Aktuelle Urol 1999; 30(7): 449-460
DOI: 10.1055/s-1999-8963
ÜBERSICHTSARBEIT
Georg Thieme Verlag Stuttgart ·New York

Oral-medikamentöse Therapie der erektilen Dysfunktion: Grundlagen, Spektrum und Grenzen

Oral Treatment of Erectile Dysfunction: Background, Spectrum and LimitationsJ. E. Altwein1 , W. F. Thon2
  • 1Urologische Klinik, Krankenhaus der Barmherzigen Brüder, München
  • 2Urologische Klinik, Klinikum Hannover/Krankenhaus Siloah
Further Information

Publication History

Publication Date:
31 December 1999 (online)

Zusammenfassung

Das Behandlungsspektrum der erektilen Dysfunktion (ED) spannt sich von der oral-medikamentösen Therapie bis zur Implantation einer Penisprothese. Die bedarfsangepaßte („on demand”) Tabletteneinnahme wird von der Mehrzahl der Patienten mit ED bevorzugt. In der Kategorie der zentralen Initiatoren der Erektion ist die wichtigste Substanz Apomorphin SL, dessen klinische Prüfungen abgeschlossen sind. In der Kategorie der peripheren Konditioner der Erektion stehen die klinischen Prüfungen der Phentolamidinmesylat oral vor dem Abschluß. Die innovativste Substanz dieser Kategorie ist Sildenafil, der erste Phosphodiesterase-5-Hemmer, der in Deutschland zugelassen ist.

Abstract

The therapeutic spectrum of erectile dysfunction comprises the oral-medical therapy at one end and the implantation of a penile prothesis at the other end. The majority of patients with erectile dysfunction favours the intake of tablets „on demand”. In the category of central initiators of erection, apomorphine SL is the most important compound, the clinical trials are now completed. In the category of peripheral conditioners of erection, the clinical trials with phentolaminmesylate per os are about to be concluded. The true novel substance in this category is sildenalfil, the first phosphodiesterase-5-inhibitor which has been approved in Germany.

