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56 Cards in this Set

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what hormone hyperpolarizes smooth muscle membranes and prevents the release of arachidonic acid?
progesterone - decreases prostaglandin synthesis - less contraction
An increase in this hormone during pregnancy causes an increase in oxytocin receptor concentraion in the uterine muscle.
estrogen
what other types of receptors increase in the uterus during pregnancy?
alpha adrenergic and angiotensin receptors -> this increases the sensitivity to contraction stimulation
During labor, this system causes contractions of the uterus to aid in delivery.
neuroendocrine system: fetal pressure on the cervix leads to local stimulation and spinal reflex -> oxytocin and prostaglandins are released -> even more contractions
Uterine muscle has receptor binding sites for these substances that aid in contractions of the uterus?
estrogen, oxytocin, alpha 1 adrenergic agonist, PGF2a, PGE2
As pregancy continues what happens to the progesterone:estrogen ratio?
early in pregnancy high:low; late in pregnancy low:high
What is the fetus' role in raising amount of estrogen and thereby decreasing the progesterone to estrogen ratio?
the fetus: increases estrogen production, produces large quantities of cortisol, increases quantities of oxytocin, prostaglandins and cytokines
These drugs are used to enhance uterine contraction to induce or augment labor; they halso help in therapeutic abortions and post partum hemorrhage control.
oxytocins (oxytocic agents)
What agent prevent premature labor by suppressing myometrial smooth mucle contractions and inhibit the synthesis or release of PGs and/or other endogenous uterine stimulants?
tocolytics
Name 3 oxytocic agents.
oxytocin, ergot alkaloids, and prostaglandins
What are the synthetic names for the endogenous oxytocin and describe it.
Pitocin, Syntocinon: oxytocin is produced in the paraventricular nucleus of the hypothalamus and is stored in the posterior pituitary, it circulates unbound and has a T1/2 of 15 minutes; it is inactivated by the liver and kidneys and is the DOC for inducing labor
When are oxytocic agents used?
pts with labor disorders; after incomplete abortion after 20 wks; after delivery of fetus using to control uterine hemorrhage; high doses will induce abortion; also an oxytocin challenge test
inappropriate use of oxytocin may lead to what?
uterine rupture, anaphylactoid and allergic rxns and maternal death
What can prolonged stimulation of uterine contractions lead to in the fetus?
uteroplacental insufficiency, sinus bradycardia, PVCs and arrhythmias, fetal death, and H2O intoxication (b.c its secondary ADH effects)
this class of drugs interacts with adrenoreceptors, 5-HT receptors, and dopamine receptors and causes vasoconstriction of small vessels and stimulation of uterine smooth muscle as well as INHIBIT the release of EDRF (endothelial-derived relaxing factor)
ergot alkaloids
name the ergots used to treat postpartum hemorrhage after fetal delivery.
ergonovine (stimulates cervical contraction) and methylergonovine - both stimulate uterine smooth muscle to contract and induce arterial vasoconstriction
why are ergots used in mother's to be?
they induce a sustained tetanic contraction where they: shorten the final stage of labor, reduce postpartum blood loss, expel placenta after delivery
Explain the pharmokinetics of ergots (metabolized, excreted).
metabolized by the liver, excreted by the kidneys, and can be found in breast milk (if prolonged use and the infant is nursing, it could vasoconstrict the infants vessels and cause death, gangrene, etc)
Explain the ADRs with ergot alkaloids.
hypertension, headaches, possible seizures, N/V, CP (chest pain), difficulty breathing, leg cramps
What are contraindications for ergot alkaloids?
angina pectoris, MI, pregnancy, hx of CVA, TIA, or hypertension
This oxytocic agent is an eicosanoid and is made from arachidonic acid.
Prostaglandin Agents
Name the naturally occuring PGE2.
dinoprostone
Name the synthetic analogue of PGF2.
carboprost tromethamine
name the PGE1 analogue.
misoprostrol
what are the indications for using dinoprostone and carboprost tromethamine?
to stimulate uterine smooth muscle contraction (**better than oxytocin thru 2nd trimester); induce abortion during wks 12-20; and dinoprostone causes cervical ripening (softening)
what are the indications for misoprostol?
cervical ripening and labor induction
What are the ADRs to these prostaglandin agents?
