Wechselwirkungen zwischen Sildenafil und Antihypertensiva - Was ist gesichert?

Zusammenfassung

Die arterielle Hypertonie ist ein bedeutender Risikofaktor für das Auftreten einer erektilen Dysfunktion (ED). Dementsprechend besteht eine hohe Koinzidenz zwischen arterieller Hypertonie und ED. Die oral-medikamentöse Therapie der ED mit Sildenafil (Viagra^®) ist sowohl bei behandelten als auch bei nicht behandelten Hypertonikern wirksam. Die wichtigsten unerwünschten Wirkungen der Sildenafil-Therapie (Kopfschmerzen, Gesichtsrötung, Hypotension) beruhen auf moderaten vasodilatierenden Eigenschaften. Bei gleichzeitiger Einnahme von Sildenafil und organischen Nitraten können sich die blutdrucksenkenden Effekte potenzieren und zu lebensbedrohlichen Blutdruckabfällen führen. Deshalb ist diese Kombination absolut kontraindiziert. Demgegenüber führt die gleichzeitige Gabe von Sildenafil und Antihypertensiva unterschiedlicher Substanzklassen (β-Blocker, α-Blocker, Diuretika, ACE-Hemmer, Ca-Antagonisten) zwar zu additiven, nicht jedoch zu sich potenzierenden blutdrucksenkenden Effekten. Daher ist bei dieser Kombination weder mit bedrohlichen und klinisch relevanten Blutdruckabfällen noch mit einer Zunahme unerwünschter Wirkungen zu rechnen. Dies gilt auch für eine antihypertensive Kombinationstherapie mit zwei oder mehr Antihypertensiva.

Abstract

Hypertension is an important risk factor for erectile dysfunction (ED). Consequently, there is a high coincidence between hypertension and ED. Oral sildenafil (Viagra^®) is an effective treatment for ED in patients with treated or untreated hypertension. The most common adverse events of sildenafil (headache, flushing, hypotension) result from its moderate vasodilating properties. The concomitant use of sildenafil and organic nitrates is contraindicated because it may lead to a potentiation of the decreases in blood pressure and thus cause life-threatening hypotension. In contrast, the concomitant use of sildenafil and different classes of antihypertensive agents (β-blockers, α-blockers, diuretics, ACE inhibitors, calcium antagonists) may lead to additive but not to potentiating blood pressure decreases. Thus, this combination is unlikely to cause clinically significant hypotension or an increased incidence of adverse events. Sildenafil is an effective and well-tolerated treatment for ED in patients taking concomitant antihypertensive medication, including those on multidrug regimens.

