Pharmacotherapy

Treatments for Benign

Prostatic Hyperplasia

Maya Ganda Ratna, MD ; Iswandi

Darwis, MD
DEPARTMENT OF PHARMACOLOGY AND
PHARMACY
MEDICAL FACULTY, LAMPUNG UNIVERSITY
 Introduction
Benign prostatic hyperplasia (BPH) is a benign
neoplasm of the prostate seen in men of
advancing age.

BPH occurs in up to 50% of men by age 50, and

the incidence increases with age.

The pathologic process is called "hyperplasia"

because there is new growth of cellular elements
of the prostate.
The proliferation of prostatic stromal cells

Enlarged prostate gland

The prostatic urethra is compressed

Restricts the flow of urine from the bladder

Frequency, urgency, nocturia, intermittency,

decreased stream, and hesitancy
 Bladder outflow obstruction is considered to be due to two components. The
static component is due to enlarged gland and the dynamic component is
due to the tone of smooth muscle cells.
The contraction of stromal smooth muscle cells is predominantly mediated
by adrenergic nerves through alpha-1A receptors.
Dihydrotestosterone (DHT) is formed from testosterone with the help of 5-
alpha reductase enzyme.
However, the role of dihydrotestosterone (DHT) in pathological enlargement
of prostate is well established.
The exact pathophisiology of BPH remains far from clear.
Pathophysiology
 Proposed algorithm for medical
therapy of benign prostatic hyperplasia
Alpha blockers

5-alpha
reductase
inhibitors (5-
ARIs)
Alpha-blockers
Work to relax the smooth muscle at
the prostate and bladder neck by
blocking alpha-1a receptors.
By relaxing the smooth muscle at
the prostate neck, the urinary
channel is opened.
Thereby reducing the dynamic
component of bladder outflow
obstruction, and providing quick
symptomatic relief.
Have a quick OOA, within 3 to 5 days
There are five main alpha-
blockers:

Terazosin
2G Doxazosin

Tamsulosin
3G Alfuzosin
Silodosin
Both terazosin and doxazosin require dose titration
because their anti-hypertensive properties.

Tamsulosin, alfuzosin, and silodosin usually do not require

dose titration and have fewer cardiovascular side.

All five agents are generally equally effective, and their side
effects include light-headedness from orthostatic
hypotension, dizziness, weakness, headache, nasal
congestion, and retrograde ejaculation.

In patients with severe allergies to sulpha, an allergic

reaction to tamsulosin has been reported, and therefore
this drug should be avoided in such patients.

Nonselective blockers also act on alpha-1B receptors

present on vascular smooth muscle cells and have
tendency to cause hypotension.
 Silodosin is super selective alpha-blockers.

t blocks alpha-1a receptors and, to a much lesser

degree, alpha-1b and alpha-1d receptors

This heightened selectivity may result in fewer

cardiovascular side effects, which are mainly
regulated by alpha-1b receptors.
 5-ARIs inhibitors
5-alpha-reductase
Inhibit the
Prostate
conversion of
decrease in size Reduce the
testosterone to
and slow the static
DHT, the main
progress of component.
mediator of BPH
prostate growth.
progression.

The OOA with 5-ARIs is slower than with alpha-

blockers, and usually takes 4 to 6 months.
The two main 5-ARIs are finasteride and
dutasteride.

Finasteride inhibits the type 2, 5-alpha

redustase isoenzyme, whereas dutasteride
inhibits both type 1 and type 2 isoenzymes.

The 5-ARIs side effects include impotence,

ejaculatory dysfunction, decreased libido,
and rarely gynecomastia.
 Generally well tolerated; sexual AEs are the most
commonly reported ESs, although it is worth noting
that there is a relatively high prevalence of sexual
dysfunction in untreated men with BPH

Furthermore, studies have shown that the incidence

of drug-related sexual AEs decreases during
prolonged treatment

The rates of decreased libido and impotence were

identical in finasteride and placebo groups after 2
years

Similarly, during 4 years of dutasteride treatment

there was a trend towards a reduction in the rate of
newly reported sexual AEs over time
 Pharmacotherapy
Treatments
for Erectile Dysfunction

Maya Ganda Ratna, MD ; Iswandi

Darwis, MD

DEPARTMENT OF PHARMACOLOGY AND

PHARMACY
MEDICAL FACULTY, LAMPUNG UNIVERSITY
 Introduction

Erectile dysfunction (ED) is a widespread problem affecting many

men across all age groups.

