Flashcards in Pharm 3 Estrogen/Progestin Deck (47):
1
Ovarian-pituitary cycle
-Elevated FSH during 1st half stimulates follicle
-Midcycle estradiol exerts positive feedback, triggers LH surge
-LH surge induces ovulation, stimulates corpus luteum and progesterone production
2
Pregnancy hormone
hCG (chorionic gonadotorpin) identical to LH, maintains estrogen and progesterone production by maintaining corpus luteum
3
Hormones interacting with endometrium
-Estrogen mediates proliferation
-Progesterone maintains secretory state
4
Base molecule for estrodiol/testosterone synthesis
Cholesterol
5
Hormone replacement therapy
Estradiol undergoes extensive first-pass metabolism, so use conjugated estrogens (estrone sulfate)
6
-Estrone sulfate-
indication
Conjugated estrogen absorbed in lower gut
-Hormone replacement therapy
7
-Ethinyl estradiol-
indication
Ethinyl substitution reduces first-pass metabolism, greater oral potency than conjugated estrogens
-Oral contraceptives
8
-Estradiol cypionate-
Insoluble in water
-Once monthly IM for HRT
9
-Medroxyprogesterone-
Breast and endometrial cancer
-Oral or IM
10
-Megestrol-
Endometrial cancer
11
-Norethindrone-
19-nortestosterone derivative Progestin
-Oral contraceptives
12
-Desogestrel-
Progesterone for oral contraceptive
-Lowest degree of androgenic activity
13
Estradiol/Progesterone transport
-Estradiol bound to SHBG (sex hormone binding globulin) high affinity
-Progesterone bound to CBG (corticosteroid binding globulin) with high affinity
-Both bound to albumin with low affinity
14
Estradiol/Progesterone Metabolism
Hepatic conjugation
-Estradiol -> estrone -> bile -> reabsorbed
-Progesterone -> pregnanediol
15
Estrogen MOA
Binds to nuclear receptor (homodimer), regulates trasncription
16
Progestin MOA
Binds to response element similar to that of corticosteroids
17
Estrogen effects on bone
-Prepubertal growth of long bones
-Pubertal closure of epiphyses
-Post pubertal decreased bone resorption
18
Estrogen effects on clotting
-Increase clotting factors
-Decrease antithrombin
-Increase platelet adhesiveness
19
Estrogen effects on lipids
Increase HDL, triglycerides
Decrease LDL
20
Estrogen effect of sex behavior
-Mediates testosterone's effect on libido
21
Estrogen other effects
-Maintain skin and blood vessel integrity
-Increase CBG, TBG, SHBG
-Increase cortisol
-Increase Na and water retention
22
Progesterone v Estrogen
Antagonize estrogen
-Decrease Na retention
-Decrease HDL
-Increase metabolism
-Downregulate receptors
23
Progesterone other effects
-Stimulate respiratory center
-Increase insulin, reduce glucose tolerance
-Acne
-Weight gain
24
Primary hypogonadic impaired development Tx
-Start estrogen at 11-13, add progestin when growht is completed
25
Hysterectomy HRT
Unopposed estrogen (don't worry about progesterone)
26
Other clinical uses for Estrogen
-Ovarian suppression for hyperandrogenism
-Ovulation suppression in dysmenorrhea
-Androgen-dependent prostate cancer (suppress gonadotropin secretion)
27
Estradiol levels postmenopausal
1/4 that of males
28
Postmenopausal HRT alleviates (5)
Sleep disturbances
Hot flashes
Urogenital changes
Osteoporosis
High cholesterol
29
HRT contraindications
Liver disease
Breast or other estrogen-dependent cancer
30
Low dose combination OC
-All use ethinyl estradiol
-Norgestrel for monophasic
-Norethindrone for bi/triphasic
31
Monophasic v Triphasic
-Triphasic eliminates period for 90 days
-Triphasic reduces total dose of progestin (reduced SE)
32
OC MOA
Inhibit gonadotropin secretion, suppress ovulation (progestin only blocks ovulation 60-80%)
-Thicken cervical mucus
-Reduce tubal secretion/motility
-Change uterine endometrium
33
OC mild AE
Breakthrough bleeding
-Tx with higher dose estrogen or different progestin
34
OC moderate AE
Acne with higher progestin doses
-Nausea, mastalgia, weight gain, headache
35
OC severe AE
-Thromboembolism (estrogen dependent)
-Myocardial infarction
-Cholestatic jaundice
36
OC neoplasm risk
Hepatic adenoma
37
OC contraindications
Impaired liver function, h/o thromboembolic disease, CAD, hyperlipidemia
38
OC caution with
Migraine, HTN, DM, gallbladder disease
39
OC drug interactions
-Decreased efficacy with antibiotics that affect GI absorption
-Insulin efficacy reduced by OC
40
Tx for endometriosis
Medroxyprogesterone Acetate (IM injection every 3 months)
-Amenorrhea side effect
41
-Clomiphene-
Antiestrogen (competitive) reduces negative feedback
-Induces ovulation
42
-Fulvestrant-
Pure estrogen receptor antagonist
-For treating hormone-responsive metastatic breast cancer in postmenopausal women
43
-Tamoxifen-
Anti-estrogen on breast
-Pro-estrogen on lipids, bones, endometrium
-Tx perimenopausal symptoms
44
-Raloxifene-
Anti-estrogen on breast, pro (1/2 strength) on bones
-Tx post-menopausal osteoporosis, BRCA
-No effect on perimenopausal symptoms
45
-Mifepristone (RU 486)-
MOA
Parent molecule
Effect
Progesterone-R antagonist, glucocorticoid-R antagonist, prostaglandin dehydrogenase inhibitor
-Norethindrone derivative
-Stimulate uterine SM contractility
46
-Mifepristone-
other use
Glucocorticoid receptor antagonist
-Tx Cushing's secondary to ectopic ACTH secretion
47