Drugs of Male GU Disorders Flashcards
Where is testosterone synthesized? What other active steroids can it be metabolized to? How is testosterone inactivated?
Synthesized by the testes
Metabolized to DHT (5alpha-reductase) or Estradiol (aromatase)
Inactivated in the liver
What are the isoforms and functions of 5alpha-reductase?
5alpha-reductase converts testosterone to DHT
Two isoforms exist:
1) Type 1 - non-gonadal tissue
2) Type 2 - gonadal tissue
What is the function of aromatase and where can it be found?
Aromatase converts testosterone to estradiol. It is produced in the liver and adipose tissue.
Note: Responsible for 85% of serum estradiol
How does testosterone exert its action directly and indirectly? Describe the difference in efficiency.
Testosterone and DHT both bind to the androgen receptor. However, DHT binds the AR with a much higher affinity.
What are the physiologic effects of testosterone?
- Increased EPO and clotting factors
- Decreased HDL with increased TG lipase
- Maintenance of sexual function
- Tissue growth (includes skeletal) and epiphysial closure
- Hair, just not on your head
- Increased sebaceous glands
- Thicker vocal cords and laryngeal growth
Describe the differences in administration routes of androgens?
Orally they are absorbed rapidly, but largely inactivated at the liver. Parenteral preparations are absorbed slower and have a longer duration of action.
What are the uses of androgens?
- Prevent protein loss following trauma
- Hypogonadism
- Delayed puberty
- Abuse in sports
- Aging - reduces osteoporosis and increases lean mm. mass and hematocrit
What are the ADRs of androgens with respect to general use and use in HRT?
General
- Sodium retention –> edema (esp.ly heart/kidney disease)
- Synthetics –> reversible cholestatic jaundice
- BPH - older pt.s
- Psychosis and psychological dependance
HRT
- Azoospermia - supraphysiologic doses as well
- Gynecomastia
- Acne
- Sleep Apnea
- Erythrocytosis
What are the CIs of androgens?
- Children
- Men with prostate CA
- Pregnant women
Describe GnRH analogs with respect to prototype, MOA, pulsatile versus continuous administration, and uses?
Prototype - Leuprolide
MOA - stimulates the production of FSH and LH
Pulsatile Admin - Every 4 hours to increase FSH and LH
Continuous Admin - Gonadotropins rise for the first 7-10 days, then negative feedback response overrides
Uses - suppression of gonadotropins (prostate CA) or stimulation of gonadotropins (infertility)
Describe GnRHR antagonists with respect to prototype, MOA, use, and benefit.
Prototype - Abarelix or degarelix (RELIX)
MOA - binds GnRHR inhibiting the production of LH and FSH
Use - Advanced prostate CA
Benefit - No testosterone spike, like with GnRH agonists
Describe 5alpha-reductase inhibitors with respect to prototypes, MOA, effects, ADR and CIs.
Protoypes - finasteride and dutasteride MOA - inhibits 5-alpha reductase effects - decreased prostate volume, increase urine flow ADRs - decreased libido and impotence CI - women and children
What is finasteride?
A Type II 5alpha-reductase inhibitor for male pattern baldness or hirsutism
What is dutasteride?
A Type I and II 5alpha-reductase inhibitor for prostate cancer and BPH
Note: longer duration
What type of drug is cyproterone and what is it used for?
Cyproterone is an AR blocker used for advanced prostate CA and possibly hirsutism
What is flutamide, bicalutamide, and nilutamide? What are there uses?
These are all nonsteroidal AR blockers which are used for metastatic prostate CA. Can also be used to inhibit the tumor surge in GnRH agonist Tx.y. May cause gynecomastia
What is spironolactone? What is it commonly used for?
Spironolactone is an inhibitor of AR, aldosterone receptors, and synthesis of testosterone/androstenedione. Commonly used for heart failure and hirsutism
Describe the approach to treating BPH.
Tx doesn’t begin until Mx.s significantly impact quality of life.
5alpha-reductase inhibitors - excellent for long-term use; reduced prostate volume and need for surgery
Alpha-adrenergic antagonists - excellent for short-term use; Less side effects when specific for alpha1A
Describe prazosin, terazosin, doxazosin, alfuzosin, and tamsulosin with respect to receptor selectivity, half-life, and ADRs.
Prazosin - short half-life with selectivity for alpha1, but no subtypes; ADRs are orthostatic hypotension
Terazosin and doxazosin - both are similar to prazosin but each with a longer half-life and less side effects
Alfuzosin - this is similar in profile to those above, but the half-life is between that of prazosin and terazosin
Tamsulosin - selective for alpha1A receptors; may experience abnormal ejaculation; half-life is similar to terazosin
Is saw palmetto effective?
Probably not
Describe PDE-5 inhibitors with respect to prototypes, effects, duration, CIs, ADRs.
Prototypes - tadalfil, sildenafil, and vardenafil
Effects - normal doses due not cause erection without sexual stimulation
Duration - most last 4 hours; tadalfil can have effects up to 36 hours
CI - alpha-antagonists and nitrates
ADRs - hypotension, syncope, visual changes, and hearing loss
What would you use if patients were refractory to PDE-5 inhibitors?
Alprostadil, a PGE1 which relaxes cavernosal smooth muscle. Direct injection.
What is oxybutynin?
Somewhat selective M3 antagonist used in the treatment of urinary urgency. ADRs include opposite dumbbels.
