Pharm - Androgens Flashcards
What tissues/cells synthesize androgens?
95% is from Leydig cells of tissue
5% is from adrenal glands
What are the natural androgens?
Testosterone
Dihydrotestosterone (DHT)
Androstenedione
Dehydroepiandrosterone (DHEA)
Describe the general process of androgen synthesis
Cholesterol is cleaved to form pregnenolone, wihch is converted to DHEA and Androstenedione. These compounds can be converted to testosterone.
What 3 outcomes can occur once testosterone diffuses into a target cell
1) Binds to androgen receptor directly
2) Converted to DHT and binds androgen receptor
3) Converted to estradiol and binds estrogen receptor
What two enzymes are responsible for converting testosterone into DHT and estradiol?
Aromatase converts testosterone to estrodiol
5alpha reductase converts testosterone to DHT
What are the reproductive functions of androgens?
Secondary male sex characteristics Puberty in females Promotes spermatogenesis (with FSH) Regulation of gonadotropin secretion
What are the anabolic functions of androgens?
Increase protein synthesis, lean body mass, skeletal muscle growth and reduce fat mass
Skeletal growth and epiphyseal closure
Growth of larynx at puberty (deepening voice)
What are the metabolic functions of androgens?
Erythropoiesis Decreased synthesis of clotting factors Increased sebum production Decrease HDL and increase LDL Androgenic alopecia
Symptoms of man with androgen deficiency
Decreased libido and erectile dysfunction
Decreased muscle mass, increased adiposity
Decreased axillary and pubic hair
Anemia
Osteoporosis
Decreased energy, sense of well being
What are the therapeutic uses of androgens?
HRT for hypogonadism
Induction of puberty
Treat osteoporosis in males
Indication for testosterone HRT
Hypogonadism
What are the major androgenic effects of androgen HRT?
Prostate growth/maturation
Growth of penis, scrotum, seminal vesicles
Development of male hair distribution
Laryngeal enlargement and vocal cord thickening
Increased muscle mass
What are the side effects of androgen HRT?
Cholestatic jaundice syndrome Liver carcinoma Benign prostatic hyperplasia (BPH) Prostate cancer Gynecomastia Acne Headache
What are contraindications of androgen HRT?
Breast cancer in men
Prostate cancer
Pregnancy
What is flutamide?
Androgen receptor antagonist used for metastatic prostate cancer and BPH
What is the mechanism of action of flutamide?
Competitive inhibition of DHT and T binding the receptor
What is the side effect of flutamide?
Hepatotoxicity Hematopoietic disorders Diarrhea Nausea Rash Hot flashes
What are contraindications of androgen receptor antagonsists?
Flutamide is contraindicated in patients with severe hepatic impairment
Flutamide, DES and leuprolide are all used for prostate cancer. Which is preferred?
Flutamide is better than DES and leuprolide for prostate cancer treatment. Especially effective in combination with medical or surgical castration.
What is spironolactone?
Androgen receptor antagonist (and mineralocorticoid receptor antagonist) used to treat: hirsutism, hypertension, acne, edema, cirrhosis, hypokalemia
What are the side effects of spironolactone?
GI hemorrhage Hyperkalemic metabolic acidosis Agranulocytosis SLE Gynecomastia Dyspepsia Abnormal menstruation/impotence
Contraindication for spironolactone
Anuria
Hyperkalemia
Acute renal insufficiency
What is finasteride?
A 5alpha reductase inhibitor used to treat BPH and androgenic alopecia
What is the mechanism of action of finasteride?
Prevents conversion of testosterone to DHT by inhibiting 5alpha reductase
