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  • Key point: This section discusses the practical management of ED in patients.
  • Key point: Not only are couples who are experiencing ED frequently burdened with significant psychological conditions, ED may also signal the presence of a more serious underlying disease. Specific points: It is medically important to diagnose and treat ED. ED is often associated with comorbid conditions that may not have been detected previously, such as cardiovascular disease, diabetes, and depression. ED-associated distress can have a serious negative impact on the patients’ overall quality of life as well as on interpersonal relationships. The evaluation of ED should include a determination of potential underlying causes and the identification of appropriate treatment following a complete medical assessment. Retention of potency is a strong motivator for men. Physicians can use this motivation to drive better medication compliance and better adherence to advice on lifestyle modification. Thus, it is important to query patients regarding sexual function. Goldstein I. Int J Impot Res . 2000;12(suppl 4):S147-S151. Goldstein I. Am J Cardiol . 2000;86(suppl):41F-45F.
  • Key point: ED is frequently associated with other serious, treatable disorders. Specific points: The strong association of ED with other conditions should prompt further diagnoses, for example: The most common condition associated with ED is hypertension. According to Burchardt et al., 68% of men with hypertension have ED. 1 A publication by Levine and Kloner in the American Journal of Cardiology in 2001 brings together the published work of Pritzker and Billups, showing that performing a lipid screen in a group of men with ED indicates that dyslipidemia is strongly associated with ED. 2 Bearing this association in mind, it is not surprising that Pritzker reports in his findings that in a group of 50 men presenting with ED, 28 (56%) had a positive stress test, and 20 of these had significant underlying coronary occlusions on angiography. The strength of this association in patients presenting to urologists remains to be confirmed. 3 The prevalence of diabetes in men with ED is about 20%; the exact number varies by study. 4 The prevalence of depression in men with ED is about 11%; the exact number varies by study. 5 1. Burchardt M et al. J Urol . 2000;164:1188-1191. 2. Levine L and Kloner R. Am J Hypertens . 2001;14:1210-1213. 3. Pritzker MR. Circulation . 1999;100(suppl 1):I-711. Abstract 3751. 4. Braun M et al. Int J Impot Res . 2000;12:305-311. 5. Seftel A. J Urol . 2004;171:2341-5
  • Main Point: The incidence of comorbidities increases as the severity of ED worsens. Results from the Cross-National Survey on Men’s Health Issues, which was a population-based, international survey of men using the health care systems of participating countries: US, Germany, UK, France, Italy and Spain. Men were 20-75 years old. A total of 28,691 men completed the screening questionnaire and provided their age. Shabsigh R, et al. J Urol 2005;174:662-667.
  • Key point: ED may be the first sign of underlying heart disease and thus may be an early warning signal for physicians. Specific points: In a study by Kaiser et al., 30 men with ED (non-neurogenic in etiology) who had no other identified medical problems and 27 age-matched normal men were recruited. Men were excluded if they had a history of recent smoking, hypertension, hyperlipidemia, or serious chronic diseases (e.g., diabetes mellitus). The men were then evaluated for systemic vascular integrity and function abnormalities, including measurements for coronary calcification, aortic pulse wave velocity, brachial and carotid artery diameters, intima-media thickness, compliance and distensibility, and brachial artery endothelium-dependent and independent response. Tests also included a blood chemistry profile and an ED questionnaire. In spite of the lack of clinical cardiovascular symptoms (other than ED) or other cardiac risk factors, there were clear indications that men with ED had a peripheral vascular abnormality in the NO-GMP pathway, as measured by brachial artery flow-mediated vasodilation (FMD) and vasodilation following sublingual nitroglycerine. This abnormality was present despite a normal CAD risk score, normal systemic vascular stiffness measures and vascular structure. This NO-GMP abnormality may be the cause of ED and be the first manifestation of CV disease. IIEF is the International Index of Erectile Function Questionnaire. The IIEF Erectile Function (EF) Domain score has a range of 1-30. Kaiser DR et al. JACC. 2004;43:179-84.
  • Key point: Men with any of these major risk factors should routinely be asked about ED. Specific points: A wide variety of situations/conditions represent major risk factors for ED: Advancing age Chronic conditions (e.g., hypertension, diabetes, depression, cardiovascular disease) Medications (e.g., thiazide diuretics, beta-blockers, serotonin reuptake inhibitors (selective or not, including fluoxetine, etc.) Unhealthy behaviors (e.g., alcohol abuse, cigarette smoking) Feldman HA et al. J Urol. 1994;151:54-61.
