Pharmacology-Androges:Anti-Androgens Flashcards
Major source of androgen in women
Zona reticularis makes 50% and ovaries make 50%, minor source in men (5%)
Main steroid hormone produced by zona reticularis?
DHEA. Androstenedione, androstenediol, and testosterone are made in minor amounts
What happens as a result of the pulse secretion of GnRH by the hypothalamus?
Anterior pituitary releases FSH and LH -> FSH stimulates spermatogenesis. LH stimulates Leydig cells to release testosterone -> testosterone completes stimulation of spermatogenesis.
What effect does testosterone have on cells that are only responsive to DHT?
It enters the cell and is reduced to DHT by 5-alpha reductase. Then DHT binds to androgen receptors causing them to dimerize. The complex then goes to the nucleus and turns genes on.
What are the effects of testosterone in growth and development?
Internal genitalia development (Wolffian development), skeletal muscle growth, deepens voice, erythropoiesis and bone.
What are the effects of DHT in growth and development?
External genitalia development and hair follicle stimulation
What are the effects of estradiol in growth and development?
Conversion of testosterone to estradiol by the aromatase is responsible for closure of epiphyseal plates.
Why can’t you take testosterone orally?
Normally it is inactivated by first pass liver metabolism and modified oral androgens at the 17alpha position can evade liver deactivation but have liver toxicity. These are also too weak to stimulate spermatogenesis.
What type of modification do we do to injectable androgens?
Fatty acids are esterified to 17beta position to prolong absorption after IM injection
What is the drug that you only inject 2x a month for testosterone replacement therapy?
Testosterone enanthate, modified at 17beta position
Nobody likes to get testosterone shots. What can you give instead of testosterone enanthate?
Testoderm patch (on scrotum), androderm patch (can be placed anywhere), androgel (rub on shoulders), testosterone buccal system and topical testosterone solution (like deodorant).
Clinical uses of androgens
Hypogonadism (LH/FSH), mutilated testicles, andropause (testosterone supplement), wasting states (HIV), hereditary angioedema, anemia (rarely).
Clinical uses of hydrocortisone or fludrocortisone in men?
CAH (21-hydroxylase deficiency): DHEA excess from lack of negative feedback by glucocorticoids can cause precocious puberty in males and virilization in females. Giving cortisol will feedback inhibit ACTH release by the hypothalamus and slow androgen production.
What clinical use of androgens prefers the orally active 17alpha alkylated androgens?
Hereditary angioedema. This is an AD disease where the 1st component of the complement cascade is low, complement is overactive and increases permeability of blood vessels causing angioedema. Danzol or stanozolol stimulates the synthesis of hepatic esterase inhibitor and can treat the condition if taken long term.
Adverse effects of androgen therapy?
Transfer of androgens to children, precocious puberty in children, virilization in women and jaundice w/orally active forms. Additionally, decreased libido, impotence, testicular atrophy, gynecomastia.
What is the pathophysiology behind testicular atrophy with steroid abuse? Gynecomastia?
Testicular atrophy: FSH & LH are inhibited by the exogenous steroids. Gynecomastia: CYP19 aromatize in liver converts testosterone to estrogen. Note that some abusers take tamoxifen with steroids to prevent gynecomastia.
When would you use anti-androgens?
Virilization prevention and BPH reduction
How does leuprolide work?
It is a GnRH agonist with stimulates continuous secretion of GnRH which causes regression of GnRH receptors in the anterior pituitary. This reduces FSH and LH secretion which will decrease testosterone production by the testis.
GnRH receptor antagonist used to treat BPH
Abarelix, prevents GnRH activation of GnRH receptor in pituitary and prevents excess release of LH and FSH, reducing testosterone production by the testis.
Anti-androgen used in hirsutism in women?
Cyproterone acetate: antagonist at the androgen receptor AND an agonist at the progesterone receptor.
Competitive androgen receptor antagonists used for metastatic prostate cancer?
Flutamine (hepatotoxic), bicalutamide (less toxic) and enzalutamide (best).
This drug blocks 5alpha-reductase type II in treatment of BPH?
Finasteride (testosterone is still able to keep muscle mass up) shrinks prostate size
This drug blocks 5alpha-reductase types I and II in all tissues for BPH treatment?
Dutasteride shrinks prostate size
How can we let the urine flow in patients with urinary hesitancy due to BPH?
Alpha1 adrenergic receptor antagonists (tamsulosin is only alpha1a antagonist, used in normotensive patients) and 5alpha-reductase inhibitors used in combination.