Literatur

• 1 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 30
• 2 Andersson K -E, Wagner G. Physiology of penile erection.  Physiol Rev. 1995;  75 191-236
• 3 Ballard S A, Gingell C J, Tang K, Turner L A, Price M E, Naylor A M. Effects of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes.  Urol. 1998;  159 2164-2171
• 4 Bauer G E, Baker J, Hunyor S N, Marshall P. Side-effects of antihypertensive treatment: A placebo-controlled study.  Clin Sci Mol Med. 1978;  55 341s-344s
• 5 Beavo J A. Cyclic nucleotide phosphodiesterases: Functional implications of multiple isoforms.  Physiol Rev. 1995;  75 725-748
• 6 Benet A E, Melman A. The epidemiology of erectile dysfunction.  Urol Clin North Am. 1995;  22 699-709
• 7 Boolell M, Allen M J, Ballard S A. et al . Sildenafil: An oraly active type 5 cyclic GMP-specific phosphodiesterase inhibitor for the treatment of penile erectile dysfunction.  Int J Impot Res. 1996;  8 47-52
• 8 Broeders M AW, Doevendans P A, Bekkers B CAM, Bronsaer R, van Gorsel E, Heemskerk J WM, oude Egbringk M AG, van Breda E, Reneman R S, van der Zee R. Nebivolol: A third-generaton b-blocker that augments vascular nitric oxide release. Endothelial β ₂ -adrenergic receptor-mediated nitric oxide production.  Circulation. 2000;  102 677-684
• 9 Bulpitt C J, Dollery C T, Carne S. Changes in symptoms of hypertensive patients after referral to hospital clinic.  Brit Heart J. 1976;  38 121-128
• 10 Burnett A L. The role of nitric oxide in the physiology of erection.  Biol Reprod. 1995;  52 485-490
• 11 Burt V L, Whelton P, Roccella E J, Brown C, Cutler J A, Higgins M. et al . Prevalence of hypertension in the US adult population. Results from the Third National Health and Nutrition Examination Survey, 1988 - 1991.  Hypertension. 1995;  25 305-313
• 12 Cannon R OI. Role of nitric oxide in cardiovascular disease: Focus on the endothelium.  Clin Chem. 1998;  44 1809-1819
• 13 Cheitlin M D, Hutter A M, Brindis R G, Ganz P, Kaul S, Russell R O, Zusman R M. ACC/AHA Expert Consensus Document: Use of Sildenafil (Viagra) in patients with cardiovascular disease.  Circulation. 1999;  99 168-177
• 14 Cremers B, Scheler M, Maack C, Gröschel A, Schäfers H J, Böhm M. Einfluss von Sildenafil (Viagra) auf die kardiale Kontraktilität und den Gefäßtonus menschlicher Arteriae mammariae und Venae saphenae magnae.  J Kardiol . 2001;  90 (Suppl 2) 208, (Abstract)
• 15 Croog S H, Levine S, Sudilovsky A, Baume R M, Clive J. Sexual symptoms in hypertensive patients: A clinical trial of antihypertensive medications.  Arch Intern Med. 1988;  148 788-794
• 16 Curb J D, Borhani N O, Blaszkowski T P, Zimbaldi N, Fotiu S, Williams W. Long-term surveillance for adverse effects of antihypertensive drugs.  JAMA. 1985;  253 3263-3268
• 17 Dawes M, Brett S E, Chowienczyk P J, Mant T GK, Ritter J M. The vasodilator action of nebivolol in forearm vasculature of subjects with essential hypertension.  Br J Clin Pharmacol. 1999;  48 460-461
• 18 Dorsch A, Erdmann E, Hempelmann G, Kupper W, Maisch B, Maurer G. Therapie-Empfehlung »VIAGRA und NO-Donatoren«; Konsensus-Konferenz, European Society of Cardiology, Wien 1998.  Herz/Kreislauf. 1998;  30 11
• 19 Feldman H A, Goldstein I, Hatzichristou D G, Krane R J, McKinkey J B. Impotence and its medical and psychological correlates: Results of the Massachusetts Male Aging Study.  J Urol. 1994;  151 54-61
• 20 Feldman R. Sildenafil in the treatment of erectile dysfunction: Efficacy in patients taking concomitant antihypertensive therapy.  Am J Hypertension. 1998;  11 10A
• 21 Ferro C J, Webb D J. Endothelial dysfunction and hypertension.  Drugs. 1997;  53 (Suppl 1) 30-41
• 22 Goldstein I, Lue T F, Padma-Nathan H, Rosen R C, Steers W D, Wicker P A, . for the Sildenafil Study Group . Oral sildenafil in the treatment of erectile dysfunction.  N Engl J Med. 1998;  338 1397-1403
• 23 Greenberg G, Brennan P J, Miall W E. Effects of diuretic and beta-blocker therapy in the medical research council trial.  Am J Med. 1984;  76 (Suppl 2A) 45-51