  • Key point: When ED is suspected, the physician should evaluate the patient’s condition comprehensively in order to characterize the ED and to identify other underlying conditions that the presence of ED may signal. Specific points: It is important to identify the underlying cause of ED in a patient. 1 Underlying causes may be due to: The presence of a chronic disease that had been undiagnosed, such as diabetes, prostate diseases, vascular disease or hypogonadism. 1 Depression 2 Extrinsic factors such as a concomitant medication or life style issues. 1 If warranted, the physician may elect to perform more specialized tests, for example if there is evidence of significant endocrine, psychogenic, or vascular disease. 1. Recommendations of the 1st International Consultation on Erectile Dysfunction. In: Jardin A et al, eds. Erectile Dysfunction . Plymouth, UK: Health Publication, Ltd; 2000:711-726. 2. Goldstein I. Am J Cardiol . 2000;86(suppl):41F-45F.
  • Key point: A number of prescription medications have been linked to ED. If a patient receiving treatment with any of these medications complains of ED, adjusting the dose of medication or switching to another therapeutic agent may be considered. Specific points: Antihypertensive agents, mainly thiazides and thiazide-like diuretics, 1 and, to a lesser extent, beta-blockers, 2 have been reported to adversely affect sexual function. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers are less likely to affect sexual function. 2 Sexual dysfunction occurs commonly in patients taking antidepressants. 3 Hormonal chemotherapeutics, particularly the antiandrogens, including 5-alpha reductase inhibitors, also increase the risk of ED. 4 Grimm RH Jr et al. Hypertension . 1997;29:8-14. Suzuki H et al. J Hypertens . 1988;6(suppl):S649-S651. Clayton AH et al. J Clin Psych. 2002;63:357-366. Higano CS. Urology . 2003;61(suppl 1):32-38.
  • Key point: The sexual history is important to determine the extent and duration of the erectile dysfunction. The medical history can help to identify the causality and facilitate determining existing comorbidities and ruling out associated co-morbidities, as appropriate. 1,2 Specific points: It is necessary to establish the partner’s awareness of the ED and gauge their interest in resolution of the condition. The most successful treatment is usually associated with the female partner’s wish to restore sexual intimacy to the relationship. Recommendations of the 1st International Consultation on Erectile Dysfunction. In: Jardin A et al, eds. Erectile Dysfunction . Plymouth, UK: Health Publication, Ltd; 2000:711-726. The Process of Care Consensus Panel. Int J Impot Res . 1999;11:59-70.
  • Key point: Screening for ED is a relatively easy way to have a major impact on patients’ lives. Specific points: Sexual dysfunction can have a large impact on a patient’s overall physical and emotional well-being. 1 ED may be a marker of a previously unrecognized condition such as hypertension, heart disease, depression, or diabetes. 1,2 Men with ED have a lower quality of life than those without sexual dysfunction. 3 Improved patient satisfaction and patient-clinician relationships are the result of open dialog on sexual dysfunction. 1 In men who have ED and clinical depression, symptoms may improve as they respond to ED treatment. 3 Eid JF, Sadovsky R. Cliniguide ® to Erectile Dysfunction . New York, NY: Lawrence DellaCorte Publications, Inc; 2001. Shabsigh R et al. Urology . 1998; 52:848-852. Seidman SN et al. Am J Psych . 2001;158:1623-1630.
  • Key point: This section discusses the practical management of ED in patients.
  • Key point: As with the management of most diseases, treatment begins with changes in patient habits, lifestyles, and other modifiable risk factors and progresses to more invasive treatments as needed. Recommendations of the 1st International Consultation on Erectile Dysfunction. In: Jardin A et al., eds. Erectile Dysfunction . Plymouth, UK: Health Publication, Ltd; 2000:711-726.
  • Key point: Unhealthy lifestyle may contribute to development of ED. Therefore, clinicians should recommend behavior modification to their patients 1-3 Specific points: The following lifestyle modifications should be encouraged: smoking cessation, 1,2 avoidance or limitation of alcohol, 1 eating a healthy diet, 2 and proper exercise 3 Recommendations of the 1st International Consultation on Erectile Dysfunction. In: Jardin A et al, eds. Erectile Dysfunction. Plymouth, UK: Health Publication, Ltd; 2000:711-726. Feldman HA et al. Prev Med. 2000;30:328-338. Derby CA et al. Urology. 2000;56:302-306.
  • Key point: A number of prescription medications have been linked to ED. If a patient receiving treatment with any of these medications complains of ED, adjusting the dose of medication or switching to another therapeutic agent may be considered. Specific points: Antihypertensive agents, mainly thiazides and thiazide-like diuretics, 1 and, to a lesser extent, beta-blockers, 2 have been reported to adversely affect sexual function. Angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers are less likely to affect sexual function. 2 Sexual dysfunction occurs commonly in patients taking antidepressants. 3 Hormonal chemotherapeutics, particularly the antiandrogens, including 5-alpha reductase inhibitors, also increase the risk of ED. 4 Grimm RH Jr et al. Hypertension . 1997;29:8-14. Suzuki H et al. J Hypertens . 1988;6(suppl):S649-S651. Clayton AH et al. J Clin Psych. 2002;63:357-366. Higano CS. Urology . 2003;61(suppl 1):32-38.
