Androgens and Anabolic Steroids and Anti-androgens.pptx

Androgens and Anabolic Steroids

1. Androgens, Anabolic Steroids and Anti-androgens By Dr. Faraza Javaid

2. Introduction Androgen anabolic steroids are synthetic types of male sex hormone – Testosterone. Anabolic – Building of muscle tissue Androgenic – Masculine characteristics Steroid – Any fat-soluble organic compounds (such as sterols, bile acids and hormones) that have specific physiological effects.

3. History 1935 – Testosterone was first synthesized, and German soldiers were reportedly using it to perform better and to become more aggressive. 1950 – During 1952 Olympics, the Russian weightlifting team won he gold medal due to synthetic steroid use. Australian pharmaceutical company develops the first anabolic steroid .

4. Classification Natural Androgens From testis: Testosterone (5-12 mg daily) Dihydrotestosterone From adrenal cortex: Dehydroepiandrosterone (Female testosterone – 0.25 – 5 mg/day [ovary + adrenals])

5. Synthetic Androgens Methyltestosterone Fluoxymesterone Orally effective: Testosterone undecanoate, Masterolone Lipid soluble ester: Propionate, Enanthate salts Oxandrolone and Stanozolol – Anabolic action only.

6. Testosterone AR receptors exist in multiple tissue type. Binds ligand in the cytoplasm and translocate into the nucleus. Upon binding, facilitate appropriate gene activation.

7. Pharmacological Actions Androgenic Effects: In the fetus , testosterone promotes development of male reproductive tract. During puberty , testosterone promotes the development of: Primary sexual characteristics Secondary sexual characteristics During adulthood , it may cause baldness, benign prostatic hyperplasia and prostate cancer.

8. Anabolic Effects: Bone growth – Thickness and length Fuse of bone and mineralization - Estrogen from testosterone Muscle building – If aided by exercise

9. Pharmacokinetics Absorption: Undergoes high first pass metabolism. Therefore, IM injections or synthetic oral preparations are used. Metabolism and Excretion: Metabolized by liver enzymes to androsterone and excreted in urine.

10. Side Effects In females , Virilization (Masculinization) Hirsutism Acne, Menstrual disorders In males , gynecomastia, salt and water retention Gall bladder stone Prostate enlargement Prostate cancer

11. Clinical Uses Replacement therapy in testicular failure Hypopituitarism AIDS related muscle wasting

12. Antiandrogens Antiandrogens , also known as  androgen antagonists  or  testosterone blockers , are a class of  drugs   that prevent  androgens   like   testosterone  and  dihydrotestosterone   (DHT) from mediating their  biological effects   in the body. They act by  blocking   the   androgen receptor   (AR) and/or  inhibiting   or   suppressing   androgen   production .

13. Flutamide Bicalutamide Nilutamide Topilutamide Enzalutamide Apalutamide Spironolactone

14. Finasteride Dutasteride Epristeride Alfatradiol

15. Flutamide Flutamide acts as a  selective   antagonist   of the  androgen receptor , competing/with  androgens   like   testosterone   and   dihydrotestosterone (DHT) for binding to ARs in tissues like the   prostate gland .  Uses: U sed primarily to treat  prostate cancer .  It is also used in the treatment of  androgen-dependent conditions   like   acne ,  excessive hair growth , and   high androgen levels   in women .

16. Side Effects: Diarrhea   and   elevated liver enzymes   can occur in both genders . F lutamide can cause   liver damage ,  lung disease ,  sensitivity to light ,  elevated methemoglobin ,  elevated sulfhemoglobin , and   deficient neutrophils . Numerous cases of  liver failure   and death have been reported, which has limited the use of flutamide.

17. Bicalutamide I t is used for  early prostate cancer   at a higher dosage as a monotherapy. It is the most widely used antiandrogen in the treatment of prostate cancer, and has been prescribed to millions of men with the disease. Bicalutamide is  well-absorbed , and its absorption is not affected by food. The   elimination half-life   of the medication is around one week. It is believed to cross the  blood–brain barrier   and affect both the body and brain

18. Uses: Bicalutamide is also used to treat  excessive hair growth   in women ,  as a component of  feminizing hormone therapy   for   transgender women ,  T o treat  early puberty   in boys

19. Side Effects: Common side effects in men include  breast enlargement ,  breast tenderness , and   hot flashes .  Other side effects in men include  feminization   and   sexual dysfunction. Rarely, it has been associated with cases of  liver damage ,   lung toxicity ,  and   sensitivity to light .   Although the risk of adverse liver changes is small,   monitoring of liver function   is recommended during treatment .

20. Spironolactone Spironolactone also possess an antiandrogenic effect which could be due to the antagonism of androgens. Spironolactone inhibits 5-alpha reductase weakly. For this reason, it is frequently used to treat a variety of  dermatological conditions   in which androgens play a role. Some of these uses include  acne ,  seborrhea ,  hirsutism , and  pattern hair loss   in women.

21. The specific actions of spironolactone as an antiandrogen are not well understood. It appears to act at two sites: I t blocks androgens at the hair follicle/sebaceous gland and I t reduces the secretion of androgens from the adrenal gland . To check the effectiveness of this therapy, the hair growth and/or acne are assessed at 2 to 4 month intervals.

22. Finasteride Finasteride is a  5α-reductase inhibitor   and therefore an  antiandrogen .  It works by  decreasing   the   production   of   dihydrotestosterone   (DHT) by about 70%, including in the  prostate gland   and the  scalp . Uses: U sed to treat  hair loss   and   benign prostatic hyperplasia   in men. It can also be used to treat   excessive hair growth   in women and as a part of  hormone therapy   for   transgender women .

23. Adverse Effects:   Adverse effects   from finasteride are rare, however, some men experience  sexual dysfunction ,  depression , and  breast enlargement .  In some men, sexual dysfunction may persist after stopping the medication. It may also hide the early symptoms of certain forms of  prostate cancer.

24. Dutasteride Dutasteride is used for treating  benign prostatic hyperplasia  (BPH); also known as an "enlarged prostate".  It is approved by the  Food and Drug Administration  (FDA) in the U.S. for this indication. It is also used for  scalp hair loss  in men and as a part of  hormone therapy  in  transgender women .

25. Side Effects: Dutasteride has overall been found to be  well tolerated  in studies of both men and women, producing minimal  side effects .  Adverse effects include  headache   and   gastrointestinal discomfort .  Isolated reports of  menstrual   changes,   acne , and   dizziness   also exist.

26. Abiraterone A cetate Abiraterone acetate , is a medication used to treat   prostate cancer . Common side effects include   tiredness ,  vomiting ,  headache ,  joint pain ,  high blood pressure ,  swelling ,  low blood potassium ,  high blood sugar ,  hot flashes ,  diarrhea , and   cough . Other severe side effects include   liver failure   and   adrenocortical insufficiency .

27. Question? A 76 year old man complains of progressive difficulty starting his urine stream and having to get up several times during each night to urinate. Rectal examination reveals a generally enlarged, smooth surfaced prostate. Prostate specific antigen (PSA) titers are elevated. Finasteride treatment is started and eventually urine flow increases and prostate size decreases. Which of the following phrases best summarizes the mechanism by which finasteride caused symptoms relief? Blocks α -adrenergic receptors Blocks testosterone receptors Inhibits dihydrotestosterone synthesis Lower plasma testosterone by increasing renal clearance

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