female reproduction

Question 1

Potency of natrual estrogens

Answer 1

Estradiol> Estrone> Estriol

Question 2

Estrogen preps

Answer 2

17B- estradiol- oral (micronized prep) because of 1st pass effect (IM, patch , creams)
Ethinyl estradiol (a semisynthetic steroid) most post available, oral C 17 ethinyl inhibits first pass metabolism- slower metabolism
Mestranol- converted to ethinyl estradiol
Conjugated equine estrogens (Premarin)- sulfate esters of estrone oral, injectable, cream, esters cleaved in the h=guy

Question 3

pharmacokinetics

Answer 3

Lipophilic majority of circulating estrogens are bound to sex steroid binding globulin and albumin, rapidly metabolized in the liver to estrone and estriol, 2 intracellular estrogen receptors ER alpha and ER Beta

Question 4

Estrogen effects

Answer 4

Dev- epiphyseal closure
During menstrual cycle- Endometrial proliferation, peristalsis, cervical mucous, feedback (neg and pos)
metabolic effects- increased bone density, increased HDL and decrease LDL, increase coagulation

Question 5

Therapuetic uses of estrogens

Answer 5

Como oral contraceptive- Ethinyl estradiol, mestranol
Failure of pituitary function and ovarian development- Equine estrogens, ethinyl estradiol, mestranol

Failure of pit function and ovarian development- equine estrogens, thinyl estradiol

Post meno hrt, conjugated equine e

Question 6

SE and contraindications

Answer 6

SE: thromboembolic events, endometrial hyperplasia, breast changes

Contraindications: pregnancy, estrogen dependent cancers - progesterone modulates risk, undiagnosed uterine bleeding, thromboembolic disorders

Question 7

Clomiphene

Answer 7

Anti estrogen,
Indication- infertility

MOA- inhibits estrogen negative feedback, increases gonadotropin release

SE- ovarian hyperstimulation syndrome, hot flushes

Question 8

Tamoxifen

Answer 8

SERM (selective estrogen receptor modulator
MOA: mixed estrogen antagonist in breast, agonist in bone, uterus

Indication- treats/ prevent breast cancer
SE- uterine cancer, thromboembolism, hot flushes

Question 9

Raloxifen

Answer 9

SERM
MOA- estrogen agonist in bone, antagonist in breast and uterus

Indication- treats breast cancer in postmenopausal women with high risk of osteoporosis

SE- thromboembolism, hot flushes, muscle cramps

Question 10

letrozole, anastrozole

Answer 10

aromatase inhibitors

MOA- Non steroidal reversible inhibitors of aromatase
indication - treats breast cancer in post menopausal women
letrozole- also trrats infertility, increase FSH, se- decreased bone density, hypercholesterolemia

anastrozole- SE hot flushes, weakness arthritis

no risk of thromboembolism

Question 11

exemestane

Answer 11

Aromatase inhibitor
MOA- Steroid, suicide substrate, IRREVERSIBLE inhibition of aromatase
Indicatedsd in post meno breast cancer
SE- hot flushes and fatigue

Question 12

Progesting

Answer 12

Cholesterol to pregnenolon (scc)
Preg-> progesterone (3 b hsd)

Binds to corticosteroid binding globulin and albumin, some binding to SHBG

Rapid first pass elimination- low oral bioavailability

2 isoform of progesterone receptor (PRA and PRB)

Question 13

progestin preparations

Answer 13

progesterone- low oral bioavailability (Micronized, injection, suppositories, gels)
Medroxyprogesterone acetate- modified progesterone esters injected some oral
Norethindrone, levonorgesterel, etonogesterl- testostesterone derivatives, good oral activity, implantable, prolonged plasma half lives
Drospirenone- a spironolactone analogue, has antimineralocorticoids, and progestin activity

Question 14

Progestin Effects

Answer 14

Aka progestation

secretory endometrium, decreased oviduct peristalsis, thinken mucus, mammary gland development

therapuetic uses- Contraceptives- norethindrone, levonorpgestresl, etonogestrel, drospirenone, medroxyprogesterone acetate