Literatur

  • 1 Andersson K E, Wagner G. Physiology of Penile Erection.  Physiological Review. 1995;  75 191-235
  • 2 De Groat W C, Steers W D. Neuroanatomy and neurophysiology of penile erection. In: Tanagho EA, Lue TF, McClare RD, Hrsg Contemporary Management of Impotence and Infertility. Baltimore; Williams & Wilkins 1988: 3-27
  • 3 Feldman H A, Goldstein I. et al . Impotence and its medical and psychosocial correlates: Results of the Massachusetts male aging study.  J Urol. 1994;  151 54-61
  • 4 Braun M, Klotz T, Reifenrath B et al. The “Cologne 8000 men survey” - Prevalence and therapy necessary of men with erectile dysfunction. First International Consultation on Erectile Dysfunction der WHO. Paris, 1 - 3. Juli 1999
  • 5 NIH Consensus Development Panel on Impotence . Impotence.  JAMA. 1993;  270 83-90
  • 6 Montague D K, Barada J H, Belker A M et al. Clinical guidelines on erectile dysfunction: Summary report on the treatment of organic erectile dysfunction.  J Urol. 1996;  156 2007-2011
  • 7 Hanash K A. Comparative results of goal oriented therapy for erectile dysfunction.  J Urol. 1997;  157 2135-2138
  • 8 Process of Care Consensus Panel . The process of care model for evaluation and treatment of erectile dysfunction.  Int J Impot Res. 1999;  11 59-74
  • 9 Rosen R C, Riley A, Wagner G et al. The International Index of Erectile Function: A multidimensional scale for assessment of erectile dysfunction.  Urology. 1997;  49 822-830
  • 10 Burnett A L. Nitric oxide in the penis: Physiology and pathology.  J Urol. 1997;  157 320-324
  • 11 Wassertheil-Smoller R et al. Effects of antihypertensives on sexual function and quality of life: The TAIM study.  Ann Int Med. 1991;  114 613-620
  • 12 Grimm R H, Grandits G A, Prineas R J et al. Long-term effects on sexual function of five antihypertensive drugs and nutritional hygienic treatment in hypertensive men and women. Treatment of Mild Hypertension Study (TOMHS).  Hypertension. 1997;  29 8-14
  • 13 Porst H. Therapie der erektilen Dysfunktion. Neuromodulatorische und molekulare Grundlagen.  Niere - Blase - Prostata. 1998;  23 (1. Suppl.) 13-31
  • 14 Weiske W H. Epidemiologie und Diagnostik der erektilen Dysfunktion.  Niere - Blase - Prostata. 1998;  23 (1. Suppl.) 5-12
  • 15 Porst H. Editorial Comment.  Int J Impot Res. 1999;  11 72-73
  • 16 Akkus E, Alici B, Ökara H. et al . Repetition of color doppler ultrasonography: Is it necessary.  Int J Impot Res. 1998;  10 51-55
  • 17 Anderson M, Nicholson B, Louie E et al. An analysis of vasculogenic erectile dysfunction as a potential predictor of occult cardiac disease.  J Urol. 1998;  159 118
  • 18 Kaiser F E, Udhoji V. et al . Cardiovascular stress test in patients with vascular impotence.  Clin Res. 1989;  37 89
  • 19 Wessels H, Fuciarelli K, Hansen J et al. Synthetic melanotropic peptide initiates erections in men with psychogenic erectile dysfunction: Double-blind, placebo controlled crossover study.  J Urol. 1998;  160 389-393
  • 20 Schlatter E KE, Lal S. Treatment of alcoholism using Dent's oral apomorphine method.  Q J Stud Alcohol. 1972;  33 430-436
  • 21 Zarrindast M R, Shokravi S, Samini M et al. Opposite influences of dopaminergic receptor subtypes on penile erection.  Gen Pharmacol. 1992;  23 671-675
  • 22 Ahlenius S, Larsson K. Apomorphine- and haloperidol-induced effects on male sexual behavior: no evidence for actions due to stimulation of central dopamine autoreceptors.  Pharmacol Biochem Behav. 1984;  21 463-466
  • 23 Melis M R, Argiolas A. Nitrit oxide synthase inhibitors prevent apomorphine- and oxytocin-induced penile erection and yawning in male rats.  Brain Res Bull. 1993;  32 71-74
  • 24 Vincent S R, Kimura H. Histochemical mapping of nitric oxide synthase in the rat brain.  Neuroscience. 1992;  46 755-784
  • 25 Melis M R, Stancampiano R, Gessa G L, Argiolas A. Prevention by morphine of apomorphine- and oxytocin-induced penile erection and yawning.  Pharmacol Biochem Behav. 1992;  42 61-66
  • 26 Heaton J PW, Varrin S J. Effects of castration and exogenous testosterone supplementation in an animal model of penile erection.  J Urol. 1994;  151 797-800
  • 27 Andersson K E, Gemalmaz H, Waldeck K. et al . The effect of sildenafil on apomorphine-evoked increases in intracavernous pressure in the awake rat.  J Urol. 1999;  161 1707-1712
  • 28 Heaton J. Apomorphine, the central initiator and the matrix of treatment strategies. International Society for Impotence Research; 8. Weltkongreß (24. - 28. 8. 98 Amsterdam)
  • 29 Padma-Nathan H, Auerbach S, Lewis R et al. Efficacy and safety of apomorphin SL vs. placebo for male erectile dysfunction.  J Urol. 1999;  161 214
