldopa
    • MoA: Centrally acting alpha agonist
    • Use: anti-hypertensive agent for pregnancy
    • SE: Somnolence
    • Not used much anymore because it doesn't lower BP very much; however it is very safe and inexpensive, so if the woman isn't very hypertensive, it could be a good choid
  3. Labetalol
    • MoA: combined alpha and beta antagonist
    • Use: Used to control acute, very high blood pressure in women with severe htn in pregnancy
    • SE: relatively few
  4. Hydralazine
    • MoA: Incr cGMP, leading to smooth muscle relaxation and vasodilation
    • Use: to control acute, very high BP in women with severe htn in pregnancy
    • SE: headache, nausea, vomiting
    • Pregnancy category: C
  5. Nifedipine
    • Use: acute management of severe htn in pregnancy and as BP control postpartum in women with preeclampsia
    • Administration: Orally
    • SE: tachycardia, palpitations, headaches
    • Pregnancy category: C
    • Note: do not use with calcium channel blockers and magnesium sulfate
  6. Should ACE inhibitors and ARBs be used in pregnancy?
    • No!
    • Use is associated with: oligohydramnios, neonatal anuria, growth abnormalities, skull hypoplasia, fetal death
  7. Magnesium Sulfate
    • Uses:
    • 1) tx eclamptic seizures: can treat active seizures and recurrent seizures (first line tx)
    • 2) prophylaxis against seizure in women with preeclampsia: superior to phenytion, nimodipine, diazepam, and placebo as seizure prophylaxis
    • 3) tx of preterm labor: slows uterine contractions and used when labor must be delayed 24-48 hr or when the mother's amniotic sac has not broken and the cervix is effaced but dilated < 4cm
    • MoA:
    • 1) Prophylaxic effect: likely due to its ability to stimulate PGI2 production by vascular endothelium
    • 2) Seizure prevention: due to vasodilation of peripheral vasculature/cerebrovasculature, protection of blood brain barrier, reduced cerebral edema formation, possible NMDA receptor blockade, and generalized CNS depression
    • SE: Muscle weakness/lack of energy, blurry vision, slurred speech, headache, N/V, flushing, stuffy nose
    • Has a narrow therapeutic range: Loss of DTRS is first sign of tox; respiratory and cardiac depression quickly follow (and then death)
    • Note: must regularly assess urine output, maternal reflexes, respiratory rate, and O2 sat
    • Lorazepam and phenytoin are second-line agents if eclamptic seizures are refractory to MgSO4
  8. Drugs used to prevent preterm labor
  9. Drugs that are tocolytic
    Magnesium sulfate, calcium channel blockers (nifedipine), beta agonists (terbutaline), COX inhibitors (indomethacin)
  10. Progesterone for preterm labor prevention
    • MoA: Inhibits secretion of pro-inflammatory cytokines and delays cervical ripening
    • Administration: IM weekly and vaginally nightly
    • Causes significant decr in preterm birth in those with prior hx of preterm delivery or with short cervix
  11. Magnesium sulfate for tocolysis
    • MoA: inhibits calcium entry into cell and prevents activation of MLCK, promoting smooth muscle relaxation
    • Note: also has neuroprotective effects on the preterm fetus
    • Probably less effective than nifedipine or indomethacin in delaying delivery
  12. Nifedipine for tocolysis
    • MoA: Inhibits calcium influx an dprevents MLCK activation (results in smooth muscle relaxation and means no uterine contractions)
    • Administration: Oral
    • SE: Less than those seen with MgSO4 and terbutaline
    • Notes: More associated with improved fetal outcomes
  13. Terbutaline for tocolysis
    • MoA: Beta agonist with bronchodilator actions
    • Label use: to prevent and tx bronchospasms associated with asthma, bronchitis, and emphysema
    • Off label use: acute tx of preterm labor and acute tx of ovarian hyperstimulation syndrome
    • Pregnancy category: C
    • SE: transient hyperglycemia, hypokalemia, MI
    • CI: Injectable should NOT be used to prevent preterm labor or tx it beyond 48-72 hrs because it incr risk for maternal heart problems and death! Oral should not be used at all for prevention/tx of preterm labor
  14. Indomethacin for tocolysis
    • MoA: Prostaglandin inhibitor