Post meno HRT- Norethindrone, levonorgestrel, Medace

SE- Blood lipid alterations- increased LDL, edema and weight gain, androgenic action, headache and breakthru bleeding

Question 15

Mifeprestone

Answer 15

Progesterone antagonist-
Mechanism- competitive progesterone receptor modulator, primarily antagonist use

Pregnancy termination- FDA approved thru 70th day, follow later with misoprostol or dinoprostone to promote expulsion of the blastocyst

SE- abdominal pain, nausea, may have serious bleeding

GC antagonist

Question 16

Ulipristal

Answer 16

Partial agonist at progesterone receptors, MOA- inhibits ovulation and alters endometrium

Use- emergency contraception effective for 5 days post intercourse

Question 17

hormonal contraception goals

Answer 17

effective, easy to use, limited side effects, reversible

Combo- estrogen and progestin or Progestin only

Question 18

Combined oral contraceptives

Answer 18

COC- pill- highly effective

Estrogen- ethinyl estradiol or mestranol
Progestin- Norethindrone, levonorgestrel, etonogestral, drospirenone

Mono or multiphasic, multiphasic variations of dosing allows decrease in hormone concentrations

Question 19

MOA of COC Action

Answer 19

Disrupts feedback, inhibits ovulation (negative feedback on hypothalamus, decreased gonadotropin levels (LH surge))
Disrupts the conditioning of endometrium, thickens cervical mucus, decreases oviduct peristalsis

Question 20

Progestin only contraception

Answer 20

MOA- suppress ovulation, thicken cervical mucous, block implantation

Oral- norethindrone, Implant (levonorgestrel, etonogestrel), IUD (Levonorgestrel), Medroxyprogesterone SE- bone lossd

Question 21

Emergency conraception- postcoital

Answer 21

Combined oral contraceptives (levonorgestrel and ethunyl estradiol - 2 doses)

Levonorgestrel alone (2 doses)

Ulipristal

Question 22

Contraceptive Adverse effects

Answer 22

Combination oral contraceptives- thromboembolic disorders, migraine headaches, others

Progestin- only Contraceptives- breathru bleeding, acne, headaches, bone thining for depot (Medroxyprogesterone)

Question 23

Drug interactions

Answer 23

Drugs that reduce the effects of OCs- penicillin V, Ampicillin, tetracycline, rifampin, Carbamazipine, phenytoin

Drugs whose effects are reduced by OCs- Warfarin, insulin and other hypoglycemic agent

Question 24

Contraindications of COCs

Answer 24

Thromboembolic or cerebrovascular disease, MI, CV disease, Cervical, endometrial or breast cancer (estrogen dependent), undiagnosed abnormal genital bleeding, pregnancy or suspected preganncy

Question 25

Uterine Fibrinoids and endometriosis treatment

Answer 25

Leuprolide
MOA- GnRH analog (agonist if pulsatile, antagonis if continuous)

Initial surge of estradiol then declines

Use- uterine fibrinoids, endometriosis central precocious puberty

SE- hot flushes, decreased libido

Contraindication- pregnancy CAt X, breast feeding

Question 26

Danazol

Answer 26

Testosterone orally active,
MOA- suppresses LH reelase, testicular, ovarian functions
Indication- Treat endometriosis and hereditary angioedema
SE- hepatotoxic, acne

Question 27

Druga to prevent labor (preterm)

Answer 27

Prevention of preterm labor- progesterone, inhibits cervical ripening and uterine contraction

Tocolytic agents- used for short term delay of labor, decrese uterine contractile activity:
Nifedipine, CCb, antihypertesnsivc, indomethacin, magnesium sulfate, tervutaline (beta agonist, No

Question 28

drugs for labor induction

Answer 28

dinoprostone- PGE2 analog, causes cervical ripening
Misoprostol- PGE1 analog, peptic ulcer, ripens cervix, increases uterine contraction
Oxytocin- enhances uterine contraction, decreases postpartum blood loss, cross reacts with vasopressin receptor

Methylergonovine- third stage of labor, strongly increases uterine contractions, decreases pospartum blood loss, contraindicated in HTN