  • Key point: Psychosocial counseling may be used alone to manage ED or may be used as an adjunct to other treatment options. Specific points: Psychosocial therapy addresses 4 main areas: anxiety reduction and desensitization, cognitive-behavioral interventions, sexual stimulation techniques, and interpersonal assertiveness with couples’ communication training. Rosen RC. Urol Clin North Am . 2001;28:269-278.
  • Key point: Phosphodiesterase type 5 inhibitors are the most frequently used type of ED treatment. Specific points: There are 3 (PDE5) inhibitors indicated for the treatment of ED: tadalafil, 1 vardenafil HCl, 2 and sildenafil citrate 3 Apomorphine 4 is also used in some patients but is not approved for use in ED in many countries Cialis ® (tadalafil) prescribing information. Lilly ICOS LLC: Indianapolis, IN, and Bothell, WA; 2003. Levitra ® (vardenafil HCl) prescribing information. Bayer Pharmaceuticals Corp: West Haven, CT; 2003. Viagra ® (sildenafil citrate) prescribing information. Pfizer Inc: New York, NY; 2002. Uprima ® (apomorphine HCl) prescribing information. Abbott Laboratories, Abbott Park, Il, 2001.
  • Key point: PDE5 inhibitors block the breakdown of cyclic guanosine monophosphate (cGMP), a secondary messenger that induces vasodilation within the smooth muscle cells in the penis, amplifying the natural signaling process during an erection. There are 3 phosphodiesterase type 5 inhibitors available that are indicated for the treatment of ED: tadalafil, vardenafil, and sildenafil. 1-3 Specific points: Penile erection during sexual stimulation is caused by increased penile blood flow resulting from the relaxation of penile arteries and corpus cavernosal smooth muscle. This response is mediated by the release of nitric oxide from nerve terminals and endothelial cells, which stimulates the synthesis of cGMP in smooth muscle cells. Increased intracellular cyclic GMP results in smooth muscle relaxation and increased blood flow into the corpus cavernosum. Phosphodiesterases are enzymes that hydrolyze cyclic nucleotides such as cGMP and cAMP. The inhibition of phosphodiesterase type 5 by PDE5 inhibitors enhances erectile function by increasing the local intracellular concentration of cGMP. Because sexual stimulation is required to initiate the local release of nitric oxide, PDE5 inhibition has no effect in the absence of sexual stimulation. Each drug is taken orally and sexual stimulation is required to obtain an erection. Cialis ® (tadalafil) prescribing information. Lilly ICOS LLC: Indianapolis, IN, and Bothell, WA; 2006. Levitra ® (vardenafil) prescribing information. Bayer Pharmaceuticals Corp: West Haven, CT; 2005. Viagra ® (sildenafil) prescribing information. Pfizer Inc: New York, NY; 2006.
  • Although it is difficult to compare different studies conducted at different times; IIEF EF domain scores at endpoint in this study appear somewhat smaller than those observed for tadalafil 5 mg in a previous study of once a day dosing 1 but appear somewhat larger than those reported for tadalafil 2.5 mg and tadalafil 5 mg in a pooled analysis of 5 studies of tadalafil dosed as needed. 2 This increase is not unexpected since the steady state plasma concentration for tadalafil is approximately 1.6 times the plasma concentration following a single dose. 3 1 Porst H et al. Eur Urol. 2006;50:351-359. 2 Brock GB et al. J Urol . 2002;168:1332-1336. 3 Forgue et al. Br J Clin Pharmacol. 2005;61:280-288. J. Rajfer, PJ Aliotta, CP Steidle, WP Fitch III, Y Zhao, A Yu Tadalafil Dosed once a day in men with erectile dysfunction: a randomized, double-blind, placebo-controlled study in the US Int J Imp Res (2006), in press, on line ahead of print
  • Key point: In addition to the PDE5 inhibitors, there are various other options available for the treatment of ED. Choice of treatment should be individualized depending on the etiology of ED and success/failure of previous treatments. Specific points: The most effective forms of testosterone replacement therapy for men with a documented hormone deficiency (e.g., androgen deficiency, hypogonadism), hormone replacement therapy 1 are intramuscular and transdermal 2 Testosterone patches and 1% gel: Testosterone levels with use of the gel are dose-dependent and stable between applications. 1 Long-acting testosterone pellets for subcutaneous implantation are available. 3 Transurethral administration or intracavernosal injection of alprostadil are localized therapies for treatment of ED. These therapies are now recommended as “second-line” therapy when oral therapy is contraindicated, intolerable, or for those who fail to respond to oral therapy. 2,4-6 Vacuum constriction devices (VCDs) are an option for men who are not interested in drug therapy or those who have specific contraindications to the available pharmacologic options. By applying negative pressure to the penis, the VCD draws blood into the cavernosal spaces. The blood is then retained by application of an elastic band to the base of the penis. A penile prosthesis may be a surgical option for patients who are intolerant to or who fail to respond to other ED treatments. This treatment option is particularly helpful for patients with specific concomitant medical conditions such as vascular or neurologic disease, or genital trauma (e.g., Peyronie’s disease) 5 For men with congenital or traumatic ED, vascular surgery may be indicated and can be curative. 2 AACE Male Sexual Dysfunction Task Force. Endocr Pract . 2003;9:77-95. Lue TF. N Engl J Med . 2000;342:1802-1813. Testopel™ pellets (testosterone) prescribing information. Physicians’ Desk Reference . 56th ed. Montvale, NJ: Medical Economics Company; 2002:3610-3611. Shabsigh R et al. Urology . 2000;55:109-113. 000;16 Recommendations of the 1st International Consultation on Erectile Dysfunction. In: Jardin A et al., eds. Erectile Dysfunction . Plymouth, UK: Health Publication, Ltd; 2000:711-726. MUSE® (alprostadil) prescribing information. Physicians’ Desk Reference. 56th ed. Montvale, NJ: Medical Economics Company; 2002:3335-3338.