    • Use: Must be used prior to 32 weeks gestational age or it will cause premature closure of ductus arteriosus
    • Note: Maximum use of 2-3 days because of renal effects on fetus that cause oligohydramnios (seen with all NSAID use)
  15. Dinoprostone and carboprost tromethamine
    • Dinoprostone (PGE2) and Carboprost tromethamine (PGF2alpha)
    • Cause marked contractile effects on pregnant uterus
    • PGE2 also produces uterine contraction and softening/ripening of the cervix
    • CI: prior c-section due to risk of uterine rupture
  16. Misoprostol
    • PGE1 analogue used transvaginally for induction of labor (not FDA approved for this)
    • Advantage: very inexpensive and stable at room temp
    • CI: prior c-section due to risk of uterine rupture
    • Note: is approved for ulcer tx because it inhibits gastric acid secretion
  17. Oxytocin for labor induction
    • MoA: Enhances calcium channel activation, incr prostaglandin production, and stimulates uterine contraction
    • Administration: Dilute IV solution; incr dose gradually
    • Adv: is easy to control because of short half life (12-15 min)
    • Potential problem: watch for volume overload and hyponatremia because it resembles vasopressin
    • Note: estrogen incr oxytocin receptor expression
  18. Methylergonovine
    • MoA: Ergot alkaloid that acts directly on uterine SMC by causing sustained, tetanic, uterotonic effect to reduce blood loss
    • Use: prevention or control of postpartum hemorrhage
    • CI: htn, toxemia, pregnancy, hypersensitivity
    • Elimination: hepatic metabolism
    • SE: htn with associated seizure or headache (more common); hypotn also reported, as well as N/V
    • Pregnancy category: C
  19. Carboprost
    • MoA: PGF2alpha to tx postpartum hemorrhage
    • Administration: IM
    • CI: asthma
    • SE: diarrhea
  20. Misoprostol
    Use: pregnancy induction (small doses) or postpartum hemorrhage (large doses)
  21. Misoprostol for postpartum hemorrhage
    • Use: postpartum hemorrhage (large doses, 800 mcg)
    • Administration: per rectum or buccally
    • Can cause transient temp elevation
    • Adv: inexpensive and stable at room temp
  22. What FDA pregnancy category is ibuprofen? Why?
    • Is an NSAID
    • Pregnancy Category: C prior to 30 weeks gestation
    • Category: D at or after 30 weeks gestation because it causes premature closure of the ductus arteriosus
  23. Should aspirin be used in pregnancy? Why?
    • It is an NSAID
    • Yes: low dose aspirin (NSAID) reduces risk of developing preeclampsia, delivering before 34  weeks, and perinatal death; well accepted in 2nd and 3rd trimesters
    • MoA: thought to correct the imbalance of pro- and anti-coagulatory factors/hormones in pregnancy that result from preeclampsia
  24. Should multiple analgesics be co-administered during pregnancy? Why?
    • No: NSAID use is associated with congenital cryptochidism in male offspring, and prevalence is higher for mothers using multiple analgesics (risk greatest during second trimester)
    • Other reasons: Risk of spontaneous abortion is greater in any woman taking nonaspirin NSAIDS early in pregnancy, with diclofenac being the worst and combinations or naproxen being second worst
  25. Do pregnant women suffer depression?
    • Yes: Prevalence in first, second, and third trimesters is 7.4%, 12.8%, and 12%, with relapse being twice as common in pregnant women who discontinue their antidepressant therapy
    • SSRIs are the most commonly prescribed
  26. Imipramine
    • TCA
    • MOA: potentiation of adrenergic synapses resulting from blocking NE reuptake by presynaptic terminals (exact mechanism not known however)
    • Pregnancy category: D
  27. When would a pregnant women be given an SSRI and what are some examples of those Rx?
    • SSRIs are used to tx depression
    • Fluoxetine is listed as category C
    • Paroxetine and carbamazepine are category D
    • Because pregnancy accelerates metabolism of some drugs, incr doses may be needed (ex. citalopram and sertraline)
  28. Should paroxetine be Rx to pregnant women? Why?
    • No: causes incr risk of CV defects in infants, as well as persistent pulmonary hypertension of the newborn (PPHN)
