Androgens, Antiandrogens, Erectile Dysfxn Flashcards
explain hypothalamic-pituitary-gonadal axis
Hypothalamus –> GnRH
GnRH –> Pituitary gonadotropes –> LH
LH –> Leydig cell –> testosterone
what do leydig cells express that converts androstenedione to testosterone
17B-hydroxysteroid dehydrogenase (17B-HSD)
___-bound testosterone is considered bioavailable
albumin
what converts testosterone to DHT
5alpha reductase
Anabolic effects of androgen:
Increases 1 synthesis and inhibits 2 breakdown
Stimulates 3 rate
Reduces bone 4 and enhances bone 5.
At puberty 6 facilitates closure of epiphyseal growth plate
Increases production of 7
- protein
- protein
- resting metabolic
- reabsorption
- formation
- estradiol
- erythropoietin
Primary or secondary androgen deficiency:
- hypergonadotropic hypogonadism
- hypogonadotropic hypogonadism
- primary
2. secondary
what are the non-steroidal anti-androgens?
flutamide and bicalutamides
MOA of nonsteroidal anti-androgens (flutamide and bicalutamides)
competitive antagonists at androgen receptor
what does flutamide and bicalutamides tx
tx prostate cancer
administered prior to GnRH analog tx to prevent testosterone surg
what anti-androgen is an AR antagonist
Enzalutamide
Enzalutamides MOA
*completely inhibits androgen binding to AR
inhibits nuclear translocation of AR
blocks DNA binding
blocks coactivator recruitment
what anti-androgens are GnRH receptor agonists?
what is the MOA
Leuprolide and goserelin
- increase LH and testosterone production
- leads to desensitization and downregulation of GnRH receptors on pituiary gonadotropes
what should you administer with Leuprolide and goserelin to decrease surge of LH and testosterone
AR antagonists (fluatmide, bicalutamide)
what does Leuprolide and goserelin tx
prostate cancer
what drug is a GnRH receptor antagonist
Degarelix
How does degarelix compare to leuprolide and goserlin tx?
- Faster onset
- No LH/testosterone surge
- Reduce LH/FSH production and release
- Decrease testosterone production
which drug is an androgen biosynthetic inhibitor?
MOA?
Abiraterone
inhibits 17alpha hydroxylase and 17,20 lyase –> increase in aldosterone production –> can cause HTN, hypokalemia, fluid retention
what are the 5a-reductase inhibitors
MOA?
Finasteride and Dutasteride (steroid like)
inhibit DHT activity and reduce levels
what does abiraterone treat?
metastatic prostate cancer
what does dutasteride treat
BPH
androgenic alopecia
what are the erectile dysfunction drugs?
PDE5 inhibitors
- Sildenfail
- Vardenafil
- Tadalafil
- Avanafil
of the PDE5 inhibitors for ED:
- longest T1/2
- fastest onset
- treat pulmonary HTN
- what else can they tx?
- Tadalafil
- Avanafil
- Sildenafil and Tadalafil
- BPH
Testosterone ester:
1 conjugated to testosterone, increases 2 of molecule, dissolved in oil and given 3, slow release and catabolism, 4 duration
- FA
- lipophilicity
- IM
- long
17a-alkylated derivatives (steroid like)
significantly 1 liver catabolism,
Administered 2,
3 toxicity and 4 cancer can occur (higher risk than ester or testosterone)
- slower
- orally
- Liver
- Hepatic
SE of androgen preps
- Musculoskeletal: premature epiphyseal closure, increase muscle and tendon injuries
- Hepatic dysfunction (17-alkylated testosterone derivatives): cholestatic jaundice, peliosis, carcinoma
- Edema, fluid retention (HTN) - renal dysfunction
- Polycythemia
- Mental disturbance: mood swings, aggression, depression, psychosis
SE of antiandrogens: flutamide and bicalutamide
mild gynecomastia,
mild reversible liver toxicity
SE of GnRH agonists: Leuprolide, goserelin
- Sexual dysfxn
- Bone mineral density loss
- Anemia
- Fatigue
- Initial surge in testosterone levels that can cause growth of prostate cancer
SE of abiraterone (androgen biosynthetic inhibitor)
- Adrenal insufficiency with concurrent infection or stress
- Hepatotoxicity
- HTN
- Hypokalemia
- Fluid retention
SE of 5a-reductase inhibitors (Finasteride and Dutasteride)
- Reduced DHT levels in male fetus can lead to abnoramlities in the external genitalia: contraindicated in pregnancy
- Impotence and gynecomastic
- Can lower PSA levels - possible false negatives with prostate cancer screening (PSA values should be doubled for comparison with normal ranges)
Side effects of PDE5 inhibitors (Sildenafil, Vardenafil, Tadalafil, Avanafil)
- Dyspepsia: inhibition of esophageal SM can reduce motility and worsen GERD
- Headache, flushing, nasal congestion
- Combination with nitrates/nitrites can cause dangerously low BP
- Serious cardiac events (rare)
- Priapism
- Rare: sudden vision loss
