Pharmacology Ii - 2/5/10

Front 1

By what 3 mechanisms can you inhibit gonadal hormones?

Back 1

(1) GnRH agonists and antagonists
(2) 5 alpha reductase inhibitors
(3) aromatase inhibitors

Front 2

Name the 3 GnRH agonists.

Name the 2 GnRH antagonists.

Back 2

Leuprolide
Goserelin
Naferelin

Cetrorelix
Ganirelix

Front 3

Name the 2 aromatase inhibitors that competitively inhibit the enzyme.

Name the 2 aromatase inhibitors that covalently bind to the enzyme.

Back 3

Anastrazole
Letozole

Exemestane
Formestane

Front 4

What are these drugs indicated for?

What is their main adverse effect?

Back 4

Treatment and prevention of metastatic breast cancer

Increase the risk of osteoporotic fractures

They are more effective than estrogen antagonists like tamoxifen in the treatment of breast cancer.

Front 5

GnRH agonists and antagonists, 5 alpha reductase inhibitors and aromatase inhibitors all inhibit gonadal hormone synthesis. What is the other main mechanism in the inhibition of gonadal hormones?
What 3 subgroups is this split into?

Back 5

Receptor antagonists

Selective ER Modulators
AR Antagonists
PR Antagonists

Front 6

What is a SERM?

Back 6

Selective Estrogen Receptor Modulator
They bind to estrogen receptors and alter the conformation. They can act as antagonists or partial agonists based on the tissue.

Front 7

Which SERM is indicated for breast cancer?
How does it work? What is its drawback?

Back 7

Tamoxifen
It is a receptor antagonist to breast tissue, but a partial agonist to bone and endometrial tissue. Therefore it increases the risk of endometrial cancer and is not used for more than 5 years at a time.

Front 8

Which SERM is indicated for bone. How do they work?

Back 8

Raloxifene - ER agonist in the bone. Decreases bone resorption and is therefore used to delay the onset of osteoporosis. It is an ER antagonist in the breast and endometrium and therefore doesn't cause an increase in the incidence of endometrial cancer while decreasing the likelihood of breast cancer.

Front 9

What is the third SERM? What does it do?

Back 9

It is an ER antagonist to the hypothalamus and pituitary gland. It therefore increases GnRH and LH/FSH release. This stimulates follicle growth and ovulation

It also is an ER partial agonist in the ovaries causing multiple follicles to grow and increasing ovarian size. It is rarely associated with ovarian hyperstimulation syndrome.

Front 10

Inhibitors of gonadal hormoes -->
Synthesis Inhibitors
Receptor antagonists --->
SERM's
AR antagonists
PR antagonists
Name the 3 AR antagonists

Back 10

Flutamide
Spironolactone
Drospirenone

Front 11

What is flutamide indicated for?

Back 11

Metastatic prostate cancer and BPH

Spironolactone is a ALD receptor antagonist with significant AR activity
Drospirenone is a spironolactone derivative

Front 12

Name the 4 different types of contraception.

Back 12

Estrogen-Progestin
Progestin
Emergency contraception (morning after pill)
Male contraception

Front 13

How does Estrogen-Progestin work?

Back 13

Feedback inhibits GnRH and FSH,LH to prevent follicle development and ovulation

Front 14

What are the 2 types of estrogen used in this formulation. Why can you not give estrogen alone?

Back 14

Ethinyl estradial
Mestranol

Estrogen has endometrial proliferative effects and will cause endometrial cancer. Progesterone must be given as well for its anti-proliferative effects.

Front 15

Depending on the progestin you use, you will have varying degrees of cross androgen effects. Which type will give high AD effect? Low AD effect? Anti-androgen effect?

Back 15

High- Norgestrel, Levonorgestrel
Low - Norethindrone, Norethindrone acetate
Anti - Drospirenone

Front 16

What are the 3 routes of administration of female contraception?

Back 16

Oral tablet
Vaginal ring
Transdermal patch

Front 17

Why is the estrogen-progestin formulation only given for 21 of the 28 days with the other 7 days being placebo?

Back 17

This removes exogenous Estrogen-progestin stimulation. This stimulates corpus luteum involution and the endometrium sloughs causing menstruation. This provides lighter menstrual periods and a more regular cycle.

Front 18

With the oral tablets, there are 3 types of contraception. Monophasic, biphasic and triphasic. Explain the difference between the 3

Back 18

Monophasic - Constant Estrogen/Progesterone for 21 days
Diphasic - Constant Estrogen for 21 days, Progesterone increases in later cycle
Triphasic - Midcycle increase in estrogen, Progesterone increases in later cycle

Front 19

What is the advantage of progesterone only contraceptive formulations?

Back 19

They are advantageous in women with high risk of breast cancer and that want to avoid estrogen supplementation

Front 20

Name the 2 progesterones used

Back 20

Norgestrel
Norethindrone

Front 21

It comes in 2 formulations, an implant and an injectable. Name each and how long it is effective.

Back 21

Etonogestrel - Effective for 3 years

Medroxy PG acetate - given parentally every 3 months

These require a higher dose than the estrogen-progesterone formulation.

Front 22

Progestin formulations have 2 mechanisms of feedback, primary and secondary. Explain each.

Back 22

The primary mechanism is that it feedback inhibits on the HPA axis and prevents the necessary LH/FSH surge for ovulation. However this is only effective 70-80% of the time.
The secondary mechanism is associated with the fact that an egg can't implant in a uterus that is constantly exposed to progesterone.

Front 23

How does emergency contraception work?

Back 23

It is a high dose of progesterone given to quickly feedback inhibit the LH surge needed for implantation

Front 24

Male contraception is challenging because even 1% spermatogenesis keeps you fertile. What is used for male contraception?

Back 24

Parenteral testosterone enanthate + oral levonorgestrel daily. The androgen/progesterone combination feedback inhibits the HPA axis.

Too much androgen increases the size of the prostate and increases the risk of prostate cancer.

Front 25

The goal of therapy for peri and post menopausal women is to prevent urogential tissue degeneration and vaginal dryness.

Back 25

Women with a uterus get estrogen and progesterone
Women without a uterus can get only estrogen.

Local delivery with a vaginal ring is preferred to avoid systemic absorption and side effects.

Therapy is indicated only to treat bothersome symptoms and only for a short period of time.

Front 26

Athletes using androgens for performance take androstenedione and dehydroepiandrosterone. This increases fat free muscle mass also causes infertility and gynecomastia. Why is this?

Back 26

The increased androgens feedback inhibit the HPA axis and decrease LH/FSH thereby suppressing gondal function.

The more androgen you give, the more is going to be converted via aromatase to estrogens. Therefore, gynecomastia.