Endocrine drugs 1: Gonadal

Question 1

estrogen full antagonist

Answer 1

fulvestrant

Question 2

androgen receptor antagonist

Answer 2

flutamide

Question 3

5-α reducatse inhibitor

Answer 3

finasteride

Question 4

progestins in disguise

Answer 4

“TUNNE”

†Tibolone
Ulipristal
Norethindrone
norethisterone
Ethynodiol

†tibolone is an agonist of the estrogen, progesterone, and androgen receptors.

Question 5

emergency contraception

Answer 5

within 72 hours, effective 99% of the time (Katzung)

conjugated estrogen 10 mg 3x daily for 5 days
ethinyl estradiol 2.5 mg 2x daily for 5 days
L-norgestrel 1.5 mg once

Question 6

OCPs decrease the risk for

Answer 6

ovarian cancer (50% risk reduction)
endometrial cancer (40% risk reduction)

ovarian cysts
benign breast disease
ectopic pregnancy

IDA, RA
(Katzung)

Question 7

DMPA’s ovulation suppression persist for as long as

Answer 7

18 months

Question 8

What is SERM and give a SERM that has no effects on endometrial tissue

Answer 8

Selective Estrogen Receptor Modulators

RALOXIFENE

• for osteoporosis
• for breast cancer prevention
• no estrogenic effects on endometrial tissue

Question 9

discuss CLOMIPHENE

Answer 9

MOA

• partial agonist of estrogen receptors in pituitary (/acts as antagonist in the presence of agonist/)
• reduces negative feedback by estradiol
• increases FSH and LH output

S/E

• Multiple pregnancies (10%)
• Ovarian enlargement
• Reversibble hair loss
• Aferimmages

NOTES
-increased risk of low-grade ovarian cancer with long-term use

Question 10

which is best given for premenopausal post MRM women

Answer 10

tamoxifen

Question 11

which drug is effective in reducing incidence of contralateral breast cancers in postmenopausal women

Answer 11

aromatase inhibitors (e.g. anastrozole)
-used as adjuvant treatment of invasive breast cancer in postmenopausal women

Question 12

BRCA cancer risks

Answer 12

BRCA1
45% seen in hereditary breast CA
80% seen in hereditary ovarian CA
85% lifetime risk for developing breast cancer
40% lifetime risk for developing ovarnian cancer

BRCA2
85% breast cancer risk
20% lifetime ovarian cancer risk
(Schwartz)

Question 13

What is danazol

Answer 13

antiandrogen
-partial agonist of progestin and androgen receptors

USES

• endometriosis
• fibrocystic dse
• hemophilia

C/I

• pregnancy
• breastfeeding

Question 14

GnRH agonists

Answer 14

Leuprolide
Goserelin
-RELIN

reduced LH and FSH secretion with PROLONGED CONTINUOUS administration

USES

• Myoma uteri
• Endometriosis
• Central precocious puberty
• ADVANCED PROSTATE CANCER

Question 15

remarks on goserelin

Answer 15

-relin: GnRH AGONIST
(brother of leuprolide)

temporary exacerbation of precocious puberty or prostate cancer apoplexy, and blindness furing first few weeks of therapy

remedy: co-adminster with FLUTAMIDE, an androgen receptor antagonist

Question 16

GnRH antagonist drugs

Answer 16

-RELIX

GANIRELIX
-prevent LH surge in controlled ovulation

DEGARELIX
-used for prostat CA

Question 17

Mifepristone

Answer 17

(RU-486)
MOA: glucocorticoid and progesterone receptor ANTAGONIST

USES

• medical abortion
• cushing syndrome

S/E
-sepsis d/t unusual organisms (Clostridium sordelli)

Question 18

SHBG tranports what hormones

Answer 18

testosterone

estrogen

Question 19

progesterone is transported by

Answer 19

Cortisol-binding globulin (CBG)
albumin

CBG

• aka transcortin
• also transports corticosteroids

Question 20

androgens in disguise

Answer 20

oxymetholone

mestrerolone

Question 21

anabolic steroids

Answer 21

oxandrolone

Question 22

androgen receptor antagonists

Answer 22

FLUTAMIDE

• BICALUTAMIDE
• NILUTAMIDE
• competitive antagnoist at androgen receptor
• prostate cancer, surgical castration (nilutamide)
• CO-ADMINISTERED with GnRH analogs (LEUPROLIDE, -RELIN) to prevent acute flare-up of prostate cancer
• less hepatotoxicity

CYPROTERONE

• antagonist at androgen receptor
• marked progestational effect that suppresses the feedback enhancement of LH and FSH 📌
• components of COC
• orphan drug status

Question 23

broter of finasteride

Answer 23

dutasteride (longer t1/2)
(5-α reducatase inhibitor)

USES

• BPH
• male pattern baldness
• 2nd-line for hirsutism

S/E
-gynecomastia, impotence, depression

controversial use in prevention of prostate cancer