2. Moderators:
Professors:
Prof. Dr. G. Sivasankar, M.S., M.Ch.,
Prof. Dr. A. Senthilvel, M.S., M.Ch.,
Asst Professors:
Dr. J. Sivabalan, M.S., M.Ch.,
Dr. R. Bhargavi, M.S., M.Ch.,
Dr. S. Raju, M.S., M.Ch.,
Dr. K. Muthurathinam, M.S., M.Ch.,
Dr. D. Tamilselvan, M.S., M.Ch.,
Dr. K. Senthilkumar, M.S., M.Ch.
Dept of Urology,GRH and KMC, Chennai. 2
3. “Man survives earthquakes, experiences the horrors of
illness, and all of the tortures of the soul. But the most
tormenting tragedy of all time is, and will be, the
tragedy of the bedroom.”
Tolstoy
3
Dept of Urology,GRH and KMC, Chennai.
4. What is ED?
ED is the inability to achieve and maintain erection
adequate for intercourse to the mutual satisfaction of
the man and his partner.
Jardin et al, 2000 .
4
Dept of Urology,GRH and KMC, Chennai.
5. RISK FACTORS
Heart disease
Hypertension
Diabetes
Chronic renal failure
Hepatic failure
Multiple Sclerosis
Severe depression
Other (vascular disease, low HDL, high
cholesterol)
Benet et al. Urol Clinic North Am. 1995; 151:54-61
5
Dept of Urology,GRH and KMC, Chennai.
7. PSYCHOGENIC
Persistent inability to achieve or maintain erection
satisfactory for sexual performance due predominantly or
exclusively to psychological or interpersonal factors.
Anxiety
Self-reported depressive symptoms
Low degrees of self-esteem
Negative outlook on life
Self-reported emotional stress
H/O sexual coercion.
7
Dept of Urology,GRH and KMC, Chennai.
8. NEUROGENIC
10% to 19% of ED is neurogenic , prevalence is much high
if iatrogenic & mixed ED included.
Parkinson's disease
Stroke
Encephalitis
Temporal lobe epilepsy
Tumors
Dementias
Alzheimer's disease
Shy-Drager syndrome
Trauma.
8
Dept of Urology,GRH and KMC, Chennai.
9. Iatrogenic impotence :
Radical prostatectomy 43% to 100%
Perineal prostatectomy for benign 29%
APR - 15% to 100%
External sphincterotomy 2% to 49% .
Nerve-sparing radical prostatectomy reduced the
incidence 100% to 30%-50%
Pelvic fracture, ED result of cavernous n’ injury or
vascular insufficiency or both .
9
Dept of Urology,GRH and KMC, Chennai.
11. ENDOCRINOLOGIC
Testosterone : enhances sexual interest, ↑ frequency of sexual acts, and
↑ frequency of nocturnal erections.
Men receiving long-term androgen ablation therapy for prostate cancer
reported poor libidoand ED .
Hyperprolactinemia- pituitaryadenoma or drugs, results in both
reproductiveand sexual dysfunction.
ED associated with both hyper- and hypothyroidism.
DM, causes ED through its vascular, neurologic, endothelial, and
psychogenic complications rather than hormone def.
11
Dept of Urology,GRH and KMC, Chennai.
12. ARTERIOGENIC
Atherosclerotic or traumatic arterial occlusive disease of hypogastric-
cavernous-helicine arterial tree .
Risk factors include HT, hyperlipidemia, cigarette smoking, DM,
blunt perineal or pelvic trauma, and pelvic irradiation.
12
Dept of Urology,GRH and KMC, Chennai.
13. CAVERNOUS (VENOGENIC)
Tunical changes- degenerative changes (Peyronie's disease, old age, and
DM) or traumatic injury to T.A (penile # )
Fibroelasticstructural alterations,
Insufficient trabecular smooth muscle relaxation,
Venous shunts. (priapism)
13
Dept of Urology,GRH and KMC, Chennai.
