Antiandrogens & Androgen Inhibitors

Question 1

T/F
Free testosterone and dihydrotestosterone (DHT) are biologically active androgens that affect various target tissues such as the pilosebaceous unit

Answer 1

True

Question 2

What is anti androgen ?

Answer 2

Agents that block the androgen receptor (AR)

Eg. Spironolactone
Flutamide
Cyproterone acetate

Question 3

What is an androgen inhibitor ?

Answer 3

Agents that block androgen synthesis

Eg
Finasteride
Dutasteride
- both 5a reductase inhibitors
Leuprolide (GnRH agonist)

Question 4

T/F

Sex hormones affect T-helper 1 (Th1)/Th2 cell balance

Answer 4

T

We now know that androgens affect this balance

Question 5

Androgen and oestrogen receptors are present on most immune competent cells

Answer 5

T

Question 6

List dermatologic androgen excess disorders

Answer 6

Acne vulgaris
Androgenetic alopecia
Hirsutism
HS

Question 7

T/F

5-a reductase type I isoenzyme is found predominantly on genital skin and sebaceous gland ducts

Answer 7

F
This is in non genital skin : sebaceous gland lobules , liver , kidney , spleen

Type 2 is found in hair follicles and sebaceous gland ducts , genital skin of men and women , urogenital tract of men

Question 8

T/F

Canrenone is the active metabolite of spironolactone

Answer 8

T

Question 9

T/F

Protein binding of spironolactone is 13-25%

Answer 9

False
13-25% protein binding for cimetidine
Spironolactone is 98% protein bound

Question 10

T/F

All antiandrogens are renally excreted

Answer 10

False

Spironolactone predominantly hepatobiliary route

Medroxyprogesterone acetate especially renal and also hepatobiliary

Cimetidine predominantly renal

Question 11

T/F

Spironolactone does not inhibit 5-a reductase

Answer 11

T

Aldosterone antagonist and a relatively weak antiandrogen that blocks the AR and inhibits androgen biosynthesis

Question 12

T/F

Food increases absorption of spironolactone

Answer 12

T

Question 13

T/F

Finasteride is extensively metabolized in the liver to inactive metabolites

Answer 13

True

Question 14

T/F

Of the antiandrogens and androgen inhibitors , Spironolactone has the greatest bioavailability

Answer 14

True >90%
Others ~60-69%

Or variable (medroxyprogesterone acetate)
Or unknown (ketoconazole)

Question 15

T/F

Drosperinone has antiandrogenic activity but no androgenic, estrogenic or glucocorticoid activity

Answer 15

True

Question 16

What is the role of type 2 5a reductase ?

Answer 16

Catalyses conversion of testosterone to DHT

Question 17

T/F

Finasteride binds to the androgen receptor

Answer 17

F

Not anti androgen

Question 18

MoA of finasteride

Answer 18

Type 2 5-a reductase inhibitor

May inhibit local level of DHT in hair follicle

May have secondary effects on AR by suppressing DHT and via feedback mechanisms that affect AR levels

Question 19

Spironolactone had half life of 2h

Answer 19

F

10-35h

Question 20

Finasteride inhibits both type 1 and 2 5a reductase

Answer 20

F
Type 2 only
Distasteride inhibits both

Question 21

Finasteride is metabolized by Cyp3A4

Answer 21

Yes

Question 22

Ketoconazole has secondary pharm effect of inhibiting cyp3a4 enzymes involved in steroid hormone biosynthesis
– reduced production of both GC and androgenic steroids

Answer 22

T

Question 23

Spironolactone increases LH

Answer 23

F

Decreased response of LH to GnRH leading to lower LH:FSH ratio

Question 24

Spironolactone is more effective at reducing hirsutism than finasteride

Answer 24

T

Question 25

Strongest CI for Spironolactone is agents that increased risk of hyperK+ Eg ACE inhibitors , ARBS, other aldosterone antagonists

Answer 25

T

Question 26

``` Half lives Spironolactone Medroxyprogesterone acetate Cimetidine Finasteride Dutasteride Ketoconazole ```

Answer 26

``` Spironolactone 10-35h Medroxyprogesterone acetate 8-9h Cimetidine 2h Finasteride 4-8h Dutasteride4-8h Ketoconazole 8h ```

Question 27

``` Protein binding of Spironolactone Medroxyprogesterone acetate Cimetidine Finasteride Dutasteride Ketoconazole ```

Answer 27

``` Spironolactone 98% Medroxyprogesterone acetate varies Cimetidine 13-25% Finasteride 90% Dutasteride 90% Ketoconazole 95-99% ```

Question 28

``` Excretion Spironolactone Medroxyprogesterone acetate Cimetidine Finasteride Dutasteride Ketoconazole ```

Answer 28

All predominantly faecal except cimetidine and medroxy is predom renal