Reproductive Medicine Pharmacology

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Author:
jknell
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208513
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Reproductive Medicine Pharmacology
Updated:
2013-03-20 11:32:35
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  1. Control of Female Hormones: Overview
  2. Control of Male Hormones: Overview
  3. Leuprolide
    • Mechanism:
    • -GnRH analog
    • -agonist properties when used in a pulsatile fashion
    • -antagonist properties when used in continuous fashion (↓FSH, LH)

    • Clinical Use:
    • -infertility (pulsatile)
    • -prostate cancer (continuous - use with flutamide)
    • -uterine fibroids (continuous)
    • -precocious puberty (continuous)

    • Toxicity:
    • -antiandrogen
    • -nausea
    • -vomiting

    "Leuprolide can be used in lieu of GnRH"
  4. Testosterone, Methyltestosterone
    • Mechanism:
    • -agonist at androgen receptors

    • Clinical Use:
    • -hypogonadism
    • -promotes development of secondary sex characteristics
    • -stimulate anabolism to promote recovery after burn or injury

    • Toxicity:
    • -causes masculinization in females
    • -reduces intratesticular testosterone in males by inhibiting release of LH → gonadal atrophy
    • -premature closure of epiphyseal plates
    • -↑ LDL
    • -↓ HDL
  5. Antiandrogens
    • Finasteride
    • Flutamide
    • Ketoconazole
    • Spironolactone
  6. Finasteride
    • Mechanism:
    • -a 5α-reductase inhibitor (decreased conversion of testosterone to DHT)

    • Clinical Use:
    • -BPH
    • -Male Pattern Baldness

    To prevent male-pattern hair loss, give a drug that will encourage female breast growth
  7. Flutamide
    • Mechanism:
    • -nonsteroidal competitive inhibitor of androgens at the testosterone receptor

    • Clinical Use:
    • -prostate carcinoma
  8. Ketoconazole
    • Mechanism:
    • -inhibits steroids synthesis (inhibits 17,20 desmolase)

    • Clinical Use:
    • -PCOS (prevent hirsutism)

    • Toxicity:
    • -gynecomastia
    • -amenorrhea
  9. Spironolactone
    • Mechanism:
    • -inhibits steroids binding (MC R antagonist that also affects androgen receptor)

    • Clinical Use:
    • -PCOS (prevent hirsutism)

    • Toxicity:
    • -gynecomastia
    • -amenorrhea
  10. Estrogens (ethinyl estradiol, DES, mestranol)
    • Mechanism:
    • -bind estrogen receptors

    • Clinical Use:
    • -hypogonadism
    • -ovarian failure
    • -menstrual abnormalities
    • -HRT in postmenopausal women
    • -in men with androgen-dependent prostate cancer

    • Toxicity:
    • -increased risk of endometrial cancer
    • -bleeding in postmenopausal women
    • -vaginal clear cell adenocarcinoma in women exposed to DES in utero
    • -increased risk of thrombi

    • Contraindications:
    • -ER positive breast cancer
    • -history DVTs
  11. Selective Estrogen Receptor Modulators (SERMs)
    • Clomiphene
    • Tamoxifen
    • Raloxifene
  12. Clomiphene
    • Mechanism:
    • -partial agonist at estrogen receptors in hypothalamus
    • -prevents normal feedback inhibition and increased release of LH and FSH from pituitary, which stimulates ovulation

    • Clinical Use:
    • -infertility
    • -PCOS

    • Toxicity:
    • -hot flashes
    • -ovarian enlargement
    • -multiple simultaneous pregnancies
    • -visual disturbances
  13. Tamoxifen
    • Mechanism:
    • -estrogen receptor antagonist on breast tissue

    • Clinical Uses:
    • -treat and prevent recurrence of ER-positive breast cancer
  14. Raloxifene
    • Mechanism:
    • -estrogen agonist on bone
    • -reduces reabsorption of bone

    • Clinical Uses:
    • -osteoporosis
  15. Hormone Replacement Therapy
    • Clinical Uses:
    • -relief or prevention of menopausal symptoms (hot flashes, vaginal atrophy)
    • -osteoporosis (increased estrogen decreases osteoclast activity)

    • Toxicity:
    • -unopposed ERT increases the risk of endometrial cancer (add progesterone)
    • -possible increased cardiovascular risk
  16. Anastrozole/Exemestane
    • Mechanism:
    • -aromatase inhibitors

    • Clinical Uses:
    • -used in postmenopausal women with breast cancer
  17. Progestins
    • Mechanism:
    • -bind progesterone receptors
    • -reduce growth and increase vascularization of endometrium

    • Clinical Use:
    • -used in OCPs
    • -used in the treatment of endometrial cancer and abnormal uterine bleeding
  18. Mifepristone (RU-486)
    • Mechanism:
    • -competitive inhibitor of progestins and progesterone receptor

    • Clinical Use:
    • -termination of pregnancy
    • -administered with misoprostol (PGE1)

    • Toxicity:
    • -heavy bleeding
    • -GI effects (N/V, anorexia)
    • -abdominal pain
  19. Oral Contraception (synthetic progestins, estrogen)
    • Mechanism:
    • -estrogen and progestins inhibit LH/FSH and thus prevent estrogen surge
    • -no estrogen surge → no LH surge → no ovulation
    • -progestins cause thickening of cervical mucus (limits access of sperm to uterus)
    • -progestins also inhibits endometrial proliferation (makes it less suitable for implantation)

    • Clinical Use:
    • -contraception

    • Contraindications:
    • -smokers > 35 years (increased risk of CV events)
    • -hx of thromboembolism and stroke
    • -hx of estrogen dependent tumor
  20. Terbutaline
    • Mechanism:
    • -β2 agonist
    • -relaxes uterus

    • Clinical Use:
    • -reduce premature uterine contractions
  21. Tamsulosin
    • Mechanism:
    • -α1-antagonist
    • -inhibits smooth muscle contraction
    • -selective for α1AD receptors on prostate (not vascular receptors)

    • Clinical Use:
    • -BPH
  22. Sildenafil, Vardenafil
    • Mechanism:
    • -inhibit PDE5
    • -causes increased cGMP → smooth muscle relaxation in corpus cavernosum
    • -increases blood flow and penil erection

    • Clinical Use:
    • -erectile dysfunction

    • Toxicity:
    • -HA
    • -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" but then Headache, Heartburn and Hypotension"
  23. Danazol
    • Mechanism:
    • -synthetic androgen that acts as partial agonist at androgen receptors

    • Clinical Use:
    • -endometriosis
    • -hereditary angioedema

    • Toxicity:
    • -weight gain
    • -edema
    • -acne
    • -hirsutism
    • -masculinization
    • -decreased HDL levels
    • -hepatotoxicity

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