Patient is 68 year-old, born in Arizona
BPH is common in men older than 50 years
As many as 14M men in U.S. have symptoms of BPH
Patient has a history of Benign Prostatic Hypertrophy, obesity
Alcohol intake
Increases the risk in the development of BPH
Nocturia, 5x per night once per night after taking doxasozin
In old age, prostate increase receptivity to growth factors some of the stromal tissue
reverts back to its embryonic state in which the prostate becomes more susceptible to
growth factors
As we age increase production of estrogen prime androgen receptors in the
prostate
Androgens in the prostate, stromal tissues is stimulated by an androgen(DHTdihydrotestosterone) which is 5-10x more potent than testosterone thus activating
androgen receptors in the prostate
Testosterone turns to DHT inside the prostate by a chemical steroid 5-alpha reductase
which is a pathway that would help to block the disease-5ARI(finasteride)
Finasteride decrease the conversion of testosterone to DHT
DHT stimulates androgen receptors on stromal cells and smooth muscle cells
growth of smooth muscle cell and icini, cuboidal and columnar epithelium
DHT and testosterone are not increased but the receptors are hyperactive due to
estrogen
Increased cells increased size of the gland pushing up against the fibrous capsule
increase pressure on urethra factor for symptoms
Factors: increased intraglandular pressure, increased smooth muscle tone in the
preprostatic sphincter as well as anterior fibromuscular zone due to smooth muscle
hypertrophy urinary retention, increased in size push in the pelvis and press the
bladder thus interfering with detrusor sphincter compression, neuron
degeneration(peripheral vascular disease) compress the nerves thus causing urinary
retention
Increased smooth muscle tone treated with alpha 1a blockerterazosin,prazosin(sphincters in preprostaic and anterior fibromuscular zone as well as
detrusor muscle and bladder is stimulated by alpha 1 adrenergic receptors muscles
will relax thus decreasing urinary retention
Non cancerous growth by multiplication of prostate cells
Prostate cells is driven by male hormone testosterone converted to another hormone DHT
leading to BPH/prostate growth
As prostate enlarges, it compresses inwards to the urethra and urinary bladder obstructing the
flow of the urine out of bladder
Occurs not only because of the enlarging size but also due to increasing number of muscle fiber
When muscle fibers increase, the muscle tone increases as well causing an squeezing effect
around the urethra
Obstruction of the urine flow may cause a weak stream, poor bladder emptying and dribbling
As the bladder tries to empty, the bladder works overtime resulting to bladder thickening so the
ability of the bladder to hold a larger amount of urine decreases as a result of increased
frequency of urination, and stronger urge to urinate
If left untreated, BPH can lead to inability to urinate/ urinary retention resulting to catheterization
to relieve urine from the bladder, weakening of the bladder, bladder stones,uti, and worse is
kidney damage.
Treatment due to:
Bothersome symptoms
Worsening symptoms
Unwanted consequences of obstruction
Treatment options:
lifestyle change and monitoring
Supplements and plant extracts
Medications to relax prostate
Medications to shrink prostate
Medication to relax bladder
Combination gtherapy
surgery
Diagnostic modalities
Serum psa(prostatic-specific antigen)
Urinalysis
Symptom assessment instrument(AUA-SS)
Serum creatinine is not recommended as initial evaluation
Flow testing
PE
DRE
Neuro exam
NON-PHARMACOLOGIC THERAPY
Watchful waiting
For AUA symptom score of <7 (mild)
For AUA symptom score of >8 (moderate or severe) who are not bothered by
symptoms/does not interfere with ADL
Watchful waiting medical therapy, minimally invasive/surgical therapy
For AUA symptom score of >8 (moderate or severe) who are bothered by
symptoms/interfere with ADL
Alpha 1 adrenergic antagonists
5 alpha reductase inhibitors
Combination
Minimally invasive or Surgical therapy
Moderate to severe
Medications did not relieved the symptoms
Presence of urinary tract obstruction, bladder stones
Transurethral resection of the prostate (TURP)
gold standard
no external incision
reaches the prostate by inserting the resectoscope about 12 inches long and half
inch in diameter through the urethra
Transurethral incision of the prostate (TUIP)
Transurethral microwave thermotherapy (TUMT)
Transurethral needle ablation (TUNA)
Laser therapy
Prostate lift
Embolization
Open or robot-assisted prostatectomy
PHARMACOLOGIC THERAPY
Alpha-adrenergic receptor antagonists
are thought to treat the dynamic aspect of BPH by reducing sympathetic tone of the
bladder outlet, thereby decreasing resistance and improving urinary flow.
5ARIs
are thought to treat the static aspect of BPH by reducing prostate volume and
having a similar, albeit delayed effect.
