Pharm Ii Exam Ii- Estrogens And Progestins

Front 1

1. Main function of Estrogens & progestins:

Back 1

a. Control of ovulation
b. Embryonic maturation
c. Development of primary and secondary sexual characteristics
d. Mineral, carbohydrate, protein and lipid metabolism

Front 2

1. Orally administered estrogens are widely used therapeutically for

Back 2

a. Postmenopausal hormonal replacement therapy
b. Primary hypogonadism
c. Contraception, in combination with progestins

Front 3

1. Estrogens/progestins are synthesized in:

Back 3

a. Ovarian granulosa cells (corpus luteum)

Front 4

1. Three major naturally occurring estrogens:

Back 4

a. estradiol,
b. estrone and
c. estriol.
• Most potent naturally occurring estrogen is estradiol.

Front 5

1. Phenolic A ring needed for

Back 5

a. selective, high affinity binding.

Front 6

1. Ethinyl substitutions at C 17

Back 6

a. increase oral potency.

Front 7

1. Alkyl substitutions on A ring

Back 7

a. impairs binding.

Front 8

1. Nonsteroidal estrogens are structurally similar to

Back 8

a. estradiol.

Front 9

1. Menstrual cycle is controlled primarily by:

Back 9

a. hypothalamus and pituitary
• Positive and negative feedback effects of estrogen and progesterone control GnRH, LH and FSH release.

Front 10

1. Metabolic effect of estrogens

Back 10

a. Blocks bone reabsorption
b. increase triglycerides, decrease cholesterol
c. increase HDL/LDL ratio
d. Alters bile composition
e. increase plasma levels of carrier protein
f. increase clotting factors, decrease antithrombin III

Front 11

1. Are estrogens lipophobic or lipophilic

Back 11

a. Lipophilic

Front 12

1. Estrogens bind to __________receptors

Back 12

a. Nuclear

Front 13

1. The estrogen receptor interacts with _________in target genes.

Back 13

a. estrogen response elements (EREs)
• Results in increased or decreased transcription of hormone-regulated genes.

Front 14

1. Natural estrogens

Back 14

a. Estradiol
b. Micronized estradiol (ESTRACE):
c. Transdermal estradiol (ESTRADERM):
d. Estrone (AQUEST):
e. Estradiol valerate (DELESTROGEN)
f. estradiol cypionate (ESTROJECT LA):

Front 15

1. facts about estradiol

Back 15

a. extensive first pass hepatic metabolism therefore not used orally
b. Plasma half-life of estradiol is in minutes

Front 16

1. Facts about Micronized estradiol (ESTRACE)

Back 16

a. small particles,
b. rapid absorption (less first pass effect than normal estradiol)

Front 17

1. facts about Transdermal estradiol (ESTRADERM):

Back 17

a. slow sustained release

Front 18

1. facts about Estrone (AQUEST):

Back 18

a. IM injection,
b. aqueous suspension,
c. rapid effect

Front 19

1. Facts about Estradiol valerate (DELESTROGEN)

Back 19

a. IM injection,
b. dissolved in oil
c. slower rate of absorption.
d. Provides 2-3 weeks of estrogenic effect

Front 20

1. Facts about estradiol cypionate (ESTROJECT LA)

Back 20

a. IM injection,
b. dissolved in oil
c. slower rate of absorption.
d. Provides 2-3 weeks of estrogenic effect

Front 21

1. CONJUGATED ESTROGENS include

Back 21

a. equilin (PREMARIN): (made from pregnant mare’s urine)
b. Cenestin (plant deived)

Front 22

1. How do conjugated esters differ from natural esters

Back 22

a. They are sulfated forms of estrone
b. They are Hydrolyzed in the intestine to remove the sulfate groups allowing estrogen to be absorbed (less first pass effect).

Front 23

1. Synthetic steroidal estrogens

Back 23

a. Ethinyl estradiol (ESTINYL) and
b. mestranol

Front 24

1. clinical use of Ethinyl estradiol (ESTINYL) and mestranol

Back 24

a. Primarily used in OCP
• Ethinyl estradiol is more common in OCP than mestanol
• Ethinyl substitution in the C 17 position inhibits first-pass hepatic metabolism.
b. Synthetic estrogens (ethinyl estradiol) have a half-life of 13-27 hours due to decreased hepatic metabolism.

Front 25

1. SYNTHETIC, NONSTERIODAL estrogens include

Back 25

a. Diethylstilbestrol (DES) and
b. chlorotrianisene (TACE)(oral form)

Front 26

1. clinical use for Diethylstilbestrol (DES)

Back 26

a. DES use limited to inoperable breast and prostatic cancer
b. DES - increased risk of vaginal and cervical cancer in women exposed in utero
c. Synthetic estrogens (ethinyl estradiol) have a half-life of 13-27 hours due to decreased hepatic metabolism..

Front 27

1. Clinical use of chlorotrianisene (TACE)

Back 27

a. Postpartum breast engorgement
b. Synthetic estrogens (ethinyl estradiol) have a half-life of 13-27 hours due to decreased hepatic metabolism.

Front 28

1. MOA of Raloxifene

Back 28

a. Selective estrogen receptor modulators

Front 29

1. Facts about Raloxifene

Back 29

a. Used primarily to treat osteoporosis
b. Has estrogen-like effects on bone and lipid metabolism
c. Estrogen antagonist in uterine and breast tissue
d. extensive first pass hepatic metabolism
e. Also undergo hepatic sulfate and glucuronide conjugation (raloxifene 1o)
f. Raloxifene is excreted in feces

Front 30

1. Clinical use of Raloxifene

Back 30

a. Decreases bone reabsorption and remodeling
b. Beneficial effects on osteoporosis and cardiovascular disease ONLY

Front 31

1. Natural estrogens are primarily bound to

Back 31

a. sex steroid binding globulin.