  • Key point: In the management of ED, lifestyle modification, psychosocial counseling, and use of oral PDE5 inhibitors are first-line treatment options. Other therapies, such as intracavernosal injection or penile prostheses may be appropriate for patients with treatment failures, contraindications to oral or topical medications, and/or preferences for alternative approaches
  • Tempe: spray lidocaina-prilocaina SS-cream: prodotti naturali D-A: Dylonina anestetico locale Alprostadil: Prostaglandina E1
  • cAMP = adenosin monofosfato ciclico; cGMP = guanosin monofosfato; MPOA = area preottica mediale dell’ipotalamo; NO = monossido di azoto E’ stato ipotizzato che il monossido di azoto agisca a livello dell’area preottica mediale dell’ipotalamo con un tono inibitorio sull’eiaculazione grazie alla riduzione del tono simpatico e d’altro canto è nota l’azione del monossido di azoto nel ridurre l’output centrale del sistema simpatico verso la periferia in molte specie animali incluso l’uomo. Questa azione può essere indotta grazie a un meccanismo dipendente dal cGMP o mediante interazione con i neurotramettitori classici; è altresì noto che la somministrazione intratecale di inibitori della PDE5 nel ratto aumenta i livelli di cGMP e di NO nell’area preottica mediale dell’ipotalamo e che i pazienti che assumono inibitori della PDE5 evidenziano anche un miglioramento della salute mentale e del benessere emotivo e vi sono evidenze che queste molecole si dimostrino poter ridurre l’ansia, rispetto al basale, nei pazienti con eiaculazione precoce con una azione sul sistema nervoso centrale simile a quella osservata sul sistema nervoso periferico.

Transcript

  • 1. TERAPIA DELLA DISFUNZIONE ERETTILE : UP-TO-DATE Slide Modified: MRW 6/04 Review: Reviewer Memo: Source: Memo: Antonio Aversa MD, PhD Dipartimento di Fisiopatologia Medica “ Sapienza” Università di Roma S APIENZA U NIVERSITA’ DI R OMA
  • 2. Why Diagnosing ED Is Important
    • ED screening may signal underlying disease:
      • Diabetes
      • Hypertension
      • Dyslipidemia and coronary artery disease (CAD)
      • Depression
    • ED can result in:
      • Anxiety
      • Decreased self-esteem
      • Reduced quality of life (QOL)
      • Negative effect on relationships
    Slide Modified: Review: Reviewer Memo: Source: Memo: Goldstein I. Am J Cardiol . 2000;86(suppl):41F-45F. Goldstein I. Int J Impot Res . 2000;12(suppl 4):S147-S151. Francis ME., et al. J Urol. 2007;178:591-596. Selvin E., et al. Am J Med. 2007;120:151-157. Jackson G., et al. J Sex Med. 2006;3:28-36.
