Hormone contraception pharmacology CIS (Linger) - MT

Question 1

Endogenously, GnRH is released in a pulsatile manner. During exogenous GnRH therapy, what are the respective actions of GnRH agonists and antagonists?

Answer 1

• Agonists will have brief flare phase of 7 days where LH and FSH are increased, but after that period, negative feedback inhibition is maintained and levels of LH and FSH are lowered
• Antagonists immediately block the pathway of LH and FSH production

Question 2

The treatment of hormone responsive breast cancer and infertility usually involves which group of pharmaceuticals?

Answer 2

• Anti estrogens

Question 3

Prevention of breast cancer and osteoporosis usually involves which group of pharmaceuticals?

Answer 3

Selective estrogen receptor modulators (SERMs)

Question 4

Medical abortions usually involve which group of pharmaceuticals?

Answer 4

anti progestins

Question 5

Hormone contraception, Tx of hyperandrogenism and hypogonadism, postmenopausal HRT can involve which group of pharmaceuticals?

Answer 5

Estrogen progestin combinations

Question 6

Endogenous estrogen effects on female maturation causes what two occurences?

Answer 6

1. required for nmml sexual maturation and growth of female
2. responsible for accelerated growth phase and closing of epiphyses of long bones occuring at puberty

Question 7

Estrogen effects on endometrium?

• on metabolic and CV effects?
• on blood coagulation?

Answer 7

• with progesterone causes regular periodic bleeding and shedding of endometrial lining
• decreases rate of bone resorption

increases HDL and TGs slightly reduces LDL, reduces Total cholesterol

• enhances coagulability of blood

Question 8

What are the two types of synthetic estrogen?

which one i more commonly used?

Answer 8

• Ethinyl estradiol, Mestranol
• Ethinyl estradiol

Question 9

Adverse effects of therapeutic Estrogen include endometrial cancer risk. What other drug is taken with estrogen to protect against this risk?

Answer 9

• Progestin concmitant use

(in women with functional uteruses)

Question 10

Estrogen is contraindicated in patients with what conditions? x7

Answer 10

1. estrogen dependent neoplasms

. 2. undiagnosed genital bleeding

3. liver disease
4. hx of thromboembolic disorder
5. heavy smoker over 35
6. CV disease
7. migraine w/ aura

Question 11

Which has the higher risk for venous thromboembolisms?

• Pregnancy or Contraceptive estrogen

Answer 11

Pregnancy

Question 12

Endogenous progestins have what effects on:

1. hypothalamus pituitary axis during luteal phase?
2. endometrium?
3. Menstruation?
4. maintenance of _________ and _________ development?

Answer 12

1. production in luteal phase decreases frequency of GnRH pulses
2. decreases estrogen driven endometrial prolif
3. abrupt decline at end of cycle is main determinant of onset of mestruation
4. key in maintaining pregnancy and mammary gland development (with estrogen)

Question 13

Progestins are primarily used for what in concurrence with Estrogen? x2

Answer 13

• HRT
• Hormonal contraception (also alone)

Question 14

benefits to using progestins include? x2

Answer 14

• multiple routes of administration, include long acting reversible contrceptives LARCs
• useful when estrogen is poorly tolerated or contraindicated

Question 15

Adverse effects of progestins? x3

Answer 15

• breakthrough bleeding is common in progestin only contraceptives
• HRT w/ estrogen and progestin may increase breast cancer risk when compared to risk in women taking estrogen alone
• Progestins with androgenic effects: weight gain, acne, hirsutism, reduced plasma HDL

Question 16

Progestin may be recommended over estrogen for contraceptive source in what situations? x6

Answer 16

• migraine HA
• age over 35 and smoker or obese
• Hx of thromboembolic disease
• Hx of CV disease
• Hypertriglyceridemia
• SLE with vascular disease, nephritis, or antiphospholipid Abs

Question 17

What are the progestatinoal agents focused on which have varying degrees of estrogeni and androgenic potencies? x4

Answer 17

• Medroxyprogesterone acetate
• Desogestrel (etonogestrel active metabolite)
• norethindrone
• L Norgestrel

Question 18

Progestational agents with more androgenic activity like acne hirsutism, weight gain include which two agents?

Answer 18

1. L norgestrel
2. norethindrone

Question 19

potential progestational agents used to treat acne are?

• why?

Answer 19

• Norgestimate, Drospirenone
• lower or anti androgenic potency

Question 20

Molecular mechanism of ER and PR induced activation of gene transcription:

1. hormone enters cell membrane (lipid soluble)

2.

3.

4.

5.

6.

7.