15. MEDICAL HISTORY
The goals of medical history-taking are
(1) to evaluate the potential role of underlying medical
conditions (e.g., atherosclerosis, diabetes) and
comorbidities (e.g., depression)
(2) to differentiate between potential organic and
psychogenic causes
(3) to assess the potential role of medication
(4) Past H/O: Prostatectomy, APR, Pelvic trauma
15
Dept of Urology,GRH and KMC, Chennai.
16. CHARACTERISTIC ORGANIC PSYCHOGENIC
ONSET GRADUAL ACUTE
CIRCUMSTANCES GLOBAL SITUATIONAL
COURSE CONSTANT VARYING
NON COITAL ERECTION POOR RIGID
PSYCHOSEXUAL
PROBLEM
SECONDARY LONG HISTORY
PARTNER PROBLEM SECONDARY AT ONSET
ANXIETY AND FEAR SECONDARY PRIMARY
16
Dept of Urology,GRH and KMC, Chennai.
17. A Practical Evaluation of Men with ED
Laboratory Tests
Fasting glucose, RFT, lipids & testosterone.
Optional : indicated by history & P/E .( Prolactin, LH, FSH,
Thyroid function.)
PSA measured >50 yrs age ,F/H ca prostate, if hormonal
replacement planned.
17
Dept of Urology,GRH and KMC, Chennai.
18. A Practical Evaluation of Men with ED
Physical Examination
Blood pressure
Examine penis (R/O Peyronie’s disease)
Determine size and consistency of testes
Digital rectal exam
Focused vascular exam/peripheral pulses
Focused neurologic exam
18
Dept of Urology,GRH and KMC, Chennai.
19. Why Use Patient Questionnaires?
Facilitate dialogue and diagnosis
Evaluate treatment changes
Drawback is reliance on self assessment.
Examples of self-administered, standardized
questionnaires
Sexual Health Inventory for Men (SHIM)1
International Index of Erectile
Function (IIEF)2
1. Rosen RC, et al. Int J Impot Res. 1999;11:319-326. 2. Rosen RC, et al. Urology. 1997;49:822-830. 19
Dept of Urology,GRH and KMC, Chennai.
21. SHIM Score Characterizes
ED Severity
22-25 Normal erectile function
17-21 Mild ED
12-16 Mild to moderate ED
8-11 Moderate ED
7 Severe ED
*Total score ranges from 5 to 25 and is based on FIRST 5 questions.
Each rated on a Likert scale of 1 = least functional to 5 = most functional.
Rosen RC, et al. Int J Impot Res. 1999;11:319-326. 21
Dept of Urology,GRH and KMC, Chennai.
22. EVALUATION OF COMPLEX PATIENT
Indications for specialized evaluation
Failure of initial treatment
Peyronie's disease
Primary ED
H/O pelvic/perineal trauma
Vascular or neurosurgical intervention
Complicated endocrinopathy
Complicated psychiatric disorder
Complex relationship problems
Medicolegal concerns .
22
Dept of Urology,GRH and KMC, Chennai.
23. SEXUAL HISTORY
Interview conducted face-to-face.
Ensure pt trust, comfort, and openness
The interviewershould determine whether patient has
cognitive understandingof genital function and penilerigidity.
Very useful in evaluatingand treating men with deep-seated
psychological problems.
23
Dept of Urology,GRH and KMC, Chennai.
24. PSYCHOLOGIC
Diagnostic interview mainstay of evaluation.
Current sexual problem and its history
Deeper causes of sexual dysfunction
Relationship &
Psychiatric symptoms.
Immediate causes –
fear of failure
performance anxiety
insufficient sexual stimulation
loss of attraction
relationship conflicts.
“Deeper” causes of psychogenic ED- unresolved parental
attachments, sexual identity, sexual trauma, and cultural-
religious taboos .
24
Dept of Urology,GRH and KMC, Chennai.
26. VASCULAR EVALUATION
First-Line Evaluation of Penile Blood Flow
Combined Intracavernous Injection and Stimulation:
A CIS test consists of intracavernous injection of a vasodilatoror
a combination of two or three vasodilators, genitalor audiovisual
sexual stimulation, and assessmentof the erection by an
observer.
This screening test is the most commonly performeddiagnostic
procedure for ED.