  • 3. ED Is Associated With Other Serious Treatable Disorders
    • 68% of men with hypertension have ED
    • 60% of men with ED have dyslipidemia
    • 56% of men with ED have a positive stress test
    • 40% of men with ED have significant coronary occlusions
    • 20% of men with ED have diabetes mellitus
    • 11% of men with ED have depression
    Billups K, Friedrich S. J Urol. 2000;163(4) Abstract 655. Braun M et al. Int J Impot Res . 2000;12:305-311. Burchardt M et al. J Urol. 2000;164:1188-1191. Levine L, Kloner R. Am J Cardiol. 2000;86:1210-1213. Pritzker MR. Circulation. 1999;100(suppl I):I-711. Abstract 3751. Seftel A. J Urol. 2004;171:2341-2345. Slide Modified: references fixed - mt Review: Reviewer Memo: Source: Memo:
  • 4. The Prevalence of Comorbid Conditions Increases With ED Severity Shabsigh R et al. J Urol. 2005;174:662-667. Comorbidity ED Severity None Mild Mild to Moderate Moderate Severe High Blood Pressure 24% 25% 32% 42% 39% High Cholesterol 20% 25% 27% 35% 38% Enlarged Prostate 10% 16% 16% 23% 26% Heart Trouble 3% 7% 10% 16% 34% Anxiety 13% 15% 18% 19% 18% Diabetes 11% 8% 11% 16% 24% Depression 8% 8% 12% 12% 12% Heart Attack/Surgery 4% 7% 8% 13% 29% Hardening of Arteries 3% 6% 7% 10% 13% Spinal Cord Injury 3% 5% 5% 3% 5% Prostate Cancer 0 1% 1% 1% 0
  • 5. ED: A First Sign of Cardiovascular (CV) Disease?
    • In a study of 30 men with ED (International Index of Erectile Dysfunction-Erectile Function domain [IIEF EF] =13.7±1.2, mean age, 46.2 years) and 27 age-matched normal men (IIEF EF domain=21.3±1.2; mean age, 46.6 years) with no history of CV disease or CV risk factors
    • Compared with normal men, men with ED had:
      • Objective evidence of clinical and penile vascular disease (mean penile peak systolic velocity=28±3 m/s)
      • Reduced brachial artery flow-mediated vasodilation (p=0.014)
      • Impaired maximal response to nitrates, 13±1.4% vs. 17.8±1.4% (p=0.02)
      • Improved ED with phosphodiesterase type 5 (PDE5) inhibitor treatment, mean change in IIEF-EF domain score=3
    Kaiser DR et al. JACC . 2004;43:179-184. Slide Modified: Review: Reviewer Memo: Source: Memo:
  • 6. Major Risk Factors for ED
    • Aging
      • Progressive decline in function
      • Psychological issues
    • Chronic diseases
      • Hypertension
      • Diabetes
      • Depression
      • CV disease
    • Medications
      • Antihypertensives
        • Thiazide diuretics
        • Beta-blockers
      • Antidepressants
        • Serotonin re-uptake inhibitors
      • Unhealthy lifestyle
        • Stress
        • Alcohol abuse
        • Smoking
    Feldman HA et al. J Urol . 1994;151:54-61. Slide Modified: Review: Reviewer Memo: Source: Memo:
  • 7. Major Risk Factors for ED: Chronic Diseases 1. Martin-Morales A et al. J Urol . 2001;166:569-575. 2. Braun M et al. Int J Impot Res . 2000;12:305-311. 3. Goldstein I. Am J Cardiol . 2000;86(suppl):41F-45F. 4. Feldman HA et al. J Urol . 1994;151:54-61. Chronic Disease Increased ED Risks* Diabetes 1,2  4.1 Prostate disease 1   2.9 Peripheral vascular disease 1  2.6 Cardiac problems 1  1.8 Hyperlipidemia 1  1.6 Hypertension 1,2  1.6 Depression 3,4  1.8 * Age-adjusted odds ratio.  Prostatic symptoms on the International Prostate Symptom Score (IPSS) questionnaire.
  • 8. Diagnosis of ED
    • Comprehensive history: medical, drug, sexual, psychosocial
    • Focused physical examination
    • Urine dipstick
    • Testosterone, lipids, fasting glucose or glycosylated hemoglobin (HbA1C), prostate-specific antigen (PSA)
    • Specialized testing (e.g., as appropriate when there is evidence of significant, endocrine, psychogenic, or vascular disease)
    Slide Modified: Review: Reviewer Memo: Source: Memo: Recommendations of the 1st International Consultation on Erectile Dysfunction. In: Jardin A et al, eds. Erectile Dysfunction . Plymouth, UK: Health Publication, Ltd; 2000:711-726.
  • 9. The Aging male ‘Pyramid’ Slide Modified: MRW 6/04 Review: Reviewer Memo: Source: Memo: Aversa A et al, IJU, in press
  • 10. The Comprehensive Sexual and Medical History
    • Sexual history
    • Erectile insufficiency
    • Altered patient or partner sexual desire
    • Ejaculation disorders
    • Orgasm
    • Partner sexual function
    • Sexually induced genital pain
    • Medical history
    • Rule out comorbid conditions
    • Atherosclerotic risk factors and vascular disease
    • Use of medications/ recreational drugs or smoking
    • History of surgeries or pelvic/perineal trauma
    • Depressive symptoms
    Recommendations of the 1st International Consultation on Erectile Dysfunction. In: Jardin A et al, eds. Erectile Dysfunction . Plymouth, UK: Health Publication, Ltd; 2000:711-726. The Process of Care Consensus Panel. Int J Impot Res . 1999;11:59-70. Slide Modified: Review: Reviewer Memo: Source: Memo:
  • 11. Diagnosis Summary
    • Most men with ED are not diagnosed or treated
    • It is important to discuss the sexual health of patients
      • ED screening may detect underlying comorbid conditions 1,2
    • Improvement in erectile function in men with ED may result in
      • Better Quality of Life (QoL) 3
      • Increased patient satisfaction 1
      • Reduced symptoms of clinical depression in patients with ED and depression 3
    • Eid JF, Sadovsky R. Cliniguide  to Erectile Dysfunction. New York, NY: Lawrence DellaCorte Publications; 2001.
