Term
| what is the effect of progesterone in the first 2 trimesters of pregnancy? |
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Definition
| progesterone *hyperpolarizes the myometrium of the uterus and *prevents release of arachidonic acid (involved in activation of the uterus). |
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Term
| what hormones and receptors are involved in uterine contractility? |
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Definition
| increased estrogen increases *oxytocin receptor concentration in uterine muscle. increased number of alpha adrenergic + angiotensin receptors increases *sensitivity to contraction stimulation. |
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Term
| what is the positive neuroendocrine feedback system in pregnancy? |
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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. |
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Term
| what is required for complete contraction of the uterine muscle? |
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Definition
| receptor binding of estrogen, oxytocin, alpha 1 adrenergic agonist (epinephrine/norepi), PGF 2 alpha, and PGE 2. |
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Term
| what is the decreased progesterone:estrogen ratio important in? |
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Definition
| timing and initiation of labor |
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Term
| what is the role of the fetus in the progesterone:estrogen ratio? |
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Definition
| the fetus helps increase estrogen and oxytocin production, release of large cortisol and prostaglandin quantities and production of cytokines |
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Term
| what characterizes the oxytocic agents? |
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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. |
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Term
| what characterizes the tocolytic agents? |
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Definition
| these drugs/hormones suppress labor and delivery by suppressing myometrial smooth muscle contraction and inhibition of synthesis/release of prostaglandins. |
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Term
| what are the 3 oxytocic agents? |
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Definition
| oxytocin, ergonovine/methylergonovine, and the prostaglandin agents. |
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Term
| what characterizes oxytocin? |
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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*. |
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Term
| what are indications for synthetic oxytocin administration? |
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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) |
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Term
| what are possible results of inappropriate oxytocin administration (too much for too long)? |
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Definition
| rupture of the uterus, anaphylactoid rxns, and maternal death |
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Term
| what *fetal ADRs are associated with prolonged stimulation of uterine contraction (via oxytocin OD)? |
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Definition
| persistent uteroplacental insufficiency, sinus bradycardia, PVCs and other arrhythmias, and fetal death. |
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Term
| what ADRs are possible for both the mother and fetus w/prolonged stimulation of uterine contraction (via oxytocin OD)? |
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Definition
| water intoxication - secondary to ADH-like effects of oxytocin |
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Term
| what characterizes the oxytocic effect of ergonovine/methylergonovine alkaloids? |
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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). |
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Term
| what is the MOA for ergonovine/methylergonovine? |
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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) |
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Term
| what are indications for ergonovine/methylergonovine? |
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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 |
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Term
| how is ergonovine/methylergonovine terminated in the body? |
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Definition
| ergonovine/methylergonovine are metabolized by the liver, excreted by the kidneys, and can be found in breast milk. |
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Term
| what can prolonged use of ergonovine/methylergonovine in the mother cause in the infant? |
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Definition
| *ergot poisoning - including gangrene in the nursing infant |
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Term
| what ADRs are associated with ergonovine/methylergonovine? |
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Definition
| HTN, seizures, chest pain b/c of alpha activity and HTN, difficulty breathing, leg cramps, and n/v |
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Term
| what are contraindications for ergonovine/methylergonovine? |
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Definition
| hx of angina pectoris, MI, hx of cerebrovascular accident (CVA), transient ischemic attack (TIA), or HTN |
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Term
| what are the oxytocic prostaglandin agents? |
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Definition
| dinoprostone (naturally occurring PGE2), carboprost tromethamine (synthetic PGF2 alpha), and misoprostol (synthetic PGE1) |
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Term
| what characterizes the oxytocic effect of the prostaglandin agents? |
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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. |
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Term
| what ADRs are associated with the oxytocic prostaglandin agents? |
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Definition
| GI disturbance (n/v, diarrhea), transient fever, *retained placental fragments, excessive bleeding, decreased diastolic BP, and headache |
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Term
| which pts should the oxytocic prostaglandin agents be used with caution in? |
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Definition
| pts w/asthma, cervicitis, vaginitis, increased/decreased BP, anemia, jaundice, DM, and epilepsy |
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Term
| who are the oxytocic prostaglandin agents contraindicated in? |
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Definition
| pts w/acute PID, drug hypersensitivity, and active renal/hepatic/CV disorders |
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Term
| what are some *important considerations* for the oxytocic prostaglandin agents? |
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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). |
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Term
| what generally characterizes the tocolytics? |
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Definition
| the tocolytics are uterine relaxants used to decrease labor when a pt is in labor prematurely (early in gestation) |
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Term
| what are ADRs generally common to the tocolytics? |
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Definition
| *mother: pulmonary edema, MI, respiratory arrest, cardiac arrest, and death. *newborn: respiratory distress, intraventricular cerebral hemorrhage, and necrotizing enterocolitis. |
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Term
| what are absolute contraindications for the tocolytics? |
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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). |
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Term
| what are the tocolytic agents? |
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Definition
| ethanol IV, beta2 adrenergic agonists (ritodrine and terbutaline), magnesium sulfate, indomethacin, nifedipine, hydroxyprogesterone, diazoxide, atosiban, prolactin, and mifepristone |
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Term
| what characterizes ethanol IV as a tocolytic drug? |
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Definition
| ethanol IV inhibits oxytocin release from the pituitary which decreases myometrial contraction. it is not used in the US anymore. |
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Term
| what characterizes the beta2 adrenergic agents as tocolytic drugs? MOA? |
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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. |
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Term
| what ADRs are associated with the beta2 adrenergic tocolytic agents? |
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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). |
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Term
| what characterizes ritodrine as a beta2 adrenergic tocolytic agent? |
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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. |
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Term
| what characterizes ritodrine as a beta2 adrenergic tocolytic agent? |
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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. |
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Term
| what ADRs are associated w/specific beta2 adrenergic tocolytic agent? |
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Definition
| ritodrine: tachycardia and hypotension. terbutaline: hyperglycemia (due to beta2 receptor activation) |
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Term
| what characterizes magnesium sulfate as a tocolytic? |
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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. |
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Term
| what ADRs are associated with magnesium sulfate? |
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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 |
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Term
| what characterizes indomethacin as a tocolytic agent? |
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Definition
| indomethacin, an NSAID will decrease PG production, leading to increased length of gestation, prolonged spontaneous labor, and interrupted premature labor. |
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Term
| what is the major ADR associated with indomethacin as a tocolytic? |
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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. |
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Term
| what characterizes nifedipine as a tocolytic agent? |
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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. |
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|
Term
| what characterizes hydroxyprogesterone as a tocolytic agent? |
|
Definition
| hydroxyprogesterone is good for uterine relaxation in wks 12-37, but may have *teratogenic potential. |
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Term
| what characterizes diazoxide as a tocolytic agent? |
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Definition
| diazoxide activates *K+ channels, which relaxes the smooth muscle via *hyperpolarization of the cell membrane. (under investigation) |
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|
Term
| what characterizes atosiban as a tocolytic agent? |
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Definition
| this is an oxytocin antagonist that decreases and stops uterine contractions. (under investigation) |
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Term
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Definition
| bromocriptine is a *dopamine agonist which is used to *end lactation as dopamine inhibits release of prolactin (which develops and maintains lactation). |
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Term
|
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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