Fitzy's drugs that antagonize receptors; 4.8

Question 1

What are bicalutamide, flutamide, and nilutamide? (what are the -lutamides?)

Answer 1

-lutamide = Non-Steroidal Anti-Androgens (NSAAs)

Question 2

Which of the NSAAs is older and has more side effects?

Answer 2

Flutamide

Question 3

How do NSAAs work?

Answer 3

NSAAs inhibit ligand binding and translocation of androgen receptors from the cytoplasm to the nucleus

Question 4

What is seen with hormone levels with NSAAs?

Answer 4

Increased release of FSH and LH → increased testosterone synthesis…but no receptors so it doesn’t do anything

Question 5

When are NSAAs used?

Answer 5

Early prostate cancer with radiation

Metastatic prostate cancer with GnRH analogs

Question 6

GnRH analogs are used long-term. Are NSAAs used long-term?

Answer 6

NO…there would be bad side effects

Question 7

What are the common side effects of NSAAs?

Answer 7

Acutely: diarrhea, N/V
Delayed: Low testosterone, reversible liver function anomalies

Question 8

What are the categories of anti-estrogens?

Answer 8

Progestins

Estrogen receptor antagonists

Question 9

What are the progestins?

Answer 9

Hydroxyprogesterone
Medroxyprogesterone
Megestrol

Question 10

What are the two classifications of estrogen receptor antagonists?

Answer 10

Selective ER Down-regulators (SERDs)

Selective ER Modulators (SERMs)

Question 11

How do SERDs work?

Answer 11

SERDs are competitive antagonists in every tissue

Question 12

What is an example of a SERD?

Answer 12

Fulvestrant

Question 13

How is fulvestrant given?

Answer 13

Fulvestrant is given IM in the butt monthly

Question 14

What enzyme metabolizes fulvestrant? Does this cause any drug interactions?

Answer 14

CYP3A4 metabolizes fulvestrant…but it has NOT been determined to have drug interactions

Question 15

What are examples of SERMs?

Answer 15

Raloxifene
Tamoxifen
Toremifene

Question 16

Which SERM is an antagonist in breast tissue and an agonist in uterine tissue?

Answer 16

Toremifene

Question 17

Which SERM is an antagonist in breast AND uterine, but is an agonist in bone?

Answer 17

Raloxifene

Question 18

Which SERM is both an antagonist and partial agonist in breast, and then an agonist in BOTH uterus and bone?

Answer 18

Tamoxifen

Question 19

How are SERMs taken? Do they work faster or slower than SERDs?

Answer 19

SERMs are taken orally and peak in 4-7 hours…compared to fulvestrant which peaks in 7 days

Question 20

Which estrogen receptor drug is used in ER+ breast cancer in premenopausal women?

Answer 20

Tamoxifen is used with a GnRH analog

can also be used for prevention

Question 21

When would raloxifene, toremifene, or fulvestrant be used?

Answer 21

The non-tamoxifen SERMs and the SERD are used in metastatic ER+ breast cancer treatment if the the disease progresses after tamoxifen or aromatase inhibitor therapy

Question 22

What side effects are common to all estrogen receptor drugs?

Answer 22

Hot flashes
N/V
Menstrual irregularities
Vaginal bleeding
Dermatitis

Question 23

Besides the normal side effects, what are some possible consequences of tamoxifen treatment?

Answer 23

Endometrial cancer (2-3x)
Stroke (w/ long term use)

Question 24

Besides the normal side effects, what other side effects are common with fulvestrant?

Answer 24

GI symptoms
Headache
Back pain
Pharyngitis
Injection site reactions