Repro Pharm from FA Flashcards
Leuprolide
Mechanism?
GnRH analog with agonist properties when used in pulsatile fashion
Antagonist properties when used in continuous fashion (downregs GnRH receptor in pituitary -> decrease in FSH/LH)
Leuprolide
Clinical Use? (4)
Infertility (pulsatile)
Prostate cancer (continuous - use with flutamide*)
Uterine fibroids (continuous)
Precocious puberty (continuous)
“Leuprolide can be used in LIEU of GnRH”
*flutamide = anti-androgen, competes with Test and DHT for receptors, used w prostate cancer
Leuprolide
Tox?
Antiandrogen, nausea, vomiting
Estrogens (ethinyl estradiol, DES, mestranol)
Mechanism?
Bind estrogen receptors
Estrogens (ethinyl estradiol, DES, mestranol)
Clinical Use? (for women and men)
Women: hypogonadism or ovarian failure, menstrual abnormalities, HRT in post-menopausal women
Men: androgen-dependent prostate cancer
Estrogens (ethinyl estradiol, DES, mestranol)
Tox? Contraindications?
- Incr risk of endometrial cancer, bleeding in post-menopausal women, incr risk of thrombi.
- Females exposed to DES in utero: clear cell adenocarcinoma of vagina
- Contra: ER+ breast cancer, history of DVTs
Selective Estrogen Receptor Modulators (SERMs)
name three?
Clomiphene
Tamoxifen
Raloxifene
Clomiphene
Class? Mech? Clinical use? Tox?
Class: SERM
Mech: antagonist at estrogen receptor in hypothalamus. Prevents normal feedback inhibition -> increases release of LH and FSH from pituitary -> stimulates ovulation.
Use: infertility treatment due to anovulation (ie PCOS).
Tox: hot flashes, ovarian enlargement, mult simultaneous pregnancies, visual disturbances
Tamoxifen
Class? Mech? Clinical use? Tox?
Class: SERM
Mech: antagonist on breast tissue; agonist at uterus and bone
Use: treatment (and recurrence prevention) of ER+ breast cancer
Tox: Associated with endometrial cancer and thromboembolisms
Raloxifene
Class? Mech? Clinical use? Tox?
Class: SERM
Use: osteoporosis treatment
Mech: decreases resorption of bone. Agonist at bone, antagonist at uterus.
Tox: increased risk of thromboembolic events
Hormone Replacement Therapy
Use (2)? Tox? Mech?
Use: –relief/prevention of menopausal symptoms (hot flashes, vaginal atrophy)
-Prev/treatment of osteoporosis
Mech (specific to osteoporosis? FA sucks): increases estrogen, decr osteoclast activity
Tox: unopposed estrogen replacement therapy increases the risk of endometrial cancer: progesterone therefore added. Possible increased CV risk
Anastrozole/Exemestane
Mech? Use?
Use: used in postmenopausal women with breast cancer
Mech: Aromatase inhibitors
Progestins
Use? Mech?
Use: in oral contraceptives, treatment of endometrial cancer and abnormal uterine bleeding
Mech: bind progesterone receptors, decrease growth and increase vascularization of endometrium
Mifepristone (RU-486)
Use? Mech? Tox?
Use: pregnancy termination. Used with misoprostol (PGE1)
Mech: Competes with progestins at progesterone receptors
Tox: Heavy bleeding, GI effects (N/V/anorexia), abd pain
Oral contraceptives (synthetic progestins, estrogens)
Mech? Contra?
Estrogens and progestins inhibit LH/FSH and thus prevent estrogen surge. No estrogen surge -> no LH surge -> no ovulation
Contraindication: smokers > 35y (increased risk of CV events), pts with hx of thromboembolism and stroke, pts with hx of estrogen-dependent tumor
Oral contraceptives – qualities of the progestin component
Progestins cause thickening of the cervical mucus, thereby limiting access of sperm to uterus. Progestins also inhibit endometrial proliferation -> endometrium less suitable for the implantation of an embryo.
Terbutaline
Use? Mech?
Decrease the frequency of contractions during labor
Mech: B2 agonist -> relaxes the uterus
Danazol
Use? Mech? Tox?
Use: for endometriosis and hereditary angioedema
Mech: synthetic androgen; acts as partial agonist at androgen receptors
Tox: Wt gain, edema, acna, hirsutism, masculinazation, decr HDL levels, hepatotoxic.
Testosterone, methyltestosterone
Mech? Use? Tox?
Mech: Agonist at androgen receptors
Use: treats hypogonadism; promotes development of secondary sex characteristics; stimulates anabolism to promote recovery after burn or injury
Tox: Females -> masculinization
Males: decreases intratesticular testosterone by inhibiting release of LH (via neg feedback) -> gonadal atrophy. Premature closure of epiphyseal plates. Increases LDL, decreases HDL.
Antiandrogens
name 4?
relevant mechanism?
- Finasteride
- Flutamide
- Ketoconazole
- Spironolactone
Remember that 5a-reductase converts testosterone to DHT (more potent).
Finasteride
Mech? Use?
Inhibits 5a-reductase.
Use: BPH, also promotes hair growth (used in male-pattern baldness)
Flutamide
Mech? Use?
Nonsteroidal competitive inhibitor of androgens at the testosterone receptor
Use: prostate carcinoma
Ketoconazole
Use? Mech? Tox?
Treats hirsutism of PCOS
Inhibits steroid synthesis (inhibits 17,20 desmolase)
Tox: amenorrhea, gynecomastia
“To prevent male pattern hair loss, give a drug that will encourage female breast growth”
Spironolactone
Use? Mech?
Treats hirsutism of PCOS
Inhibits steroid binding, 17a-hydroxylase, and 17,20 desmolase
Tox: amenorrhea, gynecomastia
“To prevent male pattern hair loss, give a drug that will encourage female breast growth”
Tamsulosin
Use? Mech?
Used to treat BPH by inhibiting smooth muscle contraction.
alpha1-antagonist. Selective for alpha1A,D receptors (on prostate) rather than alpha1B receptors (vascular)
Sildenafil, Vardenafil
Mech? Use? Tox?
Use: erectile dysfunction
Mech: inhibits phosphodiesterase 5, causing incr cGMP, smooth muscle relaxation in the corpus cavernosum, increased blood flow, penile erection
Tox: headache, flushing, dyspepsia, impaired blue-green color vision. Risk of life-threatening hypotension in patients taking nitrates.
“Sildenafil and Vardenafil FILL the penis. Hot and sweaty -> Headache, Heartburn, Hypotension”
(Uworld question)
2 types of meds for BPH?
- alpha-adrenergic inhibitors (e: doxazosin) to relax VSM at bladder neck
- 5a reductase inhibitors (prevent conversion of Test to DHT)
