Androgens/Antiandrogens Flashcards
What is the major site of androgen synthesis for females?
Zona reticularis
What is the major site of androgen synthesis for males?
Testes
What is the main hormone produced in the zona reticularis
DHEA (dehydroepiandrosterone)
Minor: androstenedione, androstenediol, testosterone
What are the different ways that androgens exist in circulation?
- Testosterone-estrogen binding protein: 30%
- Albumin bound: 68%
- Free: 2%
Active fraction: free+albumin bound
Testosterone can be converted to DHT or estrogen. What is the enzyme of each of those reactions?
Testosterone–>DHT: by 5alpha-reductase
Testosterone–>estrogen: by aromatase(CYP19)
So some of your testosterone gets converted to DHT. It acts on its androgen receptor to cause:
- Development of external genitalia (by the type II 5alpha reductase enzyme). Plays role in differentiation during gestation, and maturation during puberty (growth of penis and scrotum). In adulthood contributes to BPH
- Hair follicles (by type I 5alpha reductase enzyme). Increases hair growth during puberty and later causes facial hair and male pattern baldness.
Some of your testosterone gets converted to estrogen. It acts on its estrogen receptor to cause:
Epiphyseal closure and increased bone density
Some of your testosterone doesn’t get converted to anything and just stays its plain old self. It will act on its androgen receptor and cause:
- Development of internal genitalia, including Wolffian developing during gestation of the seminiferous tubules, seminal vesicles, epididymus, and vas deferences
- Increased muscle mass and strength during puberty
- Deepening of the voice by acting on the larynx
- Erythropoiesis
What is testosterone enanthate used for? What is it?
It is a transdermal testosterone/testosterone ester preparation.
It is used to treat hypogonadism, for example in a solider that had testicle mutilation injuries from IEDs
What is oral hydrocortisone used for?
It is used to treat 21-hydroxylase deficiency (insufficient cortisol production), which is the most common form of congenital adrenal hyperplasia
What does fludrocortisone treat?
It treats 21-hydroxylase deficiency when there is also a deficiency in mineralocorticoids
What are some treatments (3) that can be used for the treatment of andropause, which refers to the 1-2% decrease of testosterone concentration every year after 30
- Testoderm patch: tape patch onto scrotum
- Androderm patch: same as #1 but with skin permeation enhancers
- AndroGel (testosterone gel you rub on your shoulders lol)
What are Danazol and Stanozolol used for?
Hereditary Angioedema: in this disease, an impaired C1-esterase inhibitor causes overactivity of the complement cascade, leading to increased blood vessel permeability. This androgen preparation stimulates your liver to make the inhibitor of the esterase enzyme. Must be taken ORALLY and must contain the 17alpha-aliphatic group to be effective
Why can testosterone be used as a treatment for hemolytic anemia
Because, remember, testosterone can stimulate erythropoiesis!
What’s the big deal about 17-alpha and 17-beta modification of androgens
17-alpha modification (oral agents): this is what is done in oral androgens, and this makes them weak, unable to promote spermatogenesis, but it can cause liver damage.
17-beta modification (injectable agents): prolongs their absorption
Name 3 androgen receptor antagonists
- Flutamide
- Biclutamide
- Enzalutamide
What do Flutamide, Biclutamide and Enzalutamide treat?
Metastatic prostate cancer, in combination with GnRH analogues
What is cyproterone acetate and what does it treat?
It is a weak androgen receptor antagonist. Can treat hirsutism in women
What is finasteride and what does it treat?
It is a type II 5 alpha reductase inhibitor. It can treat BPH and male pattern baldness
What is dutasteride and what does it treat?
It is a type I and type II 5 alpha reductase inhibitor. It can treat BPH and male pattern baldness
We are about to start talking about drugs to treat erectile dysfunction. Before that happens, tell me what that whole thing is supposed to work.
- Parasympathetic neurons release acetylcholine (ACh) onto the M3 receptors of the endothelial cells in the corpora cavernosa
- Depolarization–>Increased Ca2+ in cell–>NO synthase is simulated to make NO
- NO goes to smooth muscle where is stimulates guanylyl cyclase to make cGMP
- cGMP activates a phosphatase that cleaves phosphate off a light chain myosin
- Myosin moves away from actin as a result, causing muscle relaxation
- Blood is then able to rush into the cavernosa, but expansion of tissue also cuts off veinous return from the cavernosa.
*cAMP can ALSO cause muscle relaxation in smooth muscle by activating PKA
How does the drug sildenafil help to treat erectile dysfunction?
It is a phosphodiesterase 5 (PD5) inhibitor. PD5 usually breaks down cGMP, so inhibiting it allows cGMP to work for long, and gives you a longer erection. You must have functioning nervous stimulation for this drug to work though.
What does tadalafil do?
Same thing as sildenafil (PD5 inhibitor). It can be used to treat:
- Erectile dysfunction
- BPH: by relaxing smooth muscle of the urethra
- Pulmonary arteriole hypertension (PD5 receptors in lung smooth muscle too)
Using sildenafil or tadalafil puts you at higher risk for…..
MELANOMA
What does alprostadil treat. How?
It is a prostaglandin E1 agonist, which can stimulate the PGE1 receptor and increase cAMP. This can treat erectile dysfunction even without functional neurons. Must be injected into the penis (unfortunately)
What does papavarine do and what does it treat?
It is a non-selective phosphodiesterase inhibitor that inhibits the breakdown of cGMP and cAMP. Treats erectile dysfunction. Also injected into the penis.
What is phentolamine and what does it treat?
It is a nonselective alpha adrenergic receptor antagonist. It blocks NE from causing vasoconstriction of the arterioles to the corpora cavernous. Treats erectile dysfunction and, you guessed it, must be injected into the penis.
What is methyl testosterone
It is a 17-alpha modified form of testosterone that increases its oral bioavailability
What’s the buccal testosterone system?
It’s a patch form of testosterone that you put inside your mouth on your upper gum. Treats hypogonadism.
