Pharm endocrine (Reproduction) drugs Flashcards
1
Q
Estrogens
A
- Sythetics undergo 1st pass metab - turn into naturally occuring steroid
- MOA:
- Activation of estrogen receptors - Transcription rates upreg
- Considerations:
- Women w/uterus give w/progestin to prevent endometrial cancer
- Clinical applications:
- Contraception - synthetics high bioavail
- Hormone therapy: post menopausal (small increase risk of breast cancer & CV events)
- Premature ovarian failure
- Hypogonadism in young female (IM admin)
- Prevention of bone loss in osteoporsis
2
Q
Estrogens Effects
A
- Mestranol - prodrug converted to ethinyl estradiol
- Adverse effects:
- Minor - breakthrough bleeding, nausea, breast tenderness
- Major - Thromboembolism, Gallbladder disease, hypertriglycerdemia, depression
- In postmeno women = breast cancer & endometrial hyperplasia
- Drug interactions:
- Combo with **CYP 450 inducer can lead to BREAKthrough bleeding & reduced contraceptive **
3
Q
Oral contraceptives & antibiotics
A
- Rifampin: used to treat TB
- Stong inducer of CYP 3A4 & 2C9
- ONLY antibiotic proven to interact with OCs
- Other antibiotics linked to decreased effectiveness ; Amoxicillin, ampicillin, tetracycline
- Combo contraceptives include doses 15-50 of Ethinyl estradiol to REDUCE thromboemolism
4
Q
Diethylstilbestrol
A
- Approved for gonorrhea, menopause, atrophic vaginitis, postpartum lactation supression
- Carcinogenic:
- DES daughters 40x more likely to have vaginal clear cell carcinoma, Tumors on repro tract and breast
- _Teratogenic: _
- Malformations in repro tract of users (Hypospadia)
5
Q
Progestins
A
- MOA: Activate progesterone receptors
- Clinical applications:
- Contraception (with or without estrogen)
- Treat hormone def
- Assisted repro tech to promote & maintain preg
- Control of dysfunctional uterine bleeding
- Dysmenorrhea (painful periods) & endometriosis
- Adverse effects:
- Weight gain
- Decrease in bone mineral density W/high doses
- May increase BP & decrease HDL
6
Q
Progesterone & synthetics
A
- Progesterone: not used due to rapid metab
- Synthetic:
- Derived from 19-nortestosterone & produce androgenix activity - oral contraceptive
- 3 generations & 3rd highest risk for Blood clots
- 4th generation = 17-a spirolactone = Drospirenone
- Medroxyprogesterone acetate (depo-provera) - injectable contraceptive (3months)
7
Q
Progestin (POP)
A
- Progestin only pills
- Low dose:
- Implants - Norplant or Mirena
- Inhibit ovulation in 50%
- Thicking cervical mucus - Reduce sperm
- Medium dose:
- Implant - Nexplanon
- Some follicular development, BUT inhibit ovulation in 99%
- Similar mucus changes
- High dose:
- Implant - depo-provera
- COMPLETE inhibit follicular development & ovulation
- Similar mucus changes
8
Q
SERM (Tamoxifen)
A
- Selective estrogen receptor mods
- MOA:
- Estrogen antagonist actions in breast tissue & CNS
- Estrogen agonist effects in liver/bone
- Clinical use:
- Prevention & adjuvant treatment of hormone responsive breast cancer
- Increase bone density in postmeno
- Adverse effects:
- Hot flashes, thromboemolism, endometrial hyperplasia
- Increase endometrial cancer
- Toremifene SIMILAR
9
Q
Other SERMs (-fene)
A
- Raloxifene: Antagonist in breast & CNS metab & Agonist in liver
- Clinical uses: Approved for osteoporosis & prevention of breast cancer In SOME post menopausal
- Clomiphene: Antagonist effect on Pit increases gonadotropin secretion
- Clinical uses: ovulation induction
- Ormeloxifene: non-hormonal & steroidal oral contraceptive
- MOA: agonist bone, antagonist uterus/breast
- Adverse effects: uterine prolaspe or urinary incontinence
- Lasofoxifene: Agonist bones, Antagonist breast/uterus
- NOT approved by FDA due to osteoporosis - used in EU
10
Q
SERD (Fulvestrant)
A
- Selective estrogen down reg (SERD)
- Monthly IM injection
- MOA
- Estrogen receptor antagonist (-) in all tissues
- Clinical use:
- 2nd line treatment for hormone-responsive breast cancer that is resistant to 1st line antiestrogen therapy
- Adverse effects:
- Hot flushes, headache, nausea, asthenia (weakness)
11
Q
Aromatase Inhibitors
A
- Large amount of estrogen made locally in endrometric cells - Estradiol also occurs in tissues
- Ex. Adipose tissue, skin fibroblasts
- GnRH agonists DO NOT inhibit peripheral estrogen production
- Aromatase inhib CAN
- MOA:
- Block aromatase enzyme -
- competitive inhbition (Anastrozole & letrozole)
- Covalently bind (Exmestane, formestane)
- Clinical: adjuvant treatment of hormone breast cancer
- Adverse effects: Muscloskeletal disorders, dyspnea, bone pain
- Serious = Osteoporotic fractures, profuse vaginal bleeding
12
Q
Danazol
A
- MOA:
- Weak cyto P450 inhibitor & partial agonist of progestin/androgen receptors
- Synthetic derive from 17-ethinyltesteroine (4th generation)
- Results = Decrease FSH & LH
- Clinical uses:
- Fibrocystic breast disease
- Endometrosis: induces anovulation, amenorrhea, endometrial atrophy (Lowered LH/FSH)
- Adverse effects: Acne, hirsutism, weight gain, decreased breast size
- Drug interactions:
- CYP450 drug interactions
13
Q
Antiprogestin - (Mifepristone)
A
- MOA: progestin & glucocorticoid receptor antagonist (-)
- Clinical uses: combo w/prostaglandin (misoprostaol) for abortion
- Adverse effects:
- GI
- Vaginal bleeding
- Atypical infection
14
Q
Testosterone (androgens)
A
- MOA
- Androgen receptor agonist
- Clinical use
- Male Hypogonadism
- Wasting syndrome - helps gain weight
- Adverse effets
- Virilization in females (Deep voice)
- High doses cause gynecomastia in men
- Testicular shrinkage & infertility
- Oral = Fluoxymesterone, methyltesto
- Esters = Testoterone cypionate (long lasting)
- Anabolic = oxandrolone, nandrolone decanoate - (liver toxicities)
15
Q
Antiandrogens (Finasteride)
A
- MOA: Inhibition of 5a reductase enzyme converts testo to dihydrotesto
- Clinical:
- Benign prostatic hyperplasia
- Male pattern hair loss
- Adverse effects:
- RARE: Gynecomastia, impotence
- Dutasteride similar
- Propecia