They have also proven to be beneficial in the prevention of BPH progression, as
measured by prostate volume, the risk of developing acute urinary retention, and
the risk of having BPH-related surgery.
The use of an alpha-adrenergic receptor antagonist and a 5ARI as combination therapy
seeks to provide symptomatic relief while preventing progression of BPH.
PDE5 inhibitors
improvement in lower urinary tract symptoms secondary to BPH
used currently in the treatment of erectile dysfunction.
sc
ALPHA 1
ADRENERGIC
ANTAGONISTS
EFFICACY
+++
SUITABILIT
Y
+++
5 ALPHA
REDUCTAS
E
INHIBITORS
PHOSPHODIESTERAS
E-5 (PDE5) INHIBITOR
COMBINATION
(alpha 1
adrenergic
antagonist
and 5-alpha
reductase
inhibitor)
SAFETY
COST
+++
ALPHA 1 ADRENERGIC ANTAGONIST
5 ALPHA REDUCTASE INHIBITOR
given to patients with symptomatic enlargement of the prostate to prevent progression of
the disease
not given to patients who do not have any evidence of prostatic enlargement
effective in partial relief of symptoms, although alpha blockers are more effective
side effects: sexual dyfunction
disadvantage: long term daily therapy
PHOSPHODIESTERASE INHIBITOR
COMBINATION (alpha 1 adrenergic antagonist and 5-alpha reductase inhibitor)
for patients with LUTS associated with prostatic enlargement
more effective in relieving and preventing progression of symptoms
reduce the risk of progression by 67% compared with doxazocin alone 39% finasteride
alone 34%
PRAZO
SIN
EFFICACY
+++
SUITABILITY
+++
TERAZO
SIN
DOXAZO
SIN
ALFUZO
SIN
TAMSULO
SIN
SILIDO
SIN
SAFETY
COST
+++
PRAZOSIN
TERAZOSIN
DOXAZOSIN
ALFUZOSIN
TAMSULOSIN
SILIDOSIN
TERAZOSIN & DOXAZUCIN
developed as BP pill
TAMSULOSIN & ALFUZOSIN
developed for BPH
FINASTERIDE
EFFICACY
+++
SUITABILITY
+++
DUTASTERIDE
SAFETY
COST
+++
FINASTERIDE
less effective than alpha blocker in improving symptoms without prostatic enlargement
reduces the risk of acute urinary retention and the need for BPH related surgery
reduce size of prostate
increase peak urinary flow rate
reduce BPH symptoms
lowers serum and intraprostatic DHT
lowers PSA but not mask the PSA-based detection of prostate cancer
demonstrate 3 point improvement in tha AUA-symptom index
ineffective in patients without enlarged prostate
reduces risk of subsequent urinary retention and the need for BPH related surgery
AE: decreased libido, breast enlargement, ejaculatory dysfunction, erectile dysfunction
reversible after the first year of therapy
interaction: grapefruit(increase the level or effect of finasteride by affecting hepatic/
intestinal enzyme CYP3A4 metabolism
MOA: selective inhibitor of type 2 isoforms of 5AR, suppress serum DHT levels by inhibiting
the conversion of testosterone to DHT
absorption
Bioavailability: 65%
onset: 6 months
peakplasma time: 2-6 hours
distribution
protein bound: 90%
Vd:76 L
metabolism
hepatic CYP3A4
metabolites: t-butyl side chain monohydroxylate, monocarboxylic acid metabolite
elimination
6 hours half life
excreted through feces and urine
Propecia tab 1 mg - 28's (P1728.06/pack)
DUTASTERIDE
similar efficacy as finasteride in terms of symptom score and flow rate improvement as
well as disease progression
interaction: grapefruit(increase the level or effect of dutasteride by affecting hepatic/
intestinal enzyme CYP3A4 metabolism
AE: decreased libido, breast enlargement, ejaculatory dysfunction, erectile dysfunction
reversible after the first year of therapy
MOA: selective inhibitor of type 1 and 2 isoforms of 5AR, suppress serum DHT levels by
inhibiting the conversion of testosterone to DHT
absorption
Bioavailability: 60%
onset: 1-2 weeks
peakplasma time: 2-3 hours
distribution
protein bound: 99%
Vd: 300-500L
metabolism
hepatic P450 enzyme CYP3A4 & CYP3A5
metabolites: 4 hydroxydutasteid, 6 hydroxydutasteride, 1,2-dihydroxydutasteride
elimination
5 weeks half life at steady state
excreted through feces and urine
Avodart soft-gelatin cap 500 mcg - 30's (P1319.47/pack)
Diagnostic Guidelines for BPH
American Urological Association Symptom Index (AUA-SI)
International Prostate Symptom Score (I-PSS)
Reliable quantitative intruments for measuring urinary symptoms in men