It allows the clinician to bypassneurologic and hormonal
influencesand to evaluatethe vascularstatus of the penis
directly and objectively
26
Dept of Urology,GRH and KMC, Chennai.
27. alprostadil alone (Caverjector Edex, 10 to 20 μg), a combination
of papaverineand phentolamine(Bimix, 0.3 mL), or a mixture of
all three of these agents (Trimix, 0.3 mL).
The technique involves injecting the medication through a 5/8-
inch needle (27 to 29 gauge) into the corpus cavernosum.
The needlesite is compressed manually for 5 minutes to prevent
hematoma formation
should not leave the office until the penis becomes flaccid
spontaneouslyor by injection of a diluted phenylephrine
solution (500 μg/mL, given 1 mL every 3 to 5 minutes until
detumescence).
27
Dept of Urology,GRH and KMC, Chennai.
28. Second-Line Evaluation of Penile Blood Flow
Duplex Ultrasonography (Gray Scale or Color-Coded)
Penile blood flow study, which consists of CIS and blood flow
measurement by duplex ultrasound, is the most reliableand
least invasiveevidence-basedassessmentof ED.
Duplex ultrasound consists of high-resolution(7 to 10 MHz)
real-time ultrasonographyand color pulsed Doppler
Visualize the dorsal and cavernousarteries selectivelyand to
perform dynamicblood flow analysis
best tool availablefor the diagnosisof high-flowpriapismand
localizationof a ruptured artery
28
Dept of Urology,GRH and KMC, Chennai.
29. Peak Systolic Velocity (PSV) and Arterial Dilation
In the Mayo Clinic series, PSV less than 25 cm/s had a sensitivity
of 100% and a specificity of 95% in patientswith abnormal
pudendalarteriography ( Lewis and King, 1994 ).
unilateral cavernousarterial insufficiency results in asymmetry
of PSV greater than 10 cm/s.
29
Dept of Urology,GRH and KMC, Chennai.
30. Duplex Ultrasound Evaluation in Veno-
occlusive Dysfunction
High systolic flow (>25 cm/s PSV) and persistent end-
diastolic flow velocity (EDV) (>5 cm/s) accompanied
by quick detumescence after self-stimulation, the
patient is considered to have venogenic impotence.
Venous leakage on cavernosometry was predicted with
a sensitivity of 90% and specificity of 56% when EDV
was greater than 5 cm/s ( Quam et al, 1989 ; Lewis and
King, 1994 ).
30
Dept of Urology,GRH and KMC, Chennai.
31. Third-Line Evaluation of Penile Blood Flow
Cavernous Arterial Occlusion Pressure (CASOP)
It involvesintracavernousinjectionof a vasodilator (usually Trimix
solution) followed by infusion of saline into the corpora cavernosaat
a rate sufficient to raise the intracavernouspressure above the
systolic blood pressure.
A pencil Doppler transduceris then applied to the side of the penile
base.
The saline infusion is stopped, and the intracavernouspressure is
allowed to fall.
31
Dept of Urology,GRH and KMC, Chennai.
32. The pressure at which the cavernousarterial flow becomes
detectable is defined as the cavernousartery systolic occlusion
pressure (CASOP).
A gradient betweenthe cavernousand the brachialartery
pressures of less than 35 mm Hg and an equal pressure between
the right and the left cavernous arteries has beendefined as
normal
32
Dept of Urology,GRH and KMC, Chennai.
33. CAVERNOSAL ARTERY FLOW
BRACHIAL SYSTOLIC AND
DIASTOLIC BP
(CASOP)-108mmHg
INTRACAVERNOSAL HEPARINIZED
SALINE FLOW
33
Dept of Urology,GRH and KMC, Chennai.
34. RESISTIVE INDEX
In 1974, Planiol and Pourcelot proposed a resistive index (RI) to
describe vascular resistance from the Dopplerspectrum.
RI = PSV - EDV/PSV.
As penile pressure equals or exceedsdiastolic pressure, diastolic flow
in the corpora will approach 0 and the value for RI approaches 1.
During tumescenceand until full rigidity, diastolic flow is antegrade
(+); the value for RI remains less than 1.0.
