Gonadal Hormone Inhibitors and Uterotonics

Question 1

What do progestins, androgens, and estrogens have in common? (precursor, type of molecule)

Answer 1

Lipophillic because their common precursor is cholesterol

Question 2

What is the most potent naturally occurring estrogen?

Answer 2

Estradiol

Question 3

Progestins give rise to ______ which give rise to _______

Answer 3

Androgens

Estrogens

Question 4

What type of feedback occurs to control the release of GnRH by the hypothalamus?

Answer 4

Negative

Question 5

How do 5a-reductase inhibitors work and what are examples?

Answer 5

Finasteride (Proscar, Propecia) and Dutasteride (Avodart)

Competitive and selective inhibition of the enzyme 5a-reductase which usually converts testosterone to dihydrotestosterone (a more potent form of testosterone) which then binds to an androgen receptor

Question 6

What are 5a-reductase inhibitors (finasteride and dutasteride) used to treat?

Answer 6

BPH and alopecia

Question 7

5a-reductase inhibitors effect which receptors?

Answer 7

Type I: skin, liver (dutasteride)

Type II: prostate and scalp(finasteride and also dutasteride)

Question 8

How do aromatase inhibitors work?

Answer 8

Inhibits the enzyme aromatase which converts androgen to estrogen.

Question 9

What type of synthesis inhibitors are anastrazole, letrazole, exemestane, and formestane and how do they differ?

Answer 9

Aromatase inhibitors
anastrazole, letrazole are competitive inhibitors
exemestane, formestane bind covalently and are irreversible

Question 10

What are aromatase inhibitors used to treat?

Answer 10

ER+(estrogen feeding tumors) breast cancer that is hormonally responsive

Question 11

AE of aromatase inhibitors are d/t what and include what?

Answer 11

d/t: profound suppression of estrogen action which is a major regulator of bone density
include: increased risk of osteoporosis and fractures

Question 12

What are SERMs?

Answer 12

Selective estrogen receptor modulators

They have tissue specific agonist/antagonist activity (mixed)- activity depends on the tissue being acted on

Question 13

What is the the SERM Tamoxifen used to treat but what can it cause?

Answer 13

Inhibits growth of estrogen dependent (ER+) breast tumors but can stimulate endometrial cancer

(breast-antag, endometrium- agonist, bone-slight agonist)

Question 14

How is the SERM Raloxifene (Evista) similar to Tamoxifen and how is it different? What is it used to prevent?

Answer 14

Also an estrogen antagonist in the breast, but does not stimulate endometrium. It is an agonist in the bone so can be used to delay or prevent osteoporosis

Question 15

What is the SERM Clomiphene (Clomid) used for and how does it work?

Answer 15

Used to induce ovulation
Estrogen receptor antagonist(shuts of neg. feedback loop) in the hypothalamus and anterior pit gland increasing GnRH which increases estrogen and ovulation

Question 16

How does the estrogen receptor antagonist, Fulvestrant work and what is it used for?

Answer 16

Pure estrogen antagonist
Competitively inhibits estrogen receptors in breast cancer cells (no effects elsewhere)
Used in hormonally responsive (ER+) breast cancer to slow tumor growth

Question 17

What are Flutamide(Eulexin) and Bicalutamide (Cadodex) used to treat and what type of drug are they?

Answer 17

Androgen Receptor Antagonists

Used to treat prostate cancer and BPH

Question 18

What is spironolactone used to treat and what type of drug is it?

Answer 18

Androgen receptor antagonist

Used to treat hirsutism

Question 19

What type of antagonist is Mifepristone (RU-486) and what is it used for?

Answer 19

Progesterone Receptor Antagonist
1st trimester termination of pregnancy
Competitive inhibition of progesterone action causing uterine lining to shed and cervix to soften?

Question 20

What medication is a PGE analogue used for GI protection that also stimulates uterine contractions causing 1st trimester termination of pregnancy(off label)?

Answer 20

Misoprostol (Cytotec)

Question 21

How can GnRH agonists and antagonists have the same effect on the body?

Answer 21

If given enough GnRH agonist causing negative feedback there will be suppression of FSH and LH release. Both medications can be used to treat cancer of the prostate and breast.

Question 22

What is the purpose of uterotonics?

Answer 22

Promote myometrial activity

Stimulate the uterus to contract

Question 23

How can uterotonics be used?(3)

Answer 23

To empty the uterus: Labor or termination
Stop Bleeding: Postpartum(immediate or late)
Subinvolution: reduction of uterus post childbirth

Question 24

Why is endogenous or exogenous oxytocin (Pitocin) used?

Answer 24

Induce labor
Augment labor
Promotion uterine contractility

Question 25

MOA of oxytoxin (Pitocin) in myometrial cells:

Answer 25

Promotes myometrial contraction by increasing free intraceullar Ca++ in myometrial cells Uterine responsiveness increased from exposure to estrogen (late in preg) Less oxytocin is needed once labor has begun d/t an upregulation in rc

Question 26

What is oxytocin's effect on the mammary glands?

Answer 26

Causes contraction of mammary glands to let milk down

Question 27

What weak but present action does oxytocin possess when used in large doses and what type of patient would you avoid use in?

Answer 27

Weak antidiuretic action d/t ADH like effect (structurally similar to vasopressin) Caution with use in cardiac, renal disease, or PIH(preg HTN)

Question 28

How is oxytocin administered and its PK?

Answer 28

IV continuous gtt Destroyed in the GI tract (can't give PO) Does not cross BBB Short half life (1-6mins in plasma), effects may last a couple of hours

Question 29

Dinoprostone (Cervadil, Prostin E2, Prepidil) is naturally occurring ______ and is used for what?

Answer 29

``` Prostaglandin E2 (PGE2) Cervical ripening ```

Question 30

MOA of Dinoprostone (Cervadil, Prostin E2, Prepidil):

Answer 30

Sensitizes myometrium to endogenous or exogenous oxytocin

Question 31

How is Dinoprostone (Cervadil, Prostin E2, Prepidil) administered?

Answer 31

Vaginal insert/suppository | Cervical gel

Question 32

What off label use does Misoprostol have?

Answer 32

Tablet per vagina can be given for surgical ripening, labor induction, or post-partum hemorrhage. (Same effect when given orally for GI s/s, category X drug)

Question 33

Lueprolide (Lupron) what type of drug and what is it used for?

Answer 33

``` GnRH agonist (inhibits LH/FSH secretion by increasing GnRH release) Used for the treatment of breast cancer and prostate cancer ``` Similar drugs include: Goserelin and Nafarelin

Question 34

GnRH receptor antagonists include:

Answer 34

Cetrorelix | Ganirelix