Fitzy's drugs that decrease steroid concentrations; 4.8

Question 1

What is the goal of inhibiting LH and FSH secretion, inhibiting 5α-reductase, and inhibiting aromatase?

Answer 1

Decrease steroid concentrations

(LH/FSH inhibition…block upstream event)
(5α-reductase inhibition…no DHT)
(Aromatase inhibition…no estrone or estradiol)

Question 2

What kind of drugs are used to inhibit LH/FSH secretion?

Answer 2

GnRH analogs

GnRH antagonists

Question 3

Are goserelin and leuprolide GnRH analogs or GnRH antagonists?

Answer 3

Goserelin and leuprolide are ANALOGS of GnRH

Question 4

How are goserelin and leuprolide administered?

Answer 4

Continuous

Long-term

Question 5

How do GnRH analogs work?

Answer 5

Transient increase in steroid hormones (→ flare of symptoms) followed by down regulation (or desensitization) of GnRH receptors → decreased testosterone/estrogen

Question 6

When are goserelin and leuprolide used?

Answer 6

Advanced prostate cancer

Premenopausal women with ER+ breast cancer

Question 7

What is an example of a GnRH antagonist?

Answer 7

Degarelix

Centrorelix and ganerelix also…the “relix”es

Question 8

Does degarelix work faster or slower than goserelin/leuprolide?

Answer 8

Antagonists work faster than agonists…less than 3 days compared to 1-4 months

Question 9

When is degarelix used?

Answer 9

Assisted reproductive procedures
Prostate cancer
Breast cancer…maybe

Question 10

Although GnRH antagonists are generally WELL TOLERATED, what types of side effects may be experienced by patients?

Answer 10

Effects of low testosterone

Effects of histamine release (less so with degarelix)

Question 11

What are dutasteride and finasteride?

Answer 11

Dutasteride and finasteride are 5α-reductase inhibitors (RIDEuctase)

Question 12

When are 5α-reductase inhibitors used?

Answer 12

BPH
Male-pattern baldness
Prevention of prostate cancer

Question 13

Are the normal low testosterone side effects experienced dutasteride/finasteride patients?

Answer 13

Yes and no…everything except NO muscle wasting or decrease in bone density

Question 14

Who should be incredibly careful handling 5α-reductase inhibitor capsules?

Answer 14

Pregnant women…can have dramatic affects on male children

Question 15

Non-steroidal aromatase inhibitors are reversible. What are examples of non-steroidal aromatase inhibitors?

Answer 15

Aminoglutethimide
Anastrozole
Letrozole

Question 16

Which of the non-steroidal aromatase inhibitors is a first generation? What else does this drug do?

Answer 16

Aminoglutethimide is a first generation non-steroidal aromatase inhibitor

Also inhibits cholesterol → pregnenolone in adrenal gland

Question 17

What side effects are potentially seen with aminoglutethimide?

Answer 17

Acutely: mild nausea, fatigue, fever
Delayed: rash, adrenal insufficiency

Question 18

How should aminoglutethimide induced adrenal insufficiency be treated?

Answer 18

Hydrocortisone

Question 19

When shouldn’t hydrocortisone be given to an adrenal insufficient patient who is taking aminoglutethimide?

Answer 19

If the body has overcome the block by increasing ACTH…which can cause myelosuppression and can be aggravated by hydrocortisone

Question 20

Anastrozole and letrozole are 3rd generation aromatase inhibitors. What is an example of a steroidal 3rd generation?

Answer 20

Exemestane

Question 21

What are the potential side effects of 3rd generation aromatase inhibitors?

Answer 21

Acutely: mild nausea, headache
Delayed: Fatigue, increased appetite, hot flushes; polyarthralgia unique to AIs; decrease in bone density; may IMPROVE lipid numbers