Naroda and associates (1994) found that an RI greaterthan 0.9 was
associated with normal resultsduring DICC in 90% of theirseries and
an RI less than 0.75 was associated withvenous leakage in 95%.
34
Dept of Urology,GRH and KMC, Chennai.
35. PHARMACOLOGIC ARTERIOGRAPHY
Best indication is young pt with ED sec to traumatic a’ disruptionor
perineal compression injury.
Intracavernous inj of vasodil agent followed by selective cannulation of
internal pudendal a’ and inj of contrast.
Anatomy and radiographic appearance of internal pudendal, and
penile arteries evaluated.
patent commonpenile, dorsal, and cavernous
arteries
nonvisualizationof commonpenile artery
and its branches
35
Dept of Urology,GRH and KMC, Chennai.
36. DICC
Dynamic infusion cavernosometry and cavernosography (DICC) is invasive
Flow rate required to maintain erection at an intracavernous pressure of
more than 100 mm Hg is reported to be less than 3 to 5 mL/min
Pressure decrease in 30 seconds from 150 mm Hg is less than 45 mm Hg.
Cavernosography is performed after cavernosometry and should reveal
opacification of the corpora cavernosa but minimal or no visualization of
venous structures or corpus spongiosum
For young men who might be candidates for penile vascular operations,
specifically those with a history of pelvic trauma or life-long ED (primary
ED).
36
Dept of Urology,GRH and KMC, Chennai.
37. Pharmacologic cavernosometry
involvessimultaneoussaline infusion and intracavernous pressure
monitoring after intracavernous injectionof a strong vasodilating
solution
Veno-occlusivedysfunctionis indicated by eitherthe inability to
increase intracavernouspressure to the levelof the mean systolic
blood pressure ora rapid drop of intracavernouspressure after
cessation of infusion
Pharmacologic cavernosography involves
the infusion of radiographic contrast solution into the corpora
cavernosum.
Leakage sites to the glans, corpus spongiosum, superficial dorsal
veins,and cavernousand crural veinscan then be detected.In the
majority of patients, more than one site is visualized
37
Dept of Urology,GRH and KMC, Chennai.
38. PHARMACOLOGIC CAVERNOSOGRAPHY
After penile # communication between
CC & CS seen 27-year-old man with primary ED, venous leakage
from crura
38
Dept of Urology,GRH and KMC, Chennai.
39. Penile Brachial Pressure Index
The penile brachial pressure index (PBI) represents
the penile systolic blood pressure divided by the
brachial systolic blood pressure.
The technique involves applying a small pediatric
blood pressure cuff to the base of the flaccid penis
and measuring the systolic blood pressure with a
continuous-wave Doppler probe.
A PBI of 0.7 or less has been used to indicate
arteriogenic impotence
39
Dept of Urology,GRH and KMC, Chennai.
41. PSYCHOPHYSIOLOGIC
Nocturnal Penile Tumescence
Nocturnalpenile tumescence (NPT) monitoringwas first described by
Halverson(1940)
Karacan and colleagues(1966)were the first to demonstratethat 80% of
NPT occursduringrapid eye movement (REM)sleep
NPT has been measured by a numberof methods:
stamp test ( Barryet al, 1980 )
snap gauges ( Diedrichet al, 1992 )
sleep laboratorynocturnal peniletumescence and rigidity(NPTR)
RigiScan(Endocare, Inc., Irvine, CA)
most recently, NPT electrobioimpedance(NEVA, American Medical
Systems, Inc., Minnetonka, MN).
41
Dept of Urology,GRH and KMC, Chennai.
42. NPT
In its classic form, NPT consists of nocturnal
monitoring devices that measure the
number of episodes
tumescence (circumference change by strain gauges)
maximal penile rigidity
duration of nocturnal erections
42
Dept of Urology,GRH and KMC, Chennai.
43. INDICATIONS
Heaton and Morales (1997) have suggested indications for NPTR
as follows:
(1) suspected sleep disorder
(2) obscure cause of ED
(3) nonresponse to therapy
(4) plannedsurgical treatment
(5) legallysensitivecase
(6) measurementof drug effects in placebo-controlleddrug trials
(7) suspected psychogeniccause
43
Dept of Urology,GRH and KMC, Chennai.
