Skip to main content
SpringerLink
Log in

Erektile Dysfunktion

Neue Medikamente unter besonderer Berücksichtigung der PDE-5-Inhibitoren

Erectile dysfunction

New drugs with special consideration of the PDE 5 inhibitors

  • Übersichten
  • Published:
Der Urologe, Ausgabe A Aims and scope Submit manuscript

Zusammenfassung

Die Erektile Dysfunktion (ED) ist gerne mit Erkrankungen assoziiert, deren gemeinsame Basis eine endotheliale Dysfunktion ist. Häufig ist die ED auch mit LUTS kombiniert, wobei dann die gemeinsame Basis eine Rho-Kinase-Erhöhung und NO-Abnahme zu sein scheint.

Da alle drei PDE-5-Inhibitoren Sildenafil, Tadalafil und Vardenafil einen gemeinsamen Wirkmechanismus, die Hemmung der PDE 5, haben, unterscheiden sie sich bezüglich Wirksamkeit und Nebenwirkungsprofil kaum, mit Ausnahme von Farbsehstörungen, die häufiger bei Sildenafil und Rücken-/Muskelschmerzen, welche häufiger bei Tadalafil auftreten. Hauptunterschiedsmerkmal unter den 3 Substanzen ist ihre Pharmakokinetik, die letztendlich dafür verantwortlich ist, dass in den bislang veröffentlichten Vergleichsstudien in Abhängigkeit vom jeweiligen Studiendesign die überwiegende Mehrzahl der Patienten sich entweder für Tadalafil, den am längsten (36 h) wirksamen PDE-5-Hemmer oder für Vardenafil als relativ schnell wirksame Substanz entschieden haben.

Alle bislang publizierten Studien haben gezeigt, dass bezüglich des kardiovaskulären Risikos (Herzinfarktrate) alle drei PDE-5-Hemmer generell besser als Placebo, wenngleich auch nicht statistisch signifikant, abgeschnitten haben. Ohne Ausnahme gilt für alle drei PDE-5-Hemmer, dass sie bei gleichzeitiger Nitrat- und Molsidominmedikation kontraindiziert sind und Interaktionen insbesondere mit nicht uroselektiven α-Blockern zeigten, weshalb eine gleichzeitige Einnahme vermieden werden muss.

In naher Zukunft könnte die chronische (tägliche) Applikation eines PDE-5-Hemmers Vorteile bringen, zumindest bei den ca. 50–60% aller ED-Fälle, bei denen aufgrund der Diagnostik (Penis-Duplex/Doppler) eine endotheliale Dysfunktion sehr wahrscheinlich ist. Mögliche Neuentwicklungen in der ED-Therapie mit einem Zeitfenster von 5–8 Jahren bis zur Marktzulassung stellen Guanylatzyklaseaktivatoren, Rho-Kinase-Inhibitoren, Melanocortin-Rezeptoragonisten, die Gentherapie und das Tissue Engineering dar.

Abstract

Erectile dysfunction (ED) tends to be associated with other diseases, the common basis of which is endothelial dysfunction. ED is also frequently combined with LUTS and the common basis for both conditions seems to be elevation of Rho-kinase activity and decrease of NO concentration.

Because all three PDE 5 inhibitors sildenafil, tadalafil, and vardenafil have a common mode of action, i.e., inhibition of PDE 5, they are not different in terms of their efficacy and safety profile except for color vision disturbances which are more common after sildenafil and back pain/myalgia more often observed after tadalafil. The main differentiating characteristics among the three PDE 5 inhibitors are their pharmacokinetics. These are ultimately responsible for the observation that in head-to-head comparative trials depending on the respective study design the overwhelming majority of the patients opted either for tadalafil as the longest acting PDE 5 inhibitor (36 h) or for vardenafil as a relatively rapidly acting drug.

All published studies so far have shown that in terms of the cardiovascular risk profile (myocardial infarction rate) all three PDE 5 inhibitors performed better than placebo although the results were not statistically significant. Without any exception it applies to all three PDE 5 inhibitors that they are absolutely contraindicated in patients taking nitrate- or molsidomine-containing medications and that they may interact in particular with non-uroselective alpha-adrenoceptor blockers. This is why their simultaneous application with PDE 5 inhibitors has to be avoided.

