Benign Prostatic Hyperplasia Flashcards
What are the functions of the prostate?
to contribute fluid to ejaculate
to constrict urethra during ejaculation to avoid contamination with urine
What are the 3 tissue types of the prostate?
epithelial tissue (aka - glandular tissue)
-responsive to testosterone
stromal tissue (aka - smooth muscle)
-rich with a1 receptors
the capsule (outer shell)
How does BPH occur?
BPH occurs when the enlarged prostate starts to push against the urethra, restricting the flow of urine
-the bladder wall begins to thicken and become irritable
-the bladder starts to contract even when it contains only small amounts of urine
-over time, the bladder weakens and loses its ability to empty itself completely, leaving urine behind
What are the contributing factors to BPH?
androgens (DHT) + aging (detrusor muscle) –> BPH
What is responsible for the enlargement of the prostate?
androgens (particularly DHT)
-ratio of stromal : epithelial tissue
–>non-BPH stromal : epithelial is 2:1
–>BPH stromal : epithelial is 5:1
Why do androgens contribute to BPH even though androgens decline with age?
increased activity of intra-prostatic 5a-reductase despite overall declining androgens with age
-5a-reductase converts T to DHT
What are the symptoms of BPH?
storage:
-frequency, nocturia, urgency, terminal dribbling
voiding:
-obstructive: weak or interrupted stream, difficulty initiating, straining, intermittency, pain while peeing
post-micturition:
-post-void dribbling, sensation of incomplete bladder emptying
What are the complications of BPH?
acute, painful urinary retention, can lead to acute renal failure
persistent or intermittent gross hematuria when tissue growth exceeds its blood supply
overflow urinary incontinence or unstable bladder
recurrent UTI that results from urinary stasis
bladder diverticula
bladder stones
chronic renal failure
What is the main reason we treat BPH?
because it is associated with a decreased QoL
What is the use of PSA?
baseline and for monitoring progression
predictor for prostate size (in combo with age)
no evidence to link to cancer
What are some drugs that can exacerbate BPH?
androgens - encourage growth
anticholinergics - cause further urinary retention
-antidepressants
-antihistamines
-antipsychotics
-muscle relaxants
stimulants - stimulate sphincter muscle and worsen sx
What are some non-pharmacological options for BPH?
limit fluid intake in evening
limit caffeine and alcohol use
limit diuretic use
limit anticholinergic use
smoking cessation
bladder training
pelvic floor exercises
stay physically active
avoid/treat constipation
watchful waiting
What are the pharmacological options for BPH?
a1-blockers
5a-reductase inhibitors
PDE5 inhibitors
What are examples of a1-blockers?
alfusozin
doxasozin
prazosin
sildosin
tamsulosin
terazosin
Which a1-blockers are uro-selective?
alfusozin
sildosin
tamsulosin
What is the MOA of a1-blockers?
block NE at a1-receptors in the prostate gland, bladder neck and urethra (i.e. sphincter)
-addresses the dynamic component of obstruction, which can improve flow rates
Which a1-blocker is the most effective for BPH?
all equally effective at improving symptoms
What is the effect of a1-blockers on the size of the prostate?
do not change size of prostate –> do not lower PSA
What is the onset of a1-blockers?
works in 1-2 weeks
-improve, not eliminate symptoms
What is the effect of dose of a1-blockers?
effects are dose-related
-including side effects
True or false: all a1-blockers are once daily
false
all except prazosin
What are the adverse effects of a1-blockers?
dizziness
-first-dose syncope, orthostatic hypotension
fatigue
rhinitis
headache
decreased volume of ejaculate (sildosin)
retrograde ejaculation
IFIS
When is IFIS a concern with a1-blockers?
tamsulosin + cataract surgery
What are the contraindications/precautions for a1-blockers?
anyone at risk for hypotension (additive effects)
caution in heart failure due to hypotension
dose adjust in renal impairment (sildosin)
liver dysfunction
What are drug interactions of a1-blockers?
3A4 inhibitors/inducers
-alfusozin, silodosin, tamsulosin are metabolized by 3A4
What are examples of 5a-reductase inhibitors?
dutasteride
finasteride
What is the MOA of 5a-reductase inhibitors?
block conversion of intra-prostatic testosterone –> DHT
-site-specific reduction of static component of obstruction
What is the use of 5a-reductase inhibitors?
to improve obstructive symptoms due to prostate size
What is the effect of 5a-reductase inhibitors on prostate volume?
decrease prostate volume by 20-30% –> can decrease PSA by 50%
What is the onset of 5a-reductase inhibitors?
take a few months to work
-up to 12 months for maximal effect
What is the convenience of 5a-reductase inhibitors?
both are once daily & no titration required
What are the adverse effects of 5a-reductase inhibitors?
sexual dysfunction
-ejaculatory dysfunction, loss of libido, impotence, gynecomastia
+ any adverse effects on mental health
Who should avoid handling 5a-reductase inhibitors?
pregnant/planning/child-bearing aged women do not handle tablets
-can cause birth defects in male fetus
What is the evidence for prostate cancer and 5a-reductase inhibitors?
reduces overall prostate cancer risk
bottom-line: not approved to prevent prostate cancer; for symptoms of BPH
How do PDE5 inhibitors work in BPH?
exact mechanism unknown, but smooth muscle relaxation in and around prostate may provide relief
-the vascular relaxation results in increased blood perfusion and may reduce BPH symptoms
Which PDE5 inhibitor can be used for BPH?
tadalafil
-daily use, not prn
Which patients see the best improvement in their BPH symptoms from PDE5 inhibitors?
younger patients
How long do PDE5 inhibitors take to work for BPH?
~ 4 weeks
What can be used for UI with BPH?
anticholinergics (carefully)
-start low, go slow, monitor, dc if no response or worsening
When do anticholinergics start to work for UI?
1 week –> 1 month
What are the Canadian guidelines recommendations for BPH?
a1 blockers: 1st line
combo if prostate enlarged
What are the best possible outcomes from BPH treatment?
less frequency
less urgency
greater force of stream
more complete emptying
as little impact as possible for AE
improved QoL
