androgen and antiandrogens Flashcards Preview

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Flashcards in androgen and antiandrogens Deck (11):
1

most important androgen hormones (endogenous)

1. testosterone.
2. Dihydroepiandosterone (DHEA).
3. 5alphadiydrotestosterone.
4. andostenedione.

2

physiological functions of androgens

androgenic:
1. development of sec and prim sex char.
2. adult women- facial, body hair, deepend voice, enlargment of clitoris, frontal baldness.
3. adult male: spermatogenesis, increased libido.
4. anabolic: nitro excretion reduced, protein synthesis increased, decreased protein breakdown.

3

steroid with anabolic and androgenic actions:

1. testosterone 1:1.
2. methyltestosterone- 1:1
3. flouxymesterone- 1:2
4. methandienone- 1:3.
5. oxymetholone- 1:3
6. ethylestrenol- 1:4-1:8.
7. oxandrolone- 1:3-1:13
8. nandrolone: 1:3-1:6
9. stanozolol- 1:3-1:6.
10. dromostanolone- 1:3-1:4.

4

indications

. 1) Male primary /secondary hypogonadism—testicular dysfunction or hypothalamus respectively.
2) Chronic wasting due to HIV or cancer.
3) Danazol- used for endometriosis or fibrocystic breast disease.
4) Danazol, stanozolol can be used for hereditary angioedema (increased C1 esterase inhibitor synthesis).
5) Illegal use in sports.

5

adverse

1) Masculinizing action in women and children (hirsutism, acne, deepening of voice).
2) Some androgens with progestational activity- increased cardiovascular risk, endometrial bleeding upon discontinuation in women.
3) sodium retention, edema.
4) C-17 alkyl substituted steroids (most anabolic agents)- hepatic dysfunction (hepatic tumors, cholestasis, bilirubin and increased AST).
5) Weight gain, acne, decreased breast size, depend voice, increased libido / hair growth.

6

adverse

contraindication:
1) Pregnancy.
2) Prostate cancer.
3) Infants and young children.
4) Breast cancer in male.

7

anabolic steroids

Anabolic steroids:
Synthetic androgens with higher anabolic but lower androgenic activity (1:3 ratio)- decreased virilizing effect. It has similar anabolic effect, same recetpors and same androgenic effects.
Examples include nandrolone propionate (injected) or nadrolone decanoate (injected), stanazolol and more.

Therapeutic uses include:
1) catabolic states- acute illness, severe trauma, major surgery etc.
2) Renal insufficiency.
3) Osteoporosis.
4) suboptimal growth in boys.
5) anemia: hemolytic and malignancy associated.
6) performance enhancement.
Can cause: jaundice, hepatitis, benign or malignant carcinoma of liver and oliospermia.

8

leuoprolide

1) androgenic suppression with GnRH-analogs- leuprolide
GnRH analogs have a longer half-life (3 hours compared with GnRH – 4 minutes), they can be given intranasally
• leuprorelin, nafarelin, goserelin, histerelin, buserelin, triptorelin
• diagnostic use:
1) delayed puberty (constitutional delay – normal LH response hypogonadotropic hypogonadism due to pituitary/hypothalamic disease – impaired LH response
therapeutic uses
1) • stimulation – pulsatile GnRH (gonadorelin) therapy: every 90 minutes – infertility caused by hypothalamic hypogonadotropic hypogonadism in both sexes
2) • suppression – continuous therapy (GnRH analogs) – prostate cancer, uterine fibroids, endometriosis, polycystic ovary syndrome, precocious puberty
3) • in vitro fertilization programs – suppression followed by exogenous gonadotropins – synchronous follicular development

9

steroid synthesis inhibitors

2) Steroid synthesis inhibitors- ketoconazole and abiraterone
1) ketoconazole (antifungal drug) inhibitor of adrenal and gonadal steroid synthesis: clinical trials in hirsutism (women) and prostate cancer – not encouraging • causes sexual disturbances during the antifungal treatment
2) 17-hydroxylase inhibitors: abiraterone – treatment of prostate cancer

10

5 alpha reductase inhibitors

3) 5-reductase inhibitors- finasteride and Dutasteride
- DHT causes hair loss and prostate enlargement.
• finasteride, dutasteride (longer acting)
• Used for BPH and baldness.
• may be useful in male baldness and female hirsutism.

11

4) Androgen receptor antagonists

4) Androgen receptor antagonists
4)A) bicalutamide, enzalutamide, flutamide, nilutamide
• strong and pure androgen antagonists
• used in the treatment of metastatic prostate cancer
• flutamide has a mild hepatotoxicity