In the near future chronic (daily) application of a PDE 5 inhibitor may show advantages, at least in those 50–60% of all patients in whom there is a high likelihood of endothelial dysfunction due to the diagnostic (penile duplex Doppler) outcome. Possible new developments in the management of ED with a time frame of 5–8 years until their market approval are guanylate cyclase activators, Rho-kinase inhibitors, melanocortin receptor agonists, gene therapy, and tissue engineering.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Abb. 1
Abb. 2
Abb. 3

Literatur

  1. Bing W, Chang S, Hypolite J et al. (2002) Obstruction-induced changes in detrusor contractility and alteration in myosin light chain phosphorylation: a role for Rho kinase. J Urol 167 (Suppl 1): 247

    Google Scholar 

  2. Braun M, Wassmer G, Klotz T (2000) Epidemiology of erectile dysfunction: results of the „Cologne Male Survey“. Int J Impotence Res 12: 305–311

    Article  CAS  Google Scholar 

  3. Braun M, Sommer F, Haupt G et al. (2003) Lower urinary tract symptoms and erectile dysfunction: Co-morbidity or typical „Aging Male“ aymptoms? Results of the „Cologne Male Survey“. Eur Urol 44: 588-594

    Article  CAS  PubMed  Google Scholar 

  4. Brock GB, McMahon CG, Chen KK et al. (2002) Efficacy and safety of tadalafil for the treatment of erectile dysfunction: Results of integrated analyses. J Urol 168: 1332–1336

    CAS  PubMed  Google Scholar 

  5. Chang S, Hypolite JA, Changolkar A et al. (2002) Diabetes associated erectile dysfunction : role of endothelin and Rho-kinase. J Urol 167 (Suppl): 237

    Google Scholar 

  6. Eardley I, Wright P, MacDonagh R, Edwards A, Yousuf E (2003) A randomized cross-over study to compare the efficacy of sildenafil and apomorphine in the treatment of men with erectile dysfunction (ED). Eur Urol (Suppl 2): 218

    Google Scholar 

  7. Eardley I, Padma-Nathan H, Kaufman J, Taylor T (2003) Earliest time of onset of erections determined in an at-home setting with vardenafil. Presentation at the 3rd World Congress on Men’s Health, October 24–26, Vienna

  8. Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB (1994) Impotence and its medical and psychosocial correlates: Results of the Massachusetts Male Aging Study. J Urol 151: 54–61

    CAS  PubMed  Google Scholar 

  9. Gbekor E, Bethell S, Fawcett L, Mount N, Phillips S (2002) Phosphodiesterase 5 inhibitor profiles against all human phosphodiesterase families: Implications for use as pharmacological tools. J Urol 167 (Suppl): 246

    PubMed  Google Scholar 

  10. Goldstein I, Lue TF, Padma-Nathan H et al. (1998) Oral Sildenafil in the treatment of erectile dysfunction. N Engl J Med 338: 1397–1404

    CAS  PubMed  Google Scholar 

  11. Govier F, Potempa AJ, Kaufman J et al. (2003) A multicenter, randomized, double blind, crossover study of patient preference for tadalafil 20 mg or sildenafil citrate 50 mg during initiation of treatment for erectile dysfunction. Clin Ther 25: 2709–2723

    Article  CAS  PubMed  Google Scholar 

  12. Hellstrom W, Gittelman M, Karlin G et al. (2002) Vardenafil for treatment of men with Erectile Dysfunction: efficacy and safety in a randomized, double-blind, placebo-controlled trial. J Andrology 23/6: 763–771

    Google Scholar 

  13. Hellstrom WJ, Overstreet J, Yu A et al. (2002) Tadalafil has no clinical relevant effect on semen characteristics. Int J Impotence Res 14 (Suppl 4): 62

    Google Scholar 

  14. Jackson G (2003) Editorial. PDE 5 Inhibitors: looking beyond. IJCP 57/3: 159

  15. Jackson G, Denne J, Emmick J et al. (2003) Interaction with nitrates no longer evident 48 hours after dosing of tadalafil. Int J Impotence Res 15 (Suppl 6): 20

    Google Scholar 

  16. Jackson G, Bedding A, Emmick J et al. (2003) Interaction between tadalafil and two alpha blockers doxazosin and tamsulosin. Int J Impotence Res 15 (Suppl 6): 60

