Pharm of androgens - french Flashcards
T is the most important androgen in ____ and _____
muscle and liver
95% synth in testes
5% in adrenals
*Hypogonadal if
Finasteride (597)
a 5a-reductase inhibitor
- decrease conversion of T to DHT
- Useful in Benign prostatic hypertrophy (BPH) and male pattern baldness
How is estrogen made in males?
Synthesized from T via C19 aromatase which is expressed in testes, bone, brain, adipose tissue
Most significant action of E in males?
Occurs in bone
- closure of epiphyseal plate
- unfort. if adolescent male abuse E - Males w/o aromatase or E receptors –> epiphyses do not fuse and long bone growth continues
- Osteoporotic
When would you use T hormone replacement therapy in elders?
- T
When would you use T hormone replacement therapy in aging men?
Only in mend with T
Would you give T for impaired spermatogenesis?
No
Only indicated for T deficiency
T suppression of gonadotropin secretion would FURTHER impair spermatogenesis
Which route of T admin gives most stable plasma T levels thru-out dosing interval?
transdermal gel
-give every 24 hours
Tradeoff: maintain stable T level throughout dosing (maintain mood, E, libido)
but MOST expensive
Parenteral T
T ethanate
T cypionate
*Tradeoff: less frequent injections, but greater fluctuations in serum T levels
Oral T
Methyltestosterone
Tradeoff:
excellent oral absorptions, but rapid hepatic degradation
How does T result in decreased spermatogenesis?
- Decreased LH/FSH (neg feedback)
- Conversion of androgens to estrogens
*return to nl fxn after discontinuation
Does androgen use result in anemia? What about increase risk to arterial thrombosis?
No
T has erythropoietic fx and HCT goes up
But you DO have increased susceptibility to arterial thrombosis
(low HDL, high LDL, Increased platelet aggregation)
Anti or pro androgen?
- GnRH antagonist
- Pulsatile admin of GnRH
- Continuous admin of GnRH
- GnRH antagonist
- Anti: w/ competitive inhib - Pulsatile admin of GnRH
- Pro: stimulation by increasing LH and FSH release from pituitary - Continuous admin of GnRH
- Anti: neg inhibition with receptor down regulation/desensitization
(prior to desen ~ 1 week, LH/FSH will transiently increase with surge in T)
Flutamide and Spirinolacton target what?
Androgen receptors and inhibit androgen (steroid) binding
Tx of Polycystic ovarian syndrome
1st line: estrogen-progestin contraceptive
- Spirinolactone
- inhibit androgen binding
or Ketoconazole
Tx of benign prostatic hyperplasia
5 a reductase inhibitors
- Finasteride
- Dutasteride
Tx of male pattern baldness (androgenic alopecia)
finasteride
a 5a reductase inhibitor
Bicalutamide and Leuprolide are usually given together for the tx of prostate cancer
Leuprolide: GnRH agonist
- will initially increase LH + FSH –> INcrease in T
- But then desensitization kicks in
Bicalutamide: #1 androgen R blocker
- needed in conjunction with Leupromide to prevent initial Increase in T w/ leupromide
Adverse effects of Leuprolide
hypogonadism
Adverse effects of finasteride-dutasteride
decreased libido
ejaculatory ED
Adverse effects of bicalutamide
androgen deprivation effects (loss of libido, gynecomastia)
Adverse effects of spirinolactone
gynecomastia
Benign prostatic hypertrophy (BPH) can be characterized by frequent urinary urgency, diminished urinary stream ect. Which of the following best describes how an a1-adrenergic antagonist improves urinary flow?
Decreases the resistance of urethral sphincter
note that relaxation of detrusor muscle of bladder is used to tx overactive bladder