  • 30 Lewis R, Agre K, Fromm S et al. Efficacy of apomorphine SL vs. placebo for erectile dysfunction in patients with hypertension.  J Urol. 1999;  161 214
  • 31 Steers W D, De Groat W C. Effects of m-chlorophenylpiperazine on penile and bladder function in rats.  Am J Physiol. 1989;  257 1449
  • 32 Pomerantz S M, Hepner B C, Wertz J M. 5 HTIA and 5-HTIC/ID receptor agonists produce reciprocal effects on male sexual behavior of rhesus monkeys.  Eur J Pharmacol. 1993;  243 227-234
  • 33 Azadzoi K M, Kim N, Wertz J M et al. Endothelium-derived nitric oxide and cyclooxygenase products modulate corpus cavernosum smooth muscle tone.  J Urol. 1992;  147 220-225
  • 34 Sikora R, Sohn M, Bosshardt R et al. Trazodone in diagnosis and therapy of erectile dysfunction.  Int J Impot Res. 1992;  4 100
  • 35 Morales A, Condra M, Owen J A et al. Is yohimbine effective in the treatment of organic impotence? Results of a controlled trial.  J Urol. 1987;  137 1168-1172
  • 36 Riley A J, Goodman R E, Kellet J M. et al . Double blind trial of yohimbine hydrochloride in the treatment of erection inadequacy.  J Sex Martial Ther. 1989;  4 17-25
  • 37 Ellis W J, Grayhack J T. Sexual function in aging males after orchiectomy and estrogen therapy.  J Urol. 1963;  89 895-899
  • 38 Heim N. Sexual behaviour of castrated sex offenders.  Arch Sex Behav. 1981;  10 11-19
  • 39 Bancroft J, Wu F C. Changes in erectile responsiveness during androgen therapy.  Arch Sex Behav. 1983;  12 59-66
  • 40 Carani C, Scuteri A, Marrama P et al. The effects of testosterone administration and visual erotic stimuli on nocturnal penile tumescence in normal men.  Horm Behav. 1990;  24 435-441
  • 41 Reiter W J, Pycha A, Schatzl G. et al . Dehydroepiandrosterone in the treatment of erectile dysfunction: A prospective, double-blind, randomised, placebo-controlled study.  Urology. 1999;  53 590-5
  • 42 Becker A J, Stief C G, Schultheiss D, Truss M C, Jonas U. Pharmakologische Therapie der erektilen Dysfunktion.  Urologe A. 1998;  37 503-508
  • 43 Furchgott R F, Zawadski J V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine.  Nature. 1980;  288 373-376
  • 44 Burnett A L, Löwenstein C J, Bredt D S et al. Nitric oxide: A physiological mediator of penile erection.  Science. 1992;  257 401-403
  • 45 Zorgniotti A W, Lizza E F. Effect of large doses of the nitric oxide precursor, L-arginine, on erectile function.  Int J Impot Res. 1994;  6 33-36
  • 46 Chen J, Wollman Y, Chernichovsky T et al. Effect of oral administration of high-dose nitric oxide donor L-arginine in men with organic erectily dysfunction: Results of a double-blind, randomized, placebo-controlled study.  Br J Urol. 1999;  83 269-273
  • 47 Brindley G S. Cavernosal alpha-blockade and human penile erection.  J Physiol. 1983;  342 24
  • 48 Stief C G, Bähren W, Gall H, Scherb W, Gallwitz A, Altwein J E. Schwellkörper-Autoinjektionstherapie (SKAT): Erste Erfahrungen bei erektiler Dysfunktion.  Urologe A. 1986;  25 63-68
  • 49 Kaplan S A, Reis R B, Kohn I J et al. Combination therapy using oral alphablockers and intracavernosal injection in men with erectile dysfunction.  Urology. 1998;  52 739-743
  • 50 Goldstein I, Ferguson D. . Vasomax Study Group . Efficacy and safety of phentolamine (Vasomax®) for the treatment of erectile dysfunction using a crossover study design.  Int J Impot Res. 1998;  10 561
  • 51 Rosen R. α-Blocker therapies for ED, including daxozosine and phentolamine. International Society for Impotence Research; 8. Weltkongreß, Amsterdam 24. - 28. 8. 1998
  • 52 Lugnier C, Komas N. Modulation of vascular cyclic nucleotide phosphodiesterases by cyclic GMP: Role in vasodilatation.  Eur Heart J. 1993;  14 141-148
  • 53 Boolell M, Gepi-Attee S, Gingell J C et al. Sildenafil, a novel effective oral therapy for male erectile dysfunction.  Br J Urol. 1996;  78 257-261
  • 54 Truss M C, Becker A J, Ückert S et al. Selective pharmacological manipulation of the smooth muscle tissue of the genitourinary tract: a glimpse into the future.  Br J Urol. 1999;  83 (Suppl. 2) 36-41
  • 55 Wallis R M, Corbin J D, Francis S H et al. Tissue distribution of phosphodiesterase families and the effects of sildenafil on tissue cyclic nucleotides, platelet function, and the contractile responses of trabeculae carneae and aortic rings in vitro.  Am J Cardiol. 1999;  83 3
  • 56 Morales A, Gingell C, Collins M et al. Clinical safety of oral sildenafil citrate (VIAGRATM) in the treatment of erectile dysfunction.  Int J Impot Res. 1998;  10 69-74
  • 57 Goldstein I, Lue T F, Padma-Nathan H et al. Oral sildenafil in the treatment of erectile dysfunction.  N Engl J Med. 1998;  388 1397-1404
