Gonadal Hormones: Androgens Flashcards
What are the various androgens?
Testosterone: natural Synthetic Androgens: 17 alkyl derivatives with increased anabolic effects: Oxandrolone Methyltestosterone Stanozolol Fluoxymesterone Nandrolone Oxymetholone Danazol
DHT: dihydrotestosterone is more potent than testosterone (testis) and androstenedione (Adrenal gland). What are some functions of testosterone and DHT?
Testosterone:
–Genitalia: development of penis, seminal vesicles, sperm, muscle mass and RBCs. Differentiation of epididymis, vas deferens, seminal vesicles. Libido and deepening of voice
DHT (dihydrotestosterone):
–differentiation of penis, scrotum and prostate
–prostate gland growth, balding and sebaceous gland activity
Testosterone via 5 alpha reductase gets converted to Dihydroxy Testosterone, what are the effects of testosterone and DHT?
Testosterone: development of penis, seminal vesicles, sperm, muscle mass and RBCs
–differentiation of epididymis, vas deferens, seminal vesicles, libido, deepening of voice, closing epiphyseal plates
DHT: early: differentiation of penis, scrotum, and prostate and late: prostate gland, growth, balding sebaceous gland activity
The drugs for androgens are what?
Androgens (Testosterone) Antiandrogens --receptor antagonists: flutamide ---5 alpha reductase inhibitor: Finasteride ---Synthesis inhibitors: ketoconazole --GnRH agonists
What are the clinical uses of Androgens?
Substitution therapy in hypogonadism
Increases bone density (prevents osteoporosis), could be used in increasing muscle mass
Some cases of aplastic anemia
Admin: transdermal, buccal, subcutaneous implant and IM
What are the adverse effects of Androgens?
Over masculinization
In women: hirsutism, suppression of menses, acne and clitoral enlargement
Hepatic adenomas and prostatic hypertrophy
Cholestatic Jaundice (elevated serum transaminations)
Aggression and Dependency
Premature closure of epiphysis
illicit use in Athletes
–over dosage of androgens can result in feminization as a result of negative feedback inhibition and conversion of exogenous testosterone into estrogen
The first drug is Danazol, what does this drug do?
Is an inhibitor of P450 in gonadal steroid synthesis
Its an androgen derivative, a partial agonist of progestin and glucocorticoid receptors
Used in endometriosis and fibrocystic disease of the breast
What are AE of Danazol?
AE: hepatitis: abnormal liver function tests and drug interaction due to P450 inhibition
It is modified testosterone shows some signs of masculinizing effects: acne, hirsutism, menstrual disturbances
What are the antiandrogen drugs?
Androgen Receptor Antagonists:
- -Flutamide
- -Bicalutamide
- -Nilutamide
- -Cyproterone
- -Spironolactone
- -Ketoconazole
What androgen receptor blockers are used for androgen receptor positive cancers?
Flutamide: a substituted anilide
Bicalutamide
Nilutamide
Primarily used in conjunction with GnRH analogs
–Leuprolide (to decrease initial tumor flare ups of prostate cancer)
How does Spiranolactone produce antiandrogen action?
Blocks aldosterone and competes with androgen receptors
–it is used in hirsutism
How does Cyproterone produce antiandrogen action?
It has progesteronal effect suppresses LH and FSH. Used in hirsutism and to decrease excessive sexual drive in men
What is ketoconazole used for?
Oral
Adrenal and Gonadal Steroid Synthesis Inhibitor
Use: in prostate cancer but not 1st line
AE: may have drug interactions with other steroids due to decrease P450
The 5 alpha reductase inhibitor is Finasteride (Propecia), what are the uses and AE?
Oral
Inhibits conversion of testosterone to DHT
Use: BPH and promote hair growth
AE: gynecomastia, teratogenicity and impotence
How do 5 alpha reductase inhibitors work in the treatment for BPH?
Finasteride and Dutasteride: act by reducing the size of the prostate gland
–tx for 6 to 12 months is generally needed before prostate size in sufficiently reduced to improve symptoms
Side Effects: decreased libido and ejaculatory or erectile dysfunction
