Fa Pharmacology 2009 - Reproductive

Front 1

Antiandrogens - Finasteride (propecia)

Back 1

Mechanism:
- 5a-reductase inhibitor (↓ conversion of testosterone to dihydrotestosterone)

Clinical use:
- BPH
- promotes hair growth - used to treat male-pattern baldness

Note:
"To prevent male-pattern hair loss, give a drug that will encourage female breast growth"

Front 2

Antiandrogens - Flutamide

Back 2

Mechanism:
- A nonsteroidal competitive inhibitor of androgens at the testosterone receptor.

Clinical use:
- Prostate carcinoma

Front 3

Antiandrogens - Ketoconazole

Back 3

Mechanism:
- Inhibits steroid synthesis

Front 4

Antiandrogens - Spironolactone

Back 4

Mechanism:
- Inhibits steroid binding

Note:
- Ketoconazole and spironolactone are used in the treatment of polycystic ovarian syndrome to prevent hirsutism.
- Both have side effects of gynecomastia and amenorrhea

Front 5

Leuprolide

Back 5

Mechanism: "LEUprolide can be used in LIEU of GnRH"
- GnRH analog with agonist propoerties when used in pulsatile fashion
- antagonist properties when used in continuous fashion

Clinical use:
- Infertility (pulsatile)
- Prostate cancer (continuous - use with flutamide)
- uterine fibroids

Toxicity:
- Antiandrogen
- Nausea, vomitting

Front 6

Sildenafil, vardenafil

Back 6

Mechanism: "SildenaFIL and vardenaFIL FILL the penis"
- Inhibits cGMP phosphodiesterase --> ↑ cGMP --> smooth muscle relaxation in the corpus cavernosum, --> ↑ blood flow --> penile erection

Clinical use:
- Treatment for erectile dysfunction

Toxicity:
- Headache
- Flushing
- Dyspepsia
- Impaired blue-green color vision
- Risk of life-threatening hypotension in patients taking nitrates

Front 7

Mifepristone (RU-486)

Back 7

Mechanism:
- Competetive inhibitor of progestins at progesterone receptors

Clinical use:
- Termination of pregnancy
- Administered with misoprist

Front 8

Oral contraceptives (synthetic progestins, estrogen)

Back 8

- Oral contraceptives prevent estrogen surge, LH surge does not occur --> ovulation does not occur.

Advantages
- Reliable (1% failure)
- ↓ risk of endometrial and ovarian cancer
- ↓ incidence of ectopic pregnancy
- ↓ pelvic infections
- Regulation of menses

Disadvantages
- Taken daily
- No protection against STDs
- ↑ triglycerides
- Depression, weight gain, nausea, hypertension
- Hypercoagulable state

Note:
- Progesterone used to combat the effects of endometrial cancer caused by estrogen and makes endometrium unsuitable for implantation

Note:
contraindications:
1. Prior Hx of thromboembolic events.
2. estrogen dependent tumors
3. women ↑ 35 yrs of age who smoke heavily.
4. Hypertryglyceridea
5. Decompensated or active liver disease
6. Pregnancy.

Front 9

Hormone replacement therapy (HRT)

Back 9

- Used for relief of prevention of menopausal symptoms (e.g. hot flashes, vaginal atrophy) and osteoporosis (due to diminished estrogen levels)

- Unopposed estrogen replacement therapy (ERT) ↑ the risk of endometrial cancer, so progesterone is added.
- Possible ↑ CV risk.

Front 10

Dinoprostone

Back 10

- PGE2 analog causing cervical dilation and uterine contraction, inducing labor

Front 11

Ritodrine/ terbutaline

Back 11

- B2-agonist that relax the uterus
- Reduce premature uterine contractions.

Front 12

Anastrozole/ exemestane

Back 12

Aromatase inhibitors used in postmenopausal women with breast cancer.

Front 13

Testosterone (methyltestosterone)

Back 13

Mechanism:
- agonist at androgen receptors

Clinical use:
- Treat hypogonadism and promote development of secondary sex characteristics
- Stimulation of anabolism to promote recovery after burn or injury
- Treat ER-positive breat cancer (exemestane)

Toxicity:
- Causes masculinization in females
- Reduces intratesticular testosterone in males by inhibiting Leydig cells
- Leads to gonadal atrophy
- Premature closure of epiphyseal plates
- ↑ LDL, ↓ HDL.

Front 14

Estrogens (ethinyl estradiol, DES, mestranol)

Back 14

Mechanism:
- Bind estrogen receptors.

Clinical use:
- Hypogonadism or ovarian failure
- menstrual abnormalities
- HRT in postmenopausal women
- used in men with androgen-dependen prostate cancer.

Toxicity:
- ↑ risk of endometrial cancer
- Bleeding in postmenopausal women.
- Clear cell adenocarcinoma of vagina in females exposed to DES in utero
- ↑ risk of thrombi
- Contraindications - ER-positive breast cancer.

Front 15

Progestins

Back 15

Mechanism:
- Bind progesterone receptors --> reduce growth and ↑ vascularization of endometrium.

Clinical use:
- Used in oral contraceptives
- Endometrial cancer.
- Dysfunction uterine bleeding.

Front 16

Estrogen partial agonists (selective estrogen receptors modulators -SERMs)
- Clomiphene

Back 16

Mechanism:
- Partial agonist at estrogen receptors in pituitary gland.
- Prevents normal feedback inhibition and ↑ release of LH and FSH from pituitary, which stimulate ovulation

Clinical use:
- Used to treat infertility and PCOS

Toxicity:
- hot flashes
- ovarian enlargement
- multiple simultaneous pregnancies
- visual disturbances.

Front 17

Tamoxifen

Back 17

Mechanism:
- Estrogen receptor antagonist on breast tissue
- agonist on endometrium and bone

Clinical use:
- used to treat and prevent recurrence of ER-positive breast cancer.

Front 18

Raloxifene

Back 18

Mechanism:
- Estrogen receptor agonist on bone
- Antagonist on bone and endometrium

Clinical use:
- reduces resorption of bone --> used to treat osteoporosis