Anti-Androgenic Drugs

ANTI-ANDROGENIC DRUGS

• MOA: Acts by inhibiting synthesis, activation or action of androgens.

Drug groups:

I) Steroid synthesis inhibitors:

• Drugs included: Ketoconazole & Abiraterone.

Ia) Ketoconazole:

• MOA:
  • Inhibits synthesis of adrenal & gonadal hormones.
  • On prolonged use – Serious toxicity limits usage in treatment of prostatic carcinoma.
• Adverse effects:
  • Cause gynaecomastia – Due to increase in estradiol:testosterone ratio.

Ib) Abiraterone:

• Orally active prodrug.
• MOA: 
  • Acts by inhibiting 17-α-hydroxylase & 17, 20-lyase.
• Reduces synthesis of both cortisol & androgens.
• Approved for castration-resistant refractory prostate cancer.

II) 5-α reductase inhibitors:

• 5-α reductase –
  • Most testosterone actions are mediated by its conversion to DHT by 5-α reductase.
  • Actions mediated include growth of prostate, male pattern baldness & hirsutism in females.
• Drugs: Finasteride & dutasteride.
• Uses: BHP treatment, male pattern baldness & hirsutism – By reducing DHT production.

III) Androgen receptor inhibitors:

• MOA: 
  • Acts as antagonists of androgen receptors.
• Drugs: 
  • Cyproterone, cyproterone acetate, flutamide, bicalutamide, enzalutamide, nilutamide.
• Cyproterone acetate:
  • Marked progestational activity.
  • A component of contraceptive pills.
  • Inhibits feedback enhancement of LH & FSH.
• Uses: 
  • Hirsutism treatment.
  • Treatment of prostatic carcinoma.
• Flutamide:
  • Cause gynaecomastia & reversible liver damage.
  • Combined with GnRH agonists (like leuprolide) – To reduce initial flare-up reaction.

IV) Aldosterone antagonist:

• Spironolactone:
  • Competes with DHT for its receptor.
  • Used for hirsutism treatment & in heart failure.

Don’t Forget to Solve all the previous Year Question asked on ANTI-ANDROGENIC DRUGS