Answer 20

2. Nuclear receptor and Heat shock protein complex forms intracellularly
3. NR and hormone complex dissociates from HSP
4. NR/hormone complex forms dimer with another NR/homone complex
5. dimer enters nuclus through nuclear pore
6. NR dimer binds coactivator and RNA polymerase and sims production of mRNA
7. mRNA goes into cytoplasm and is translated into proteins that change cell function

Question 21

Combination oral contraceptives work by?

• what is suppressed? x3

Answer 21

preventing ovulation via feedback inhibition of HPA

• LH and FSH levels suppressed, Mid cycle surge of LH is absent, endogenous steroid levels diminished

Question 22

Progestin only contraceptives are highly efficacious but block ovulation in only about 60% of cycles. Their affectiveness is thought to stemm from what? x3

Answer 22

• thickening of cervical mucus (decreases sperm penetration.
• and endometrial alterations that impair implantation
• decreases GnRH pulse frequency

Question 23

Tow types of preparatinos used for oral contraceptives include combinations of estrogens and progestins, and Continuous progestin therapy w/o estrogen.

What are the two forms of combo E/P contraceptives?

Answer 23

1. Monophasic form = constant dose of both components
2. Biphasic/Triphasic forms = dosage of one or both components that is changed once (bi) or twice (tri) during cycle

Question 24

continuous progestin therapy may be beneficial to patients in which estrogen use carries more risk.

What is the concern with using continuous progestin oral contraceptives? (higher incidence of what ADR?)

Answer 24

Abnormal bleeding risk increases

Question 25

Transderm preparations of combo E/P contraceptives are beneficial for what reason?

Answer 25

- Bypass first pass effect of liver metabolism

Question 26

Cytochrome P450 inducing agents that may increase liver catabolism of estrogen or progestin include? x2

Answer 26

phenytoin/ rifampin

Question 27

A 25 year old sexually active healthy woman presents to your clinic asking for a morning after pill because of having unprotected sex the night before. You prescribe her a drug that isn't indicated for post coital emergency contraceptive, but effectively terminates \>95% of pregnancis when dministered during the 1st 7 weeks of conception. 1. What is the MOA? 2. What is the major ADR? 3. usually used in combo with what?

Answer 27

1. norsteroid that acts as a progesterone Receptor antagonist and induces luteolysis 2. major ADR is prolonged bleeding, requires intervention in 5% of cases. 3. synthetic prostaglandin E1 (misoprostol) mifepristone

Question 28

What is Mifepristone labeled for use as in the United states?

Answer 28

Pregnancy termination agent

Question 29

Mornin after agents (postcoital emergency contraceptives) include? x2

Answer 29

- Levonorgestrel (plan B one step, next choice) - Ulipristal acetate (ella)

Question 30

A 24 year old woman goes and picks up a morning after agent at the pharmacy w/o a presciption. She has read that this agent is more effective than estrogen-progesterone combinations and less likely to cause Nausea and vomiting, prompting her choice of this agent. 1. What is its MOA? 2. Can it stope a pregnancy that has already occured?

Answer 30

1. Progesterone receptor agonist 2. Does not stop pregnancies that have occured

Question 31

99% of postcoital contraceptives are effectivee when administered within what time frame?

Answer 31

within 72 hours of coitus

Question 32

Absolute contraindications of estrogen therapy include? x5

Answer 32

1. active or Hx of TE disease 2. Undiagnosed abnormal genital bleeding 3. Known or suspect Hx of estrogen dependent neoplasia 4. impaired liver function 5. known or suspected pregnancy

Question 33

What may worsen with estrogen and/ or progestin therapies? x6

Answer 33

1. gallbladder disease 2. hypertiglyceridemia 3. asthma 4. migraines 5. epilepsy 6. SLE

Question 34

SERM agents include? x3

Answer 34

Tamoxifen, toremifene, Raloxifene

Question 35

MOA of SERM Tamoxifen

Answer 35

competitive partial agonist inhibitors of estradiol at Estrogen Reeptors (antagonist on breast, agonist on other tissues)

Question 36

Tamoxifen is used to treat what?

Answer 36

Estrogen responsive (ER+) breast cancer and chemoprevention of breast cancer in high risk individuals

Question 37

Raloxifene MOA

Answer 37

agonist effects on lipids and bone; antagonist on endometrium and breast

Question 38

Aromatase inhibitors include? x3 - MOA - used to treat?

Answer 38

- anastrazole, letrozole, exemenstane - inhibit function of aromatase (enzyme required for biosynth of estrogens from androgens) - treat beast cancer in postmenopausal women

Question 39

Advantage of Aromatase inhibitors over SERMs

Answer 39

significantly less incidence of vaginal bleeding, discharge, hot flashes, endometrial cncer, DVT when compared to SERMs