    Article  CAS  Google Scholar 

  17. von Keitz A, Rajfer J, Segal S et al. (2004) A multicenter, randomized, double-blind, crossover study to evaluate patient preference between tadalafil and sildenafil. Eur Urol 45: 499–509

    Article  PubMed  Google Scholar 

  18. Kloner RA, Brown M, Prisant LM et al. (2001) Effect of Sildenafil in patients with erectile dysfunction taking antihypertensive therapy. Am J Hypertens 14: 70–73

    Article  CAS  PubMed  Google Scholar 

  19. Kloner RA, Mohan P, Segerson T et al. (2003) Cardiovascular safety of vardenafil in patients receiving antihypertensive medications: a posthoc analysis of five placebo-controlled clinical trials. J Am Coll Cardiol 41 (Suppl A): 276 A. Presented at ACC 2003, Chicago

    Article  Google Scholar 

  20. Klotz T, Sachse R, Heidrich A et al. (2001) Vardenafil increases penile rigidity and tumescence in erectile dysfunction: a RigiScan and pharmacokinetic study. World J Urol 19: 32–39

    Article  CAS  PubMed  Google Scholar 

  21. Kumamoto Y, Tsukamoto T, Satoh T et al. (2000) Epidemiological study on aging changes of sexual activity in Japanese men and women. The Aging Male 3 (Suppl 1): 9

    Google Scholar 

  22. Milligan PA, Marshall SF, Karlsson MO (2002) A population pharmacokinetic analysis of sildenafil citrate in patients with erectile dysfunction. Br J Pharmacol 53: 45S–52S

    Article  CAS  Google Scholar 

  23. Mitchell M, Kloner RA, Watkins V et al. (2002) Cardiovascular profile of tadalafil, a new PDE 5 inhibitor. Int J Impotence Res 14 (Suppl 4): S60

    Article  Google Scholar 

  24. Montorsi P, Montorsi F, Schulman CC (2003) Is erectile dysfunction the „tip of the iceberg“ of a systemic vascular disorder? Eur Urol 44: 352–354

    Article  PubMed  Google Scholar 

  25. Nichols DJ, Muirhead GJ, Harness JA (2002) Pharmacokinetics of sildenafil after single oral doses in healthy male subjects: absolute bioavailability, food effects, and dose proportionality.Br J Clin Pharmacol 53: 5S-12S

    Article  CAS  PubMed  Google Scholar 

  26. Padma-Nathan H, Rosen RC, Shabsigh R et al. (2001) Tadalafil (IC 351) provides prompt response and extended period of responsiveness for the treatment of men with erectile dysfunction (ED) Int J Impotence Res 13 (Suppl 5): S33

  27. Padma-Nathan H, Gaser DB, Stecher VJ et al. (2002) Minimum time to onset of erection after Viagra (sildenafil citrate): Results of a randomized, double-blind, placebo-controlled trial. Int J Impotence Res 14 (Suppl 4): S15

    Article  Google Scholar 

  28. Padma-Nathan H, Eardley I, Kloner RA, Laties AM, Montorsi F (2002) A 4-year up-date on the safety of sildenafil citrate (Viagra®) Urology 60 (Suppl 2B): 67–90

  29. Patterson B, Bedding A, Hayley J, Chris P, Male M (2002) Dose-normalized pharmacokinetics of tadalafil administered as single dose to healthy volunteers. Eur Urol (Suppl 1): 152

    Article  Google Scholar 

  30. Porst H, Rosen R, Padma-Nathan H et al. (2001) The efficacy and tolerability of vardenafil, a new oral, selective phosphodiesterase type 5 inhibitor, in patients with erectile dysfunction: the first at-home clinical trial. Int J Impotence Res 13: 192–199

    Article  CAS  Google Scholar 

  31. Porst H, Kloner RA, Mohan P et al. (2002) Cardiovascular safety of the selective PDE 5 inhibitor vardenafil in patients with erectile dysfunction: an analysis of five placebo-controlled clinical trials. Int J Impotence Res 14 (Suppl 4): S22

