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birth delivery agents
R-GU II
47
Medical
Graduate
10/23/2010

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Term
what is the effect of progesterone in the first 2 trimesters of pregnancy?
Definition
progesterone *hyperpolarizes the myometrium of the uterus and *prevents release of arachidonic acid (involved in activation of the uterus).
Term
what hormones and receptors are involved in uterine contractility?
Definition
increased estrogen increases *oxytocin receptor concentration in uterine muscle. increased number of alpha adrenergic + angiotensin receptors increases *sensitivity to contraction stimulation.
Term
what is the positive neuroendocrine feedback system in pregnancy?
Definition
increased oxytocin/prostaglandins increase the stretching of the cervix which increases the local receptor stimulation/a spinal reflex, which increases oxytocin/prostaglandins and so on.
Term
what is required for complete contraction of the uterine muscle?
Definition
receptor binding of estrogen, oxytocin, alpha 1 adrenergic agonist (epinephrine/norepi), PGF 2 alpha, and PGE 2.
Term
what is the decreased progesterone:estrogen ratio important in?
Definition
timing and initiation of labor
Term
what is the role of the fetus in the progesterone:estrogen ratio?
Definition
the fetus helps increase estrogen and oxytocin production, release of large cortisol and prostaglandin quantities and production of cytokines
Term
what characterizes the oxytocic agents?
Definition
these drugs/hormones are used clinically to enhance uterine contraction for: induction of labor, augmentation of labor, therapeutic abortion, post partum hemorrhage control, prevention of early membrane rupture, and aid in placental insufficiency.
Term
what characterizes the tocolytic agents?
Definition
these drugs/hormones suppress labor and delivery by suppressing myometrial smooth muscle contraction and inhibition of synthesis/release of prostaglandins.
Term
what are the 3 oxytocic agents?
Definition
oxytocin, ergonovine/methylergonovine, and the prostaglandin agents.
Term
what characterizes oxytocin?
Definition
oxytocin is natural 8 AA hormone produced in the hypothalamus, stored in the posterior pituitary, circulates unbound and has a half life of only 15 min (inactivated by the liver/kidney). it is the *DOC for induction of labor*.
Term
what are indications for synthetic oxytocin administration?
Definition
labor disorders, incomplete abortion occurring after *20 wks of gestation, after delivery to control hemorrhaging of the uterus, induction of abortion (high dose), and the challenge test (fetal heartbeat should increase w/administration)
Term
what are possible results of inappropriate oxytocin administration (too much for too long)?
Definition
rupture of the uterus, anaphylactoid rxns, and maternal death
Term
what *fetal ADRs are associated with prolonged stimulation of uterine contraction (via oxytocin OD)?
Definition
persistent uteroplacental insufficiency, sinus bradycardia, PVCs and other arrhythmias, and fetal death.
Term
what ADRs are possible for both the mother and fetus w/prolonged stimulation of uterine contraction (via oxytocin OD)?
Definition
water intoxication - secondary to ADH-like effects of oxytocin
Term
what characterizes the oxytocic effect of ergonovine/methylergonovine alkaloids?
Definition
direct stimulation of the uterine smooth muscle (increased muscle tone and enhanced rate/force of rhythmic contraction), stimulation of cervical contraction (just ergonovine), and *induction of arterial vasoconstriction (have to carefully monitor BP).
Term
what is the MOA for ergonovine/methylergonovine?
Definition
these alkaloids are partial agonists of the *alpha agonist receptors and have relatively weak blocking activity (source of "partial" activity). they also have some 5-HT/dopamine activity and *inhibit the release of EDRF (endothelial-derived relaxation factor)
Term
what are indications for ergonovine/methylergonovine?
Definition
*induction of sustained tetanic contraction* - used to shorten the *final stage of labor, aid in the reduction of postpartum blood loss, for routine expulsion of the placenta after delivery, and postpartum/postabortal atony/hemorrhage
Term
how is ergonovine/methylergonovine terminated in the body?
