Flashcards in Reproductive Deck (52)
What is the mechanism of Leuprolide?
GnRH analog with agonist properties when used in pulsatile fashion; antagonist properties when used in continuous fashion (downregulates GnRH receptor in pituitary → ↓ FSH/LH).
What is the clinical use of Leuprolide?
Infertility (pulsatile), prostate cancer (continuous—use with flutamide), uterine fibroids (continuous), precocious puberty (continuous)
What are the toxicities of Leuprolide?
Antiandrogen, nausea, vomiting
What is the mechanism of Estrogens (ethinyl estradiol, DES, mestranol)?
Bind estrogen receptors
What is the clincal use of Estrogens (ethinyl estradiol, DES, mestranol)?
Hypogonadism or ovarian failure, menstrual abnormalities, HRT in postmenopausal women; use in men with androgen-dependent prostate cancer
What are the toxicities of Estrogens (ethinyl estradiol, DES, mestranol)?
↑ 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 + breast cancer, history of DVTs
Selective estrogen receptor modulators (SERMs) - What are the key features of Clomiphene?
Antagonist at estrogen receptors in hypothalamus. Prevents normal feedback inhibition and ↑ release of LH and FSH from pituitary, which stimulates ovulation. Used to treat infertility due to anovulation (e.g., PCOS). May cause hot flashes, ovarian enlargement, multiple simultaneous pregnancies, and visual disturbances.
Selective estrogen receptor modulators (SERMs) - What are the key features of Tamoxifen?
Antagonist on breast tissue; agonist at uterus, bone; associated with endometrial cancer, thromboembolic events. Primarily used to treat and prevent recurrence of ER + breast cancer.
Selective estrogen receptor modulators (SERMs) - What are the key features of Raloxifene?
Agonist on bone; antagonist at uterus; also ↑ risk of thromboembolic events; ↓ resorption of bone → used to treat osteoporosis.
What are the key features of Hormone Replacement Therapy?
Used for relief or prevention of menopausal symptoms (e.g., hot flashes, vaginal atrophy) and osteoporosis (↑ estrogen, ↓ osteoclast activity).
Unopposed estrogen replacement therapy (ERT) ↑ the risk of endometrial cancer, so progesterone is added. Possible increased cardiovascular risk.
What are the key features of Anastrozole/exemestane?
Aromatase inhibitors used in postmenopausal women with breast cancer
What is the mechanism of Progestins?
Bind progesterone receptors, ↓ growth and ↑ vascularization of endometrium
What is the clinical use of Progestins?
Used in oral contraceptives and in the treatment of endometrial cancer and abnormal uterine bleeding
What is the mechanism of Mifepristone (RU-486)?
Competitive inhibitor of progestins at progesterone receptors.
What is the clinical use of Mifepristone (RU-486)?
Termination of pregnancy. Administered with misoprostol (PGE1).
What are the toxicities of Mifepristone (RU-486)?
Heavy bleeding, GI effects (nausea, vomiting, anorexia), abdominal pain.
How to the oral contraceptives, synthetic progestins and estrogen) work?
Estrogen and progestins inhibit LH/FSH and thus prevent estrogen surge. No estrogen surge → no LH surge → no ovulation.
Oral contraception - What are the unique features of progestin as an oral contraceptive?
Progestins cause thickening of the cervical mucus, thereby limiting access of sperm to uterus.
Progestins also inhibit endometrial proliferation, thus making endometrium less suitable for the implantation of an embryo.
What are the contraindications of oral contraceptives (synthetic progestins, estrogen)?
Smokers > 35 years old (↑ risk of cardiovascular events), patients with history of thromboembolism and stroke or history of estrogen-dependent tumor
What are the key features of Terbutaline?
β2-agonist that relaxes the uterus; used to ↓ contraction frequency in women during labor.
What is the mechanism of Danazol?
Synthetic androgen that acts as partial agonist at androgen receptors
What is the clinical use of Danazol?
Endometriosis and hereditary angioedema
What are the toxicities of Danazol?
Weight gain, edema, acne, hirsutism, masculinization, ↓ HDL levels, hepatotoxicity.
What is the mechanism of Testosterone and methyltestosterone?
Agonist at androgen receptors
What is the clinical use of Testosterone and methyltestosterone?
