Repro Drugs Flashcards
Leuprolide: Mechanism
GnRH analog with agonist properties when used in a pulsatile fashion.
ANTAGONIST when used in a continuous fashion (downregulates GnRH receptor in pituitary –> decreased FSH/LH)
Leuprolide: Clinical Use
Pulsatile – infertility
Continuous – Prostate cancer, Uterine fibriouds, Precocious puberty
For prostate cancer, use continuous or pulsatile leuprolide? Also, with what other drug
Treat prostate cancer with continuous leuprolide and co-administer with flutamide (competitive inhibitor of androgens)
Leuprolide: Toxicity
Antiandrogen, nausea, vomiting
Testosterone, Methyltestosterone: Mechanism
Agonist at androgen receptors
Testosterone: Clinical Use
Treats hypogonaidism and promotes development of secondary sex characteristics; stimulation of anabolism to promote recovery after burn or injury
Testosterone: Toxicity
Causes masculinization in females; reduces intratesticular testosterones in males by inhibiting release of LH (via negative feedback), leading to gonadal atrophy. Premature closure of epiphyseal plates.
Testosterone effect on cholesterol
Increased LDL; Decreased HDL
Enzyme for conversion of testosterone to DHT
5-alpha reductase. DHT is more potent than testosterone
Finasteride
5-alpha reductase inhibitor (decreases conversion of testosterone to DHT).
Finasteride Uses
Useful for BPH (as DHT is primary mediator that causes hyperplasia in prostate). Also promotes hair growth - used to treat male pattern baldness
Flutamide
A non steroidal competitive inhibitor of androgens at the testosterone receptor. Used in prostate carcinoma.
Ketoconazole
Inhibits steroid synthesis (inhibits 17, 20 desmolase).
Spironolactone
Inhibits steroid binding.
Rx for polycystic ovarian syndrome to prevent hirsuitism
Spironolactone and Ketoconazole. Can cause gynecomastia and amenorrhea
Estrogens - name them
Ethinyl, Estradiol, DES, mestranol
Estrogen: Mechanism
Bind estrogen receptors
Estrogen: Clinical Use
Hypogonadism or ovarian failure.
Menstrual abnormalities,
HRT in postmenopausal women;
use in men with androgen dependent prostate cancer
Estrogen: Toxicity
Increased risk of endometrial cancer
- bleeding in postmenopausal women
- clear cell adenocarcinoma of vagina in females exposed to DES in utero
- increased risk of thrombi
Contraindications of Estrogen use
- ER-positive breast cancer
- history of DVTs
Selective Estrogen Receptor Modulators (SERMs)
Clomiphene, Tamoxifen, Raloxifene
Clomiphine
SERM - partial agonist at estrogen receptors in hypothalamus.
Prevents normal feedback inhibition and increases release of LH and FSH from pituitary which stimulates ovulation
Clomiphine: Use
Treat infertitility and polycystic ovarian syndrome. May cause hot flashes, ovarian enlargement. Multiple simultaneous pregancies, and visual disturbances
Raloxifene
SERM. Agonist on bone; Reduces resorption of bone; Used to treat osteoporosis.
Tamoxifen
Antagonist at breast tissue; Used to treat and prevent recurrence of ER-positive breast cancer.
Hormone replacement therapy
Used for relief or prevention of menopausal symptoms (e.g. hot flashes, vaginal atrophy) and osteoporosis (increases estrogen, decreases osteoclast activity)
Discuss risks of HRT of cancer, CV dises
Unopposed estrogen replacement therapy (ERT increases risk of endometrial cancer, so progesterone is added. Possible INCREASED CV risk
Anastrozole/ Exemestane
Aromatase inhibitors used in postmenopausal women with breast cancer
Progestins : Mechanism
Bind progesterone receptors, reduce growth and increase vascularization of endometrium.
Progestin: Clinical Use
Used in oral contraceptive and in the treatment of endometrial cancer and abnormal uterine bleeding
Mifepristone (RU-486): Mechanism
Competitive inhibitor of progestins at progesterone receptors
Mifepristone (RU-486): Clinical Use
Termination of pregnancy. Administered with misprostol (PGE1)
Mifepristone (RU-486): Toxicity
Heavy bleeding, GI effects (nausea, vomiting, abdominal pain)
Oral contraception (synthetic progestins, estrogen)
Estrogen and progestins inhibit LH/FSH and thus prevent estrogen surge. No estrogen surge –> no LH surge –> no ovulation
Discuss progestins and pregnancy prevention
Progestins cause thickening of cervical mucus, thus limiting access of sperm to uterus. Also inhibit endometrial proliferation, thus making endometrium less suitable for implantation of an embryo.
Contraindications of OCP
Smokers > 35 y.o
Increased risk of CV events
Patients with a hx of thromboembolism and stroke or hx of estrogen dependent tumor
Terbutaline
B2 agonist that relaxes the uterus; reduces premature uterine contractions
Tamsulosin
Alpha 1 antagonist used to treat BPH by inhibiting smooth muscle contraction. Selective alpha 1AD receptors (found on prostate) vs. vascular alpha 1 B receptors `
Sildenafil, vardenafil
Phosphodiesterase inhibitors
Sildenafil, Vardenafil: Mechanism
Inhibit phosphodiesterase 5, causing increase in cGMP smooth muscle relaxation in the corpus canvernosum, increased blood flow and penile erection
Sildenafil, Vardenafil: Clinical Use
Treatment of erectile dysfunction
Sildenafil, Vardenafil: Toxicity
Headache, flushing, dyspepsia, impaired blue-green vision. Risk of life threatening hypotension in patients taking nitrates
“Hot and sweaty”, but then “Headache”, “Heartburn, “Hypotension”
Danazol: Mechanism
Synthentic androgen that acts as partial agonist at androgen receptors.
Danazol: Clinical Use
Endometriosis and hereditary angiodema
Danazol: Toxicity
Weight fain, edema, acne, hirsuitism, masculinization. Decreased HDL levels, hepatotoxicity