GI disturbances (NVD); transient fever, retained placental fragments, excessive bleeding, decrease diastolic BP, and headache
In what types of patients should you be cautious in giving prostaglandins?
asthmatics, cervicitis, vaginitis, increased or decreased BP, anemia, jaundice, diabetes, and epilepsy
In what types of patients should you not used prostaglandins in?
acute PID, drug hypersensitivity, and active renal, hepatic, or CV disorders
What is potentially carcinogenic and should NOT be used with oxytocin and why?
prostaglandins - with oxytocin there is a risk of uterine rupture
These group of drugs causes uterine relaxationa and are used to inhibit labor early in gestation.
tocolytics (uterine relaxants)
What is premature labor?
labor occurs before week 37
List the ADRs of tocolytics in the mother.
Pulmonary edema, MI, respiratory arrest, cardiac arrest, and death
List the ADRs of tocolytics in the newborn.
respiratory distress, intraventricular hemorrhage and necrotizing enterocolitis
List the absolute contraindications of tocolytics.
acute fetal distress, chorioamnionitis, eclampsia or severe preeclampsia, fetal demise, maturity, and maternal hemodynamic instability
Name some agents that inhibit contractions and thus prolong pregnancy.
alcohol, B2 adrenergic agonist, Mg2+ sulfate, PG synthesis inhibitors, Ca2+ channel blockers and hydroxyprogesterone
How does alcohol inhibit contractions?
it ihibits oxytocin release from the pituitary (no longer used)
Name the 2 B2 adrenergic agonist that prevent premature labor 20wks or more in gestation and can arrest preterm labor for 48-72 hours.
ritodrene and terbutaline
What is the mechanism of action of B2 adrenergic receptor activity?
activates adenylate cyclase, increases cAMP, activates cAMP dependent protein kinase, decreases intracellular Ca2+, reduces the effect of calcium on muscle contraction
what is given to premature babies to help inflate their underdeveloped lungs?
corticosteroids
What are the Side-effects of B2 adrenergic agonists?
they may have residual B1 receptor (not completely selective) activity such as palpitations, tremors, N/V, nervousness, anxiety, CP, SOB, ECG changes, hyperglycemia, hypokalemia, hypotension; SERIOUS SEs: Pulmonary edema, cardiac insufficiency, arrhythmias, MI, death
When you give _____ you have to monitor CV responses in mother and fetus.
ritodrene - preference for B2
what is special about terbutaline and its package labeling?
PDR says it shouldn't be used for tocolysis (uterine relaxation) but it is in the hospital setting
Of the 2 tocolytics, which one commonly leads to hypoglycemia?
terbutaline
of the 2 tocolytics, which one commonly leads to tachycardia and hypotension?
ritodrine
this drug not only prevents uterine contraction but prevents convulsions in preeclampsia by competing for Ca++ binding sites (decreasing Ca++uptake); it also directly uncouples excitation/contraction in myometrial cells thru inhibition of cellular action potentials.
Magnesium sulfate
Magnesium sulfate is preferred over Beta adrenergic agents in what types of patients?
diabetics, HTN, Heart dz, and hyperthyroidism
With increasingly toxic levels of magnesium you can get the following:
(need at least 5.5mEq/L) first get loss of pateller reflex -> respiratory depression -> respiratory paralysis -> cardiac arrest
name some other (less serious) SE of Mg2+ sulfate.
sweating, dry mouth, dizzy, palpitations, warmth, nausea, nystagmus, ECG changes, flushing, vomiting, headache
Since prostaglandins increase contractions it makes sense that NSAIDs like _____ prolong pregnancy.
Indomethacin - decrease PG production, prolong spontaneous labor, interrupt premature labor
what is indomethacin commonly used for after delivery in a fetus. Why may this be a problem during pregnancy?
indomethacin is used to close a premature baby's fetal ductus arteriosus; if the pregnant mother is taking indomethacin to prolong the fetal growing, it could prematurely close the FDA
What are the possible problems with a pregnant woman taking long term indomethacin?
the newborm may have primary pulmonary hypotension and increased incidence of intraventricular hemorrhage
This Ca++ channel blocker impairs Ca++ entry into myometrial cells and thus prevents contraction.
nifedipine (more studies needed)
When during pregnancy is hydroxyprogesterone used in preventing preterm labor and why is it not currently used much.
it is used during weeks 12-37 but may have teratogenic potentials
Name some other unapproved drugs that are under study to be used as tocolytics.
diazoxide (anti-HTN, relaxes smooth muscle); atosiban (oxytocin antagonist, inhibits binding); prolactin?, bromocriptine (dopamine agonist - supresses prolactin)
Name the antiprogestin agent that blocks the binding of progesterone and is an abortive agent used in early pregnancy.
mifepristone (RU 486)