Definition
ergonovine/methylergonovine are metabolized by the liver, excreted by the kidneys, and can be found in breast milk.
Term
what can prolonged use of ergonovine/methylergonovine in the mother cause in the infant?
Definition
*ergot poisoning - including gangrene in the nursing infant
Term
what ADRs are associated with ergonovine/methylergonovine?
Definition
HTN, seizures, chest pain b/c of alpha activity and HTN, difficulty breathing, leg cramps, and n/v
Term
what are contraindications for ergonovine/methylergonovine?
Definition
hx of angina pectoris, MI, hx of cerebrovascular accident (CVA), transient ischemic attack (TIA), or HTN
Term
what are the oxytocic prostaglandin agents?
Definition
dinoprostone (naturally occurring PGE2), carboprost tromethamine (synthetic PGF2 alpha), and misoprostol (synthetic PGE1)
Term
what characterizes the oxytocic effect of the prostaglandin agents?
Definition
*dinoprostone (PGE2) and carboprost tromethamine (PGF2 alpha) stimulate uterine smooth muscle contraction (part of feedback cycle) more strongly than oxytocin up through the 2nd trimester. they can be used to induce abortion during weeks 12-20. *misoprostol (synthetic PGE1) has been shown to support cervical ripening (which dinoprostone will do, but carboprost will not) and induce labor.
Term
what ADRs are associated with the oxytocic prostaglandin agents?
Definition
GI disturbance (n/v, diarrhea), transient fever, *retained placental fragments, excessive bleeding, decreased diastolic BP, and headache
Term
which pts should the oxytocic prostaglandin agents be used with caution in?
Definition
pts w/asthma, cervicitis, vaginitis, increased/decreased BP, anemia, jaundice, DM, and epilepsy
Term
who are the oxytocic prostaglandin agents contraindicated in?
Definition
pts w/acute PID, drug hypersensitivity, and active renal/hepatic/CV disorders
Term
what are some *important considerations* for the oxytocic prostaglandin agents?
Definition
the oxytocic prostaglandin agents are *potentially carcinogenic and are *NOT to be used concomitantly w/oxytocin (can lead to rupture/tearing of the uterus).
Term
what generally characterizes the tocolytics?
Definition
the tocolytics are uterine relaxants used to decrease labor when a pt is in labor prematurely (early in gestation)
Term
what are ADRs generally common to the tocolytics?
Definition
*mother: pulmonary edema, MI, respiratory arrest, cardiac arrest, and death. *newborn: respiratory distress, intraventricular cerebral hemorrhage, and necrotizing enterocolitis.
Term
what are absolute contraindications for the tocolytics?
Definition
acute fetal distress, chorioamnionitis, eclampsia/severe preeclampsia, fetal demise (why keep a dead baby?), fetal maturity (why keep a mature baby?), and maternal hemodynamic instability (suppression of labor might kill both mother and baby).
Term
what are the tocolytic agents?
Definition
ethanol IV, beta2 adrenergic agonists (ritodrine and terbutaline), magnesium sulfate, indomethacin, nifedipine, hydroxyprogesterone, diazoxide, atosiban, prolactin, and mifepristone
Term
what characterizes ethanol IV as a tocolytic drug?
Definition
ethanol IV inhibits oxytocin release from the pituitary which decreases myometrial contraction. it is not used in the US anymore.
Term
what characterizes the beta2 adrenergic agents as tocolytic drugs? MOA?
Definition
these are used for uterine relaxation/suppression of premature labor between 20 and 33 weeks and are active for 2-3 days. MOA: activation of adenylate cyclase, which increases cAMP, which activates cAMP-dependent protein kinase, which *decreases intracellular Ca++, which reduces the effect of Ca++ on muscle contraction.
Term
what ADRs are associated with the beta2 adrenergic tocolytic agents?
