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pharmacology > Gonadal drugs > Flashcards

Gonadal drugs Flashcards

1
Q

What is a synthetic GnRH?

A

Gonadorelin

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2
Q

What is gonadorelin used for?

A

Pulsatile treatment for infertility

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3
Q

What is GnRH stimulation test?

A

Differentiates between hypothalamic or pituitary defects

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4
Q

What are some GnRH agonists?

A

Leuprolide, nafarelin, goserelin,

-relin

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5
Q

MoA of GnRH agonists

A

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

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6
Q

What are Leuprolide, nafarelin, goserelin?

A

GnRH agonists

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7
Q

Uses of GnRH agonist

A

Pulsatile treatment- infertility and delayed puberty

Continuous treatment- endometriosis, precocious puberty and prostatic carcinoma.

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8
Q

Adverse effects of GnRH agonists

A

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

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9
Q

What are some GnRH antagonists?

A

Cetrorelix, Ganirelix

-relix

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10
Q

MoA of GnRH antagonists

A

Competitively block GnRH receptor inhibiting FSH and LH secretion.

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11
Q

Uses of GnRH antagonists

A

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

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12
Q

What is ovarian hyperstimulation syndrome (OHSS)?

A

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

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13
Q

What are the actions of estrogen?

A

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

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14
Q

Where is the estrogen receptor located?

A

It is a nuclear receptor, located inside nucleus.

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15
Q

What are the natural and synthetic estrogens?

A

Natural- estradiol, estrone and estriol

Synthetic- ethinylestradiol and diethylstibestrol

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16
Q

What are the uses of estrogen?

A

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

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17
Q

What are the adverse effects of estrogen?

A

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

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18
Q

What are side effects of diethylstibestrol?

A

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

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19
Q

What are some contraindications of estrogen?

A

Thromboembolic disorders, breast endometrial cancer, pregnancy and smokers.

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20
Q

What is MoA of clomiphene?

A

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

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21
Q

What is the use of clomiphene?

A

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

22
Q

What are the adverse effects of clomiphene?

A

OHSS, increased risk of ovarian and endometrial cancer.

23
Q

What is MoA of fulvestrant?

A

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

24
Q

What is the use of fulvestrant?

A

Treatment for metastatic breast cancer unresponsive to tamoxifen.

25
Q

What are some selective estrogen receptor modulators?

A

Tamoxifen, raloxifene

26
Q

What is MoA of Tamoxifen?

A

Estrogen antagonist at- breast, blood vessels

Estrogen partial agonist at- uterus, bone, liver

27
Q

What is the use of Tamoxifen?

A

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.

28
Q

What are the adverse effects of Tamoxifen?

A

Hot flushes, increases risk of thromboembolism.

29
Q

What is MoA of raloxifene?

A

Estrogen antagonist at- endometrium and breast

Estrogen partial agonist at- bone and CVS

30
Q

What is the use of raloxifene?

A

Osteoporosis in post menopausal women.

31
Q

What are some aromatase inhibitors?

A

Letrozole, exemestane

32
Q

What is MoA of aromatase inhibitors?

A

Inhibits aromatization, near total estrogen deprivation

33
Q

What is the use of aromatase inhibitors?

A

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

34
Q

What are some progestins?

A

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

35
Q

What are the adverse effects of progestins?

A

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

36
Q

What are the uses of progestins?

A

Threatened/habitual abortion
Contraceptives
Dysfunctional uterine bleeding
Endometriosis

37
Q

What is MoA of mifepristone?

A

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

38
Q

What are the uses of mifepristone?

A

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

39
Q

What is MoA of danazol?

A

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

40
Q

What are the uses of danazol?

A

Heriditary angioneurotic edema
Endometriosis
Fibrocystic breast disease
Gynaecomastia

41
Q

What is MoA of combination oral contraceptives?

A

Estrogen + progestin- suppress midcycle LH surge, prevents ovulation

42
Q

What are the adverse effects of combination oral contraceptives?

A

Thromboembolism
Hepatomas
Increased risk of breast cancer
decreases ovarian cancer

43
Q

What are some testosterone 17-alkyl derivatives?

A

They are resistant to 1st pass metabolism.

Methyltestosterone, fluoxymesterone

44
Q

What are the uses of androgens (testosterone)?

A 
Hereditary angioneurotic edema 
Testicular failure
delayed puberty
hypopituitarism
As anabolic 
Anemias- Fanconi’s, sickle cell
45
Q

What are the adverse effects of androgens (testosterone)?

A

Oligospermia
azospermia
Prostatic hyperplasia

46
Q

Why does exogenous androgen cause infertility?

A

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

47
Q

What is MoA of 5α reductase inhibitors?

A

Finasteride- 5α reductase inhibitor- reduction of dihydrotestosterone synthesis

48
Q

What are the uses of 5α reductase inhibitors?

A

Benign prostatic hypertrophy

Male pattern of baldness with minoxidil

49
Q

What is MoA of competitive androgen receptor antagonists?

A

Flutamide-↑ LH secretion by blocking feedback inhibition

50
Q

What are the uses competitive androgen receptor antagonists?

A

Prostate cancer

51
Q

What is the treatment of prostate cancer?

A

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

pharmacology (8 decks)

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