Flashcards in Pharmacology of Androgens Deck (34)
What are the 3 androgens?
3. Dehydroepiandrosterone (DHEA)
What is the main difference between testosterone and estradiol?
- methyl group on testosterone's 4 ring structure
What produces androgens?
- testis= leydig cells
- adrenal glands
- ovary= theca cells
Can production of testosterone come from progesterone?
YES via cytochrome P450 to androstenedione and then to testosterone.
To what is testosterone metabolized in the prostate?
- 5-alpha dihydrotestosterone (DHT) via 5 alpha reductase.
*testosterone is unchanged in other tissues (muscle, kidney...)
What is the most potent androgen required for sex development?
What regulates androgen production?
- LH from the anterior pituitary
*receptors for LH are found on Leydig cells in the testes.
Where else are androgens produced?
- adrenal cortex
What regulates sertoli cells in the testes?
- FSH from the anterior pituitary
What stimulates the adrenal glands to secrete cortisol and sex steroids?
What is sex hormone binding globulin (SHBG)?
- serum glycoprotein derived from liver that binds testosterone in circulation
What INCREASES sex hormone binding globulin (SHBG)? (aka less free testosterone in the circulation)
What DECREASES sex hormone binding globulin (SHBG)? (aka more free testosterone in circulation)?
What are the pharmacologic actions of androgens?
- sperm production
- positive nitrogen balance
- growth/development of hair, bone, and muscle.
*** What is the major use for androgens?
- replacement therapy in men who have reduced testosterone production (primary testicular insufficiency).
What are the available IM injection testosterones?
- cypionate= 2-3 weeks
- enanthate= 2-3 weeks
- propionate= 1-3 days
Where is a testosterone transdermal patch applied?
- scrotal skin bc it's thinner than other epidermis.
What are the actions of anabolic steroids (synthetic derivatives of testosterone)?
- increase muscle mass
- increase physical performance
- increase linear growth (children)
**** What is OXANDROLONE (anavar; oxandrin)?
- anabolic steroid used for PRIMARY and SECONDARY testicular failure.
- increases expression of secondary sex characteristics
*** What is secondary testicular failure?
- insufficient stimulation of testes by pituitary gonadotropins (hypogonadotropic hypogonadism).
What is an ADR of using androgen therapy to increase height of short children?
- premature closure of epiphyseal plates and virilization.
*best to combine with GH
What are the therapeutic uses of androgens?
- treatment of aplastic anemia (erythropoiesis)
- inoperable breast cancer
- postpartum breast pain
**** What is DANAZOL (danocrine)?
WEAK androgen used for the treatment of:
- fibrocystic breast disease
What was the result of using testosterone supplementation to treat men with multiple sclerosis (MS)?
- improvement in cognitive performance
- slowing of brain atrophy
- increase in lean body mass
- potential neuroprotective effects in men with relapsing-remitting MS
What are some dose related ADRs of androgens (due to feedback inhibition as dose increases)?
- priapism (sustained erection); not due to feedback inhibition.
- suppression of gonadotropin
- decreased size of testis
- decreased spermatogenesis
- weight gain
- Na+ retention (edema, HTN)
- decreased HDL (atherosclerosis)
- hepatotoxic (jaundice, carcinoma)
- prostatic cancer
What are some ADRs of androgen use in females?
- DO NOT use in pregnancy (category x)
What is "Roid Rage"?
- feeling of invincibility to physical challenges
What must AndroGel and Testim now do on product labels?
- include boxed warning of ADRs
What are some toxic effects of anabolic steroids used by weightlifters?
- acne conglobata= papules, pustules, abscesses, and deep ulcerations.
What are contraindications for androgens?
- breast carcinoma
- prostate carcinoma
- serious cardiac, hepatic, or renal disease
- pregnancy (female)
**** How can we suppress synthesis of androgens (primarily used to treat SYMPTOMS of men with prostate cancer)?
1.stimulate feedback inhibition= GnRH agonists (LEUPROLIDE; lupron), which decreases testosterone production over time.
2. GOSERELIN ACETATE implant= LHRH analogue (GnRH analogue)
3. NAFARELIN= GnRH analogue nasal spray.
4. DEGARELIX= LHRH ANTagonist, which decreases testosterone rapidly.
5. suppress synthesis of androgen= KETOCONAZOLE, which decreases cytochrome P450.
6. 5 alpha-reductase inhibitors (FINASTERIDE and DUTASTERIDE)= suppress synthesis of androgen.
7. CYP17 inhibitor (ABIRATERONE)= suppress androgen synthesis in other cells other than the prostate.
8. blockade of androgen receptor= FLUTAMIDE, ENZALUTAMIDE, and SPIRONOLACTONE
*** What is a problem with ketoconazole?
- can block production of cortisol, so you may need to add corticosteroid when using this to suppress androgen synthesis.
Does finasteride or dutasteride (5 alpha-reductase inhibitors) suppress synthesis of androgen more quickly?
*dutasteride has a longer half-life though.