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1 Tocolytics
Scammell
112
Pharmacology
Graduate
04/22/2010

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Term
what happens to the myometrium during pregnancy?
Definition
undergoes extensive hypertrophy
Term
what types of receptors are on myometrial cells?
Definition
excitatory and inhibitory
Term
3 excitatory receptors on myometrial cells?
Definition
1. alpha1 adrenergic
2. oxytocin
3. prostaglandin
Term
what are the inhibitory receptors on myometrial cells?
Definition
beta adrenergic
Term
how is labor initiated in humans?
Definition
elevated cortisol + depressed progesterone
Term
how is the uterus primed for initiation of labor in humans?
Definition
mediated by hormones

increase the density of oxytocin receptors and PGE
Term
what is the goal of initiation of labor/priming the uterus?
Definition
increase the frequency and organization of contractions
Term
how do receptors on the myometrium inhibit contration?
Definition
B adrenergic agonists --> increase cAMP --> inhibit contraction
Term
how do receptors on the myometrium cause contration?
Definition
they are coupled to PLC --> IP3 --> increase Ca --> contraction
Term
4 uses of drugs that stimulate the uterus?
Definition
1. induction of labor
2. control of postpartum atony and hemorrhage
3. induction of uterine contractions after C section or uterine surgery
4. therapeutic abortion in first trimester
Term
what drug is used to induce labor?
Definition
oxytocin
Term
3 drugs used to control postpartum atony and hemorrhage?
Definition
1. oxytocin
2. ergonovine
3. misoprostol
Term
what drug is used for induction of uterine contractions after C section or uterine surgery?
Definition
ergonovine
Term
2 drugs used for therapeutic abortion?
Definition
1. prostaglandin
2. mifepristone
Term
oxytocin is secreted from where?

what other hormone is secreted from the same organ?

where are these hormones made?
Definition
posterior pituitary

vasopressin/ADH

made in hypothalamus
Term
what are conditions in which the induction of labor may be indicated (11)?
Definition
1. prolonged pregnancy
2. preeclampsia
3. chronic HTN
4. diabetes mellitus
5. Rh isoimmunization
6. previous stillbirth
7. advanced maternal age
8. intrauterine death
9. intrauterine growth retardation
10. major fetal anomalies
11. hydramnios
Term
administration of oxytocin?
Definition
infused IV because it is a peptide and not orally active
Term
half life of oxytocin
Definition
5 mins
Term
mechanism of action of oxytocin?
Definition
binds to receptors on myometrium - increases electrical activity
Term
effects of oxytocin?
Definition
increases strength and organization of contractions
Term
when is the uterus very responsive to oxytocin and why?
Definition
in late gestation

because the receptors have increased
Term
what is important about administering oxytocin and why?
Definition
IV must be started slowly until see increase in contractile strength

because responses are variable even though the uterus is very responsive in late gestation
Term
contraindications for oxytocin?
Definition
1. previous uterine surgery
2. abnormal fetal position
3. evidence of fetal distress
Term
side effects of oxytocin?
Definition
rare

1. nausea
2. fetal trauma
3. uterine rupture
4. water intoxication
Term
why is water intoxication a side effect of oxytocin?
Definition
because of it's ADH-like activity
Term
can induction of labor be elective?
Definition
NO not without medical indications
Term
chemical nature of oxytocin?
Definition
physiological substance; peptide
Term
nature of uterine contraction with oxytocin?
Definition
contraction followed by relaxation
Term
sensitivity of uterus to oxytocin?
Definition
increases with duration of pregnancy

most sensitive at term; immature uterus is resistant
Term
can oxytocin be administered orally?
Definition
NO

it is a peptide
Term
duration of action of oxytocin?
Definition
very short
Term
onset of action of oxytocin?
Definition
IV - immediate
IM - 2.5 mins
Term
uses of oxytocin?
Definition
1. induction of labor
2. postpartum uterine atony
Term
onset of ergonovine?
Definition
rapid

but has prolonged actions
Term
does sensitivity to ergonovine increase at term?
Definition
YES

but can be used before term as well
Term
actions of ergonovine on the uterus?
Definition
alpha-adrenergic and serotoninergic