44. The patient is awakenedduring maximal tumescence, and the
erection is photographed and axial rigidity measured with a
device applied to the tip of the penis.
A buckling resistance of 500 g is considered the minimum for
vaginalpenetration; 1.5 kg is considered complete rigidity
according to the original Karacan (1970) criteria.
Because NPT occurs during REM sleep, tumescence monitoring
repeated over two to three nights to overcome the so-called first-
nighteffect.
44
Dept of Urology,GRH and KMC, Chennai.
45. RIGISCAN
In 1985, the RigiScan was introduced
first device to provide automated, portable NPTR
recording.
The device combines the monitoring of radial rigidity,
tumescence, number, and duration of erectile events
It consists of a recording unit that can collect data for
three separate nights for a maximum of 10 hours each
night.
45
Dept of Urology,GRH and KMC, Chennai.
46. RIGISCAN
The mechanicsconsist of two
loops: one is placed at the
base of the penisand the
other at the coronal sulcus.
By constricting the loops, the
device records penile
tumescence (circumference)
and radial rigidity at the
penile base and tip
46
Dept of Urology,GRH and KMC, Chennai.
47. NPTR CRITERIA
Cilurzo and colleagues (1992) recommend the following as normal
NPTR criteria:
four to five erectile episodes per night
mean duration longerthan 30 minutes
an increase in circumference of more than 3 cm at the base and
more than 2 cm at the tip
maximal rigidity above 70% at both base and tip
47
Dept of Urology,GRH and KMC, Chennai.
48. TWO EPISODES OF WELL-SUSTAINED,
COMPLETELY RIGID NOCTURNAL
ERECTIONS
TWO EPISODES OF POORLY
SUSTAINED, POORLY RIGID
NOCTURNAL ERECTIONS
RigiScan
48
Dept of Urology,GRH and KMC, Chennai.
49. ADVANTAGES:
relativefreedom from psychologic influencesand its abilityto detect
sleep-related abnormalities.
Thedocumented presence of a full erection indicatesthat the
neurovascular axis is functionally intact and that the cause of the ED
is most likelypsychogenic.
DISADVANTAGES:
costly, because it is ideallydonewith a RigiScanin a speciallyequipped
sleep center.
Not recommendedas a routinepart of ED evaluation
49
Dept of Urology,GRH and KMC, Chennai.
50. NEVA
Uses electrobioimpedance to assess volumetricchanges in penis
during nocturnal erections.
Record number, duration of erectile episodesand penile length and
blood volume changes at night .
Small recording device is attached to pt's thigh, and three small
electrode pads applied to hip , penile base and glans.
An undetectable alternating current is sent from glans electrode to
hip ground. The penile base electrode measures impedance and
changes in penile length.
Relationship to rigidity and volume change needs to be established.
50
Dept of Urology,GRH and KMC, Chennai.
51. Neurologic Evaluation
Somatic Nervous System
Biothesiometry
This test is designedto measure the sensory perception threshold
to various amplitudesof vibratory stimulation produced by a
hand-heldelectromagneticdevice (biothesiometer) placed on
the pulp of the index fingers, both sides of the penileshaft, and
the glanspenis.
51
Dept of Urology,GRH and KMC, Chennai.
52. Sacral Evoked Response—Bulbocavernosus
Reflex Latency
This test is performed by placing two stimulating ring
electrodes around the penis, one near the corona and the
other 3 cm proximal.
Concentric needle electrodes are placed in the right and
left bulbocavernous muscles to record the response
abnormal latency time, defined as a value more than 3
standard deviations above the mean (30 to 40 ms), denotes
a high probability of neuropathology
52
Dept of Urology,GRH and KMC, Chennai.
53. Dorsal Nerve Conduction Velocity
averageconduction velocity of 23.5 m/s with a range of 21.4 to 29.1
m/s in normal subjects.
Genitocerebral Evoked Potential
This test involveselectrical stimulation of the dorsal nerve of the
penisas described for the BCR latency test.
study records the evoked potential waveformsoverlyingthe
sacral spinal cord and cerebral cortex
53
Dept of Urology,GRH and KMC, Chennai.