    • Seidman SN et al. Am J Psych . 2001;158:1623-1630.
    • Shabsigh R et al. Urology . 1998;52:848-852.
    Slide Modified: Review: Reviewer Memo: Source: Memo:
  • 12. Trattamento della Disfunzione Erettile Slide Modified: MRW 6/04 Review: Reviewer Memo: Source: Memo:
  • 13. Evoluzione della terapia per DE: Verso una funzione normale
    • Epoca Terapia
    • Pre 1960 Chirurgia /
            • rimedi naturali
    • 1960 Vacuum
    • 1960/70 Impianti
    • 1980 Iniezioni “galeniche”
    • 1992 FIC PGE1
    • 1998 Farmaci orali
    • 2010 Terapia genica
    Disperazione Aspettativa Goal Qualsiasi miglioramento Erezione valida Vita sessuale normale
  • 14. Management of ED: World Health Organization Guidelines Slide Modified: MRW 6/04 Review: Reviewer Memo: Source: Memo: Recommendations of the 1st International Consultation on Erectile Dysfunction. In: Jardin A et al., eds. Erectile Dysfunction . Plymouth, UK: Health Publication, Ltd; 2000:711-726. Oral Agents (unless contraindicated), Sexual Counseling and Education ED Unresolved ED Unresolved Alter Modifiable Risk Factors and Causes Local Therapies Surgical Treatments ED resolved. Patient satisfied. ED Unresolved
    • Intracavernosal injections
    • Intraurethral prostaglandin E1
    • Vacuum device
  • 15. Management of ED: Lifestyle Modification
    • Stop smoking 1,2
    • Limit or avoid alcohol 1
    • Follow healthy diet 2
    • Exercise regularly 3
    1. Recommendations of the 1st International Consultation on Erectile Dysfunction. In: Jardin A et al., eds. Erectile Dysfunction . Plymouth, UK: Health Publication, Ltd; 2000:711-726. 2. Feldman HA et al. Prev Med . 2000;30:328-338. 3. Derby CA et al. Urology . 2000;56:302-306. Slide Modified: MRW 6/04 Review: Reviewer Memo: Source: Memo:.
  • 16. Management of ED: Adjust Concomitant Medications
    • Consider modifying medications associated with drug-induced ED
      • Antihypertensives 1,2
      • Antidepressants 3
      • Antiandrogens and other hormone therapy 4
    1. Grimm RH Jr et al. Hypertension . 1997;29:8-14. 2. Suzuki H et al. J Hypertension . 1988;6(suppl):S649-S651 3. Clayton AH et al. J Clin Psych. 2002;63:357-366. 4. Higano CS. Urology . 2003;61(suppl 1):32-38. Slide Modified: MRW 6/04 Review: Reviewer Memo: Source: Memo:
  • 17. Management of ED: Psychosocial Counseling
    • Useful as monotherapy or as adjunctive treatment and may include
      • Anxiety reduction/desensitization
      • Cognitive-behavioral interventions
      • Sexual stimulation techniques
      • Interpersonal assertiveness/couples’ communication training
    Rosen RC. Urol Clin North Am . 2001;28:269-278. Slide Modified: MRW 6/04 Review: Reviewer Memo: Source: Memo:
  • 18.
