Pharmacology Androgens And Antagonists as well as prostate cancer

Question 1

GnRH in normal conditions

Answer 1

Is pulsatile fashion release which causes FSH and LH release in both males and females

In males

• LH = leydig cells = testosterone that goes directly to Sertoli cells
• FSH = serotli cells = spermatogenesis and inhibin. Also produces ABP proteins ton bind testosterone to prevent its degradation and also allow testosterone to get out of Sertoli cells. Can also induce activin if FSH isnt at proper levels.

Negative feedback

• testosterone levels inhibit all levels of axis
• inhibin is release by Sertoli cells with FSH to inhibit anterior pituitary release of FSH (slight LH effect also but FSH is far more inhibited)

Question 2

What enzyme promotes conversion of androgens to estrogen?

Answer 2

Aromatase
- this is why osteoporosis is rare in males since males have this enzyme in bulk that always converts testosterone to low dose estrogen
(Enough to prevent osteoporosis but not enough to induce female 2nd characteristics)

Question 3

BPH vs prostate cancer

Answer 3

Both affect the prostate can causes gland hyperplasia

Both have the following symptoms

• urinary urgency
• trouble to urinate or need to push urine
• weak urine stream
• bladder always feels full

Prostate symptoms:

• painful or burning urination
• blood in urine or semen
• issues with erection and ejactulation

BPH is way more common (1:2) and is benign

Prostate cancer is less common (1:6) and can be malignant

Question 4

Ways to diagnosis BPH or prostate cancer

Answer 4

Prostate-specific antigen (PSA) test

Digital rectal exam

Urine flow and post-void residual volume in bladder

Ultrasound or biopsy of prostate if needed

Question 5

BPH usual treatment

Answer 5

Mild- moderate symptoms
- a1-blockers and 5a-reductase inhibitors

Severe symptoms
- surgical options

Question 6

What is a normal ranges for PSA total?

Answer 6

4ng/mL

Question 7

Digital rectal exam vs PSA lab values with respect to sensitivity and specificity

Answer 7

PSA

• 75% sensitivity
• 65% specificity
• positive predictive value = 45%

DRE

• 80% sensitivity
• 90% specificity
• Positive predictive value = 30%

Question 8

Common site for Mets with prostate cancer

Answer 8

1 = bone (90% chance)

Question 9

Goals of therapy in prostate cancer

Answer 9

Stage 1-3A = cure it

Stage 3B and 4 = maintain QOL and prolong survivial since its not curable

Question 10

Two types of surgery in prostate cancer

Answer 10

1) radical prostatectomy
- is a definitive surgery that cures usually
- side effects = 50% impotence, urinary incontinence, strictures, fistula formation

2) Transurethral resection of the prostate (TURP)
- used exclusively in local advanced disease
- side effects = high chance for UTIs and retrograde ejaculation, impotence and Erectile dysfunction

Question 11

What mutations are common in prostate cancer

Answer 11

Androgen receptor gene

CYP17

Question 12

What diet aspects increase risk of prostate cancer

Answer 12

2x increase with high meat and high fat diet

Low vitamin D levels, lay opens and B-carotene

Question 13

What three classes of drugs that aren’t chemotherapy are used in inhibiting prostate cancer growth

Answer 13

5a-reductase inhbitors
- finasteride

Androgen receptor antagonist
- Flutamide and Bicalutamide

GnRH agonists
- Leuprolide and any “relin” drug

Question 14

Chemotherapy options most commonly used in prostate metastatic cancer

Answer 14

If asymptomatic
- monotherapy with Sipuleucel-T

If symptomatic

• Doetaxel + prednisone = 1st line
• carbazitaxel or Abiraterone + prednisone = 2nd line