54. Hormonal Evaluation
Historically, hypogonadismas a cause of ED was thought to be
rare
recent data support a significantincrease of hypogonadismwith
age.
The interrelationshipsamong hypogonadism,depression,and
ED are now recognized
In male sexual dysfunction most endocrinopathiescenter
around testosterone
54
Dept of Urology,GRH and KMC, Chennai.
55. morning testosterone values below 350 ng/dL in a young man
with chronicallyelevatedgonadotropins -- hypogonadism.
blood should be drawn between8:00 AM and 11:00 AM. For
screening, a total testosterone usually adequate.
If the testosterone level is belowor at the low limit of normal, it
should be confirmed with a second determinationtogetherwith
assessmentof luteinizing hormone (LH) and prolactin.
One or more of the following serum laboratoryvalues may be
required to diagnose hormone deficiencies:
(1) total/free/bioavailabletestosterone; (2) SHBG; (3) LH; and (4)
follicle-stimulatinghormone (FSH).
55
Dept of Urology,GRH and KMC, Chennai.
57. Lifestyle Change
Obesitywas associated with ED (P=.006), with baselineobesity
predicting a higherrisk regardlessof follow-up weight loss.
Physical activity was also associated with ED (P= .01), with the
highestrisk among men who remained sedentary
The beneficialeffect of using a statin drug to lowercholesterol in
men in whom the only risk factor for ED is hypercholesterolemia(
Saltzman 2004)
cigarette smoking significantly increased impotence associated
with cardiovasculardisease, hypertension,and medication use (
Derbyet al, 2000 ).
57
Dept of Urology,GRH and KMC, Chennai.
58. Long-distance bicycling is another risk factor -
genital numbness and ED.
58
Dept of Urology,GRH and KMC, Chennai.
59. ALTERNATE THERAPIES
Acupuncture
Androstenedione/DHEA
Ginkgo biloba
Korean red ginseng
L-Arginine -A precursor to nitric oxide.
Yohimbine
Zinc
Avena saliva and other potential cholesterol and blood-pressure
reducers and Tribulus terrestris (precursor to DHEA)
Antioxidants in combinationwith orally approved FDA
medications
59
Dept of Urology,GRH and KMC, Chennai.
60. Psychosexual Therapy
cognitive-behavioral interventionsfocused on challengingor
correcting maladaptivecognitions
behavioraltechniques such as desensitizationand assertiveness
exercises
psychodynamicexplorationsexploring the role of past
developmentalexperienceson present behavior
systemic and couples therapy.
in mixed psychogenicand organic ED, psychosexual therapy may
help relieveanxiety and remove unrealistic expectations
associated with medical or surgical therapy.
60
Dept of Urology,GRH and KMC, Chennai.
64. Mechanism of Action of
PDE5 Inhibitors
Adapted with permission from Lue TF. N Engl J Med. 2000;342:1802-1813. 64
Dept of Urology,GRH and KMC, Chennai.
65. PDE5 Inhibitors: Pharmacokinetics
Cmax=change in maximum plasma concentration
Tmax=time to maximum plasma concentration
t1/2=plasma half-life
nd=not determined
nr =not reported
*Median
1. Viagra prescribing information, January 2000. 2. Padma-Nathan H, Giuliano F. Urol Clin North Am. 2001;28:321-334.
3. Patterson B, et al. Poster presented at: 4th Congress (Biennial Meeting) of the European Society for Sexual and
Impotence Research; September 30, 2001; Rome. 4. Data on file, Lilly ICOS LLC. 5. Klotz T, et al. World J Urol.
2001;19:32-39. 6. Stark S, et al. Eur Urol. 2001;40:181-190. 7. Sorbera LA, et al. Drugs Future. 2001;26:141-144.
Parameter Sildenafil1,2 Tadalafil3,4 Vardenafil5-7
Bioavailability 40% nd nr
Cmax with food 29% no change nr
Tmax (h) 1* 2* <1
t1/2 (h) 3-5 17.5 ~4
65
Dept of Urology,GRH and KMC, Chennai.
