Drug therapy of benign prostatic hyperplasia

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.