Gonadal drugs

Question 1

What is a synthetic GnRH?

Answer 1

Gonadorelin

Question 2

What is gonadorelin used for?

Answer 2

Pulsatile treatment for infertility

Question 3

What is GnRH stimulation test?

Answer 3

Differentiates between hypothalamic or pituitary defects

Question 4

What are some GnRH agonists?

Answer 4

Leuprolide, nafarelin, goserelin,

-relin

Question 5

MoA of GnRH agonists

Answer 5

Transient stimulation of gonadotropin secretion which later causes down regulation of GnRH receptor inhibiting FSH and LH secretion.

Question 6

What are Leuprolide, nafarelin, goserelin?

Answer 6

GnRH agonists

Question 7

Uses of GnRH agonist

Answer 7

Pulsatile treatment- infertility and delayed puberty

Continuous treatment- endometriosis, precocious puberty and prostatic carcinoma.

Question 8

Adverse effects of GnRH agonists

Answer 8

Hot flushes, decreased bone density, anaphylaxis, pituitary apoplexy and ovarian hyperstimulation syndrome (OHSS)

Question 9

What are some GnRH antagonists?

Answer 9

Cetrorelix, Ganirelix

-relix

Question 10

MoA of GnRH antagonists

Answer 10

Competitively block GnRH receptor inhibiting FSH and LH secretion.

Question 11

Uses of GnRH antagonists

Answer 11

Advanced prostate cancer, endometriosis, in vitro fertilization. no risk of OHSS.

Question 12

What is ovarian hyperstimulation syndrome (OHSS)?

Answer 12

Rapid accumulation of fluid in peritoneal cavity, thorax and pericardium.
Multiple follicular development causes ovarian enlargement.

Question 13

What are the actions of estrogen?

Answer 13

increases blood coagulability, decreases LDL, sensitizes myometrium for oxytocin and maintains normal structure of the skin.

Question 14

Where is the estrogen receptor located?

Answer 14

It is a nuclear receptor, located inside nucleus.

Question 15

What are the natural and synthetic estrogens?

Answer 15

Natural- estradiol, estrone and estriol

Synthetic- ethinylestradiol and diethylstibestrol

Question 16

What are the uses of estrogen?

Answer 16

Gonadal dysgenesis, hormone replacement therapy, components of oral contraceptives.

Question 17

What are the adverse effects of estrogen?

Answer 17

Thromboembolism/ stroke, hepatic adenoma, premature closure of epiphysis in children, breast and endometrial cancer.

Question 18

What are side effects of diethylstibestrol?

Answer 18

Teratogenic, causes adenocarcinoma of vagina and cervix in female offspring.

Question 19

What are some contraindications of estrogen?

Answer 19

Thromboembolic disorders, breast endometrial cancer, pregnancy and smokers.

Question 20

What is MoA of clomiphene?

Answer 20

Partial estrogen agonist, increases positive feedback of estrogen- increases FSH and LH leading to enhanced follicular maturation.

Question 21

What is the use of clomiphene?

Answer 21

Used for infertility due to failure of ovulation. Given in cycles max. 6 times

Question 22

What are the adverse effects of clomiphene?

Answer 22

OHSS, increased risk of ovarian and endometrial cancer.

Question 23

What is MoA of fulvestrant?

Answer 23

Selective estrogen receptor downregulator. Inhibits estrogen receptor dimerization- enhances receptor degradation.

Question 24

What is the use of fulvestrant?

Answer 24

Treatment for metastatic breast cancer unresponsive to tamoxifen.

Question 25

What are some selective estrogen receptor modulators?

Answer 25

Tamoxifen, raloxifene

Question 26

What is MoA of Tamoxifen?

Answer 26

Estrogen antagonist at- breast, blood vessels | Estrogen partial agonist at- uterus, bone, liver

Question 27

What is the use of Tamoxifen?

Answer 27

Treat breast cancer- adjuvant post mastectomy Prophylaxis of women with increase chance of breast cancer, use less than 5 years because increased risk of endometrial cancer.

