Androgens, Antiandrogens, and Erectile Dysfunction-Burkin Flashcards
What are the antiandrogen drugs?
- Danazol
- Finasteride
- Bicalutamide
- Flutamide
- Leuprolide
- Spironolactone
- Cyproterone acetate
What are the androgen drugs?
Methytestosterone Fluoxymesterone Stanozolol Testosterone esters PDEII inhibitors
What is this:
Enzyme that converts testosterone to DHT
5alpha-reductase
What is this:
androgen receptor agonists used for anabolic effects
Anabolic steroid
What is this:
genetic disease characterized by C1 esterase inhibitor deficiency
Hereditary angioedema
What do androgens do?
convert early bipotential gonad into testes
masculinization of the male fetus (penis and scrotum formation)
support sperm production
vocal chord enlargement
regulate sex drive and aggression
inhibit fat deposition
increase muscle mass
What does androgen do to skin?
growth of facial and body hair
baldness
What does androgen do to male sex organs?
sperm production
prostate growth
erectile function
What does androgen do to muscle?
muscle mass and strength
What does androgen due to bone marrow?
red blood cell production
What does androgen due to bone?
bone density maintenance
How many carbons do androgens have?
19 carbons
In males (blank) perecent of androgens are synthesized by the testes (leydig cells, under regulation of LH), 5% by the (blank)
95%
adrenal cortex
Adrenal pro-androgens are converted to androgens (DHT) in the (blank X 3)
liver, skin, and in adipose tissue
Where are androgens synthesized in females?
ovaries and adrenal cortex
Plasma testosterone concentration in males is (blank) times higher than in females
15 (2.5-10 mg/day males; .3 mg/day females)
(blank) percent of testosterone circulating in blood is bound to (blank)
98% plasma proteins (albumin and sex hormone-binding globulin)
The (blank) secrete small quantities of DHT. Larger quantities of DHT are synthesized from (blank) by their respective target cells.
testes
testosterone (via 5-alpha-reductase)
What are the 5 types of androgens?
Testosterone 5a-dihydrotestosterone (DHT) Dehydroepiandrosterone (DHEA) Androstenedione (Andro) Androstenediol
What is this:
a metabolite of testosterone
more potent than testosterone
produced by the adrenal cortex
DHT
What is this:
produced from cholesterol in the adrenal cortex and is th precursor of natural estrogens
DHEA (dehydroepiandrosterone)
What is this:
produced in the testes, adrenal cortex and ovaries
converted metabolically testosterone and other androgens
Androstenedione (Andro)
What stimulates leydig cells to secrete testosterone?
LH
What are the active metabolites of testosterone?
Dihydrotestosterone
Estradiol
What are the inactive metabolites of testosterone?
Androsterone
Etiocholanolone
What does FSH do to the male genitalia?
stimulates sperm cells to make sperm
What does inhibin do?
inhibits hypothalamic GnRH
Fill in the blank
GhRh->LH-> testis-> testosterone-> (blank) -> dihydrotestosterone
5 alpha reductase
What does testosterone do?
- gonadotropin regulation
- spermatogenesis
- sexual differentiation of Wolffian stimulation
What does DHT?
puberty stuff
- external virilization
- sexual maturity at puberty
Normal function of the androgen receptor.
Testosterone (T) enters the cell and, if (blank) is present, is converted into dihydrotestone (DHT). Upon steroid binding, the androgen receptor (AR) undergoes a conformational change and releases (blank). Phosphorylation (P) occurs before or after steroid binding. The AR translocates to the nucleus where (blank), (blank), and the recruitment of (blank) occur. Target genes are transcribed (mRNA) and translated into proteins
5-alpha-reductase
heat-shock proteins (hsps)
dimerization, DNA binding, coactivators
When are plasma testosterone highest during gestation? When is the next time it peaks? When is it the highest after?
2nd trimester
6 months old
17-80
What are the 2 types of androgens?
anabolic and androgenic
What do anabolic androgens do?
increases skeletal muscle growth and stimulates erythropoiesis
What do androgenic androgens do?