    Article  Google Scholar 

  32. Porst H, Padma-Nathan H, Giuliano F et al. (2003) Efficacy of Tadalafil for the treatment of erectile dysfunction at 24 and 36 hours after dosing: a randomized controlled trial. Urology 62: 121–125

    Article  PubMed  Google Scholar 

  33. Porst H, Stief C, Beneke M, Ulbrich E, Saenz de Tejada I (2003) Influence of prior sildenafil use on the efficacy of vardenafil in men with erectile dysfunction: Retrospective analysis of a two year study. Presented at the European Society of Andrological Urology (ESAU), Capri, October 23, 2003

    Google Scholar 

  34. Porst H, Arnds S, Kleingarn M (2003) What patients prefer and why—Sildenafil vs.Tadalafil in a real life at home setting. Int J Impotence Res 15 (Suppl 6): 21

    Article  Google Scholar 

  35. Porst H (2003) Therapie der erectile Dysfunktion im Jahr 2005. Urologe A 42: 1330–1337

    Article  CAS  PubMed  Google Scholar 

  36. Porst H, Arnds S, Kleingarn M (2004) The 3 PDE 5 inhibitors sildenafil, tadalafil, and vardenafil: results of an independent intraindividual comparative study. Eur Urol (Suppl): 104

    Article  Google Scholar 

  37. Rees RW, Foxwell NA, Ralph DJ, Kell PD, Moncada S, Cellek S (2003) Y 27632, a Rho-kinase inhibitor, inhibits proliferation and adrenergic contraction of prostatic smooth muscle cells. J Urol 170: 2517–2522

    CAS  PubMed  Google Scholar 

  38. Rosen R, Altwein J, Boyle P et al. (2003) Lower urinary tract symptoms and male sexual dysfunction: The Multinational Survey of the Aging Male (MSAM-7). Eur Urol 44: 637–649

    Article  Google Scholar 

  39. Sachse R, Rohde G, Stark S, Klotz T (2000) Safety, tolerability and pharmacokinetics of BAY 38–9456 in patients with erectile dysfunction. J Urol 163 (Suppl): 204

    Google Scholar 

  40. Sadowsky R, Miller T, Moskowitz M, Hackett G (2001) Three year update of sildenafil-citrate (Viagra) efficacy and safety. Int J Clin Pract 55: 115–128

    PubMed  Google Scholar 

  41. Sairam K, Kulinskaya E, McNicholas TA, Boustead GB, Hanbury DC (2002) Sildenafil influences lower urinary tract symptoms. BJU International 90: 836–839

    Article  CAS  PubMed  Google Scholar 

  42. Sommer F, Klotz T, Mathers M et al. (2004) A comparative randomized multicentre study of the maximum dose of sildenafil, tadalafil and vardenafil. Eur Urol (Suppl): 105

    Google Scholar 

  43. Souverein PC, Egberts ACG, Meuleman EJH, Urquhart J, Leufkens HGM (2002 Incidence and determinants of sildenafil discontinuation: the Dutch cohort of sildenafil users. Int J Impotence Res 14: 259–265

    Article  CAS  Google Scholar 

  44. Ströberg P, Murphy A, Costigan T (2003) Switching patients with erectile dysfunction from sildenafil citrate to tadalafil: results of a European multicenter, open-label study of patient preference. Clin Ther 25: 2724–2737

    Article  PubMed  Google Scholar 

  45. Wilkes N, White S, Cosgrove DJ, Rajasekaran M (2002) Y-27632,an inhibitor of Rho-kinase, improves erectile response in male hypertensive rats. J Urol 167 (Suppl): 238

    PubMed  Google Scholar 

  46. Wilkes N, White S, Rajasekaran M (2003) PDE-V inhibitors synergizes Rho-kinase antagonism and enhances erectile response in male hypertensive rats. J Urol 169 (Suppl): 360

    Google Scholar 

Download references

Interessenkonflikt:

Keine Angaben

Author information

Authors and Affiliations

  1. Hamburg

    H. Porst

  2. Neuer Jungfernstieg 6a, 20354, Hamburg

    H. Porst

Authors
  1. H. Porst
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to H. Porst.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Porst, H. Erektile Dysfunktion. Urologe [A] 43, 820–828 (2004). https://doi.org/10.1007/s00120-004-0618-2

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00120-004-0618-2

Schlüsselwörter

Keywords

Search

Navigation