Androgen Receptor Antagonists

Question 1

Which are the Androgen Receptor Antagonists?

Answer 1

• Spironolactone (Aldactone)
• Flutamide (Eulexin) -tid
• Bicalutamide (Casodex) -QD
• Nilutamide (Nilandron)
• Cyproterone and Cyproterone Acetate

Question 2

What are the characteristics of Spironolactone (Aldactone)?

Answer 2

• competitively antagonizes the binding of DHT and aldosterone at their respective receptors
• used as a diuretic and to treat hirsutism in women usually in combination with estrogen

Question 3

What are the characteristics of:
Flutamide (Eulexin) -tid Bicalutamide (Casodex) -QD
Nilutamide (Nilandron)

Answer 3

• Pure androgen receptor blockers
• Used in prostate gland carcinoma
• Blocks testosterone receptor in prostate but also inhibits feedback mechanism in hypothalamus so more FSH and LH will be released; this leads to excess testosterone production by Leydig cells which tends to counteract the antagonism
• GnRH analog agonists are co-administered continuously to prevent further release of FSH and LH and hence reduce testosterone production
• Frequently causes gynecomastia (probably by increasing testicular estrogen production) GI disturbances, and hepatoxoicity
• Bicalutamide (Casodex) QD dosing – less GI disturbances
• Nilutamide (Nilandron) – approved for use after surgical castration (most toxic of the 3 agents)
• Flutamide can be hepatotoxic

Question 4

What are the characteristics of Cyproterone and Cyproterone Acetate?

Answer 4

• Act by competitively blocking the testosterone (androgen) receptor in target organs
• Used to treat hirsutism (doubles as a contraceptive) in women
• Decreases excess sex drive in men
• Orphan Drug status in US
• The acetate form has marked
  progestational ( agonist ) activity which can produce negative feedback on the hypothalamic progesterone receptor to counteract the enhancement of LH and FSH resulting from the blockade by of the hypothalamic feedback androgen receptor →leads to a more potent anti-androgen effect