    • SSRI
    • Pregnancy category: D
  29. What is the relationship of prenatal SSRI exposure and the development of autism spectrum disorders?
    There is an incr risk of ASD associated with SSRI tx in the mother during the year before delivery, with the strongest effect being associated with tx during the first trimester
  30. Oral contraceptives: combination
    • Contain both estrogen and progestin
    • Primary MoA: prevent ovulation by suppressing LH and FSH
    • Secondary MoA: progesterone thickens cervical mucus, acting as barrier to sperm; endometrial changes decrease implantation
    • Application: 21 day or 28 day packs, with 7 day placebo
    • Adverse effects: venous thromboembolism, htn, triglycidemia, worsening migraines
    • SE: Nausea, edema, headaches, breakthrough bleeding
    • CI: smokers > 35 yrs
    • No difference seen in risk of breast cancer development
    • There is doubling of hepatic cancer risk after 4-8 yr of use, but the absolute risk is low because these are rare cancers
    • Effectiveness: "perfect use" is 99%
    • Some benefits: Decr endometrial and ovarian cancer risk, decr ovarian cyst and fibrocystic breast disease, less iron-deficiency anemia, decr dysmenorrhea and endometriosis sx, decr ectopic pregnancies and PID
  31. Progestin-only oral contraception
    • AKA "minipill"
    • MoA: GnRH suppression; also incr cervical mucus viscosity (acts as physical barrier to sperm penetration)
    • SE: may cause more acne, but no evidence of incr thromboemboli
    • Noteworthy problem: Rapid first-pass metabolism means it doesn't keep therapeutic effect long and so being late on the dose can incr risk of getting pregnant (more so than the combined pills, even if you are just an hour or two late)
    • Applicatoin: Same dose taken daily (no placebo week)
    • Effectiveness: "Perfect use" < combination OCs (~92%)
  32. Transdermal contraception
    • Ortho evra patch
    • Is a combo of estorgen and progestin
    • Application: to buttock, abdomen, upper arm, or torso that is applied weekly for 3 weeks and then off for one week for withdrawal bleed
    • SE: sensitivity to adhesive
    • Effectiveness: 95-99%, tend to be more effective than OCPs because use is better
  33. Contraceptive ring (nuvaring)
    • Combination of estrogen and progestin
    • Application: 3 weeks in place followed by 1 week off for withdrawal bleed
    • Transmucosal absorption
    • Note: Some issues with expulsion during sex but as long as the ring is replaced within an hour that does not cause serious adverse effects
    • Effectiveness: 95-99%, more effective than OCPs due to better adherence
  34. Contraceptive implant (etonogestrel/implanon/nexplanon)
    • Lasts 3 years
    • Adverse effects: head ache, weight gain, mood changes, acne, local infection, difficult removal
    • Irregular vaginal bleeding is expected and the pattern is unpredictable
    • CI: pt with hx or predisposition to thromboemboli (ex. facor V Leiden deficiency)
    • Effectiveness: 99% effective
  35. Medroxyprogesterone acetate
    • Contraceptive injection known as Depo-Provera
    • Given IM
    • Lasts 12 weeks
    • Causes irregular vaginal bleeding with eventual amenorrhea
    • Adverse effects: head ache, mood changes, weight gain due to incr appetite that stabilizes, decr HDL, incr LDL, decr bone density
    • Note: return to fertility can be delayed
    • CI: pt with hx or predisposition to thromboemboli
  36. Levonorgestrel (Mirena)
    • Hormone-containing intrauterine device that has 5 year effectiveness
    • MoA: Local progestin concentration that is 1000 x more than systemic levels leads to thickening of cervical mucus (prevents sperm penetration); may inhibit ovulatoin in some; also has local effects on endometrium
    • SE: Spotting for up to 3 months, then light and irregular menses or amenorrhea
  37. ParaGard
    • Copper-containing IUD that lasts 10 years
    • MoA: Local inflammatory response creates spermicidal effect; if fertilization does occur (unlikely), inflammatory effect on blastocyte; also leads to inhospitable endometrium
    • Menses are likely to be 20% heavier
    • Screen for gonorrhea/chlamydia at insertion
    • Appropriate for nulliparous and teens
    • Perforation risk: Higher in breastfeeding women (1/300) than the general population (1/1000)
  38. Levonorgestrel (Plan B and Plan B One-Step)
    • Progestin only emergency contraception
    • MoA: prevents ovulation, blocks implantation, and increases cervical mucus viscosity
    • Most effective within 72 hr of unprotected sex (but can be given up to 5 days after intercourse)
  39. Ulipristal (Ella)
    • Selective progesterone receptor modulator
    • MoA: inhibits ovulation via inhibition of LH release and may block implantation of fertilized egg (uncertain)
