This document discusses the pathophysiology and treatment of benign prostatic hyperplasia (BPH). BPH causes bladder outlet obstruction which leads to bladder wall thickening and overactivity. Common treatments include alpha-1 blockers, 5-alpha reductase inhibitors, phosphodiesterase type 5 inhibitors, and anticholinergics. Each class of drugs has different mechanisms of action and side effect profiles for treating lower urinary tract symptoms from BPH. Combination therapy may provide greater relief of symptoms than single agents alone.

1. Nehal M. Ramadan
Lecturer of clinical pharmacology

2.  Prostatic enlargement 
urethral compression 
bladder outlet obstruction 
bladder wall is thickened
and becomes more
sensitive
 Increased sensitivity
(detrusor overactivity) 
cause overactive bladder
symptoms (urinary urgency,
frequency, and incontinence)
even with small volumes of
urine.

3. Storage symptoms
Post micturition
symptoms
Voiding symptoms
• Urgency
• Frequency
• Nocturia
• Urgency
incontinence
• Feeling of
incomplete bladder
emptying
• Urinary retention
• Post-micturition
dribble
• Hesitancy
• Slow stream
• Intermittent stream
• Straining to pass
urine
• Splitting or
spraying of stream
• Terminal dribbling
Detrusor
overactivity
Bladder
outlet
obstruction

4. A. Prostatic enlargement
is hormonal
dependant 
depends in
dihydrotestosterone
(DHT)  formed from
circulating
testosterone by the
action of type II 5-α
reductase enz.

5.  α-adrenergic Rs
are found
throughout the
body.
 The α1A receptor
 the
predominant
subtype found in
the bladder neck
and prostate

7.  MOA  competitive
blockers of α1 Rs 
prostatic smooth
muscle relaxation 
improved urine flow
 Terazosin &
doxazosin  block
α1A & α1B Rs 
relaxation of vascular
smooth muscles 
decrease peripheral
vascular resistance 
hypotension
 Tamsulosin &
silodosin  block
selectively α1A Rs 
minimal effect on BP.
Non-
uroselective
α1 blockers
Uroselective
α1A blockers

8.  Have a rapid onset (7-10 days)  significant symptom
improvement (30% to 45%)  first choice in BPH.
 They are all about the same in efficacy
 Choice should consider differences in α1A specificity, adverse-
effect profile, and tolerability.

9. 1. Orthostatic
hypotension
2. Fatigue
3. Dizziness
4. Nasal
congestion
5. Ejaculatory
dysfunction
 block α1
Rs in
ejaculatory
ducts 
inhibition of
ejaculation &
retrograde
ejaculation.

10. 6. Intraoperative floppy iris syndrome: 
miosis & iris prolapse in patients
undergoing cataract surgery while on α1
blocking drugs (esp. tamsulosin)  surgery
complications.
Before initiating α-blocker  a physician must
ask patients about planned cataract surgery
 α-blocker therapy should be delayed in
patients planning to undergo cataract surgery.

11.  Absorption of tamsulosin &
silodosin  ↑ with food 
taken with supper
 Substrate for P-glycoprotein
(P-gp)
 Needs dose adjustment in
renal dysfunction.
 Inducers of CYP450 (carbamazepine
, phenytoin)  ↓ plasma conc.
 Inhibitors of CYP 450 (verapamil,
diltiazem)  ↑ plasma conc.
 Inhibitors of P-gp (cyclosporine)  ↑
silodosin conc.
 Alfuzosin  QT prolongation 
caution with other drugs causing QT
prolongation (class III antiarrhythmics).
Metabolized by
CYP450 system

12.  MOA both inhibit type II 5-α
reductase enzyme  inhibit
conversion of testosterone to the
more active form
(dihydrotestosterone; DHT)  reduce
prostate size by 30% improved
urine flow.
 Dutasteride  more potent than
finasteride.
 Uses
1. BPH  Slow onset of action (6-12
months)  used in combination with
α1 blockers.
2. Alopecia

14. Sexual  decreased libido, ejaculatory
dysfunction, erectile dysfunction,
oligospermia & gynecomastia.
Not given during pregnancy or lactation
 feminization of a male fetus.

15. α-adrenrgic R
blockers
5-α reductase
inhibitors
Decrease prostate size No Yes
Peak onset 7-10 days 6-12 months
Sexual dysfuction + ++
Hypotensive effects ++ +
Efficacy Symptom
improvement
Symptom improvement
+ decrease risk of
disease progression
(↓acute urinary
retention or ↓ need for
BPH-related surgery)
Combination of an α1-blocker and a 5-α reductase
inhibitor  ↓ symptoms and risk of disease
progression to a greater extent than either agent
alone.

16.  PDE-5 inhibitors (-afil)  used mainly for
treatment of erectile dysfunction.
 MOA  inhibit PDE-5 enz. which is
degradation of cGMP  accumulation of
cGMP  relaxation of corporal smooth
muscles  ↑ blood flow  penile erection.
Normally  sexual stimulation  ↑ NO activates
guanylyl cyclase enz. converts GTP to
cGMP  ↓ intracellular Ca++ & ↑ K+  smooth
ms. relaxation.
PDE-5 enz. is also found in the prostate and its
inhibition relaxes prostatic smooth muscle.
Tadalafil  the only drug of this class approved
for the treatment of BPH symptoms

17. 1. Headache, flushing &
nasal congestion  VD
2. Loss of blue/green
discrimination  due to
inhibition of PDE-6 in retina
 rare with tadalafil.
3. muscle pain  inhibition of
PDE-11 in skeletal muscles
 more with Tadalafil
4. Dyspepsia
5. Priapism  painful prolonged erection
6. Used cautiously in cardiac patients  periprheral VD  VR  ↑
cardiac work

18.  Tadalafil  slow
onset of action (2h) &
longer t1/2 (18 h) 
once daily dosing.
 Metabolized by
CYP450 3A4.
 Tadalafil  avoided in
patients with severe
hepatic or renal
dysfunction.
 Contraindicated in patients on organic
nitrates therapy  both act via ↑ NO 
severe hypotension
 Used caustiously with α-adrenergic
blockers  hypotension  start PDE-5
inhibitors in low doses and increase
gradually.
 ↑ or ↓ dose with inducers/inhibitors of
CYP 450 3A4

19.  Muscarinic blockers were historically
contraindicated in men with BPH 
concerns of inducing urine retention.
 Use  in the treatment of overactive
bladder symptoms (urinary urgency,
frequency, and incontinence) in men with BPH.
 MAO  block muscarinic (M3)
receptors within the detrusor muscle 
resulting in relaxation  greater symptom
improvement when added to α-blockers 
↓ overactive bladder symptoms

20.  MOA  activates β3-
adrenergic receptors in the
bladder wall  promotes
detrusor relaxation & inhibits
detrusor overactivity.
 An alternative to muscarinic
blockers  when the patient can
not tolerate anticholinergic side
effects.