• 24 Greenstein A, Chen J, Miller H, Matzkin H, Villa Y, Braf Z. Does sevirity of ischemic coronary disease correlate with erectile function?.  Int J Impot Res. 1997;  9 123
• 25 Grimm R H, Grandits G A, Prineas R J, McDonald R H, Lewis C E, Flack J M, Yunis C, Svedsen K, Liebson P R, Elmer P J. 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
• 26 Herrmann H C, Chang G, Klugherz B D, Mahoney P D. Hemodynamic effects of sildenafil in men with severe coronary artery disease.  N Engl J Med. 2000;  342 1622-1626
• 27 Ishizuka N, Saito K, Akima M, Matsubara S, Saito M. Hypotensive interaction of sildenafil and nicorandil in rats through the cGMP pathway but not by KATP channel activation.  Jpn J Pharmacol. 2000;  316 316-324
• 28 Jackson G, Benjamin N, Jackson N, Allen M J. Effects of sildenafil citrate on human hemodynamics.  Am J Cardiol. 1999;  83 (Suppl 5A) 13C-20C
• 29 Kloner R A, Brown M, Prisant L M, Collins M. for the Sildenafil Study Group . Effect of sildenafil in patients with erectile dysfunction taking antihypertensive therapy.  Am J Hypertens. 2001;  14 70-73
• 30 Lepore J J, Pereira N, Maroo A, Ginns L, Bigatello L M, Dec, GW, Rubin R, Zapol W M, Bloch K D, Semigran M J. Sildenafil is a pulmonary vasodilator which augments and prolongs vasodilatation by inhaled nitric oxide in patients with pulmonary hypertension.  Circulation. 1999;  100 (Suppl 1) 1240, (Abstract)
• 31 Morales A, Gingell C, Collins M, Wicker P A, Osterloh I H. Clinical safety of oral sildenafil citrate (Viagra) in the treatment of erectile dysfunction.  Int J Impot Res. 1998;  10 69-74
• 32 NIH consensus development panel on impotence . Impotence.  JAMA 2. 1993;  70 83-90
• 33 Panza J A. Endothelial dysfunction in essential hypertension.  Clin Cardiol. 1997;  20 26-33
• 34 Parenti A, Filippi S, Amerini S, Granger H J, Fazzini A, Ledda F. Inositol phosphate metabolism and nitric-oxide synthase activity in endothelial cells are involved in the vasorelaxant activity of nebivolol.  J Pharmacol Exp Ther. 2000;  292 698-703
• 35 Parums D V, Charleton R, Johnson N, Cindrova T, Skepper J, Phillips S, Ridden J, Burslem F. Immunohistochemical (ICH), in situ hybridisation (ISH) and biochemical characterisation of phosphodiesterase type 5 (PDE5) in normal and ischeamic human cardiac tissue.  Eur Heart J . 2000;  21 (Suppl) 616, (Abstract)
• 36 Phillips B G, Kato M, Pesek C A, Winnicki M, Narkiewicz K, Davison D, Somers V K. Sympathetic activation by sildenafil.  Circulation. 2000;  102 3068-3073
• 37 Prisant L M, Carr A A, Bottini P B, Solursh D S, Solursh L P. Sexual dysfunction with antihypertensive drugs.  Arch Intern Med. 1994;  154 730-736
• 38 Rajfer J, Aronson W J, Bush P A, Dorey F J, Ignarro L J. Nitric oxide as a mediator of relaxation of the corpus cavernosum in response to nonadrenergic, noncholigernic neurotransmission.  N Engl J Med. 1992;  326 90-94
• 39 Rerkpattanapipat P, Stanek M S, Kotler M N. Sex and the heart: What is the role of the cardiologist?.  Eur Heart J. 2001;  22 201-208
• 40 Riley A J, Steiner J A, Cooper R, McPherson C K. The prevalence of sexual dysfunction in male and female hypertensive patients.  Sex Marital Ther. 1987;  2 131-138
• 41 Rolf C, Nieschlag E. Sildenafil (Viagra) bei erektiler Dysfunktion. Effektive Behandlung mit beachtenswerten Wechselwirkungen.  Dtsch Med Wochenschr. 1998;  123 1356-1361
• 42 Slag M F, Morley J E, Elson M K, Trence D L, Nelson C J, Nelson A E. et al . Impotence in medical clinic outpatients.  JAMA. 1983;  249 1736-1740
• 43 Sperling H, Michel M C. Sildenafil.  Dtsch Med Wochenschr. 1999;  124 151-153
• 44 Webb D J, Freestone S, Allen M J, Muirhead G J. 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 (Suppl 5A) 21C-28C
• 45 Zusman R M, Morales A, Glasser D B, Osterloh I H. Overall cardiovascular profile of sildenafil citrate.  Am J Cardiol. 1999;  83 35C-44C
• 46 Zusman R M, Prisant L M, Brown M J. for the Sildenafil Study Group . Effect of sildenafil citrate on blood pressure and heart rate in men with erectile dysfunction taking concomitant antihypertensive medication.  J Hypertens. 2000;  18 1865-1869

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