Uterine Drugs - Trachte

Question 1

Why does Oxytocin only work in the last trimester?

Answer 1

Estrogen upregulates Oxytocin receptors in the last trimester

Question 2

What is the benefit of intense uterine contractions after delivery?

Answer 2

Clamp down on blood vessels to prevent hemorrhage

Question 3

What are tocolytics used for?

Answer 3

Reduce uterine contractility and suppress uterine smooth muscle contractions (stop premature labor)

Question 4

What are the reasons to give Oxytocics?

Answer 4

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

Question 5

How is cellular smooth muscle contraction initiated?

Answer 5

Oxytocin receptors

Gq-PCR

Stimulate PLC => IP3 + DAG

Increase in intracellular Calcium => depolarizes membrane

Open voltage-gated calcium channels

Smooth muscle contraction

Question 6

How is cellular smooth muscle relaxation initiated?

Answer 6

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

Question 7

What kind of receptor is the Oxytocin receptor?

Answer 7

G protein coupled to phospholipase C

Question 8

Where is oxytocin synthesized?

Answer 8

paraventricular and supraoptic nuclei of the Hypothalamus

Question 9

What is the oxytocin protein carrier protein?

Answer 9

neurophysin

Question 10

Oxytocin is released in vesicles from the posterior pituitary in response to what stimuli?

Answer 10

Cervical dilation

Mechanical stimulation of vagina, uterus

Suckling reflex

Question 11

The Oxytocin Receptor is present in what parts of the body?

Answer 11

Myoepithelial cells of the mammary gland

Pregnant Myometrium (more so in late stage pregnancy)

CNS

Question 12

What is the physiological function of Oxytocin?

Answer 12

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

Question 13

What is the pharmacologic utility of Oxytocin?

Answer 13

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

Question 14

How is Oxytocin administered?

Answer 14

Parenteral, sublingual or nasal administration

It is a peptide, so can’t be given orally

Question 15

What situations is Synthetic Oxytocin most commonly used?

Answer 15

Drug of choice for labor induction:

Post- due date

Augment dysfunctional labor

Speed up labor in risk situations (Chronic hypertension/Preeclampsia)

Question 16

What are the contraindications to Synthetic Oxytocin administration?

Answer 16

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

Question 17

What situations are Prostaglandins used for?

Answer 17

promote uterine contractions and expel uterine contents

Question 18

Why is Ibuprofen the best treatment for menstrual pain?

Answer 18

PGE2 contracts the uterus and produces hyperalgesia => so blocking this makes women feel a lot better!!!

Question 19

What effect do PGE2 and PGF2 usually have on the uterus?

Answer 19

PGE2: promotes softening of cervix and uterine contraction (PGER is Gs coupled)

PGF2: causes uterine contractions (PGFR is Gq and stimulates IP3)

Question 20

How are prostaglandins a major component of physiological labor?

Answer 20

Levels rise in amniotic fluid during parturition

Induce local myometrial contractions

Promote cervical ripening prior to delivery

Question 21

What is Indomethacin used for in labor and delivery?

Answer 21

reduces oxytocin-induced uterine contractions through its action to reduce PG production via inhibition of Cyclo-oxygenases

Question 22

What is the natural PGE drug that may be used to treat hydatidiform moles (a chorionic growth from the implantation of a nonviable embryo)?

Answer 22

Dinoprostone

Question 23

What is the synthetic PGE that can be used to ripen (dilate) the cervix for labor promotion and as an abortifacient?

Answer 23

Misoprostol

Question 24

What is the natural PGF2-alpha agent that we need to know?

Answer 24

Dinoprost

Question 25

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?

Answer 25

Carboprost

Question 26

What is the pharmacological utility of Ergots?

Answer 26

1. 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)

2. Contraction of blood vessels by ergotamine => Used to treat migraine headache (Cafergot has both caffeine and ergotamine)

Question 27

What receptors do Ergonovine/Ergometrine act on?

Answer 27

Acts via alpha adrenergic, dopaminergic and 5 HT2 receptors

Question 28

What receptors do Beta-2 agonists act on?

Answer 28

Gs protein coupled receptors

AC => cAMP

Increased PKA => MLCK

Calmodulin => phosphorylates Myosin

Contraction

Question 29

What is the ß2 selective agonist that activates adenylyl cyclase, raising cAMP levels, that is used for

Answer 29

Terbutaline

Question 30

What adverse things can ß2 selective agonists cause?

Answer 30

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)

Question 31

Why is Magnesium Sulfate sometimes administered IV during pregnancy?

Answer 31

Prevents seizures associated with eclampsia (Competes with Calcium and relaxes smooth muscle)

Question 32

What is the only oxytocin receptor antagonist approved for clinical use that delays labor by inhibiting oxytocin receptor inositol triphosphate activation?

Answer 32

Atosiban (Tractocile)

Has fewer maternal side effects than ß receptor agonists

Also increased fetal mortality