Transcript Erectile Dysfunction - | Pharmaceutical Sciences

Group 3
ธนวัต จางคกู ล
43076140
้ั ตติพร
กนกพร ตงจิ
Erectile Dysfunction
Meaning :
“ The inability to achieve and maintain a penile
erection satisfactory for sexual intercourse”
(Does not include ejaculation disorders)
History
• The first description of erectile
dysfunction, about 2000 B.C., was
set down on Egyptian.
• Hippocrates concluded that too
much horseback riding was the
cause of disease.
• Aristotle, air influx into penis.
Anatomy of the penis
• Tunica Albuginea
• Corpora Cavernosa
-- Sinusoid
• Corpus Spongiosum
-- Sinusoid
• Glans Penis
• Artrial supply
• Venous drainage
• Nerve
Arterial Supply
• Internal iliac artery
• internal pudendal artery
[main]
– Dorsal artery
– Bulbourethral artery
– Cavenous artery
• External iliac, Obturator,
vesical and femoral
artery. [accessory]
Venous drainage
• Emissary veins,
transformed from
peripheral sinusoids
• Deep dorsal vein [main]
• Bulbourethral vein,
Cavernous vein
[ accessory]
Mechanism of erection :
Dilatation arterioles&arteries
expanding of sinusoids
compression of subtunical
venular plexuses
Emissary veins enclosed
increasing of intracavernous
pressure to raise the penis
Mechanism of Detumescence
Transient intracorporeal pressure increase
[smooth muscle contraction]
Pressure decrease slowly
[slow reopening of the venous channels]
Pressure decrease fast
[venous outflow capacity is fully restored]
Neuroanatomy of penile erection
• Peripheral pathways
Sympa, - NE release
Parasym, + NO & Ach release
Somatic, +Ach release
– autonomic [ C. Cavenosa & C. Spongiosum]
– somatic [ Glans Penis & C. Spongiosum]
Neuroanatomy of penile erection
• Supraspinal pathways
[ hypothalamus, limbic system and cerebral cortex]
dopaminergic & adrenergic recepters
serotonin recepters
promotes sexual
drive
inhibits sexual
drive
Classification of Erectile
Dysfunction
•
•
•
•
•
•
•
Psycogenic
Neurogenic
Endocrinologic
Arteriogenic
Cavernosal (Venogenic)
Drug-induced
Erectile dysfunction associated with
aging, systemic disease & others
Cause of Erectile Dysfunction
Alcohol Abuse
Anxiety
or Depression
Coronary Artery Disease
Diabetes
Hormonal Abnormalities
Hypertension
Peripheral Vascular Disease
Renal or
Hepatic Failure
Anemia
Smoking
Surgery(Pelvic or Perineal)
Trauma
to pelvic or spine
Medication : AntiHT, Antidepressant,
Treatments
of
Erectile Dysfunction
Treatments of Erectile Dysfunction
Drug Therapy :
Orally Administration
Intracarvernous Injection
MUSE or Intraurethral
Suppository
Vacuum Devices
Horrmone Replacement Therapy
Surgery
Others
Treatments of Erectile Dysfunction
•
Drug Therapy : Orally Administration
Yohimbine
Phentolamine
Apomorphine
Sildenafil
Treatments of Erectile Dysfunction
Drug Therapy : Orally Administration
Yohimbine
alpha 2 -antagonist
Side effect : anxiety, ปั สสาวะบ่อย,
tachycardia,
่ arterial pressure
เพิม
Treatments of Erectile Dysfunction
Drug Therapy : Orally Administration
Phentolamine
vasoactive Drug
Side effect : orthostatic hypotension,
tachycardia
Treatments of Erectile Dysfunction
Drug Therapy : Orally Administration
Apomorphine (Sublingual)
Stimulate brain dopaminergic mechanism
Side effect : nausea, vomit, yawn
Treatments of Erectile Dysfunction
Drug Therapy : Orally Administration
Sildenafil
Phosphodiesterase Inhibitor
Side effect : headache, flushing, dyspepsia
visual disturbance
Contraindication : co-administration with nitrate
MI, CHF
Treatments of Erectile Dysfunction
Intracavernous Injection
ใช้ vasoactive agents ในการฉี ดเข้า corpora
cavernosa
่ั
ทาให้เส้นเลือดขยายต ัว เกิดการคงของเลื
อดที่
penis ทาให้เกิด erection
Vasoactive Agent
Papaverine
Phentolamine
Alprostadil
TreatmentsInjection
of Erectile Dysfunction
Intracavernous
Side effect : priapism, small nodule,
subcutaneous
hemorrhage, pain, trauma,
scar
*combination therapy จะให้
่ กว่า monotherapy
ผลการร ักษาทีดี
่ oral alpha-blocker
*การเพิม
์
(Doxazosin) จะเสริมฤทธิในการ
Treatments of Erectile Dysfunction
Intraurethral suppositories
“MUSE” (Medicated urethral system
for erection)
มีหลอดบรรจุ alprostadil สาหร ับสอดเข้า
ทาง urethra โดยจะออก
์
ฤทธิภายใน
8-10 นาที
อาการไม่พงึ ประสงค์ : ปวด อาการบวมแดง
Treatments of Erectile Dysfunction
Vacuum Devices
Pump จะดู ดอากาศออกจาก
cylinder ทาให้เกิด
สู ญญากาศเกิดแรงดึงเลือด
เข้า penis และ elastic
band จะป้ องกันไม่ให้เลือด
ไหลย้อนกลับ
Treatments of Erectile Dysfunction
Hormone Replacement
Therapy :
Testosterone
เพิม
่ sexual function
มีทงั ้ ในรูปแบบการฉีด การ
Treatments of Erectile Dysfunction
Surgery
- ผ่าตัดใส่ Paired rod
เข้าใน
corpora cavernosa
- ผ่าตัด repair
arteries จะช่วยได้ใน
กรณี obstruction
Treatments of Erectile Dysfunction
Others
: Alprostadil gel
่
ทาที่ glans penis จะทาให้เพิม
penile rigidity
Comparision of Treatments
Oral
Use :
Medica
tion
AUA
guildline :
Intracarv
enous
MUSE
Injection
AUA
guildline :
Injectio
n
1st
Line(Now)
1st
Line(Old)
alternat
ives
effective in effective in
definable & definable &
undefinabl undefinabl
e cause
e cause
Vacuum
Device
Oldest
Treatm
ent
HR
T
Surg
ery
Androp Last
ause choice
or
Arterial
revascula
rize
and
venous
ligament
in
Comparision of Treatments
Oral
Medica
tion
Agent Sildenafil
s:
Yohimbine
Intracarv
enous
Injection
Alprostadil
Papaverine
MUSE
Vacuum
Device
HR
T
Surg
ery
Alprost
adil
-
Testoste
rone
-
4065%
90 %
up
61
%
-
Phentolami Phentolami
ne
ne
Apomorphi
ne
Effecti Silden.
