Repro - Pharmacology Flashcards
Pg. 589-592 Sections include: -Control of reproductive hormones -Leuprolide -Estrogens (ethinyl estradiol, DES, mestranol) -Selective estrogen receptor modulators - SERMs -Hormone replacement therapy -Anastrozole/Exemestane -Progestins -Mifepristone (RU-486) -Oral contraception (synthetic progestins, estrogen) -Terbutaline -Danazol -Testosterone, methyltestosterone -Antiandrogens -Tamsulosin -Sildenafil, vardenafil
What are the mechanisms of Leuprolide?
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”
What are 4 clinical uses for Leuprolide? Specify its form/context of use in each case.
(1) Infertility (pulsatile) (2) Prostate cancer (continuous - use with flutamide) (3) Uterine fibroids (continuous) (4) Precocious puberty (continous)
In what way is Leuprolide given to treat prostate cancer? With what other drug is it combined for this treatment?
Prostate cancer (continuous - use with flutamide)
What are 3 toxicities of Leuprolide?
(1) Antiandrogen (2) Nausea (3) Vomiting
What are 3 examples of drugs used as Estrogens?
Estrogens (ethinyl estradiol, DES, mestranol)
Again, what are 3 examples of Estrogens? What is their mechanism?
Estrogens (ethinyl estradiol, DES, mestranol); Bind estrogen receptors
What are 3 clinical uses for Estrogens (ethinyl estradiol, DES, mestranol) in women? What is a clinical use for these drugs in men?
Hypogonadism or ovarian failure, Menstrual abnormalities, HRT in postmenopausal women; Use in men with androgen-dependent prostate cancer
What are 4 toxicities of Estrogens? What are 2 contraindications of Estrogens?
(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
What are 3 examples of selective estrogen receptor modulators (SERMs)?
(1) Clomiphene (2) Tamoxifen (3) Raloxifene
Where does Clomiphene act, and what is its mechanism?
Antagonist at estrogen receptors in hypothalamus. Prevents normal feedback inhibiton and increases release of LH and FSH from pituitary, which stimulates ovulation.
In what context is Clomiphene used clinically? Give a prominent example of this context.
Used to treat infertility due to anovulation (e.g., PCOS)
What are 4 side effects associated with Clomiphene?
May cause (1) hot flashes, (2) ovarian enlargement, (3) multiple simultaneous pregnancies, and (4) visual disturbances.
What kind of drug is Tamoxifen? What are its mechanisms, and where does it act?
Selective Estrogen Receptor Modulator (SERM); Antagonist on breast tissue; Agonist at uterus, bone
What are 2 complications/toxicities associated with Tamoxifen use?
Associated with endometrial cancer, thromboembolic events
How is Tamoxifen primarily used clinically?
Primarily used to treat and prevent recurrence of ER + breast cancer
What kind of drug is Raloxifene? What are its mechanisms, and where does it act?
Selective Estrogen Receptor Modulator (SERM); Agonist on bone; Antagonist at uterus
What side effect/complicaion is associated with Raloxifene use? What other SERM shares this same risk?
Inreased risk of thromboembolic events; Tamoxifene
How is Raloxifene used clinically, and why?
Decrease resorption of bone => used to treat osteoporosis
What are 2 uses for hormone replacement therapy?
Used for relief or prevention of menopausal symptoms (e.g., hot flashes, vaginal atrophy) and osteoporosis (increase estrogen, decrease osteoclast activity)
What risk does estrogren replacement therapy (ERT) increase? How is this risk managed?
Unopposed estrogen replacement therapy (ERT) increases the risk of endometrial cancer, so progesterone is added.
Besides endometrial cancer, what other risk may possibly be increased by ERT?
Possible cardiovascular risk
What other drug functions like Anastrozole? What is their mechanism? How are they used clinically?
Anastozole/Exemestane; Aromatase inhibitors used in postmenopausal women with breast cancer
What are the mechanism and effects of Progestins?