66. PDE5 Inhibitors:
Onset and Duration of Activity
*RigiScan with visual sexual stimulation; oral dosing, empty stomach.
†Home setting; stopwatch recording.
‡Home setting; journal recording based on time frames.
nr =not reported.
1. Viagra prescribing information, January 2000. 2. Boolell M, et al. Int J Impot Res. 1996;8:47-52. 3. Padma-Nathan H.
J Urol. 2001;165(suppl):224, Abstract 923. 4. Sorbera LA, et al. Drugs Future. 2001;26:141-144.
PDE5 Inhibitor Onset (min) Duration (h)
Sildenafil1,2 30-60* 4*
Tadalafil3 30-45*;16† 24*‡
Vardenafil4 nr nr
66
Dept of Urology,GRH and KMC, Chennai.
67. PDE5 Inhibitors Meet
Important Patient Needs
Most patients prefer oral therapy1
Mechanism of action is physiologically-based
Newer agent(s) may offer an opportunity to
increase spontaneity/flexibility
Consideration of partner needs and satisfaction1
Long-term improvement in quality of life1,2
1. Jarow JP, et al. J Urol. 1996;155:1609-1612. 2. Marwick C. JAMA. 1999;281:2173-2174. 67
Dept of Urology,GRH and KMC, Chennai.
68. Tadalafil Effect on
Successful Intercourse
*Did your erection last long enough to have successful intercourse?
†All randomized patients. Studies LVBN, LVCE, LVCO, and LVDJ.
Brock GB, et al. J Urol. 2002;168:1332-1336. 68
Dept of Urology,GRH and KMC, Chennai.
69. Tadalafil Treatment Effect on
Improved Erections
*Has the treatment you have been taking improved your erections?
†All randomized patients. Studies LVBN, LVCE, LVCO, and LVDJ.
Brock GB, et al. J Urol. 2002;168:1332-1336.
70. Tadalafil: Most Common
Treatment-Related Adverse Events
*Phase II/Ill – Adverse Events 2%.
McMahon CG. Paper presented at: 4th Congress (Biennial Meeting) of the European Society for Sexual and Impotence
Research; September 30-October 3, 2001; Rome.
Adverse Event
% of Patients Reporting Event
Placebo
(n=758)
Tadalafil
(n=1561)
Headache 4 11
Dyspepsia 1 7
Back pain 3 4
Myalgia 1 4
Nasal congestion 2 4
Flushing 1 4
70
Dept of Urology,GRH and KMC, Chennai.
71. Vardenafil: Tolerability
*Phase IIb – Adverse Events 5%.
Porst H, et al. Int J Impot Res. 2001;13:192-199.
Adverse Event
% of Patients Reporting Event
Placebo
(n=152)
Vardenafil
(n=438)
Headahe 4 10
Flushing 1 11
Dyspepsia 0 3
Rhinitis 3 5
71
Dept of Urology,GRH and KMC, Chennai.
72. WARNING
Myocardial infarction within the previous 90 days
▪ Unstable angina or angina occurring during sexual intercourse
▪ New York Heart Association class II or greater heart failure in the previous 6
months
▪ Uncontrolled arrhythmias, hypotension (>90/50 mm Hg), or uncontrolled
hypertension (>170/100 mm Hg)
▪ Stroke within the previous 6 months
▪ Known hereditary degenerative retinal disorders, including retinitis
pigmentosa
▪ Tendency to develop priapism (e.g., sickle cell anemia, leukemia)
Certain drugs, such as ketoconazole and itraconazole, and protease inhibitors,
such as ritonavir, can impair the metabolic breakdown of PDE-5 inhibitors by
blocking the CYP3A4 pathway.
Severe kidney or hepatic dysfunction may require dose adjustments or warnings
72
Dept of Urology,GRH and KMC, Chennai.