Front 32

1. Synthetic estrogens are bound primarily to

Back 32

a. albumin.

Front 33

1. Progestins bind to

Back 33

a. corticosteroid binding globulin.

Front 34

1. What is the major urinay metabolite of synthetic estrogens

Back 34

a. Rapidly metabolized in the liver
b. Conversion to estriol (major urinary metabolite)

Front 35

1. Estrogens and their metabolites are excreted primarily in the

Back 35

a. Urine

Front 36

1. Raloxifene is excreted in the

Back 36

a. feces

Front 37

1. estrogens are helpful in treating __________

Back 37

a. Postmenopausal hormone replacement therapy
• Osteoporosis
• Vasomotor symptoms
• Prevention of cardiovascular disease

Front 38

1. Common agents used for Postmenopausal hormone replacement therapy

Back 38

a. conjugated estrogens (PREMARIN) + progestin (commonly medroxyprogesterone acetate)
• Hysterectomy - estrogen used alone
• Addition of MPA limits endometrial hyperplasia

Front 39

1. How do estrogens effect osteoporosis

Back 39

a. Prevents bone loss, should initiate treatment before significant loss
b. Continuous use
• Appropriate diet + weight bearing exercise

Front 40

1. How do estrogens affect Vasomotor symptoms

Back 40

a. “Hot flashes” alternating with chilly sensations, inappropriate sweating and/or paresthesias.
b. Due to deficiency of estrogen
c. Estrogen therapy very effective

Front 41

1. How do estrogens prevent cardiovascular disease

Back 41

a. Increase in incidence of cardiovascular disease in women after menopause
b. Protective effect of estrogens may be due to effects on plasma lipoprotein profiles (increase HDL/LDL ratio)

Front 42

1. Categories of Progesterone/Progestins

Back 42

a. Esters (increase half-life)
b. Synthetic Progestins (19-Norprogestins)

Front 43

1. Ester progestins include

Back 43

a. Megestrol,
b. hydroxyprosgesterone caproate and
c. medroxyprogesterone acetate (MPA)

Front 44

1. Synthetic Progestins include

Back 44

a. Estranes
• Norethindrone
• norethynodrel

b. Gonanes
• Levo-norgestrel,
• desogestrel, and
• norgestimate
*****Desogestrel and norgestimate have lessened androgenic activity

Front 45

1. therapudic uses of progesterone/progestins

Back 45

a. Hormone replacement regimen/Contraception
b. OSTEOPOROSIS
c. Postpartum breast engorgement
d. PRIMARY HYPOGONADISM

Front 46

1. When using progesterone for Hormone replacement regimen/Contraception …Describe the difference between the “Cyclic” vs “Continuous” regimen

Back 46

a. “Cyclic” regimen - Premphase
• Estrogen alone for 14 days
• MPA + estrogen for last 14 days

b. “Continuous” regimen
• Combi-patch or Prempro
• Estrogen + progestin given throughout 28 day cycle

Front 47

1. Oral versus transdermal administration of progesterone

Back 47

a. ORAL
• é SSBG levels
• é secretion of cholesterol into the bile
• é the exposure of the liver to high concentrations of estrogens
• Relieves vasomotor symptoms and protects against bone loss
b. TRANSDERMAL
• ê beneficial changes in plasma lipoprotein profiles
• Skin reaction to patches
• Relieves vasomotor symptoms and protects against bone loss
• Consistent blood levels

Front 48

1. What drug do you use for Postpartum breast engorgement

Back 48

a. Chlorotrianisene

Front 49

1. Tx of PRIMARY HYPOGONADISM

Back 49

a. Examples of primary hypogonadism
• Ovarian dysgenesis with dwarfism
• Hypopituitarism
b. Estrogens are given to mimic the natural cyclic pattern
c. Progestins, growth hormone and/or androgens also given

Front 50

1. Adverse reactions to Estrogens & progestins

Back 50

a. Common Side Effects
• Nausea, vomiting, breast tenderness
• Migraine, edema, mood lability
• Hot flashes - Raloxifene
b. Serious or Life-threatening Effects
• Thromboembolism/stroke
• Gallbladder disease
• Hypertension
• May reactivate endometriosis

Front 51

1. DRUG INTERACTIONS with estrogens and progestins

Back 51

a. Inhibits metabolism of
• cyclosporine,
• tricyclic antidepressants
b. increase risk of liver toxicity
• Dantrolene,
• methotrexate
c. increase hepatic synthesis of Vit. K clotting factors
• Decreased effects of warfarin
d. Hepatic enzyme inducing drugs
• Increased metabolism of estrogens

Front 52

1. CONTRAINDICATIONS of estrogens / progestins

Back 52

a. Breast cancer
b. Thromboembolic disorders
c. Endometrial cancer
d. Pregnancy:
• Increased incidence of vaginal and cervical adenocarcinoma in women exposed to estrogens in utero
• Increased incidence of genital abnormalities

Front 53

1. CANCER CONCERNS of estrogens and progestins

Back 53

a. Estrogens can induce tumors of the breast, uterus, testis, bone, kidney and other tissues.
b. HOWEVER:
• Earlier studies used much higher doses of estrogens and progestins.
• Use of progestins in combination with estrogen greatly diminishes the risk of endometrial cancer.
c. New studies of the currently used doses show little, if any, increased risk of breast cancer.
d. Doses used for hormone replacement therapy are much lower than those used for contraception (2-3 times less).