Repro - Pharmacology

Question 1

What are the mechanisms of Leuprolide?

Answer 1

GnRH analog with agonist properties when used in pulsatile fashion; Antagonist properties when used in continuous fashion (downregulates GnRH receptor in pituitary => low FSH/LH); Think: “LEUprolide can be used in LIEU of GnRH”

Question 2

What are 4 clinical uses for Leuprolide? Specify its form/context of use in each case.

Answer 2

(1) Infertility (pulsatile) (2) Prostate cancer (continuous - use with flutamide) (3) Uterine fibroids (continuous) (4) Precocious puberty (continous)

Question 3

In what way is Leuprolide given to treat prostate cancer? With what other drug is it combined for this treatment?

Answer 3

Prostate cancer (continuous - use with flutamide)

Question 4

What are 3 toxicities of Leuprolide?

Answer 4

(1) Antiandrogen (2) Nausea (3) Vomiting

Question 5

What are 3 examples of drugs used as Estrogens?

Answer 5

Estrogens (ethinyl estradiol, DES, mestranol)

Question 6

Again, what are 3 examples of Estrogens? What is their mechanism?

Answer 6

Estrogens (ethinyl estradiol, DES, mestranol); Bind estrogen receptors

Question 7

What are 3 clinical uses for Estrogens (ethinyl estradiol, DES, mestranol) in women? What is a clinical use for these drugs in men?

Answer 7

Hypogonadism or ovarian failure, Menstrual abnormalities, HRT in postmenopausal women; Use in men with androgen-dependent prostate cancer

Question 8

What are 4 toxicities of Estrogens? What are 2 contraindications of Estrogens?

Answer 8

(1) Increased risk of endometrial cancer (2) Bleeding in postmenopausal women (3) Clear cell adenocarcinoma of vagina in females exposed to DES in utero (4) Increased risk of thrombi; Contraindications- ER + breast cancer, History of DVTs

Question 9

What are 3 examples of selective estrogen receptor modulators (SERMs)?

Answer 9

(1) Clomiphene (2) Tamoxifen (3) Raloxifene

Question 10

Where does Clomiphene act, and what is its mechanism?

Answer 10

Antagonist at estrogen receptors in hypothalamus. Prevents normal feedback inhibiton and increases release of LH and FSH from pituitary, which stimulates ovulation.

Question 11

In what context is Clomiphene used clinically? Give a prominent example of this context.

Answer 11

Used to treat infertility due to anovulation (e.g., PCOS)

Question 12

What are 4 side effects associated with Clomiphene?

Answer 12

May cause (1) hot flashes, (2) ovarian enlargement, (3) multiple simultaneous pregnancies, and (4) visual disturbances.

Question 13

What kind of drug is Tamoxifen? What are its mechanisms, and where does it act?

Answer 13

Selective Estrogen Receptor Modulator (SERM); Antagonist on breast tissue; Agonist at uterus, bone

Question 14

What are 2 complications/toxicities associated with Tamoxifen use?

Answer 14

Associated with endometrial cancer, thromboembolic events

Question 15

How is Tamoxifen primarily used clinically?

Answer 15

Primarily used to treat and prevent recurrence of ER + breast cancer

Question 16

What kind of drug is Raloxifene? What are its mechanisms, and where does it act?

Answer 16

Selective Estrogen Receptor Modulator (SERM); Agonist on bone; Antagonist at uterus

Question 17

What side effect/complicaion is associated with Raloxifene use? What other SERM shares this same risk?

Answer 17

Inreased risk of thromboembolic events; Tamoxifene

Question 18

How is Raloxifene used clinically, and why?

Answer 18

Decrease resorption of bone => used to treat osteoporosis

Question 19

What are 2 uses for hormone replacement therapy?

Answer 19

Used for relief or prevention of menopausal symptoms (e.g., hot flashes, vaginal atrophy) and osteoporosis (increase estrogen, decrease osteoclast activity)

Question 20

What risk does estrogren replacement therapy (ERT) increase? How is this risk managed?

Answer 20

Unopposed estrogen replacement therapy (ERT) increases the risk of endometrial cancer, so progesterone is added.

Question 21

Besides endometrial cancer, what other risk may possibly be increased by ERT?

Answer 21

Possible cardiovascular risk

Question 22

What other drug functions like Anastrozole? What is their mechanism? How are they used clinically?

Answer 22

Anastozole/Exemestane; Aromatase inhibitors used in postmenopausal women with breast cancer

Question 23

What are the mechanism and effects of Progestins?

Answer 23

Bind progesterone receptors, decreasing growth and increasing vascularization of endometrium

Question 24

What are 3 clinical uses for Progestins?

Answer 24

Used in (1) oral contraceptives and in the treatment of (2) endometrial cancer and (3) abnormal uterine bleeding

Question 25

What is another name for Mifepristone?

Answer 25

Mifepristone (RU-486)

Question 26

What is the mechanism of Mifepristone (RU-486)?

Answer 26

Competitive inhibitor of progestins at progesterone receptors

Question 27

What is the clinical use of Mifepristone (RU-486)? With what other drug is it administered?

Answer 27

Termination of pregnancy. Administered with misoprostol (PGE1)

Question 28

What are 3 toxicities associated with Mifepristone (RU-486)?

Answer 28

(1) Heavy bleeding, (2) GI effects (nausea, vomiting, anorexia), (3) Abdominal pain

Question 29

What 2 drugs are used for oral contraception? What are their shared mechanism and effects?

Answer 29

Oral contraception (synthetic progestins, estrogen); Estrogen and progestins inhibit LH/FSH and thus prevent estrogen surge. No estrogen surge => no LH surge => no ovulation.