    • Phosphodiesterase type 5 (PDE5) inhibitors
      • Tadalafil 10-20 mg (Cialis®) 1
      • Tadalafil 5 mg DAILY (Cialis®)
      • Vardenafil HCl 10-20 mg (Levitra®) 2
      • Sildenafil citrate 50-100 mg (Viagra®) 3
    Management of ED: Oral Medications 1. Cialis ® (tadalafil) prescribing information. Lilly ICOS LLC: Indianapolis, IN, and Bothell, WA; 2006. 2. Levitra ® (vardenafil HCl) prescribing information. Bayer Pharmaceuticals Corp: West Haven, CT; 2005. 3. Viagra ® (sildenafil citrate) prescribing information. Pfizer Inc: New York, NY; 2006. Slide Modified: MRW 6/04 Review: Reviewer Memo: Source: Memo:
  • 19. Distribuzione nei tessuti e specificità delle varie isoforme di fosfodiesterasi Wallis RM, et al. Am J Cardiol 1999 , modificato Isoform of PDE Tissue distribution Specificity for PDE1 Vascular smooth muscle, cardiomyocytes, brain cAMP, cGMP PDE2 Vascular smooth muscle, cardiomyocytes, brain, corpus cavernosum cAMP, cGMP PDE3 Vascular smooth muscle, cardiomyocytes, corpus cavernosum, platelets cAMP PDE4 Vascular smooth muscle, cardiomyocyte cAMP PDE5 Corpus cavernosum, vascular smooth muscle, skeletal muscle, platelets cGMP PDE6 Retina cGMP PDE7-10 Various cAMP or cGMP PDE11 Skeletal muscle, heart (?), vascular smooth muscle cAMP or cGMP
  • 20. Nitric Oxide-cGMP Mechanism of Penile Erection Slide Modified: Review: Reviewer Memo: Source: Memo: cGMP-dependent protein kinase Endothelial cell Guanylate cyclase GTP cGMP K + Ca 2+ Decreased Ca 2+ Smooth muscle relaxation and erection Nitric oxide Smooth muscle cell 5'GMP PDE5 Cavernous nerve Sexual stimulation PDE5 inhibitors cGMP, cyclic guanosine monophosphate
  • 21. Aspetti generali dei PDE5-i Sildenafil Tadalafil Vardenafil Kloner RA. Circulation 2004; 110: 3149-55. Emivita plasmatica 4 ore 4 – 5 ore 17.5 ore Eventi avversi > 2% Cefalea, Flushing, Dispepsia, L.U.T.S., Congestione nasale, Visione blu, Diarrea. Cefalea, Flushing, Rinite, Sinusite, Dispepsia, Nausea, Incremento CK Cefalea, Flushing, Dispepsia, Congestione nasale, Mialgie, Dolori lombari Aggiustamento dosaggio Età avanzata, Sofferenza epatica, Insuff. Renale grave, Uso inibitori P450 Età avanzata Sofferenza epatica, Inibitori CYP3A4, Eritromicina Insuff. Renale grave, Sofferenza epatica, Inibitori CYP3A4
  • 22. Sildenafil Tadalafil Vardenafil Kloner RA. Circulation 2004; 110: 3149-55. Aspetti generali dei PDE5-i
    • Donatori di NO
    • (uso continuo e/o intermittente)
    • - Nitroglicerina
    • Isosorbite mononitrato
    • Isosorbite dinitrato
    • Altri stimolatori della guanil-ciclasi.
    • Controindicazione assoluta se uso continuo.
    • Washout di 24 ore prima di assumere SILD
    • In caso di angina:
    • -non somm. NO donatori
    • -Si ß-bloccanti, calcio antagonisti, aspirina, ossigeno, eparina, morfina, statine, ecc.
    • In caso di IMA:
    • - Somm. Aspirina, trombolitici, antiaggreganti, angioplastica.
    • - Se il pz ha assunto SIL occorre washout di 24 h. prima di somm. Nitrati.
    Non sono disponibili recenti studi sulla interazione Vardenafil e Nitrati. Un solo studio pubblicato che consiglia washout di 24 ore dall’ assunzione Valgono le stesse raccomandazioni del SILD. In considerazione della lunga emivita del TAD è raccomandato un washout di 48 ore tra l’assunzione dei due farmaci. Nei pazienti cardiopatici è opportuno il monitoraggio dello specialista ed un attento studio emodinamico. Valgono le stesse raccomandazioni del SILD. ma, con washout di 48 ore
  • 23. Sildenafil Tadalafil Vardenafil Kloner RA. Circulation 2004; 110: 3149-55. Aspetti generali dei PDE5-i
    • α-bloccanti
    • Doxazosina
    • Terazosisa
    • Tamsulosin
    • ( α 1 -selettivo)
    • Precauzione 50-100 mg:
    • può determinare effetti ipotensivi sintomatici.
    • Washout di 4 ore.
    • - Può essere fatto uso concomitante di 25 mg.
    • Controindicato 10-20 mg:
    • può determinare effetti ipotensivi sintomatici.
    • Effetti meno marcati in pz IPB in terapia a lungo termine o con α 1 - selettivi.
    • Washout di 4 ore.
    Controindicato 10-20 mg: - può determinare effetti ipotensivi sintomatici. - Può essere assunto in sicurezza in associazione con α 1 -bloccante selettivo (Tamsulosin). Altre precauzioni d’uso Non evidenziati eventi avversi legati all’uso concomitante di farmaci antiipertensivi. - Associato a un modesto incremento del QT. - Cautela in pz con prolungamento congenito QT e uso concomitante di antiaritmici classe IA (chinidina,procainamide) e classe III (amiodarone, sotalolo). - Non ci sono dati relativi casi di Torsione di Punta. Non evidenziati eventi avversi legati all’uso concomitante di farmaci antiipertensivi.