  • 58 Steers W D. and the Sildenafil Study Group . Meta-Analysis of the efficacy of sildenafil (Viagra®) in the treatment of severe erectile dysfunction.  J Urol. 1998;  159 238
  • 59 Hartmann U, Meuleman E JH, Cuzin B et al. Sildenafil (Viagra®): Analysis of preferred doses in a European, 6-month, double-blind, placebo-controlled, flexible dose-escalation study in patients with erectile dysfunction. The 8th World Meeting on Impotence Research, 25 - 28 August 1998, Amsterdam.  Int J Impot Res. 1998;  10 (Suppl. 3) 255
  • 60 Vroege J A. Letter to the Editor. The sexual health inventory for men (IIEF-5).  Int J Impot Res. 1999;  11 177
  • 61 Hültling C. Partner's perceptions of efficacy of sildenafil (Viagra®) in the treatment of erectile dysfunction.  Int Impot Res. 1988;  10 (Suppl. 3) 246
  • 62 Young J. Sildenafil (Viagra®) in the treatment of erectile dysfunction: A 12-week, flexible-dose study of assess efficacy and safety. The 8th World Meeting on Impotence Research, 25 - 28 August 1998, Amsterdam.  Int J Impot Res. 1988;  10 (Suppl. 3) 253
  • 63 Montorsi F, McDermott T E, Morgan R et al. Efficacy and safety of fixed-dose oral sildenafil in the treatment of erectile dysfunction of various etiologies.  Urology. 1999;  53 1011-1018
  • 64 Dinsmore W W, Hodges M, Hargreaves C et al. Sildenafil citrate (Viagra®) in erectile dysfunction: near normalization in men with broad-spectrum erectile dysfunction compared with age-matched healthy control subjects.  Urology. 1999;  53 800-805
  • 65 Feldman R, Waterbury C T. and the Sildenafil Study Group . Sildenafil in the treatment of erectile dysfunction: efficacy in patients taking concomitant antihypertensive therapy.  Am J Hypertension. 1998;  11 10
  • 66 Rendell M S, Rajfer J, Wicker P A, Smith M D. Sildenafil for treatment of erectile dysfunction in men with diabetes: a randomized controlled trial.  Sildenafil Diabetes Study Group JAMA. 1999;  280 421-426
  • 67 Giuliano F, Hultling C, El Masry W S, Smith M D, Osterloh I H, Orr M, Maytom M. Randomized trial of sildenafil for the treatment of erectile dysfunction in spinal cord injury. Sildenafil Study Group.  Ann Neurol. 1999;  46 15-21
  • 68 Zippe C D, Kedia A W. Treatment of erectile dysfunction after radical prostatectomy with sildenafil citrate (Viagra®).  Urology. 1998;  52 963-966
  • 69 Hackett G, Gingell C et al. Long-term safety and efficacy after 2 years of Viagra® (sildenafil citrate) treatment in erectile dysfunction and the overall incidence of myocardial infarction.  J Urol. 1999;  161 214
  • 70 Wagner G, Maytam M, Smith M D et al. Analysis of the efficacy of sildenafil (Viagra®) in the treatment of male erectile dysfunction in elderly patients.  J Urol. 1998;  157 912
  • 71 Zelefsky M J, McKee A B, Lee H, Leibel S A. Efficacy of oral sildenafil in patients with erectile dysfunction after radiotherapy for carcinoma of the prostate.  Urology. 1999;  53 775-778
  • 72 Drory Y, Shapira Y, Fishman E Z et al. Myocardial ischemia during sexual activity in patients with coronary artery disease.  Am J Cardiol. 1995;  75 835-837
  • 73 Drory Y, Fisman E Z, Shapira Y et al. Ventricular arrhythmias during sexual acitivty in patients with coronary artery disease.  Chest. 1996;  109 922-924
  • 74 Jackson G, Benjamin N, Jackson N et al. Effects of sildenafil citrate on human hemodynamics.  Am J Cardiol. 1999;  83 13
  • 75 Conti C R, Pepine C J, Sweeney M et al. Efficacy and safety of sildenafil citrate in the treatment of erectile dysfunction in patients with ischemic heart disease.  Am J Cardiol. 1999;  83 29
  • 76 Webb D J, Freestone S, Allen M J et al. Sildenafil citrate and blood-pressure-lowering drugs: results of drug interaction studies with an organic nitrate and a calcium antagonist.  Am J Cardiol. 1999;  83 21
  • 77 Muirhead G J, Allen M J, James G C et al. Pharmacokinetics of sildenafil (VIAGRA), a selective cGMP PDE5 inhibitor, after single oral doses in fasted and fed healthy volunteers.  Brit J Clin Pharmacol. 1996;  42 259-282
  • 78 Goldenberg M M. Safety and efficacy of sildenafil citrate in the treatment of male erectile dysfunction.  Clin Ther. 1998 Nov - Dec;  20(6) 1033-1048
  • 79 Arzneimittel-Kommission der deutschen Ärzteschaft . Hinweis zur sicheren Anwendung von Sildenafil (Viagra®).  Deutsches Ärzteblatt. 1998;  95 2014
  • 80 Langtry H D, Markham A. Sildenafil: a review of its use in erectile dysfunction.  Drugs. 1999;  57 967-989

Prof. Dr. med. J. E. Altwein

Chefarzt an der Urologischen Abteilung Krankenhaus der Barmherzigen Brüder

Romanstr. 93

80639 München

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