Definition
more incidental: palpitations, tremors, n/v, nervousness, anxiety, chest pain, SOB, EKG changes, hyperglycemia, hypokalemia, and hypotension. serious: pulmonary edema, cardiac insufficiencies, arrhythmias, myocardial ischemia, and maternal death (mainly due to these drugs having some partial beta1 activity due to imperfect beta2 or flooding of receptors).
Term
what characterizes ritodrine as a beta2 adrenergic tocolytic agent?
Definition
ritodrine is an IV preferential beta2, but can have some beta1 activity therefore *some cardiovascular responses are common and maternal HR/BP need to be monitored as well as fetal HR. its effect only lasts about *30 min.
Term
what characterizes ritodrine as a beta2 adrenergic tocolytic agent?
Definition
terbutaline is indicated for asthma, however it does have off-label use as a tocolytic and is often administered as such b/c it can be taken in repeated dosages as it is PO unlike ritodrine.
Term
what ADRs are associated w/specific beta2 adrenergic tocolytic agent?
Definition
ritodrine: tachycardia and hypotension. terbutaline: hyperglycemia (due to beta2 receptor activation)
Term
what characterizes magnesium sulfate as a tocolytic?
Definition
magnesium sulfate prevents convulsions in preeclampsia by directly uncoupling excitation/contraction in myometrial cells through inhibition of cellular action potentials. this is accomplished by decreasing Ca++ uptake (competes for binding sites on the myosin light chain), activating adenylate cyclase, and stimulating Ca-dependent ATPase (promotes Ca++ uptake by sarcoplasmic reticulum). it is *preferred tx in pts w/DM, heart problems (i.e. increased BP) or hyperthyroidism.
Term
what ADRs are associated with magnesium sulfate?
Definition
magnesium has a very narrow therapeutic range, where at least 5.5 mEq/L is needed, but much higher and toxic affects may occur (loss of patellar reflex, respiratory depression/paralysis, and cardiac arrest). also: EKG changes, sweating, dry mouth, dizziness, palpitations, warmth, nausea, nystagmus, flushing, vomiting, and headache
Term
what characterizes indomethacin as a tocolytic agent?
Definition
indomethacin, an NSAID will decrease PG production, leading to increased length of gestation, prolonged spontaneous labor, and interrupted premature labor.
Term
what is the major ADR associated with indomethacin as a tocolytic?
Definition
in the newborn, NSAID use can lead to *premature closure of the fetal ductus arteriosus (which may be therapeutic if it hasn't closed and the baby is already born). prolonged NSAID use can also cause primary pulmonary hypotension and increased incidence of intraventricular hemorrhage.
Term
what characterizes nifedipine as a tocolytic agent?
Definition
MOA: impairs Ca++ entry into cells (voltage dependent Ca++ channel blocker, decreases the Ca++ available for muscle contraction). *studies are currently underway to determine nifedipine's tocolytic potential - but need to be aware of this effect if a pregnant mother is on this rx for another condition.
Term
what characterizes hydroxyprogesterone as a tocolytic agent?
Definition
hydroxyprogesterone is good for uterine relaxation in wks 12-37, but may have *teratogenic potential.
Term
what characterizes diazoxide as a tocolytic agent?
Definition
diazoxide activates *K+ channels, which relaxes the smooth muscle via *hyperpolarization of the cell membrane. (under investigation)
Term
what characterizes atosiban as a tocolytic agent?
Definition
this is an oxytocin antagonist that decreases and stops uterine contractions. (under investigation)
Term
*what is bromocriptine?
Definition
bromocriptine is a *dopamine agonist which is used to *end lactation as dopamine inhibits release of prolactin (which develops and maintains lactation).
Term
*what is mifepristone?
Definition
mifepristone/RU 486 is an *anti-progestin agent (prevents progesterone from binding to its receptor). it is used along with a *prostaglandin (misoprostol usually) to first calm the uterus (block progesterone) then suddenly cause it to contract (prostaglandin) - to induce abortion. it may cause maternal death and can only be obtained by physicians in abortion clinics (PA state law).
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