Pharmacology of Androgens and Anti-Androgens Flashcards
STEROIDOGENESIS:
Where are Androgens secreted from?
What does LH stimulate?
What does FSH stimulate?
- Testes (Leydig cells), Ovaries (Theca cells) and Zona Reticularis of adrenal glands
- Leydig cells for Testosterone/DHT production
- Sertoli cells for AMH, Inhibin B secretion and Spermatogenesis
TESTOSTERONE:
What’s its function?
What’s its role in Sexual Differentiation?
How it converted to DHT?
→ Where does this occur?
Dihydrotestosterone (DHT):
How does it act?
What’s its role in Sexual Maturity?
What does it cause?
What will happen if theres a Deficiency in 5-α Reductase?
Adverse Effects:
What are the main ones?
What promotes hair loss?
→ So, how can the Male pattern baldness be treated?
How is Gynaecomastia caused?
- Initiates and maintains Spermatogenesis
- Development of Wolffian (Mesonephric) duct into INTERNAL genitalia
- By 5-α REDUCTASE
→ Every cell type, EXCEPT MUSCLE
- Binds to same receptor as Testosterone, but is MORE POTENT - amplification of the actions of testosterone
- Development of secondary sexual characteristics, and acts on EXTERNAL genitalia to develop into male form
- • Enlargement of Penis and Prostate at puberty
• Facial hair, Acne, RECEEDING HAIRLINE - No DHT = - Testes develop but without prostate and External genitalia resemble those of females
- • Ca, Na, and Water retention = HTN and Oedema
• Liver cancer, Cholestatic Jaundice
• Suppression of HPG axis - ↓↓↓LH/FSH leads to Testicular regression and reduced Spermatogenesis
• Premature fusion of epiphyses of long bones
• Virilisation, Hirsutism, Male pattern baldness
• Headache, Anxiety, Depression, Gynaecomastia
(due to over-conversion of Testosterone to Oestrogens by Aromatase) - DHT
→ 5α-reductase inhibitors - Over-conversion of Testosterone to Oestrogens by AROMATASE
ANABOLIC STEROID ABUSE:
What are Large doses effective in?
What occurs with Steroid use?
How does it affect the Testes? What does this lead to?
How does it affect the Liver?
- Increasing muscle mass and performance
- Virilisation - Libido, Hair growth, Aggression, Acne, Weight gain
- Suppression of Testicular growth and Spermatogenesis = Infertility
- Hepatoxicity, Inflammation, Malignancies
PHARMACOLOGY:
Synthetic GnRH - Example? How can it be given? What’s the effect?
GnRH Agonists - Example? What does it cause initially? What does it become after this initial effect?
GnRH Antagonists - Example? How does its effect differ from GnRH Agonists?
Androgen Antagonists - Example? What does it do?
What is DANZOL?
- GONADORELIN;
o Given Continuously to disrupt the pulsatile rhythm, leading to ↓LH/FSH
o Given in Intervals to mimic GnRH pulses for use in GnRH replacement - BUSERELIN;
o Cause an initial surge in LH/FSH before acting as Antagonists in the long term - CETRORELIX;
o No initial surge in LH/FSH - CYPROTERONE;
o Inhibits peripheral androgen receptors - Androgen derivative, but isn’t converted to Oestrogen, therefore there is no negative feedback on GnRH and LH/FSH
HYPOGONADAL SYNDROMES:
What’s Delayed Puberty?
What can cause Primary Delayed Puberty? What is it?
→ How is it treated?
What can cause Secondary Delayed Puberty? What is it?
→ How is it treated?
What can Precocious Puberty be treated with?
- Where testes fail to produce Testosterone in response to LH (Primary), or where there’s a deficiency of LH/FSH (Secondary)
- Klinefelter syndrome - High LH/FSH due to lack of Testosterone and negative feedback
→ Treated with Testosterone and GH - Kallmann syndrome - Low LH/FSH
→ Treated with GONADORELIN or LH/FSH - Androgen antagonists e.g. Cyproterone
PROSTATE CANCER AND HYPERPLASIA:
What stimulates Prostate growth?
What can be given to treat this hyperplasia/cancer?
- TESTOSTERONE and DHT
- • Androgen antagonists
• GnRH analogues given continuously to ↓LH/FSH
• GnRH antagonists given to ↓LH/FSH
• Oestrogens given to ↓androgen-dependent prostate cancer
• Anti-androgens compete with Testosterone and DHT
• 5-α Reductase Inhibitors suppress prostate cancer cells and inhibit androgen-dependent prostate cancers
