Androgens agonists and antagonists

What are androgens ? Steroid derived from cholesterol found in males and females Androgens produced by testes: 1.Testesterone (principal one) 2.Dihydrotesterone 3.Dehydroepiandrosterone 4.Androstenedione

Where is test. Produced? Testes Adrenal glamd Ovaries

Test. Produced from: Progesterone Dihydroepiandrosterone

Physiological effects of androgens Anabolic effects: – Increase body growth – Muscle mass – Red blood cells production Androgenic effects – Growth of larynx and skeleton – Facial hair – Darkening skin

Synthetic androgens Testosterone cypionate Oxandrolone Stanozolol Fluoxymesterone

Route of administration Injection Some can given orally like oxandrolon All of them have significant first pass effect – Hepatotoxic

Clinical uses Replacement therapy in male hypogonadism Promote growth in prepubertal boys

Toxicity of synthetic androgens Behavioral effects – Aggressiveness – Hostility Increase LDL\HDL ratio Stunted growth due to premature closure of epiphyseal plates In women:hairsutism,acne,clitoral enlargement In males decrease the spermatogenesis,testicular atrophy,prostatic hypertrophy,acne gynecomastia

Androgen antagonists 1.GnRH (which method of adm.? 2.Receptor inhibitors – Flutamide – Cyproterone 3.Steroid synthesis inhibitor – Ketoconazole – Spironolactone 4.5-alpha reductase inhibitor – Finasteride

Receptor inhibitors Cyproterone Flutamide – In combination with GnRH analogue to treat prostate cancer

Receptor inhibitors Cyproterone – Used to treat hairsutism in women – In combination with estrogens as OC

Synthesis inhibitor Ketoconazole – Inhibit CYP enzymes in adrenal gland – Not useful in females suffering from increased androgens – No promosing results in prostatic hypertrophy – Side effect:review

5 –alpha reductase inhibitor Finasteride – In combination with GnRH analogue or alone to treat prostate cancer – Benign prostatic hypertrophy5mg\d – Hairsutism 1mg\day – Propecia :frontal hair loss Side effects – Antiandrogenic SE – Erectile dysfunction – Hepatitis – Teratogenicity

Drugs used to treat erectile dysfunction 1.Sildenafil (viagra) 2.Vardenafil (levitera) 3.Tadalafil (cialis)

Mechanism of action Phosphodiesterase -5 inhibitor Increase cGMP Activate nitric oxide synthase release NO Relaxation of corpora carvenosa

Side effects Headache Flushing Alteration in color vision Pirapism In combination with nitrates cause hypotension