1. G.M. reports urinary symptoms including difficulty initiating urination, decreased urinary stream, occasional midstream stoppage, postvoid dribbling, nocturia, and daytime urinary frequency. 2. On physical exam, G.M.'s prostate is severely enlarged, firm, and rubbery. 3. Objective tests find elevated BUN and creatinine levels as well as a large post-void residual urine volume of 900mL, indicating urinary retention from bladder outlet obstruction due to BPH.

1. Benign Prostatic
Hyperplasia (BPH)
By: Haftom Niguse
(B.Pharm, MSc)
Clinical Pharmacy Unit
School of Pharmacy, CHS,
MU

2. Introduction
• Benign prostatic hyperplasia (BPH) occurs as a
result of androgen-driven prostate growth.
• It is a common cause of urinary dysfunction
symptoms in elderly men
• BPH rarely is detected in men <40 years of age.
• After age 40, the prevalence of BPH is age
dependent.
• Approximately 75% of men who live to the age of
70 develop clinical symptoms of BPH.
• the initiation of BPH may not be environmentally
or genetically influenced.

3. Pathophysiology
• The cause of BPH is unclear
• most hypotheses are based on hormonal and aging
processes.
• normally functioning testes are essential for BPH to
develop
• For testosterone to be active, it must be metabolized
to dihydrotestosterone (DHT) by 5 α-reductase
• DHT is responsible for normal and hyperplastic
prostate growth.
• 5 α-reductase (type I and type II). Type II is found
predominantly in the prostate

5. Pathophysiology
• There is both a static and a dynamic
component to prostate enlargement.
– Static (gradual enlargement of the prostate)
– Dynamic (increase α-adrenergic tone and constrict
the prostate and bladder neck)
• Drugs that can exacerbate symptoms:
– testosterone, α-adrenergic agonists
(e.g.decongestants), and anticholinergic agents
(e.g., antihistamines, phenothiazines, TCA,
anticholinergics).

6. Clinical presentation
• Obstructive signs and symptoms
– result when dynamic and/or static factors reduce bladder
emptying.
– Patients experience urinary hesitancy; urine dribbles out of
the penis, and the bladder feels full even after voiding.
• Irritative signs and symptoms
– result from long-standing obstruction at the bladder neck.
– Patients experience frequency, urgency, and nocturia.
• Symptoms vary over time.
– Mild disease may stabilize whereas other patients
experience progressive disease over time.

7. BPH Pathophysiology
Normal BPH
Hypertrophied
detrusor muscle
Obstructed
urinary flow
PROSTATE
BLADDER
URETHRA
Kirby RS et al. Benign prostatic hyperplasia. Health Press, 1995.

8. Diagnosis
• objective measures of bladder emptying (e.g.,
peak and average urinary flow rate, post-void
residual urine volume)
• laboratory tests (e.g. urinalysis, blood urea
nitrogen, and prostate-specific antigen [PSA]).
• Medication history and dietary supplements.
• On digital rectal examination, the prostate is
usually, enlarged (more than 20 g), soft, smooth,
and symmetric.

9. Desired outcome
BPH Treatment Success measured by:
• ↓ bothersome symptoms
• ↑ QOL
• ↓ prostate size or arrest further growth
• ↑ in peak flow rate / Relieve obstruction
• Prevention of long-term complications
• Acceptable adverse events profile

10. Treatment
• Management options
– Watchful waiting
– Drug therapy
– Surgical intervention.
• The choice depends on the severity of signs and
symptoms.

11. Watchful waiting
• Watchful waiting involves reassessment at yearly intervals.
• It is appropriate for patients with mild disease and for those
with moderate disease with only symptoms
• Patients should be educated about behavior modifications
– fluid restriction before bedtime
– avoiding caffeine and alcohol
– frequent emptying of the bladder,
– avoiding drugs that exacerbate symptoms.

12. Pharmacologic therapy
• It is appropriate for patients with moderately
severe and as an interim measure in severe BPH.
• It interferes with the stimulatory effect of
testosterone on prostate gland
– -adrenergic blockers
– Dynamic component
– 5 -reductase inhibitors
– Anatomic component
– Anticholinergic Therapy
– Storage Sx’s

13. • Initial therapy with an α-adrenergic antagonist
provides faster onset of symptom relief.
• A 5α-reductase inhibitor is preferred as initial
therapy in patients with a prostate gland >40g.
• Combination therapy should be considered for
symptomatic patients with a prostate gland
>40 g and PSA ≥1.4 ng/mL

14. α-Adrenergic Antagonists
• α-Adrenergic antagonists relax the smooth
muscle in the prostate and bladder Neck
– increase urinary flow rates by 2 to 3 mL/sec in 60%
to 70% of patients
– reducing post-void residual urine volumes.
• Terazosin, doxazosin,and alfuzosin are second-
generation α-adrenergic antagonists.
• their adverse effects include first dose syncope,
orthostatic hypotension, and dizziness.
– (b/c they antagonize peripheral vascular α1-
receptors )

15. α-Adrenergic Antagonists
• these drugs should be taken at bedtime
– to minimize orthostatic hypotension and first-dose
syncope with terazosin and doxazosin.
• Alfuzosin is less likely to cause cardiovascular
adverse effects than other second-generation
agents.
• Tamsulosin and Doxazosin produce durable
responses for 6 and 10 years, respectively
• Patients should be slowly titrated to a
maintenance dose

17. α-Adrenergic Antagonists
Tamsulosin
• The only third-generation α-adrenergic
antagonist,
• It is selective for prostatic α1a -receptors.
• It does not cause peripheral vascular smooth
muscle relaxation.
• It is suitable for patients who want to avoid the
delay of dose titration.
• Dose : 0.4 mg at bed time 2 hours after dinner