stimulates contraction
Term
side effects of ergonovine?
Definition
HTN
Term
uses of ergonovine?
Definition
prevention of postpartum uterine atony and hemorrhage
Term
chemical nature of ergonovine?
Definition
natural ergot alkaloid
Term
nature of uterine contraction with ergonovine?
Definition
tonic contractions
Term
sensitivity of uterus with ergonovine?
Definition
increases at term

non-pregnant and immature uterus also stimulated
Term
administration of ergonovine?
Definition
oral, IM, IV
Term
onset of action of ergonovine?
Definition
IV - immediate
IM - 5 min
Term
duration of ergonovine?
Definition
prolonged

particularly after high dose
Term
uses of ergonovine?
Definition
prevention of postpartum uterine atony and hemorrhage
Term
what is a PGF2-alpha tocolytic agent?
Definition
dinoprost
Term
what is a PGE1 tocolytic agent?
Definition
misoprostol
Term
admin of prostaglandins?
Definition
intra-amniotic injection or vaginal suppository
Term
what are prostaglandins used in combo with for termination of first term pregnancy?
Definition
mifepristone or methotrexate
Term
prostaglandins are used in combo with mifepristone or methotrexate for what?
Definition
termination of first term pregnancy
Term
what is the direct action of prostaglandins as tocolytics?
Definition
induce contractions of the uterus
Term
what is a secondary action of prostaglandins?
Definition
also used to soften the cervix prior to delivery
Term
side effects of prostaglandins?
Definition
1. uterine rupture
2. transient pyrexia
3. nausea
4. diarrhea
Term
why can prostaglandins cause a transient pyrexia?
Definition
they stimulate receptors in the hypothalamus
Term
chemical nature of prostaglandins?
Definition
physiological substance

fatty acid derivative
Term
nature of uterine contraction with prostaglandins?
Definition
contraction followed by relaxation
Term
sensitivity of uterus with prostaglandins?
Definition
contracts uterus in all stages of pregnancy and also non-pregnant and immature uterus
Term
administration of prostaglandins?
Definition
oral, intra-vaginal, IV, intra-amniotic
Term
uses of prostaglandins?
Definition
abortion
Term
uses of oxytocin?
Definition
1. induction of labor
2. uterine atony
3. hemorrhage
Term
what 2 hormones are secreted by the posterior pituitary?
Definition
1. oxytocin
2. vasopressin/ADH
Term
ADH function in vasculature?
Definition
activates V1 receptors --> Ca increase --> SM contraction --> vasoconstriction

very potent
Term
how does the V1 receptor in the vasculature lead to vasoconstriction?
Definition
ADH binds --> coupled to PLC --> stimulates IP3 production --> increases Ca
Term
ADH function in the kidney?
Definition
activates V2 receptors --> coupled to AC --> increase cAMP --> causes water absorption
Term
effects of ADH?
Definition
vasculature - V1 receptor leads to vasoconstriction

kidney - V2 receptor leads to water reabsorption
Term
what is a vasopressin V1 receptor selective agonist?
Definition
terlipressin
Term
terlipressin is what kind of drug?
Definition
vasopressin V1 receptor selective agonist
Term
how does terlipressin differ from vasopressin?
Definition
more selective than vasopressin - only activates V1
Term
use of terlipressin?
Definition
1. bleeding
2. esophageal varices
3. hemorrhagic shock
Term
administration of terlipressin?
Definition
IV or directly to blood vessels
Term
what is a vasopressin V2 receptor selective agonist?
Definition
desmopressin
Term
what type of drug is desmopressin?
Definition
vasopressin V2 receptor selective agonist
Term
uses of desmopressin?
Definition
1. diabetes insipidus
2. bleeding disorders
Term
what is diabetes insipidus?
Definition
inability to secrete or make normal ADH
Term
how does desmopressin work in diabetes insipidus?
Definition
mediates water reabsorption through V2 receptor
Term
administration of desmopressin?
Definition
intranasal preparation