ED is defined as a difficulty in initiating or maintaining penile

erection adequate for sexual activity.

Its etiology is multifactorial.

Risk factors include age, diabetes mellitus, neurologic diseases,

smoking and cardiovascular diseases (CVD).
Although the disorder has been described for more than 1000
years, the molecular basis and mechanisms of ED have yet to be
completely understood.
 PDE5
The family of phosphodiesterases is
comprised of 11 catalytic enzymes.

It regulates the second messenger activity

in cells by cleavage of the phosphodiester
bond of either cyclic adenosine
monophosphate (cAMP) or cyclic guanosine
monophosphate (cGMP)

PDE5 is present in high concentrations in

the smooth muscle of corpora cavernosa of
the penis and in the smooth muscle of the
pudendal arteries.

Therefore, phosphodiesterase 5 inhibitors

(PDE5) are the major initial line of
pharmacotherapy for erectile dysfunction
(ED).
 PDE5 Inhibitors
PDE5 inhibitors act by inhibiting PDE5, resulting in
decreased breakdown of cGMP, thus PDE5 inhibitors
increase blood flow of the smooth muscle.

PDE5 inhibitors are degraded in the liver.

The most common reported side effects include

headaches, dyspepsia, and nasal congestion.

In regard to cardiovascular (CV) safety, PDE5 inhibitors

have proven to be safe in patients with CV disease.

PDE5 inhibitors are contraindicated in ED patients taking

nitrates due to unpredictable hypotension.

PDE5 inhibitors seem to be less effective in studies where

male subjects have comorbid diseases such as diabetes.
Sildenafil Udenafil Avanafil

It is a long-acting
Onset of action Is highly selective
drug with a half-
usually within 25 PDE5 inhibitor.
time (t1/2) of 11
60 minutes.
13 hours.

Avanafil showed a
It has a relatively
higher selectivity,
Absorption of the fast absorption
drug is slowed with the plasma against PDE5 than
with food. concentration both sildenafil and
after ingestion. vardenafil.

Minor side effects Rapid absorption

were headaches, Udenafil has been with a tmax
flushing, reported to be a approximately 35
indigestion, and well tolerated.
minutes and a
visual changes.
short t1/2 of less
than 1.5 hours
Lodenafil Tadalafil Vardenafil

Has proven to be Vardenafil is

Is a newer PDE5 efficacious in ED effective for ED
inhibitor. is due to which was a
diabetes, result of
Lodenafil was radiation diabetes,
shown to be therapy for
prostatic cancer, chemotherapy,
approximately depression,
two fold more spinal cord
injury, and lower hypertension,
potent than
sildenafil for urinary tract and spinal cord
inhibition of the infection. injury.
breakdown of
cGMP.

Has only mild to

moderate
adverse
reactions.
Table 1. Comparison of All Currently Available PDE5 Inhibitors in the United States

Avanafil Sildenafil Vardenafil Tadalafil

Onset of 15-30 30-60 30-60 60-120
action minutes minutes minutes minutes
Plasma half- 3 hours 4 hours 4 hours 17.5 hours
life
Duration of Up to 6 Up to 12 Up to 10 Up to 36
action hours hours hours hours
Effect of Not affected High-fat High-fat Not affected
food intake meals meals
decrease decrease
efficacy efficacy
Unique side Vision Vision Back pain,
effects abnormalitie abnormalitie myalgias
s C,
PDE6 = phosphodiesterase 6. From Gingell (PDE6) s (PDE6)
et al[10]; Hatzimouratidis K, et al[11]; Gupta M, et al[12];
Coward RM, et al[13]; and Forgue ST, et al.[14]
HANUPIS