Monotherapy
ve :
65-93%
70-74%
Others is
lower
Combined
90 %
Comparision of Treatments
Oral
Medica
tion
Advan Comfortabl
tage
e,
Non
invasive
Intracarv
enous
Injection
High
effective,
no death
evidence
MUSE
Vacuum
Device
HR
T
Surg
ery
High
Maintai High
effectiv
n
effectiv
Invasiv
e
e
e
BMD
Less
than
inj.
and
no
death
evidenc
e
Improve
sex
fn.,moo
d
&
emotion
Increase
muscle
strength
Comparision of Treatments
Oral
Medica
tion
Dis Have Death
evidence
Advan
data
tage
lower
effective
in some
case
as DM
Intracarv
enous
Injection
50 % reject
the
long term
treatment
cause :
decrease in
response
MUSE
Vacuum
Device
HR
T
Penile
pain
Surg
ery
Patients Use only Expensi
and
ve,
in
urethral
uncomf
andropa
Partner’
ort.
bleedin
use
s
g
long
term :
satisfati
More on less Anemia,
less interest expensi than inj.
increase
in sex
ve
bl.
problem of
than
Viscosit
self inj.
injectio
y
Penile
n
CI in
Comparision of Drug Therapy
Apo
Papaver
ine
Phentola morph
mine
ine
Mecha Phosphodie Syn. PG. E
Like Phosphod Alpha Stimulat
nism
sterase
ies- terase1,2e
alphaAlprost
inhibitors
inhibitors
adrenagic
adil
Brain
: increase
: Inhibit adrener
blocking
dopamin
NO
smooth gic
agent
ergic
: increase
muscle
:Carvenous
mechani
cGMP
receptor
smooth
sm
contractio
muscle
that
n
blocking
relax
effect
65-93% Monotherapy 4040-60
40-45
65
:Dilate
Effecti
70-74%
:Arterioles
65%
%
%
erection
%
avg. 75
arterial
ve
smooth
%
Combined
vessel
90muscle
%
Age
nts
Sildena
fil
Alprosta
dil
MUSE
Comparision of Drug Therapy
Age
nts
Sildena
fil
Admin.
oral
route
usual
dose
25-100
mg
Apo
Papaver
ine
Phentola morph
mine
ine
Intraur
oral
subling
intracarve
ethral intracarve or
ual
nous
nous
supposi
Intracarv
injection
tory
enous
injection
by
5-20 mcg 50-1000 Single 10- injection
40-80
applicat
mcg
60mg
mg
or
Combine
3-5mg
Alprosta
dil
MUSE
(Papa+Ph
ento
or
Comparision of Drug Therapy
Age
nts
Sildena
fil
Alprosta
dil
Use in
Definable
and
Definable
and
case
undefinable
such as
DM,
Olderly
with HT
- pt. Use
spinal
cord
Contra injury
nitrate,
Heart
indicati depression
Disease,
on
Renal&He
patic
undefinab
le
such as
DM,
Apo
Papaver
ine
Phentola morph
mine
ine
Alprost like
like Psycho
adil alprostadi
genic
l
injectio
alprosta Type
n
dil
MUSE
alternat
ive
Olderly
Ab.
Heart
with
HT
Predisposition Penile Disease
to
priapismAnatomy
spinal
cord eg
Urethriti
anemia,leuke
injury
s
mia
risk of
NA.d
ata
NA.d
ata
Comparision of Drug Therapy
Age
nts
Sildena
fil
ADR
16%
Headache
10%
Flushing
7%
Dyspepsia
Dis
Advant
age
3% Visual
Disturb
Have
Death
evidence
s
Apo
Papaver
ine
Phentola morph
mine
ine
35 %
30 %
Papa +
Nausea
Penile Pain Penile
Phentolamine
Vomit
2%
Pain 0.4 % Penile
Yawn
Priasism or
Pain
5%
Urethral 8 %
Priapism
Fibrosis
and
Alprosta
dil
MUSE
bleeding
fibrosis
6%
only Alprostadil has approved in
Drowsiness
USA
sweating,H
Phentolamine
ypot.
has carcinogenic
potential effect in rat
The End