Bind progesterone receptors, decreasing growth and increasing vascularization of endometrium
What are 3 clinical uses for Progestins?
Used in (1) oral contraceptives and in the treatment of (2) endometrial cancer and (3) abnormal uterine bleeding
What is another name for Mifepristone?
Mifepristone (RU-486)
What is the mechanism of Mifepristone (RU-486)?
Competitive inhibitor of progestins at progesterone receptors
What is the clinical use of Mifepristone (RU-486)? With what other drug is it administered?
Termination of pregnancy. Administered with misoprostol (PGE1)
What are 3 toxicities associated with Mifepristone (RU-486)?
(1) Heavy bleeding, (2) GI effects (nausea, vomiting, anorexia), (3) Abdominal pain
What 2 drugs are used for oral contraception? What are their shared mechanism and effects?
Oral contraception (synthetic progestins, estrogen); Estrogen and progestins inhibit LH/FSH and thus prevent estrogen surge. No estrogen surge => no LH surge => no ovulation.
What are 2 mechanisms and effects that progestins have?
(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.
What are 3 contraindications for oral contraception (synthetic progestins, estrogen)?
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.
What is the mechanism of Terbutaline, and what effect does it have? How is it used clinically?
Beta2-agonist that relaxes the uterus; Used to decrease contraction frequency in women during labor
What is the mechanism of Danazol?
Synthetic androgen that acts as partial agonist at androgen receptors
What are 2 clinical uses for Danazol?
(1) Endometriosis and (2) Hereditary angioedema
What are 7 toxicities associated with Danazol?
(1) Weight gain (2) Edema (3) Acne (4) Hirsuitism (5) Masculinization (6) low HDL levels (7) Hepatotoxicity
What is another drug with the same mechanism as Testosterone? What is their mechanism?
Testosterone, Methyltestosterone; Agonist at androgen receptors
What are 2 clinical uses of Testosterone, Methyltestosterone?
(1) Treats hypogonadism and promotes development of secondary sex characteristics; (2) Stimulation of anabolism to promote recovery after burn or injury.
What are 4 toxicities of Testosterone, Methyltestosterone?
(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
What is the normal purpose of 5alpha-reductase?
5 alpha reductase converts Testosterone => DHT (more potent)
What are 4 examples of antiandrogens?
(1) Finasteride (2) Flutamide (3) Ketoconazole (4) Spironolactone
What is the mechanism of Finasteride? What are 2 clinical uses of this drug?
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.
What is the mechanism of Flutamide? How is it used clinically?
A nonsteroidal competitive inhibitor of androgens at the testosterone receptor. Used in prostate carcinoma.
What is the mechanism of Ketoconazole?
Inhibits steroid synthesis (inhibits 17,20-desmolase)
What is the mechanism of Spironolactone?
Inhibits steroid binding, 17alpha-hydroxylase, and 17,20-desmolase.
What kind of drug is given to prevent male-pattern hair loss? Give an example of such a drug.
To prevent male-pattern hair loss, give a drug that will encourage female breast growth; E.g., Finasteride
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?
Ketoconazole and Spironolactone are used in the treatment of polycystic ovarian syndrome to prevent hirsuitism. Both have side effects of gynecomastia and amenorrhea.
What is the mechanism of Tamsulosin? What is it used to treat, and how? For what receptors is Tamsulosin selective?
Alpha1-antagonist used to treat BPH by inhibiting smooth muscle contraction. Selective for alpha1A,D receptors (found on prostate) vs. vascular alpha1B receptors
What other drug functions like Sildenafil? What are their mechanism and effects?
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”
How are Sildenafil and Vardenafil used clinically?
Treatment of erectile dysfunction
What are 5 toxicities associated with Sildenafil, Vardenafil?
(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.”
In what patient population does Sildenafil, Vardenafil increase the risk of life-threatening hypotension?
Risk of life-threatening hypotension in patients taking nitrates
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.
See p. 589 in First Aid 2014 for visual at left of page
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.
See p. 589 in First Aid 2014 for visual at right of page
