SEXUAL DYSFUNCTION

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SEXUAL DYSFUNCTION

• Pudchong Srisethnil, MD, FACE
• Chairman, Department of Medicine Barnert
  HospitalUMDNJ-SOM
  Paterson, New Jersey

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A. ERECTILE DYSFUNCTION (ED)

• PREVALENCE
• PATHOPHYSIOLOGY OF ED
• ETIOLOGY OF ED
• TREATMENT OPTIONS
• PSYCHOTHERAPY
• PROSTAGTADANDINS
• INJECTABLES
• TRANSURETHRAL ADMINISTRATION
• VACUUM DEVICE
• PENILE PROSTHESIS
• WHICH IS THE BEST PDE 5 INHIBITOR
• TESTOSTERONE

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Prevalence of ED
Men aged 40 to 70 years (N1290)
Complete(10)
No erectile dysfunction(48)
Erectile dysfunction(52)
Moderate(25)
Minimal(17)
Massachusetts Male Aging Study. Adapted from
Feldman et al. J Urol. 199415154-61.
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Association Between Age and Prevalence of ED
Feldman et al. J Urol. 199415154-61.
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Mechanism of Erection
Flaccid
Erect
Boolell M et al. Int J Impot Res.
1996847-52. Process of Care Consensus Panel.
Int J Impot Res. 19991159-74.
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Nitric Oxide Pathway
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Treatment of Erectile Dysfunction With Oral PDE-5
Inhibitors
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PDE-5 Inhibition
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PDE-5 Inhibition
Guanosine moiety binds to active site on PDE-5
Cyclic GMP
Sildenafil
Vardenafil
Tadalafil
Vardenafil proposed product insert Sildenafil
product insert 28th National Medicinal Chemistry
Symposium San Diego, Ca.
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PDE-5 Inhibitors Time Course
Corbin and Francis, ICJP 2002453.
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PDE IsoenzymesSystem/Organ Distribution

• PDE-1 Heart, lung, brain, vascular smooth
  muscle
• PDE-2 Adrenal cortex, brain, heart, olfactory
  neurons
• PDE-3 Pancreas, smooth muscle, platelets,
  heart, adipose
• PDE-4 Brain, lung, lymphocytes
• PDE-5 Corpus cavernosum, platelets,
  bladder, urethra, heart, leg muscle, lung,
  brain, kidney, liver
• PDE-6 Retina
• PDE-7 Skeletal muscle, lymphocytes
• PDE-8 Testis, eye, liver, skeletal muscle,
  heart
• PDE-9 Kidney
• PDE-10 Testis, brain
• PDE-11 Testis, skeletal muscle, prostate,
  kidney, liver, pituitary, and salivary
  glands

Uckert et al. World J Urol. 20011914-22
Fawcett et al. PNAS. 20009737023707.
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Sildenafil Failure
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Managing Expectations

• Sexual function likely will not be what it once
  was (or what the patient remembers it as being)
• PDE-5 inhibitors have no direct effect on
  libido
• Success with use of PDE-5 inhibitors requires
  sexual stimulation and arousal

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Sildenafil Efficacy With Repeated Use
1.0
0.9
0.8
0.7
0.6
Cumulative Probability ofAchieving First Success
0.5
0.4
2nd Attempt
0.3
Mild to Moderate ED Severe ED
1st Attempt
0.2
0.1
0.0
0
10
20
30
Number of Attempts
Carson CC. Int J Impot Res. 200214(Suppl
1)S29-S34. Based on retrospective analysis of
the intent-to-treat population from 12
double-blind, placebo-controlled, flexible-dose,
clinical trials.
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Food Interaction

• When sildenafil is taken with a high-fat meal,
  absorption is decreased
• Mean delay in time to maximum serum
  concentration (Tmax) 60 minutes
• Mean decrease in maximum serum concentration
  (Cmax) 29

Physicians Desk Reference. 57th ed. 20032653.
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Food Interaction

• Vardenafil and tadalafil appear to have less
  interaction with food

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Vardenafil Pharmacokinetics
Effect of a Moderate-Fat Evening Meal
30
PM fasting
25
30 fat-calorie dinner
20
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Mean Plasma Concentration, µg/L
10
5
0
0
2
4
6
8
10
12
Mean (SD) Plasma Vardenafil Concentration-time
Profiles
Rajagopalan et al. IJIR. 200314(S4)260-267.
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Vardenafil Pharmacokinetics Effect of Alcohol
(0.5 g/kg)
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Vardenafil 20 mg alone
Vardenafil 20 mg with alcohol
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Vardenafil PlasmaConcentration (µg/L)
10
5
0
0
2
4
6
8
10
12
14
16
Bauer et al. Pharmacotherapy. 200222(3)418.
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Selectivity

• PDE-5
• Corpora cavernosum, systemic vascular, pulmonary
  and visceral smooth muscle, platelets
• Thus, most common side effects of PDE-5
  inhibition (headache, flushing, indigestion,
  nasal congestion, red eyes and lowered blood
  pressure) are expected to be class effects

Corbin and Francis, ICJP 2002453.
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Sildenafil Adverse Events
Sildenafil () Placebo ()
Flushing 16.9 2.3 Headache 14.7 0 Visual changes
3.7 1.1 Rash 2.2 0 Dyspepsia
2.2 0 Diarrhea 1.5 0 Dry
mouth 1.5 0 Abdominal pain
0.7 1.1 Myalgia 0 1.1
Physicians Desk Reference. 57th ed. 20032606.
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Vardenafil Adverse Events
Placebo Vardenafil Adverse Event (n793)
(n1812)
Headache 5.5 15.6 Cutaneous flushing 0.6 11.7 Rhin
itis 3.8 10.3 Dyspepsia 0.8 3.9 Accidental
injury 2.4 3.2 Sinusitis 0.8 3.1 Flu
syndrome 2.3 2.7 Dizziness 0.9 2.4 Nausea 0.8 2.3
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Tadalafil Adverse Events
Placebo Tadalafil Adverse Event (n758)
(n1561)
Headache 4 11 Dyspepsia 1 7 Back pain 3
4 Myalgia 1 4 Nasal congestion 2
4 Flushing 1 4
Phase 2/3 adverse events ?2. McMahon. Paper
presented at 4th Congress (Biennial Meeting) of
the European Society for Sexual and Impotence
Research September 30-October 3, 2001 Rome.
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Response to Sildenafil Following Radical
Prostatectomy
72
N91
50
Ability to Penetrate ()
15
Zippe, Jhaveri, et al. Urology. 200055241-245.
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Dosage of Sildenafil Required Following Radical
Prostatectomy
71
Positive Responders ()
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Zippe, Jhaveri, et al. Urology. 200055241-245.
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Efficacy of Vardenafil Following Radical
Prostatectomy (GAQ)
20 mg
71
65
With Improved Erections
Brock et al. European Urology. 200042152.
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Vacuum Constriction Devices
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Vasoactive Pharmacotherapy
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Penile Prosthesis
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Testosterone Replacement in the Aging Male
Testosterone Replacement
Increasing Age
Target Organ Or Function
Tenover, Int J Androl. 1999.
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B. PREMATURE EJACULATION (P.E.)

• PREVALENCE
• PATHOPHYSIOLOGY OF P.E.
• TREATMENT OPTIONS
• PSYCHOTHERAPY
• LOCAL ANESTHETIC
• PDE INHIBITORS
• SSRI
• ON DEMAND SSRI

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