enough is absorbed from nasal mucosa to be effective
Term
how is desmopressin used in treatment of bleeding disorders?
Definition
increases von Willebrand factor
Term
mechanism of action of ethanol as a tocolytic agent?
Definition
1. inhibition of endogenous oxytocin and ADH release
2. depression of myometrium
3. antagonism to prostaglandins
Term
why is ethanol no longer used as a tocolytic agent?
Definition
because the incidence of fetal distress syndrome is not reduced
Term
use of drugs that inhibit uterine contractions?
Definition
to delay premature labor and slow or arrest delivery
Term
drugs that inhibit uterine contraction on average work for how long?
Definition
48 hours
Term
why is the window of time that drugs inhibit uterine contraction important?
Definition
during that time a corticosteroid is given to promote lung surfactant development
Term
many patients respond to what instead of drugs to inhibit uterine contraction?
Definition
bed rest and hydration
Term
contraindications for tocolytics?
Definition
1. membranes already ruptured
2. fetal distress
Term
admin of magnesium sulfate?
Definition
IV in the hospital
Term
mechanism of action of magnesium sulfate?
Definition
divalent cation that blocks Ca effect --> reduces excitability of uterus
Term
magnesium sulfate is administered IV to a final concentration of what?
Definition
3-7 mEq/L
Term
excretion of magnesium sulfate?
Definition
by kidneys
Term
side effects of magnesium sulfate?
Definition
1. resp depression
2. hypotension
3. cardiac arrest
Term
3 Ca channel blockers used as tocolytic agents?
Definition
1. verapamil
2. nifedipine
3. nicardipine
Term
mechanism of action of Ca channel blockers as tocolytic agents?
Definition
block Ca entry into myometrial cells
Term
administration of Ca channel blockers?
Definition
orally
Term
side effects of Ca channel blockers?
Definition
1. headaches
2. hypotension
3. reflex tachycardia
Term
ritodrine and terbutaline are what type of drug?
Definition
beta2-adrenergic agonists
Term
administration of ritodrine and terbutaline?
Definition
IV or oral
Term
mechanism of ritodrine and terbutaline as tocolytics?
Definition
stimulate cAMP in myometrium
Term
side effects of ritodrine and terbutaline in the mother?
Definition
1. tachycardia
2. hyperglycemia
3. pulmonary edema
Term
side effects of ritodrine and terbutaline in the fetus?
Definition
1. tachycardia
2. dysrythmias
Term
administration of indomethacin?
Definition
rectal or oral
Term
administration of COX-2 inhibitors?
Definition
IV
Term
mechanism of action of indomethacin or COX-2 inhibitors?
Definition
inhibit prostaglandin synthesis
Term
indomethacin or COX-2 inhibitors are useful how as tocolytic agents?
Definition
short term use
Term
side effects of indomethacin or COX-2 inhibitors?
Definition
1. nausea
2. diarrhea
3. allergic rash
4. oligohydramnios
Term
what is oligohydramnios?
Definition
< 300 mL of amniotic fluid at term
Term
what is the biggest risk with use of indomethacin or COX-2 inhibitors?
Definition
premature closure of the ductus arteriosus

prostaglandins normally maintain patency in the fetus
Term
how are synthetic corticosteroids used in tocolytic therapy?
Definition
to mature surfactant in the lungs
Term
what women are given progesterone or 17 hydroxyprogesterone?
Definition
women at high risk for premature delivery - those who have miscarried before
Term
is progesterone or 17 hydroxyprogesterone used as a tocolytic agent?
Definition
NO
Term
effect of progesterone or 17 hydroxyprogesterone on miscarriage rates?
Definition
reduces incidence of miscarriage by 30%
Term
when is progesterone or 17 hydroxyprogesterone?
Definition
starting at 14-16 weeks gestation for women who are at high risk for premature delivery
Term
Tocolytic therapy delays labor by an average of:

a. 4 hours
b. 48 hours
c. 2 weeks
d. 2 years
Definition
b. 48 hours
Term
Oxytocin is an excellent drug for the induction of labor because:

a. It can be administered orally
b. It also causes cervical ripening
c. The plasma half-life is a few minutes
d. The plasma half-life is a few hours
Definition
c. The plasma half-life is a few minutes
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