Wechselwirkungen zwischen Sildenafil und Antihypertensiva - Was ist gesichert?

Dtsch Med Wochenschr 0120472 001; 126: 1144–1149 © Georg Thieme Verlag Stuttgart · New York Ü b e r s i c h t e n In den westlichen Industriestaaten leiden etwa 25% der Bevölkerung an einer arteriellen Hypertonie (11). Knapp die Hälfte der Hypertoniker wird mit Antihypertensiva behandelt (11). Sowohl bei behandelten als auch bei nicht behandelten Hypertonikern ist die erektile Dysfunktion (ED) häufig (4, 6, 9, 15, 19, 24, 25, 37, 40, 42). So zeigte die MassachusettsMale-Aging-Studie (MMAS) an 1290 Männern, dass die alterskorrigierte Wahrscheinlichkeit für das Auftreten einer ED positiv mit dem Vorhandensein einer arteriellen Hypertonie sowie einer antihypertensiven Medikation korreliert (19). Seit 1998 steht mit Sildenafil (Viagra®) eine effiziente Substanz zur oral-medikamentösen Therapie der ED zur Verfügung (22), die auch bei Hypertonikern wirksam ist (20, 29). Als unerwünschte Wirkungen sind geringe hämodynamische Effekte mit moderater Senkung des arteriellen Blutdrucks bekannt (45). Somit stellt sich die Frage, ob mögliche additive bzw. sich potenzierende kreislaufdepressive Effekte von Sildenafil und Antihypertensiva zu klinisch relevanten Blutdruckabfällen führen können. Für den klinischen Alltag ist von Relevanz, ob und mit welchen Antihypertensiva Sildenafil (Viagra®) sicher kombiniert werden kann. Im Folgenden soll daher ein Überblick über die Datenlage zur Effizienz der Sildenafil-Therapie bei Hypertonikern sowie zu hämodynamischen Effekten und der klinischen Sicherheit einer kombinierten Behandlung mit Sildenafil und Antihypertensiva gegeben werden. Die Arbeit basiert auf einer Literatur-Recherche in NLM PubMed MedLine (Suchwörter: erectile dysfunction, impotence, sildenafil, hypertension, antihypertensive drugs/agents, drug safety).

[1]  M. Kotler,et al.  Sex and the heart: what is the role of the cardiologist? , 2001, European heart journal.

[2]  V. Somers,et al.  Sympathetic Activation by Sildenafil , 2000, Circulation.

[3]  Morris J. Brown,et al.  Effect of sildenafil citrate on blood pressure and heart rate in men with erectile dysfunction taking concomitant antihypertensive medication , 2000 .

[4]  K. Saito,et al.  Hypotensive interaction of sildenafil and nicorandil in rats through the cGMP pathway but not by K(ATP) channel activation. , 2000, Japanese journal of pharmacology.

[5]  H. Herrmann,et al.  Hemodynamic effects of sildenafil in men with severe coronary artery disease. , 2000, The New England journal of medicine.

[6]  H. Granger,et al.  Inositol phosphate metabolism and nitric-oxide synthase activity in endothelial cells are involved in the vasorelaxant activity of nebivolol. , 2000, The Journal of pharmacology and experimental therapeutics.

[7]  P. Chowienczyk,et al.  The vasodilator action of nebivolol in forearm vasculature of subjects with essential hypertension. , 1999, British journal of clinical pharmacology.

[8]  I. Osterloh,et al.  Overall cardiovascular profile of sildenafil citrate. , 1999, The American journal of cardiology.

[9]  G. Jackson,et al.  Effects of sildenafil citrate on human hemodynamics. , 1999, The American journal of cardiology.

[10]  D. Webb,et al.  Sildenafil citrate and blood-pressure-lowering drugs: results of drug interaction studies with an organic nitrate and a calcium antagonist. , 1999, The American journal of cardiology.

[11]  R. Cannon Role of nitric oxide in cardiovascular disease: focus on the endothelium. , 1998, Clinical chemistry.

[12]  A. Morales,et al.  Clinical safety of oral sildenafil citrate (VIAGRATM) in the treatment of erectile dysfunction , 1998, International Journal of Impotence Research.

[13]  S. Ballard,et al.  Effects of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes. , 1998, The Journal of urology.

[14]  R. Feldman,et al.  Sildenafil in the treatment of erectile dysfunction: Efficacy in patients taking concomitant antihypertensive therapy , 1998 .

[15]  J. Panza Endothelial Dysfunction in Essential Hypertension , 1997, Clinical cardiology.

[16]  R. Morgan,et al.  Does severity of ischemic coronary disease correlate with erectile function? , 1997, International Journal of Impotence Research.

[17]  G. Muirhead,et al.  Sildenafil: an orally active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction. , 1996, International journal of impotence research.

[18]  J. Beavo,et al.  Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms. , 1995, Physiological reviews.

[19]  P Whelton,et al.  Prevalence of hypertension in the US adult population. Results from the Third National Health and Nutrition Examination Survey, 1988-1991. , 1995, Hypertension.

[20]  A. Burnett Role of nitric oxide in the physiology of erection. , 1995, Biology of reproduction.

[21]  L. Prisant,et al.  Sexual dysfunction with antihypertensive drugs. , 1994, Archives of internal medicine.

[22]  L. Ignarro,et al.  Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic, noncholinergic neurotransmission. , 1992, The New England journal of medicine.

[23]  J. Clive,et al.  Sexual symptoms in hypertensive patients. A clinical trial of antihypertensive medications. , 1988, Archives of internal medicine.

[24]  A. Riley,et al.  The Prevalence of Sexual Dysfunction in Male and Female Hypertensive Patients , 1987 .

[25]  N. Borhani,et al.  Long-term surveillance for adverse effects of antihypertensive drugs. , 1985, JAMA.

[26]  P. Brennan,et al.  Effects of diuretic and beta-blocker therapy in the Medical Research Council Trial. , 1984, American Journal of Medicine.

[27]  F. Nuttall,et al.  Impotence in medical clinic outpatients. , 1983, JAMA.

[28]  C. Dollery,et al.  Change in symptoms of hypertensive patients after referral to hospital clinic. , 1976, British heart journal.

[29]  R. Kloner,et al.  Effect of sildenafil in patients with erectile dysfunction taking antihypertensive therapy. Sildenafil Study Group. , 2001, American journal of hypertension.

[30]  I. Goldstein,et al.  Oral sildenafil in the treatment of erectile dysfunction. Sildenafil Study Group. , 1998, The New England journal of medicine.

[31]  S. Kaul,et al.  ACC/AHA expert consensus document. Use of sildenafil (Viagra) in patients with cardiovascular disease. American College of Cardiology/American Heart Association. , 1999, Journal of the American College of Cardiology.

[32]  C. Lewis,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) , 1997, Hypertension.

[33]  H A Feldman,et al.  Impotence and its medical and psychosocial correlates: results of the Massachusetts Male Aging Study. , 1994, The Journal of urology.

[34]  J. Baker,et al.  Side-effects of antihypertensive treatment: a placebo-controlled study. , 1978, Clinical science and molecular medicine. Supplement.