Question 28

What are the adverse effects of Tamoxifen?

Answer 28

Hot flushes, increases risk of thromboembolism.

Question 29

What is MoA of raloxifene?

Answer 29

Estrogen antagonist at- endometrium and breast | Estrogen partial agonist at- bone and CVS

Question 30

What is the use of raloxifene?

Answer 30

Osteoporosis in post menopausal women.

Question 31

What are some aromatase inhibitors?

Answer 31

Letrozole, exemestane

Question 32

What is MoA of aromatase inhibitors?

Answer 32

Inhibits aromatization, near total estrogen deprivation

Question 33

What is the use of aromatase inhibitors?

Answer 33

Early breast cancer in ER+ve Advanced breast cancer with tamoxifen failure Can only be used in post menopausal women Accelerates bone loss- predisposes to bone fractures

Question 34

What are some progestins?

Answer 34

Synthetic progestins- Medroxyprogesterone acetate, megesterol acetate 19-nortestosterone derivatives- Norethindrone, desogestrel

Question 35

What are the adverse effects of progestins?

Answer 35

Weight gain Edema ↑ LDL and ↓ HDL levels Precipitate diabetes –glucose intolerance Breast engorgement Teratogenic effect- masculinization of female fetus

Question 36

What are the uses of progestins?

Answer 36

Threatened/habitual abortion Contraceptives Dysfunctional uterine bleeding Endometriosis

Question 37

What is MoA of mifepristone?

Answer 37

Antiprogestational, antiglucocorticoid, antiandrogenic activity. Partial agonist & competitive antagonist at progesterone receptor. Attenuates midcycle LH surge-failure of ovulation and blocks progesterone support to endometrium.

Question 38

What are the uses of mifepristone?

Answer 38

Termination of pregnancy along with misoprostol Postcoital contraceptive Cushing’s syndrome

Question 39

What is MoA of danazol?

Answer 39

Partial agonist at progesterone, androgen and glucocorticoid receptors. Inhibits LH and FSH surge

Question 40

What are the uses of danazol?

Answer 40

Heriditary angioneurotic edema Endometriosis Fibrocystic breast disease Gynaecomastia

Question 41

What is MoA of combination oral contraceptives?

Answer 41

Estrogen + progestin- suppress midcycle LH surge, prevents ovulation

Question 42

What are the adverse effects of combination oral contraceptives?

Answer 42

Thromboembolism Hepatomas Increased risk of breast cancer decreases ovarian cancer

Question 43

What are some testosterone 17-alkyl derivatives?

Answer 43

They are resistant to 1st pass metabolism. | Methyltestosterone, fluoxymesterone

Question 44

What are the uses of androgens (testosterone)?

Answer 44

``` Hereditary angioneurotic edema Testicular failure delayed puberty hypopituitarism As anabolic Anemias- Fanconi’s, sickle cell ```

Question 45

What are the adverse effects of androgens (testosterone)?

Answer 45

Oligospermia azospermia Prostatic hyperplasia

Question 46

Why does exogenous androgen cause infertility?

Answer 46

Androgen inhibits FSH and LH Leydig cells synthesize less androgen Sertoli cells then reduce synthesis of androgen binding protein Seminiferous tubules degenerate –no sperm

Question 47

What is MoA of 5α reductase inhibitors?

Answer 47

Finasteride- 5α reductase inhibitor- reduction of dihydrotestosterone synthesis

Question 48

What are the uses of 5α reductase inhibitors?

Answer 48

Benign prostatic hypertrophy | Male pattern of baldness with minoxidil

Question 49

What is MoA of competitive androgen receptor antagonists?

Answer 49

Flutamide-↑ LH secretion by blocking feedback inhibition

Question 50

What are the uses competitive androgen receptor antagonists?

Answer 50

Prostate cancer

Question 51

What is the treatment of prostate cancer?

Answer 51

Leuprolide + flutamide First 7-10 days of leuprolide increase androgen levels Add androgen receptor antagonist flutamide to avoid flare up