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Block II Pharmacology of the Uterus


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oxytotic drugs
-induce or help labor
-prevent postpartum hemorrhage
-help in breast feeding
-induce or manage abortion
myometrial contractility
-smooth muscle
-involves membrane Ca channels
-spread of excitation by gap junctions
-gap junctions increase through pregnancy by steroid hormones
-gap junctions allow for spontaneous, synchronized contractions
Uterine innervation
-parasympathetics from pelvic nerve
-sypmathetics from inferior mesenteric and hypogastric ganglia
Nerve Receptors of the Uterus
-alpha 1: excitatory
-beta 2: inhibitory
--Beta sensitivity increases late in pregnancy
-excitatory receptors on the myometrium
-sensitivity increases by increasing receptor numbers throughout pregnancy
-levels of oxytocin increase also
Prostaglandins E & F
E1, E2, and F2 alpha have oxytocic effects
-have effects throughout pregnancy
-their effects also increse through pregnancy
-can be used early in pregnancy
Estrogen and Progesterone
-estrogen increses in last 2-3 weeks of pregnancy
-leads to the increased censitivity to oxytocin and prostaglandins
-progesterone decreases at the same time
Stages of Labor
Stage 1: cervical dilation
Stage 2: delivery of fetus
Stage 3: delivery of placenta
Stage 1
-cervical dilation
-complets at 10cm
-cervix soften and stretches
Stage 2
-delivery of placenta
-uterus contracts to a very small size
-placenta is separated from the uterine wall
-smooth muscle clamps blood vessels to prevent bleeding
Causes of Postpartum Bleeding
-uterine atony (doesn't contract)
-trauma or lacerations (can't contrace properly)
-retained placenta (can't contract enough)
-maternal hemorrhagic disease (mother can't clot)
Milk Ejection
-neurogenic/hormonal reflex
1-suckling sensation
2-hypothalamic release of oxytocin
3-contraction of alveolar myoepithelial cells
4-milk expression
Oxytocic Drugs
-ergot alkaloids
Indications for Oxytocin
-initiate or manage labor
-initiate milk let-down
Adverse Effects of Oxytocin
high doses have an ADH effect leading to water toxicity
-they have similar structures
Effects of Oxytocin
-produces rhythmic uterine contractions with appropriate time of relaxation
-short half-life (12-17min) allows moment to moment control
Contraindications to Oxytocin
-unfavorable fetal position (ex: breech)
-potential uterine ruptrue (by many previous pregnancies or c-sections)
-maternal exhaustion
-fetal distress
Administration of Oxytocin
-IV-allows best fine control, but highest risk for water toxicity
-IM-for labor and lactation induction
-intranasal-for lactation
Oxytocin Dangers to Fetus
-anoxia-contractions decrease circulation
-abruptio placentae (early separation)
-damage to fetus by too quick birth through too small pelvis
Prostaglandins in Use
-dinoprostone: PGE2
-carboprost: 15 methyl PGF2 alpha
-misoprostol: PGE1 analogue
PG for Labor Termination
-first trimester (up to 7 weeks)
-misoprostol with mifepristone (approved) or methotrexate (off label)
-PG only contracts uterus and must use something to kill fetus
PG in Postpartum Bleeding
-misoprostol (advantage in storage, oral dose and cost)
PG in Stage 1 of Labor
-dinopristone--at doses below initiation of contraction
-often used with oxytocin to allow lower doses of both
PG in Induction of Labor
-misoprostol or dinoprostone
-not approved but easy storage and low cost
ERgot Alkaloids
-alpha adrenergic and serotinergic agonist
-increase lenght and force of uterine contractions
-sensitive early in pregnancy, but incresed later
-also trests Parkinson's and migraine
Indications for Ergot Alkaloids
-limited to postpartum or post abortion bleeding
-causes very strong contractions that have a high risk of stillbirth
-most potent ergot alkaloid
-also the least toxic
Tocolytic Drugs
-used to delay labor or treat dysmenorrhea
-special circumstances
-50% respond to rest and hydration
-must have < 4cm dilation and < 80% effecement
-only druint weeks 20-36
-NOT if membranes are ruptured (risk of infection)
-also give drugs for lung maturation
Calcium Agonist
Nifedipine (Procardia)
-blocks surface membrane Ca channels
-used in preterm labor and to treat dysmenorrhea
-systemic risk of hyotension, tachycardia, and flushing
Beta 2 Agonists
-ritodrine, terbutaline, fenotorol, albuterol
-stimulate beta 2 receptors and decrease intracellular Ca
-decreases uterine contractions
Indications for Beta 2 Agonists
-pretern labor (ritodrine)
-abnormal uterine activity
-complications of C-section
-dysmenorrhea (terbutaline)
Magnesium Sulfate
-competes with Ca for binding
-controls siezures associated with eclampsia and severe preeclampsia
-higher doses prevent uterine contractions
-usefullness is questionable
Prostaglandin Synthesis Inhibitors
-Indomethecin (Indocin) and NSIDs
-block MAO and COX
-used to prevent dysmenorrhea
-risk of GI distress and bleeding
-NOT used to slow labor b/c blocks synthesis if PGI2
--get premature closure of ductus arteriosus and maternal bleeding and GI problems

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