Uterine Drugs - Trachte Flashcards
Why does Oxytocin only work in the last trimester?
Estrogen upregulates Oxytocin receptors in the last trimester
What is the benefit of intense uterine contractions after delivery?
Clamp down on blood vessels to prevent hemorrhage
What are tocolytics used for?
Reduce uterine contractility and suppress uterine smooth muscle contractions (stop premature labor)
What are the reasons to give Oxytocics?
induce or augment labor at term
control postpartum hemorrhage
correct postpartum uterine atony
produce uterine contractions after Caesarean section or other uterine surgery
expel conceptus
can initiate and enhance rhythmic uterine contraction at any time, but relatively high doses are required for such
responses in early pregnancy
How is cellular smooth muscle contraction initiated?
Oxytocin receptors
Gq-PCR
Stimulate PLC => IP3 + DAG
Increase in intracellular Calcium => depolarizes membrane
Open voltage-gated calcium channels
Smooth muscle contraction
How is cellular smooth muscle relaxation initiated?
Gs-protein coupled to cAMP inducing phosphorylation cascade => promotes dilation
Not sure of the signal transduction cascade but should involve phosphorylation by Protein kinase A
Might involve activation of a K channel
What kind of receptor is the Oxytocin receptor?
G protein coupled to phospholipase C
Where is oxytocin synthesized?
paraventricular and supraoptic nuclei of the Hypothalamus
What is the oxytocin protein carrier protein?
neurophysin
Oxytocin is released in vesicles from the posterior pituitary in response to what stimuli?
Cervical dilation
Mechanical stimulation of vagina, uterus
Suckling reflex
The Oxytocin Receptor is present in what parts of the body?
Myoepithelial cells of the mammary gland
Pregnant Myometrium (more so in late stage pregnancy)
CNS
What is the physiological function of Oxytocin?
Important in relationship bonding
released in both sexes during orgasm
If one ablates Oxytocin receptor, monogamous mammals fail to bond with mates
ethanol inhibits oxytocin release
What is the pharmacologic utility of Oxytocin?
Uterine contractions => Permissive effects of estrogens (Works well only in third trimester of pregnancy)
Milk let-down => Myoepithelial cell contraction
Antidiuretic and vasoactive at high concentrations => ADH-like effects
How is Oxytocin administered?
Parenteral, sublingual or nasal administration
It is a peptide, so can’t be given orally
What situations is Synthetic Oxytocin most commonly used?
Drug of choice for labor induction:
Post- due date
Augment dysfunctional labor
Speed up labor in risk situations (Chronic hypertension/Preeclampsia)
What are the contraindications to Synthetic Oxytocin administration?
Not intended as an abortifacient
Cephalo-pelvic disproportion (baby’s head or body is too large to fit through the mother’s pelvis, large baby, abnormal fetal positions, small pelvis)
hypertonic uterine contractions
Use in women with previous Caesarean section comes with increased risk of uterine rupture
What situations are Prostaglandins used for?
promote uterine contractions and expel uterine contents
Why is Ibuprofen the best treatment for menstrual pain?
PGE2 contracts the uterus and produces hyperalgesia => so blocking this makes women feel a lot better!!!
What effect do PGE2 and PGF2 usually have on the uterus?
PGE2: promotes softening of cervix and uterine contraction (PGER is Gs coupled)
PGF2: causes uterine contractions (PGFR is Gq and stimulates IP3)
How are prostaglandins a major component of physiological labor?
Levels rise in amniotic fluid during parturition
Induce local myometrial contractions
Promote cervical ripening prior to delivery
What is Indomethacin used for in labor and delivery?
reduces oxytocin-induced uterine contractions through its action to reduce PG production via inhibition of Cyclo-oxygenases
What is the natural PGE drug that may be used to treat hydatidiform moles (a chorionic growth from the implantation of a nonviable embryo)?
Dinoprostone
What is the synthetic PGE that can be used to ripen (dilate) the cervix for labor promotion and as an abortifacient?
Misoprostol
What is the natural PGF2-alpha agent that we need to know?
Dinoprost
What is the synthetic PGF2-alpha agent that can be used in any trimester (not dependent on estrogen to prime uterus) as an abortifacient or to induce labor?
Carboprost
What is the pharmacological utility of Ergots?
- Contraction of uterus mediated by ergonovine:
Utilized pharmacologically to control postpartum bleeding
Uterine contractions compress blood vessels to reduce bleeding (raise pressure > capillary, venous and potentially arterial)
- Contraction of blood vessels by ergotamine => Used to treat migraine headache (Cafergot has both caffeine and ergotamine)
What receptors do Ergonovine/Ergometrine act on?
Acts via alpha adrenergic, dopaminergic and 5 HT2 receptors
What receptors do Beta-2 agonists act on?
Gs protein coupled receptors
AC => cAMP
Increased PKA => MLCK
Calmodulin => phosphorylates Myosin
Contraction
What is the ß2 selective agonist that activates adenylyl cyclase, raising cAMP levels, that is used for
Terbutaline
What adverse things can ß2 selective agonists cause?
Can elevate heart rate and cause pulmonary edema in mothers
Headaches
Can cause hyperglycemia (acts on Beta-2 receptors in liver and skeletal muscle, has EPI-like effect, breakdown glycogen stores)
Can precipitate myocardial infarction by increasing oxygen demand (increase heart rate)
Why is Magnesium Sulfate sometimes administered IV during pregnancy?
Prevents seizures associated with eclampsia (Competes with Calcium and relaxes smooth muscle)
What is the only oxytocin receptor antagonist approved for clinical use that delays labor by inhibiting oxytocin receptor inositol triphosphate activation?
Atosiban (Tractocile)
Has fewer maternal side effects than ß receptor agonists
Also increased fetal mortality
