Antiandrogens & Androgen Inhibitors Flashcards
T/F
Free testosterone and dihydrotestosterone (DHT) are biologically active androgens that affect various target tissues such as the pilosebaceous unit
True
What is anti androgen ?
Agents that block the androgen receptor (AR)
Eg. Spironolactone
Flutamide
Cyproterone acetate
What is an androgen inhibitor ?
Agents that block androgen synthesis
Eg Finasteride Dutasteride - both 5a reductase inhibitors Leuprolide (GnRH agonist)
T/F
Sex hormones affect T-helper 1 (Th1)/Th2 cell balance
T
We now know that androgens affect this balance
Androgen and oestrogen receptors are present on most immune competent cells
T
List dermatologic androgen excess disorders
Acne vulgaris
Androgenetic alopecia
Hirsutism
HS
T/F
5-a reductase type I isoenzyme is found predominantly on genital skin and sebaceous gland ducts
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
T/F
Canrenone is the active metabolite of spironolactone
T
T/F
Protein binding of spironolactone is 13-25%
False
13-25% protein binding for cimetidine
Spironolactone is 98% protein bound
T/F
All antiandrogens are renally excreted
False
Spironolactone predominantly hepatobiliary route
Medroxyprogesterone acetate especially renal and also hepatobiliary
Cimetidine predominantly renal
T/F
Spironolactone does not inhibit 5-a reductase
T
Aldosterone antagonist and a relatively weak antiandrogen that blocks the AR and inhibits androgen biosynthesis
T/F
Food increases absorption of spironolactone
T
T/F
Finasteride is extensively metabolized in the liver to inactive metabolites
True
T/F
Of the antiandrogens and androgen inhibitors , Spironolactone has the greatest bioavailability
True >90%
Others ~60-69%
Or variable (medroxyprogesterone acetate) Or unknown (ketoconazole)
T/F
Drosperinone has antiandrogenic activity but no androgenic, estrogenic or glucocorticoid activity
True
What is the role of type 2 5a reductase ?
Catalyses conversion of testosterone to DHT
T/F
Finasteride binds to the androgen receptor
F
Not anti androgen
MoA of finasteride
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
Spironolactone had half life of 2h
F
10-35h
Finasteride inhibits both type 1 and 2 5a reductase
F
Type 2 only
Distasteride inhibits both
Finasteride is metabolized by Cyp3A4
Yes
Ketoconazole has secondary pharm effect of inhibiting cyp3a4 enzymes involved in steroid hormone biosynthesis
– reduced production of both GC and androgenic steroids
T
Spironolactone increases LH
F
Decreased response of LH to GnRH leading to lower LH:FSH ratio
Spironolactone is more effective at reducing hirsutism than finasteride
T
Strongest CI for Spironolactone is agents that increased risk of hyperK+
Eg ACE inhibitors , ARBS, other aldosterone antagonists
T
Half lives Spironolactone Medroxyprogesterone acetate Cimetidine Finasteride Dutasteride Ketoconazole
Spironolactone 10-35h Medroxyprogesterone acetate 8-9h Cimetidine 2h Finasteride 4-8h Dutasteride4-8h Ketoconazole 8h
Protein binding of Spironolactone Medroxyprogesterone acetate Cimetidine Finasteride Dutasteride Ketoconazole
Spironolactone 98% Medroxyprogesterone acetate varies Cimetidine 13-25% Finasteride 90% Dutasteride 90% Ketoconazole 95-99%
Excretion Spironolactone Medroxyprogesterone acetate Cimetidine Finasteride Dutasteride Ketoconazole
All predominantly faecal except cimetidine and medroxy is predom renal