    • Effective for up to 120 hours after unprotected sex
    • SE: self-limited headache and abdominal pain
  40. What is the opinion on combination estrogen-progesterone as emergency contraception?
    • It is less effective and is associated with more nausea and vomiting
    • There is also concerns for thromboemboli
  41. Copper IUD as emergency contraceptive
    • Most effective, with only a 1% failure rate if inserted up to 5 days after unprotected sex
    • Provides 10 yrs of contraception
  42. Mifepristone
    • Progesterone receptor antagonists
    • MoA: causes decidual breakdown, blastocyt detachment, and decr hCG production; decr hCG results in decreased progesterone secretion from corpus luteum, which leads to further decidual breakdown
    • Decr progesterone production and receptor blockade leads to incr PG levels, myometrial contractions, and cervical softening
    • Typically used with misoprostol to incr uterine contractions
    • Effectiveness: >90% effective if pregnancy is < 63 days (9 weeks GA) but a surgical procedure is required if it fails or if there is hemorrhaging
    • SE: vaginal bleeding, cramping, nausea/vomiting/diarrhea, and a rare but serious infection with clostridium sordellii
    • CI: if pt is on chronic glucocorticoid therapy
    • Use: Pregnancy termination
  43. Misoprostol
    • Use: miscarriage management
    • Effectiveness: 85% if used within 7 days, but it varies based on type (anembryonic = least, missed = less, incomplete = most)
    • Route of administration: orally, vaginally, bucally (bucally preferred due to decr infection risk)
    • Dose can be repeated in 24 hr if not effective
  44. Methotrexate
    • A folic acid antagonist that is an antimetabolite
    • Use: managing ectopic pregnancies that are < 3.5 cm, have no cardiac activity, are hemodynamically stable, and can adhere to follow up
    • MoA: disrupts rapidly proliferating trophoblast
    • SE: liver/lung damage; damage to lining of mouth/stomach/intestines; incr risk of lymphoma, serious/life-threatening skin rxs, immunosuppression
    • Also used to tx certain types of cancers (like gestational trophoblastic disease->choriocarcinoma), psoriasis, and RA
    • Can be used to terminate intrauterine pregnancy, followed by misoprostol to induce uterine contractions (mostly this is replaced by mifepristone now)
  45. Conjugated estrogens
    • Use: Turner's and other gonadal dysgenesis syndromes
    • Oral or transdermal estradiol that is started at 10-12 yrs
    • Progestin is added once target dose has been slowly reached
    • Tx is delayed until after GH tx produces greater height
  46. Medroxyprogesterone or micronized progesterone
    • Use: Turner's and gonadal dysgenesis syndromes
    • Added to optimize breast development and allow menstruation to prevent endometrial hyperplasia
  47. Conjugated estrogen with medroxyprogesterone (if uterus is present)
    • Hormone replacement therapy
    • Use: tx menopausal sx
    • Effects: decr vasomotor sx and vaginal dryness, improved bone mineral density, decr fractures, and decr colorectal cancer
    • Adverse effects: incr thromboemboli, stroke, coronary artery disease, breast cancer
  48. Pharmacologic agents used to tx menopause
    • Hormone replacement therapy with conjugated estrogen and medroxyprogesterone (if uterus is present)
    • Phytoestrogens
    • Herbal extracts (black cohosh)
    • SSRIs
    • Clonidine
    • Gabapentin
  49. How do we tx endometriosis?
    • Goal is to create a hypoestrogenic state in the peritoneal cavity where ectopic endometrial tissue is located
    • Combo OCs: suppress gonadotropin secretion
    • Medroxyprogesterone: promotes decidualization of ectopic endometrial tissue
    • Levonorgestrel IUD: similar effect
    • GnRH agonists (leuprolide/goserelin/nafrelin): plus add-back therapy (for vasomotor sx and decr bone density); low-dose synthetic estrogen, high-dose progestin (norethindrone)
  50. How do we tx hirsuitism?
    • Combo OCs: suppress LH, which decr ovarian steroidgenesis (decr testosterone), and incr sex hormone binding globulin (binds more testosterone)
    • GnRH agonists: inhibits gonadotropin secretion and thus secretion of androgen and estrogen from ovary
    • Spironolactone: aldosterone antagonist that is an antiandrogen and competes for androgen receptors; inhibits cytochrome P450 enzymes required for androgen synthesis
  51. How can we induce ovulation in infertility?
    • Clomiphene citrate
    • MoA: Estrogen antagonist that blocks the inhibitory effect of gonadotropin release from pituitary
    • Effect: incr gonadotropin secretion (FSH > LH), which stimulates ovulation
    • SE: ovarian hyperstimulatoin, multiple gestatoin, ovarian cysts, headache, hot flushes, blurry vision, luteal phase defect due to inadequate progesterone production, and possible incr ovarian cancer risk with prolonged use
    • Gonadotropins (FSH>LH): concentrated from menopausal urine (given IM) or recombinant (give SC)
    • hCG: also urine-derived vs recombinant, same routes
    • Progesterone replacement: due to suppression of LH surge that normally sustains the corpus luteum
    • Insulin sensitizers: metformin