73. SILDENAFIL VARDENAFIL TADALAFIL
Cmax ( ng/ml) 450 20.9 378
Tmax ( hr) 0.8 0.7-0.9 2
Onset of action 15 min-1 hr 15 min- 1 hr 15min-2 hr
Half life 3-5 hr 4-5 hr 17.5 hr
Bioavailability 40 % 15 min% Not tested
Fatty food Reduced
absorption
Reduced
absorption
No effect
Dosage 25,50,100 mg 5, 10, 20 mg 5, 10, 20 mg
SIDE EFFECTS
Headache,flushing yes yes Yes
Back ache, Myalgia rare rare Yes
Blurred/blue
vision
yes rare Rare
Precautionwith
antiarrythmics
no yes No
C/I with Nitrates yes yes yes
73
Dept of Urology,GRH and KMC, Chennai.
75. Intraurethral Therapy
Alprostadil, the synthetic formulation of PGE1, is the only
pharmacologicagentwith FDA approval for ED managementby
both intracavernousand intraurethral routes.
When inserted into the urethra, the drug is absorbed from the
urethra by the corpus spongiosum and then transported to the
corpus cavernosum through venous channels.
75
Dept of Urology,GRH and KMC, Chennai.
76. MUSE
The medicated urethral
system for erection
(MUSE; Vivus, Inc, CA)
consists of a very small
semisolid pellet (3 β1
mm) administered into
the distal urethra (3 cm)
by a proprietary
applicator (MUSE).
76
Dept of Urology,GRH and KMC, Chennai.
77. Penile pain is a ubiquitous side effect of alprostadil-
based therapies
The reported penile pain rate was 33% in MUSE trials.
Hypotension and syncope have been noted in 1% to
5.8%, mandating the office setting for initial
administration.
77
Dept of Urology,GRH and KMC, Chennai.
78. INTRACAVERNOUS AGENTS
Drug Dose Range Advantages Disadvantages/Side Effects
Papaverine 7.5-60 mg Low cost; Stableat room
temp
Fibrosis, priapism; Elevation
of liver enzymes
Papaverine + phentolamine 0.1-1 mL More potent than papaverine
alone
Fibrosis, priapism
Alprostadil 1-60 μg Metabolized in penis;
Priapism rare
Painful erection; Requires
refrigeration; Relatively
expensive
Moxisylyte 10-30 mg Priapism rare Less potent
Papaverine + phentolamine+
alprostadil
0.1-1.0 mL Most potent Requires refrigeration
78
Dept of Urology,GRH and KMC, Chennai.
79. Centrally Acting Drugs
Yohimbine
α2-adrenergic antagonist obtained from the bark
of the yohim tree
acts centrally to promote sexual behavior by
blocking presynaptic autoreceptors and
increasing adrenergic receptor activity, which also
alters serotonin and dopamine transmission
no efficacy of yohimbine over placebo in patients
with organic ED.( AUA 1996)
79
Dept of Urology,GRH and KMC, Chennai.
80. Trazodone
commonly prescribed mild antidepressantwith a rare incidence
of priapism.
positive effecton nocturnal penile erection ( Saenzde Tejada et
al, 1991 ) and sexually stimulated erection ( Lal et al, 1987 ).
Apomorphine
dopaminergicagonist, activating D1 and D2 receptors.
Dopaminergicstimulation is proerectile
Sexual arousal is necessary to enhance the effect of apomorphine
80
Dept of Urology,GRH and KMC, Chennai.
81. Vacuum Constriction Device
The vacuum constriction device consists of a plastic cylinder
connected directly or by tubing to a vacuum-generatingsource
(manual or battery-operatedpump).
After the penis is engorged by the negative pressure,a
constricting ring is applied to the base to maintain the erection.
To avoid injury, the ring should not be left in place for longer
than 30 minutes
81
Dept of Urology,GRH and KMC, Chennai.
83. In severe proximal venousleakage or arterial insufficiency, fibrosis
secondaryto priapism, or an infection from a prosthesis- may not
produce adequateerection.
The devicecan be used successfully by men with a malfunctioning
penile prosthesis in place and after explantationto prevent
shortening.
In men with severevascular insufficiency, combining intracavernous
injectionwith the vacuum constrictiondevice may enhance the
erection
Patientstaking aspirin or warfarin should exercise caution when
using thesedevices.
The patientsatisfaction rate has been reported to range from 68% to
83%
83
Dept of Urology,GRH and KMC, Chennai.