Question 30

What are 2 mechanisms and effects that progestins have?

Answer 30

(1) Progestins cause thickening of the cervical mucus, thereby limiting access of sperm to uterus. (2) Progestins also inhibit endometrial proliferation, thus making endometrium less suitable for the implantation of an embryo.

Question 31

What are 3 contraindications for oral contraception (synthetic progestins, estrogen)?

Answer 31

Contraindications - (1) smokers > 35 years old (increased risk of cardiovascular events), (2) patients with history of thromboembolism and stroke or (3) history of estrogen-dependent tumor.

Question 32

What is the mechanism of Terbutaline, and what effect does it have? How is it used clinically?

Answer 32

Beta2-agonist that relaxes the uterus; Used to decrease contraction frequency in women during labor

Question 33

What is the mechanism of Danazol?

Answer 33

Synthetic androgen that acts as partial agonist at androgen receptors

Question 34

What are 2 clinical uses for Danazol?

Answer 34

(1) Endometriosis and (2) Hereditary angioedema

Question 35

What are 7 toxicities associated with Danazol?

Answer 35

(1) Weight gain (2) Edema (3) Acne (4) Hirsuitism (5) Masculinization (6) low HDL levels (7) Hepatotoxicity

Question 36

What is another drug with the same mechanism as Testosterone? What is their mechanism?

Answer 36

Testosterone, Methyltestosterone; Agonist at androgen receptors

Question 37

What are 2 clinical uses of Testosterone, Methyltestosterone?

Answer 37

(1) Treats hypogonadism and promotes development of secondary sex characteristics; (2) Stimulation of anabolism to promote recovery after burn or injury.

Question 38

What are 4 toxicities of Testosterone, Methyltestosterone?

Answer 38

(1) Causes masculinization in females; (2) Low intratesticular testosterone in males by inhibiting release of LH (via negative feedback) => gonadal atrophy. (3) Premature closure of epiphyseal plates. (4) High LDL, Low HDL

Question 39

What is the normal purpose of 5alpha-reductase?

Answer 39

5 alpha reductase converts Testosterone => DHT (more potent)

Question 40

What are 4 examples of antiandrogens?

Answer 40

(1) Finasteride (2) Flutamide (3) Ketoconazole (4) Spironolactone

Question 41

What is the mechanism of Finasteride? What are 2 clinical uses of this drug?

Answer 41

A 5alpha-reductase inhibitor (low conversion of testosterone to DHT). (1) Useful in BPH. (2) Also promotes hair growth - used to treat male-pattern baldness.

Question 42

What is the mechanism of Flutamide? How is it used clinically?

Answer 42

A nonsteroidal competitive inhibitor of androgens at the testosterone receptor. Used in prostate carcinoma.

Question 43

What is the mechanism of Ketoconazole?

Answer 43

Inhibits steroid synthesis (inhibits 17,20-desmolase)

Question 44

What is the mechanism of Spironolactone?

Answer 44

Inhibits steroid binding, 17alpha-hydroxylase, and 17,20-desmolase.

Question 45

What kind of drug is given to prevent male-pattern hair loss? Give an example of such a drug.

Answer 45

To prevent male-pattern hair loss, give a drug that will encourage female breast growth; E.g., Finasteride

Question 46

What 2 drugs are used in the treatment of PCOS to prevent hirsuitism? What are 2 side effects associated with the use of these drugs?

Answer 46

Ketoconazole and Spironolactone are used in the treatment of polycystic ovarian syndrome to prevent hirsuitism. Both have side effects of gynecomastia and amenorrhea.

Question 47

What is the mechanism of Tamsulosin? What is it used to treat, and how? For what receptors is Tamsulosin selective?

Answer 47

Alpha1-antagonist used to treat BPH by inhibiting smooth muscle contraction. Selective for alpha1A,D receptors (found on prostate) vs. vascular alpha1B receptors

Question 48

What other drug functions like Sildenafil? What are their mechanism and effects?

Answer 48

Sildenafil, Vardenafil; Inhibit phosphodiesterase 5, causing increased cGMP, smooth muscle relaxation in the corpus cavernosum, increased blood flow, & penile erection; Think: “sildenaFIL and vardenaFIL FILL the penis”

Question 49

How are Sildenafil and Vardenafil used clinically?

Answer 49

Treatment of erectile dysfunction

Question 50

What are 5 toxicities associated with Sildenafil, Vardenafil?

Answer 50

(1) Headache (2) Flushing (3) Dyspepsia (4) Impaired blue-green color vision. (5) Risk of life-threatening hypotension in patients taking nitrates; Think: “‘Hot and sweaty,’ but then Headache, Heartburn, Hypotension.”

Question 51

In what patient population does Sildenafil, Vardenafil increase the risk of life-threatening hypotension?

Answer 51

Risk of life-threatening hypotension in patients taking nitrates

Question 52

Draw the products/interactions between the Hypothalamus, Anterior pituitary, and Ovary, including and labeling the effects of the following drugs: (1) Clomiphene (2) GnRH anatogonists (3) GnRH agonists (4) Oral contraceptives, Danazol (5) Ketoconazole, Danazol (6) Anastrozole, Others (7) Fulvestrant (8) SERMs.

Answer 52

See p. 589 in First Aid 2014 for visual at left of page

Question 53

Draw the products/interactions between the Hypothalamus, Anterior pituitary, and Testis, including and labeling the effects of the following drugs: (1) GnRH antagonists (2) GnRH agonists (3) Ketoconazole, Spironolactone (4) Finasteride (5) Flutamide, Cyproterone, Spironolactone.

Answer 53

See p. 589 in First Aid 2014 for visual at right of page