Men's Health Flashcards
Men's Health Drugs: Androgens AR Antagonists 5alpha reductase I Alpha1 antagonists PDE5 Misc minoxidil
Androgens - hypogonadism, HIV wasting, red blood cell production stimulation (sludgy)
AR Antagonists - Prostate cancer (usually in castrated males). Only useful when testes are taken out (massive release of LH and testosterone from blocking negative feedback that outcompete antagonist features)
5alpha reductase I’s - male pattern baldness, BPH
alpha 1 antagonists - Relax prostrate so urine can flow from urethra to the outside
PDE5 I’s - Biggest class, big problem.
Misc - minoxidil (vasodilator BP drug that is noticed to grow hair)
PDE5 inhibitor mechanism
SE particularly
Androgens
Synthetic anabolic steroids “Lones”
testosterone, oxymetholone, oxandrolone, nadrolone
For decreased libido, ED, decreased vitality, muscle mass, increased adiposity, depression, osteoporosis
Androgen deficiency
Functional and actual lack of testosterone Late onset hypogonadism ADAM PADAM testosterone deficiency syndrome andropause
Measure this with total testosterone levels (total testosterone <250ng/dL or free t <6.5ng/dL) = hypogonadal (less in the morning, higher in the evening
How high is normal testosterone levels?
Free testosterone levels can be 4x as high as the low level cut-off
Androgen SE
Linked to CV disease (questionable), but if given to hypogonadal males the levels do not exceed normal levels and therefore do not experience the sodium and fluid retention in the kidneys.
Obstructive sleep apnea - problem in abusers, not so much old men
Erythropoesis - helpful if anemic patients (common in older people, but keep your eye on it)
Prostate cancer - even if hypogonadal, do not give to african americans, first degree relative with prostate cancer, PSA > 3ng/mL
Personal thought is to not give these unless hypogonadal.
How does androgen therapy work in HIV patients?
Increase lean body mass
Improve weight gain and well-being
May not be more effective than appetite stimulants
Concern in females
AR antagonists
Flutamide, Biclutamide, NIlutamide, Enzalutamide
Used primarily for prostate cancer (only useful in castrated males)
Stage I - IV (metastatic and invasive is stage 4)
Prostate cancer - prostate cancer does not cause urinary retention (unlike BPH). Diagnosed by digital examination and PSA levels. PSA levels are only useful when individual levels are compared over time.
What does the prostate do?
Controls urinary flow
If removed, common SE is incontinence
Prostetectomy causes erectile dysfunction because of damage to the pelvic and pudendal nerves. Robotic surgeries lessen the likelihood of damage to these nerves. (Controls blood flow to the penis which controls erection) Detruser muscle goes all around the…
Chemical castration
GnRH agonists cause chemical castration
Prostate gland histology
Gleason stages (1-5) Histological irregularities that occur as the cancer progresses
- Small uniform gland, well-differentiated
- More space between glands
- Irregular masses, few glands
- Lack of glands, sheets of cells, poorly differentiated
5 alpha steroid reductase inhibitors
Finasteride, dutasteride
Used for BPH, MPB
Dose differs between the two applications
Shrink prostrate driven by androgens
Inhibitors prevent formation of DHT (10x more potent than T)
MPB dose of finasteride is 1mg/day compared to 5mg/day for BPH
Hair growth phases
Irregular hair growth throughout life, 4 phases
- Anagen - growing phase (2-7 years) of individual hair follicle
- Catagen - regression (10 days)
- Telogen - resting (up to 3 months)
- Go back to growth phase - Early anagen/anagen onset OR exogen (shedding)
Finasteride will not work overnight for MPB because a population of hair has to be influenced.
Target of DHT in hair follicles
Dermal papilla in the bottom of the hair shaft
DHT in hair follicles
DHT activates androgen receptors in the dermal papilla which causes death (miniaturization) in hair follicles. Hair falls out, get sparse hair. Prevent conversion of T to DHT can effectively make a difference in the number of functional hair follicles left on the scalp. Finasteride prevents formation of this toxic compound in hair follicles.
Who can benefit from finasteride in MPB?
Not men who are already bald. People who are going bald but not have lost many of their hair follicles yet.
What does minoxidil do in MPB?
It shortens telophase in the hair growth cycle. It is reversible when you stop taking finasteride.
Other finasteride counseling points
MPB - If you stop, the hair growth effects are reversible
Extremely teratogenic to male fetuses
Primitive gonad
XY male, XX female
Start off bipotent, male or female
Primitive gonad is precursor to either testes or ovaries
Puff of DHT/T, primitive gonad goes towards testes
Mullerian ducts give rise to uterus and tubes
Wolffian ducts - vas deferent and epididymus
Testosterone causes regression on Mullerian ducts and expansion of Wollfian ducts.
Y chromosome is important in this (has sex-determining region, which induces puff of testosterone)
End up with testes and no fallopian tubes/uterus
Highly dependent on testosterone. If you block formation of DHT, then will feminize a masculine fetus that is genotypically XY
Default is female
6-8 weeks is the window. No problems with female fetuses.
Alpha-1 receptor antagonists
Same as hypertension
Short acting, non-selective: prazosin, alfuzosin
Long acting, non selective: Terazosin, Doxazosin
Long acting, alpha-1 selective: tamsulosin, silodosin
Used for urinary retention secondary to BPH
Relax prostate and relax the smooth muscle; increase size of the pipe.
Indication: hypertension and BPH
LUTS (obstructive systems like urinary retention or irruptive symptoms lie burning and urgency to urinate)
Anatomic issues like enlarged prostate (most males)
Dynamic issues - state of muscle contraction of smooth muscle in neck of the bladder and the tissue that is the prostate.
How much of the urethral pressure is due to the alpha adrenergic tone and how much is due to the state of the prostate?
They are about equal. 40% due to alpha adrenergic tone and 53% due to the state of the prostate. So alpha-1 antagonists reduce the 40% due to the alpha adrenergic tone.
Can give centrally or locally in the smooth muscles surrounding the urethra
BPH
> 50% by age 60
90% by age 80
Hypertrophy of bladder neck
Contraction of smooth muscle = obstructive voiding
What are some of the obstruction symptoms of BPH?
hesitancy, weak stream, straining to void, prolonged voiding, incomplete bladder emptying
