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26 Cards in this Set

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Uterine Stimulants (Oxytocics)
Oxytocin
Ergonovine and Methylergonovine
Dinoprostone and Carboprost Tromethamine
Oxytocin - General info
- Peptide hormone of post. pituitary that elicits milk ejection in lactating women
- Can be used to induce uterine contractions and maintain labor
- During second half of pregnancy, uterine SM inc expression of oxytocin receptors and become sensitive to action of endogenous oxytocin
- Pharmacologic conc of oxytocin powerfully stimulate uterine contraction
Oxytocin - MOA
Oxytocin --> Gprotein receptor --> (i) activation of phospholipase C, (ii) activation of voltage-gated calcium channels
also
Oxytocin --> increases local PG synthesis --> further stimulation of uterine contractions
Oxytocin - Clinical Uses
- induction of labor (DOC!!)
- augmentation of dysfunctional labor (prolonged latent phase of cervical dilation; arrest of dilation or descent)
- postpartum hemorrhage
- oxytocin challenge test
- induction of abortion
Oxytocin - Pharmacokinetics
IV infusion - for labor induction
IM injection - control of postpartum bleeding
Nasal spray - promote milk ejection
Oxytocin - Adverse Effects
- excessive stimulation of uterine contractions --> fetal distress, placental abruption, uterine rupture
- high conc of oxytocin --> activate vasopressin receptors --> excessive fluid retention, or water intoxication leading to hypontaremia, heart failure, seizures, and death
- bolus injections of oxytocin can cause hypotension (to avoid this, oxytocin is admin IV as dilute solutions at a controlled rate)
Oxytocin - Contraindications
- fetal distress
- prematurity
- abnormal fetal presentation
- cephalopelvic disproportion
Ergonovine and Methlyergonovine - General information
- partial agonists for alpha-adrenergic receptors and some serotonin receptors
- sensitivity of the uterus to the stimulant effects of ergot alkaloids increases dramatically during pregnancy
- in small doses can evoke rhythmic contraction and relaxation of the uterus
- at higher conc induce powerful and prolonged contractions
Ergonovine and Methylergonovine - Clinical uses
Ergonovine and methylergonovine are given IM as second line agents (behind oxytocin) for postpartum hemorrhage

**Ergot derivatives should ONLY be used for control of LATE uterine bleeding and should NEVER be given before delivery
Ergonovine and Methylergonovine - Adverse effects
- HTN, headache, possible seizures
Ergonovine and Methylergonovine - Contraindications
- Angina pectoris, MI, PREGNANCY, history of CVA, TIA, or HTN
- Can be found in breast milk so neither should be admin longer than necessary --> can lead to ergot poisoning (ergotism) including gangrene in the nursing infant
Dinoprostone and Carboprost Tromethamine - General info
Dinoprostone = PGE2
Carboprost tromethamine = synthetic analogue of PGF2-alpha

- PG's are more effective stimulants of uterine contraction thru the second trimester than is oxytocin
- Inhibition of PG synthesis with a NSAID can increase the length of gestation, prolong spontaneous labor, or interrupt premature labor
Carboprost Tromethamine - Clinical uses
- induction of abortion in 2nd trimetster
- control of postpartum hemorrhage due to uterine atony (3rd line behind oxytocin and ergonovine)
Dinoprostone - Clinical uses
- induction of abortion in 2nd trimester
- evacuation of uterine contents (missed abortion)
- mgmt of benigh hydatidiform mole
- ripening of cervix for inductino of labor in pts at or near term
Dinoprostone and Carboprost Tromethamine - PK
Carboprost tromethamine = IM
Dinoprostone = vaginal insert, vaginal suppository, cervical gel
Uterine Relaxants (Tocolytics)
- Beta-2-adrenoreceptor agonists (ex: Terbutaline)
- Magnesium sulfate
- Indomethacin
- Nifedipine
- Atosiban
Beta-2-adrenoreceptor agonists - General info
- can arrest preterm labor for at least 48-72 hrs
- even though most commonly used in US, not always effective in treating preterm labor
Beta-2-adrenoreceptor agonists - MOA
agonist --> B-2-adrenoreceptor on myometrium --> adenylyl cyclase --> cAMP --> 2 things happen:
(i) - decreased intracellular Ca --> reduced effect of Ca on muscle contraction
(ii) - protein kinase A --> phosphorylates smooth-muscle myosin light chain kinase (SmMLCK) --> lower affinity of SmMLCK for Ca-calmodulin complex --> no phosphorylation of myosin by SmMLCK --> muscle relaxes
Beta-2-adrenoreceptor agonists - Adverse effects
- palpitations, tremor, nausea, vomiting, nervousness, anxiety, chest pain, SOB, hyperglycemia, hypokalemia, hypotension
- serious = pulm edema, cardiac insuff., arrhythmias, MI, maternal death
Terbutaline
- mgmt of premature labor (not FDA-approved for it though)
- specific B2-adrenoreceptor agonist
- can decrease frequency, intensity, and duration of uterine contractions
- prevents premature labor esp more than 20wks into gestation and have no indication of ruptured fetal membranes or in whom labor is not far advanced
- should be given initially in hospital setting
- given orally or subcutaneously or IV
Magnesium sulfate - MOA
- Uncouples excitation-contraction in myometrial cells thru inhibition of cell action potentials
- Decreases Ca uptake by competing for its binding sites, activating adenylyl cyclase, and stimulating Ca uptake by the sarcoplasmic reticulum
Magnesium sulfate - Clinical use
- Preferred over B-adrenergic agents in pts with heart disease, diabetes, HTN, or hyperthyroidism
Magnesium sulfate - AE
- Toxicity = life-threatening (in increasing doses):
- loss of patellar reflexes
- resp. depression
- resp. paralysis --> arrest
- cardiac arrest
Indomethacin
- an NSAID (acts as an inhibitor to PG synthesis) used to delay preterm labor
- given orally or rectally
- AE = premature closure of fetal PDA (bc of the fetus's ability to inhibit PG synthesis) [more sensitive beyond 32 wks]
Nifedipine
- Ca channel blocker
- acts by impairing entry of Ca into myometrial cells via voltage-dep Ca channels (so inhibits contractility)
- given orally
Atosiban
- competitive antagonist at oxytocin receptors
- decreases and stops uterine contractions
- not available in US