  • 24. Historical Comparison: IIEF EF Domain Scores Tadalafil Once-a-Day and On-Demand Dosing 0 5 10 15 20 25 30 Once-a-Day Dosing Rajfer et al. Interim data 12 week Once-a-Day Dosing Porst et al. 12 week On-Demand Dosing Brock et al. 5 pooled studies 12 week IIEF EF Domain Score at 12 weeks Brock GB et al. J Urol . 2002;168:1332-1336. Porst H et al. Eur Urol. 2006;50:351-358. Rajfer J, et al. Int. J. Impot. Res. 2007;19:95-103 Placebo Tadalafil 2.5 mg Tadalafil 5 mg Tadalafil 10 mg Tadalafil 20 mg
  • 25. Management of ED: Other Treatment Options
    • Testosterone – oral, transdermal, subcutaneous, or intramuscular 1-3
    • Prostaglandin E1 4-6 (alprostadil) – intracavernosal injection or transurethral therapy
    • Vacuum constriction devices
    • Surgical treatment – penile prosthesis, vascular surgery 2
    1. AACE Male Sexual Dysfunction Task Force. Endocr Pract . 2003;9:77-95. 2. Lue TF. N Engl J Med . 2000;342:1802-1813. 3. Testopel™ pellets (testosterone). Physicians’ Desk Reference . 56th ed. Montvale, NJ: Medical Economics Co; 2002:3610-3611. 4. Shabsigh R et al. Urology . 2000;55:109-113. 5. Recommendations of the 1st International Consultation on Erectile Dysfunction. In: Jardin A et al., eds. Erectile Dysfunction . Plymouth, UK: Health Publication, Ltd; 2000:711-726. 6. MUSE ® (alprostadil) prescribing information. Physicians’ Desk Reference. 56th ed. Montvale, NJ: Medical Economics Company; 2002:3335-3338. Slide Modified: MRW 6/04 Review: Reviewer Memo: Source: Memo:
  • 26. TERAPIA INTRACAVERNOSA: CAVERJECT
    • Dosi : 5-20  g i.c.
    • Dose di ingresso : 5  g
    • Finestra : 5 – 60 minuti.
    • Modalità di assunzione : on demand
    • Effetti collaterali : bruciori, priapismo, placche.
    • Indicazioni : DE grave. Pazienti con controindicazioni ai PDE5i
  • 27. Second-Line Treatment Options MUSE 1000 mcg Vacuum Constriction Device
  • 28. Inflatable Prosthesis 3-Piece MENTOR AMS
  • 29. Management of ED: Summary
    • Psychosocial counseling
    • Evaluate potential drug-induced ED:
      • Antihypertensives
    • Therapy with oral ED medications
      • PDE5 inhibitors OD
      • PDE5 inhibitors once-a-day
    • Other treatment options:
      • Intracavernosal injection, constriction devices,
      • Combination Therapies
      • Penile prostheses
    Slide Modified: MRW 6/04 Review: Reviewer Memo: Source: Memo:
  • 30. Rationale for Combination therapy in ED Aversa et al, Ther Adv Urol, 2009
  • 31. Lifelong Premature Ejaculation
    • “ male sexual dysfunction characterized by ejaculation which always or nearly always occurs prior to or within about one minute of vaginal penetration, and the inability to delay ejaculation on all or nearly all vaginal penetrations, and negative personal consequences, such as distress, bother, frustration and/or the avoidance of sexual intimacy”
    McMahon et al, JSM 2008; 5: 1590-1606
  • 32.  
  • 33. APPROCCI TERAPEUTICI ALLA EP
    • Trattamenti topici
    • (EMLA; Tempe spray, SS-cream, dylonine-alprostadil)
    • α -bloccanti daily
    • (Alfuzosina, Terazosina)
    • SSRI (Daily – On Demand)
    • (Paroxetina, Sertralina, Duloxetina)
    • Tramadolo on demand
    PRILIGY (Dapoxetina) attualmente unico SSRI approvato al bisogno per la terapia della Eiaculazione Precoce nell’uomo
  • 34.  
  • 35. Potenziale di impiego degli inibitori della PDE5 nell’EP IA Abdel-Amid, Drugs 2004;64(1):13-26 Modulazione della risposta contrattile di dotti deferenti, vescicole seminali, prostata e uretra Tramite le vie NO/cGMP e cAMP Tramite inibizione della neurotrasmissione adrenergica Tramite azione diretta Induzione di uno stato di analgesia periferica Probabilmente tramite la via NO/cGMP Riduzione delle risposta simpatica centrale Tramite la via NO/cGMP e azione su MPOA Interazione con i classici neurotrasmettitori Prolungamento della durata dell’erezione Accumulo di cGMP nelle cellule cavernose Miglioramento dell’ossigenazione del tessuto penieno INIBITORI DELLE PDE5 MIGLIORAMENTO DELLA EP
  • 36.