Drug therapy OF

Benign Prostatic Hyperplasia

By
Ahlam Elmasry
Ass. Professor of Clinical
Pharmacology
Faculty of Medicine / Mansoura
university
 Learning Outcomes
By the end of the lecture, the students will be able to:
Answer questions about
1. α1-Adrenergic antagonists
2. 5-α Reductase inhibitors
3. Phosphodiesterase-5 inhibitor
12/17/2022 PRESENTATION TITLE 3
 1.α1-Adrenergic antagonists
Terazosin
doxazosin selective α1A & α1B
receptor,
alfuzosin
tamsulosin
selective α1A receptor,
silodosin

N.B α1A receptors are found in the prostate, α1B receptors are found in the
prostate and vasculature

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 1.α1-Adrenergic antagonists
Mechanism of action
blocking the α1A and α1B receptors in the
prostate, the α-blockers cause prostatic
smooth muscle relaxation, which leads to
improved urine flow
tamsulosin is more selective for the α1A
receptor, less effect on blood vessels

Drug therapy OF
12/18/2022 Benign Prostatic Hyperplasia 5
 1.α1-Adrenergic antagonists
Pharmacokinetics
well absorbed following oral administration.
Food increase the absorption of tamsulosin, alfuzosin
Metabolized by cytochrome P450 system.
Silodosin requires dosage adjustment in renal impairment and
is contraindicated in patients with severe renal dysfunction.

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 1.α1-Adrenergic antagonists
Adverse effects
α-Blockers may cause
fatigue nasal congestion headache
drowsiness orthostatic hypotension.
tamsulosin and silodosin are more selective for the α1A
relatively minimal effects on blood pressure

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 1. α1-Adrenergic antagonists
Drug interactions
• Verapamil, diltiazem may increase their plasma
concentrations
• carbamazepine, phenytoin, may decrease their plasma
concentrations.

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5-α Reductase
inhibitors
Finasteride and dutasteride
 5-α Reductase inhibitors
Mechanism of action
• inhibit the enzyme 5-α reductase, which is responsible for
converting testosterone to the more active
dihydrotestosterone (DHT), so the prostate shrinks, and urine
flow improves.
• dutasteride is more potent and causes a greater decrease in
DHT

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12/17/2022 PRESENTATION TITLE 11
 α-blockers versus 5-α reductase
• α-blockers, provide relief
from BPH symptoms within 7
to 10 days, while 5-α
reductase take up to 12
months to relieve symptoms.
• Dutasteride and tamsulosin
are available as a
combination product for this
indication.

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12/17/2022 PRESENTATION TITLE 13
 α-blockers versus 5-α reductase

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 α-blockers versus 5-α reductase
Pharmacokinetics
Food does not affect the absorption of finasteride or
dutasteride.
Both agents are highly protein bound and metabolized by the
CYP450 system.

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 α-blockers versus 5-α reductase
Adverse effects
sexual dysfunction , such as decreased ejaculate, decreased
libido,
Gynecomastia
oligospermia.
No drug interaction except with testosterone

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Phosphodiesteras
e-5 inhibitor
Tadalafil
 Phosphodiesterase-5 inhibitor
Mechanism of action
inhibition of PDE-5 so prevent degradation of cGMP allows for
vasodilation and relaxation of the smooth muscle of the
prostate and bladder, which thereby improves symptoms of
BPH.

Pharmacokinetics:
Reduced dose with renal impairment

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 Phosphodiesterase-5 inhibitor
Adverse effects
nasal congestion
flushing
dyspepsia

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PRESENTATION TITLE
 Which is CORRECT regarding finasteride?
A. Finasteride is associated with significant hypotension.
B. Finasteride is associated with birth defects.
C. Finasteride is effective within 2 weeks of initiation.
D. Finasteride is renally eliminated.

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 A 73-year-old man presents to his primary care physician
complaining of a weak stream and nocturia four times at
night. He is very sensitive to the medication side effects and is
reluctant to take medications for this reason. Physical
examination reveals a mildly enlarged prostate. Treatment of
this condition may involve the use of which of the following
agents to minimize side effects?
(A) Alfuzosin
(B) Doxazosin
(C) Prazosin
(D) Tamsulosin
(E) Terazosin
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 A 51-year-old man presents to the urology clinic with difficulty starting and
stopping his stream during urination. The symptoms have been worsening
over the past year. He also reports that he does not feel he empties his
bladder completely. He is started on tamsulosin for benign prostatic
hyperplasia. What is a common side effect of tamsulosin?

(A) Cough

(B) Hemorrhagic cystitis

(C) Hypercoagulable state

(D) Impaired blue-green vision

(E) Orthostatic hypotension

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 Which describes an important difference between terazosin and
tamsulosin?
A. Terazosin blocks α1A receptors, whereas tamsulosin blocks α1A
and α1B receptors.
B. Terazosin blocks α1A and α1B receptors, whereas tamsulosin
blocks α1A receptors.
C. Terazosin blocks 5-α reductase, whereas tamsulosin blocks PDE-
5.
D. Terazosin must be taken with food, whereas tamsulosin can be
taken on an empty stomach.
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 A 70-year-old man with BPH and an enlarged prostate continues
to have urinary symptoms after an adequate trial of tamsulosin.
Dutasteride is added to his therapy. In addition to tamsulosin, he
is also taking hydrochlorothiazide, testosterone, and vardenafil as
needed. Which of his medications could have an interaction with
dutasteride?
A. Hydrochlorothiazide
B. Tamsulosin
C. Testosterone
D. Vardenafil
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 A 56-year-old man presents to his primary care physician
complaining of difficulty urinating. Digital rectal exam reveals an
enlarged prostate. The patient is started on a trial of terazosin,
after which his symptoms improve dramatically. Which of the
following side effects is he most likely to experience?
(A) Diarrhea
(B) Dizziness
(C) Flatulence
(D) Headache
(E) Priapism
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 A 76-year-old man presents to the clinic for follow-up of his
benign prostatic hyperplasia. He has been doing well with his
symptoms since starting finasteride. He no longer has as much
difficulty starting his stream and feels that he empties his bladder
completely. What is the mechanism of action of finasteride?
(A) 5α-Reductase inhibitor
(B) a1-Antagonist
(C) GnRH agonist
(D) GnRH antagonist
(E) Nonsteroidal competitive inhibitor at the testosterone receptor
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 Case Discussion/reflection
Proper medical management of BPH ??

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 References or further readings
1) Kaplan USMLE STEP1, lecture notes
Pharmacology latest edition.

2) Lippincott’s illustrated review:

Pharmacology, latest edition
Thank you