Treats hypogonadism and promotes development of 2° sex characteristics; stimulation of anabolism to promote recovery after burn or injury.
What are the toxicities of Testosterone and methyltestosterone?
Causes masculinization in females; ↓ intratesticular testosterone in males by inhibiting release of LH (via negative feedback) → gonadal atrophy. Premature closure of epiphyseal plates. ↓ LDL, ↑ HDL.
What reaction do Antiandrogens target?
Testosterone → DHT (more potent). This reaction is catalyzed by 5α-reductase.
Antiandrogens - What are the key features of Finasteride?
A 5α-reductase inhibitor (↓ conversion of testosterone to DHT). Useful in BPH. Also promotes hair growth—used to treat male-pattern baldness.
Antiandrogens - What are the key features of Flutamide?
A nonsteroidal competitive inhibitor of androgens at the testosterone receptor. Used in prostate carcinoma.
Antiandrogens - What are the key features of Ketoconazole?
Inhibits steroid synthesis (inhibits 17,20-desmolase).
Antiandrogens - What are the key features of Spironolactone?
Inhibits steroid binding, 17α-hydroxylase, and 17,20-desmolase.
Antiandrogens - What features of Ketoconazole and Spironolactone have in common?
Ketoconazole and spironolactone are used in the treatment of polycystic ovarian syndrome to prevent hirsutism. Both have side effects of gynecomastia and amenorrhea.
What are the key features of Tamsulosin?
α1-antagonist used to treat BPH by inhibiting smooth muscle contraction. Selective for α1A,D receptors (found on prostate) vs. vascular α1B receptors.
What is the mechanism of Sildenafil and vardenafil?
Inhibit phosphodiesterase 5, causing ↑ cGMP, smooth muscle relaxation in the corpus cavernosum, ↑ blood flow, and penile erection.
What is the clinical use of Sildenafil and vardenafil?
Treatment of erectile dysfunction
What are the toxicities of Sildenafil and vardenafil?
Headache, flushing, dyspepsia, impaired blue-green color vision. Risk of life-threatening hypotension in patients taking nitrates.
What proerectile drug works by inhibiting cGMP breakdown and causing smooth muscle relaxation and vasodilation?
Sildenafil and vardenafil inhibit cGMP breakdown
What do exclusively breastfed infants require?
Vitamin D supplementation
Testosterone is converted to DHT by 5α-reductase. What drug inhibits 5α-reductase?
What is the treatment for Hydatidiform mole?
Dilation and curettage and methotrexate. Monitor β-hCG
What is the treatment for Gestational hypertension (pregnancy-induced hypertension)?
Antihypertensives (α-methyldopa, labetalol, hydralazine, nifedipine), deliver at 39 weeks
What is the treatment for Preeclampsia?
Antihypertensives, deliver at 34 weeks (severe) or 37 weeks (mild), IV magnesium sulfate to prevent seizure
What is the treatment for Eclampsia?
Antihypertensives, IV magnesium sulfate, immediate delivery
What is the treatment for Endometritis?
Gentamicin + clindamycin with or without ampicillin
What is the treatment for Endometriosis?
NSAIDs, OCPs, progestins, GnRH agonists, surgery
Polycystic ovarian syndrome (Stein-Leventhal syndrome) - What is the treatment for hirsutism and acne?
Polycystic ovarian syndrome (Stein-Leventhal syndrome) - What is the treatment for infertility?
Clomiphene citrate (blocks negative feedback of circulating estrogen, ↓ FSH, LH)
Metformin (↑ insulin sensitivity, ↓ insulin levels, results in ↓ testosterone; enables LH surge)
Polycystic ovarian syndrome (Stein-Leventhal syndrome) - What is the treatment for endometrial protection?
Cyclic progesterones (antagonizes endometrial proliferation)
What is the treatment for Acute mastitis?
Dicloxacillin and continued breast-feeding
What drugs cause Gynecomastia?
Some Dope Drugs Easily Create Awkward Hairy DD Knockers - Spironolactone, marijuana [Dope], Digitalis, Estrogen, Cimetidine, Alcohol, Heroin, Dopamine D2 antagonists, Ketoconazole)
What is the treatment for Benign prostatic hyperplasia?
α1-antagonists (terazosin, tamsulosin), which cause relaxation of smooth muscle; finasteride