18. α-Adrenergic Antagonists
• Tamsulosin
• It is a good choice for patients who cannot
tolerate hypotension;
– (pts who have severe coronary artery disease, volume
depletion, cardiac arrhythmias, severe orthostasis, or
liver failure; or are taking multiple anti-hypertensives).
• Potential drug interactions.
– Tamsulosin decreases metabolism of cimetidine and
diltiazem.
– Carbamazepine and phenytoin increase catabolism of
α-adrenergic antagonists

19. 5α-Reductase Inhibitors (5α-RI)
• 5α-RI (Dutasteride and Finasteride)interfere
with the stimulatory effect of testosterone.
• They slow disease progression and decrease
the risk of complications.
• Dutasteride inhibits types I and II 5α-
reductase, whereas finasteride inhibits only
type II.
• Dutasteride more quickly and completely
suppresses intraprostatic DHT (vs. 80% to 90%
for finasteride) and decreases serum DHT by
90% (versus 70%).

20. 5α-Reductase Inhibitors (5α-RI)
• 5α-RI may be preferred in patients with:
– uncontrolled arrhythmias,
– poorly controlled angina,
– use of multiple antihypertensives,
– inability to tolerate hypotensive effects of α-adrenergic
antagonists.
• 5α-RI reduce serum PSA levels by 50%.
• PSA should be measured at baseline and repeated
after 6 months.
• If PSA does not decrease by 50% after 6 months of
therapy in a compliant patient, the patient should
be evaluated for prostate cancer.

21. 5α-Reductase Inhibitors (5α-RI)
• Disadvantages of 5α-RI
– requiring 6 months to maximally shrink an enlarged
prostate,
– being less likely to induce objective improvement,
– causing more sexual dysfunction.
• 5α-RI are in FDA pregnancy category X and are
therefore contraindicated in pregnant females.
• Pregnant and potentially pregnant women should
not handle the tablets or have contact with
semen from men receiving 5α-reductase
inhibitors

22. Surgical intervention
Therapy Brief Description Comments
Transurethral
resection of
the prostate
(TURP)
A resectoscope is
inserted into the
urethra and
obstructing tissue is
removed a piece at a
time.
• considered the
“gold standard”
for the treatment
of BPH
Post-TURP syndrome: potentially life
threatening, caused by the absorption of
irrigating fluid. Cerebral edema and seizures
may result from hypervolemia and
hyponatermia.
Late complications: erectile dysfunction (up to
30%), urinary incontinence, and bladder neck
contractures, retrograde ejaculation(75%).
Transurethral
incision of
the prostate
(TUIP)
Shallow incisions in
the prostatic urethra
area relieve bladder
outflow obstruction.
Advantageous in high-risk patients such as the
elderly because it can be performed under local
anesthesia.

23. Therapy Brief Description Comments
Transurethral
dilation of the
prostate (TUDP)
Balloon catheter is
positioned in the
prostatic urethra
and inflated.
Appropriate for men with
smaller prostates who wish to
avoid potential side effects of
other procedures.
Visual laser
ablation of the
prostate gland
(VLAP)
Laser is used to
partially remove
obstructing prostate.
Used in men with smaller
prostates.
Transurethral
microwave
hyperthermia
Local microwave
hyperthermia,
delivered
transurethrally or
transrectally.
Not as effective as surgical
therapy but can be completed
as an outpatient in 1 hour.

24. Surgical intervention
• TURP is the gold standard for treatment of
patients with moderate or severe symptoms and
for all patients with complications.
complications of prostatectomy procedures.
• Retrograde ejaculation in 75% of transurethral
prostatectomy
• Other in 2% to 15% of patients include
– bleeding,
– urinary incontinence
– erectile dysfunction

25. Phytotherapy
• Although widely used in Europe for BPH,
phytotherapy with products such as:
– saw palmetto berry (Serenoa repens),
– stinging nettle (Urtica dioica), and
– African plum (Pygeum africanum) should be avoided.
• Studies of these herbal medicines are
inconclusive,
• The purity of available products is questionable.

26. Evaluation of therapeutic outcomes
• Monitor restoring adequate urinary flow without
causing adverse effects.
• Outcome depends on the patient’s perception of
effectiveness and acceptability of therapy.
• Objective measures of bladder emptying (e.g., uro-
flow meter and post-void residual urine volumes)
are also useful after
– 6 to 12 months of 5α-RI therapy or
– 3 to 4 weeks of α-adrenergic antagonist therapy.
• Laboratory tests (e.g., BUN, SCr, PSA) and urinalysis
should be monitored regularly.
• patients should have an annual DRE.

27. • G.M., a 72-year-old man, presents to the emergency department with
severe lower abdominal discomfort of 4 days' duration. His history
consists of having increasing difficulty initiating urination, a significant
decrease in the force of his urinary stream, occasional midstream
stoppage, and postvoid dribbling.
• Physical examination is unremarkable except for the abdominal and
rectal examination. Abdominal examination reveals distention,
tenderness, and increased dullness in the hypogastrium with a large
mass, believed to be the bladder. On rectal examination, the prostate is
found to be severely enlarged, firm, and rubbery without nodules or
undue hardness.
• G.M. gives a history of nocturia (approximately four to five times a night)
and daytime urinary frequency (eight to ten times a day). G.M. indicates
that when he is able to urinate he does not feel relieved.
• Laboratory findings are as follows: BUN, 45 mg/dL (normal, 8–18); SrCr,
3.2 mg/dL (normal, 0.6–1.2); serum prostatic acid phosphatase, 3 U/L;
and serum PSA, 7.1 ng/mL (normal, 0.1–4.0). A urethral catheter was
inserted, and 900 mL of urine was obtained.
• What subjective & objective findings in G.M. are associated with BPH?