- male reproductive phenotype
- growth of male genitalia at puberty
- stimulation of long bone growth and eventual epiphyseal plate closure at puberty
- maintenance of male characteristics
- increased libido and aggressive behavior
What type of testosterone is this:
aqueous suspension for intramuscular use; 10-50 mg three times weekly
Testoject-50
What type of testosterone is this:
oily solution for intramuscular use: 10-25 mg 2 to 3 times weekly
Testex
What type of testosterone is this:
oily solution for intramuscular use: 50-400 mg every 2 to 4 weeks
Delatesiryl
What type of testosterone is this:
long acting oily solution for intramuscular use: 50-400 mg every 2 to 4 weeks
Depo-testosterone
Alkylation of the (blank) position decreases hepatic metabolism allowing these agents to be administered orally.
17a
Esterified derivative of testosterone decreases dissolution from depo injection allowing for (blank) administration
infrequent
What 17a -alkylated androgens are orally effective because they are able to decreae hepatic metabolism?
Danazol-danocrine
Methyltestosterone-oreton methyl, testre, virilon
What are the four types of 17a-alkylated androgens?
- Danazol (danocrine)
- Fluoxymesterone (halotestin)
- Methylotestosterone (oreton methyl, testred, virilon)
- Oxandrolone (oxandrin)
What do you use androgens for?
- hypogonadism
- reverse negative nitrogen balance in certain catabolic states
- stimulate erythropoiesis in severe anemia
- stimulation of bone growth in children
What is this:
infantile genitalia, long arms and legs, poor muscular development, increased body fat, reduced peak bone mass, high-pitched voice, sparse male-pattern body hair.
Prepubertal hypogonadism
Clinical manifestations of prepubertal androgen deficiency are usually obvious and associated with (blank)-the diagnosis is rarely missed.
How do you treat this?
Psychosocial distress Testosterone ester injections 2-3 years of therapy -T ethanate -Cypionate -Proprionate
What is used to treat low T, post-pubertal hypogonadism, delayed puberty and is used orally?
What are the long term or high dose side effects?
Methyltestosterone (android, testred, virilon)
Heart disease, stroke, liver disease, ruptured tendons/ligaments, improper bone development in adolescents
When is testosterone therapy recommended in men?
for men with consistent symptoms AND unequivocally low serum T
Men will get testosterone therapy if they have a serum total testosterone level < (blank) or serum free testosterone level < (Blank)
8 nmol/L
225 pmol/L
T or F
Do not offer testosterone to older men with low T w/out clincally signif symptoms of androgen deficiency
T
What are the sexual indications for T therapy?
low libido
erectile dysfunction
What are the musculoskeletal indications for T therapy?
- osteoporosis or high risk for fracture due to low bone mineral density
- decreased muscle mass or strength in men > 65
What are the neuropsychological indications for T therapy?
impaired cognition, irritability, other, mood changes, or declining energy and stamina
What are the testosterone formulas?
testosterone gel (androgel, testim) metered-dose pump (fortesta) Transdermal patch (androderm) Testosterone injections (2-4 weeks IM) Buccal tablet Subq pellet Oral preparations
What are the IM testosterone injections?
Testosterone cypionate
Testosterone enanthate
What are the subq pellets of T?
testosterone proprionate
What are the oral preparations of T?
Testosterone undecanoate
mesterolone
What are the adverse effects of T?
- erthrocytosis: monitor hematocrit levels
- acne, oily skin
- Prostate cancer: monitor PSA and rectal exam
- May increase CV events
- Induction or worsening of obstructive sleep apnea
- Gynecomastia or Breast tenderness
- Reduced HDL cholesterol
- Formulation specific adverse effects
What are the contraindications for T?
Breast cancer PROSTATE CANCER ERYTHROCYTOSIS obstructive sleep apnea Heart failure lower urinary tract symptoms due to BPH Desire for fertility
What is fluoxymesterone? What is the half life of it? Is it more or less potent than methyltestosterone?
Anabolic steroid
Long half life (9.5 hrs)
5x as potent as methyltestoterone
What is fluoxymesterone used to treat?
hypogonadism and delayed puberty
In women, for breast neoplasms
Androgen receptor agonist are used for (blank) effects. How does it work?
anabolic
mimics testosterone to build muscle tissue and promote muscle repair
What are anabolic steroids used to treat?
breast cancers, endometriosis
(small/large) doses required to produce profound effects on skeletal muscle growth
Large
What is stanozolol?
How is it taken?
What is it used to treat?
A synthetic anabolic steroid derived from DHT
High oral bioavailability
Anemia, and hereditary angioedema
What are the three synthetic anabolic steroids?
Stanozolol
Nadrolone
Methenolone