Clinical uses of Anti-Androgen drugs

Question 1

What are the three classes of drugs that can be used to oppose the work of androgens?

Answer 1

1) Androgen receptor antagonists
2) androgen synthesis enzyme antagonists
3) H-P axis inhibitors

Question 2

what are the AR antagonist drugs? what are their side effects/which is worse? how many times a day are they administered?

Answer 2

flutamide, biclutamide
flutamide is the original, biclutamide is the newer drug, and has less hepatotoxicity and is 1qD
other side effect is loss of H-P axis negative feedback -> hot flashes and loss of libido, requiring co-administration of a H-P axis inhibitor

Question 3

what are the H-P axis inhibitors?

Answer 3

leuprolide, degarelix

Question 4

what is the main indication for H-P axis inhibs? what is the natural history of treatment with these drugs?

Answer 4

Prostate cancer, since it is steroid sensitive

initially they work well, but over time, the cancer loses its sensitivity and pts are prone to relapse

Question 5

what’s the difference between the two HP axis inhibs?

Answer 5

Leuprolide acts only on the GnRH receptor and therefore causes a transient spike in levels of T before desensitization takes place
Degarelix is a GnRH ANTAGONIST, that also inhibits gonadotropin release, meaning that there will be no transient spike in T levels

Question 6

what are the 5alpha reductase inhibitors called?

Answer 6

Finasteride (propecia/proscar)

dutasteride (avolve/avodart)

Question 7

what are the two targets of the 5 alpha reductase inhibitors; what are their specificities; where are these enzymes located?

Answer 7

there are two forms of 5a-reductase, types 1 and 2
finasteride is relatively selective for type 2, but has some type 1 activity
dutasteride has activity at both
type 1 is mainly located at hair follicles
type 2 is mainly in the urogenital tract

Question 8

what are the main indications for these drugs? what are their limitations in these roles?

Answer 8

hair loss and BPH; BPH is limited (20% reduction in size, only if over 40ml) because the decrease in DHT levels is accompanied by an increase in T levels (10x) and/or inhibition of 5aR-ase causes a loss of a ligand for ERbeta which keeps prostate growth in check

Question 9

contraindications of finasteride/dutasteride

Answer 9

pregnant women due to birth defects (lack of sexual development in male fetuses); 3L of sperm, wow

Question 10

what is the treatment for CRPC (castrate resistant prostate cancer)?

Answer 10

a CYP17A1 inhibitor; specifically, abiraterone

Question 11

what are the effects of the CYP17A1 inhibitor?

Answer 11

blocks the formation of 17 hydroxyprogesterone from pregnenolone

Question 12

what must be co-administered with a CYP17A1 inhibitor?

Answer 12

prednisone; because you’ve blocked the creation of GCs