HOME SUBSCRIPTIONS CURRENT ISSUE PAST ISSUES CARDIOSOURCE SEARCH HELP FEEDBACK		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Figures Only Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Webb, D. J. Articles by Dinsmore, W. W. Search for Related Content PubMed PubMed Citation Articles by Webb, D. J. Articles by Dinsmore, W. W.

CLINICAL STUDIES

Sildenafil citrate potentiates the hypotensive effects of nitric oxide donor drugs in male patients with stable angina

David J. Webb, MD^*, Gary J. Muirhead, BSc, Maria Wulff, BSc, J. Andrew Sutton, MD, Roberto Levi, MD and Wallace W. Dinsmore, MD^||

^* Department of Medicine, The University of Edinburgh, Western General Hospital, Edinburgh, United Kingdom
Pfizer Central Research, Sandwich, Kent, United Kingdom
Guildford Clinical Pharmacology Unit, Royal Surrey County Hospital, Guildford, United Kingdom
Department of Pharmacology, Cornell University, Weill Medical College, New York, New York, USA
^|| Department of Genitourinary Medicine, The Royal Victoria Hospital, Belfast, United Kingdom

Manuscript received June 29, 1999; revised manuscript received January 18, 2000, accepted March 24, 2000.

Reprint requests and correspondence: David J. Webb, University Department of Medical Sciences, The University of Edinburgh, Western General Hospital, Edinburgh EH4 2XU, United Kingdom
D.J.Webb{at}ed.ac.uk

OBJECTIVE

We sought to study the effects of a single oral dose of sildenafil citrate (50 mg) on blood pressure (BP) in men taking the nitric oxide (NO) donor drugs isosorbide mononitrate (ISMN) or glyceryl trinitrate (GTN) for stable angina.

BACKGROUND

Sildenafil, a selective phosphodiesterase type 5 inhibitor, is an orally effective treatment for erectile dysfunction. The presence of phosphodiesterases in the vasculature suggests the possibility of an interaction between sildenafil and NO donor drugs.

METHODS

Two double-blind, placebo-controlled, randomized, two-way crossover trials were undertaken. Sixteen male patients received oral ISMN (20 mg twice a day) for five to seven days before their dose of sildenafil or placebo and continued receiving ISMN daily until administration of the alternate drug seven days later. For the second study, 15 male patients received sublingual GTN (500 µg) 1 h after sildenafil or placebo on each of two study days, which were seven days apart. Sitting or standing BP was measured before and for 6 h after the administration of the study drug.

RESULTS

The effects of sildenafil plus ISMN on BP (standing mean maximum reductions from baseline in systolic/diastolic BP, –52/–29 mm Hg) were greater than the effects of placebo plus ISMN on BP (–25/–15 mm Hg; p < 0.001). Sildenafil plus GTN also resulted in greater sitting mean maximum reductions from baseline in systolic/diastolic BP (–36/–21 mm Hg) compared with placebo plus GTN (–26/–12 mm Hg; p < 0.01).

CONCLUSIONS

Coadministration of sildenafil with ISMN or GTN produced significantly greater reductions in BP than ISMN or GTN alone. Based on these data, sildenafil should not be administered to patients taking nitrates.

Abbreviations and Acronyms   AUEC = area under the effect curve   BP = blood pressure   cGMP = cyclic guanosine monophosphate   ED = erectile dysfunction   GTN = glyceryl trinitrate   HR = heart rate   ISMN = isosorbide mononitrate   NO = nitric oxide   PDE5 = phosphodiesterase type 5

This article has been cited by other articles:

				M. R. Wilkins, J. Wharton, F. Grimminger, and H. A. Ghofrani Phosphodiesterase inhibitors for the treatment of pulmonary hypertension Eur. Respir. J., July 1, 2008; 32(1): 198 - 209. [Abstract] [Full Text] [PDF]

				J. J. Oliver, V. P. Melville, and D. J. Webb Effect of Regular Phosphodiesterase Type 5 Inhibition in Hypertension Hypertension, October 1, 2006; 48(4): 622 - 627. [Abstract] [Full Text] [PDF]

				C. E. Teixeira, F. B. M. Priviero, and R. C. Webb Differential Effects of the Phosphodiesterase Type 5 Inhibitors Sildenafil, Vardenafil, and Tadalafil in Rat Aorta J. Pharmacol. Exp. Ther., February 1, 2006; 316(2): 654 - 661. [Abstract] [Full Text] [PDF]

				S D Robinson, C A Ludlam, N A Boon, and D E Newby Phosphodiesterase type 5 inhibition does not reverse endothelial dysfunction in patients with coronary heart disease Heart, February 1, 2006; 92(2): 170 - 176. [Abstract] [Full Text] [PDF]

				F. Mahler and I. Baumgartner More Potential for Sildenafil Than Potency Circulation, November 8, 2005; 112(19): 2894 - 2895. [Full Text] [PDF]

				M. Gupta, A. Kovar, and B. Meibohm The Clinical Pharmacokinetics of Phosphodiesterase-5 Inhibitors for Erectile Dysfunction J. Clin. Pharmacol., September 1, 2005; 45(9): 987 - 1003. [Abstract] [Full Text] [PDF]

				M. Kekilli, Y. Beyazit, T. Purnak, S. Dogan, and E. Atalar Acute Myocardial Infarction After Sildenafil Citrate Ingestion Ann. Pharmacother., July 1, 2005; 39(7): 1362 - 1364. [Abstract] [Full Text] [PDF]

				S. M Setter, J. L Iltz, J. E Fincham, R K. Campbell, and D. E Baker Phosphodiesterase 5 Inhibitors for Erectile Dysfunction Ann. Pharmacother., July 1, 2005; 39(7): 1286 - 1295. [Abstract] [Full Text] [PDF]

				R. A. Kloner Cardiovascular Effects of the 3 Phosphodiesterase-5 Inhibitors Approved for the Treatment of Erectile Dysfunction Circulation, November 9, 2004; 110(19): 3149 - 3155. [Full Text] [PDF]

				R. A. Kloner, A. M. Hutter, J. T. Emmick, M. I. Mitchell, J. Denne, and G. Jackson Reply J. Am. Coll. Cardiol., June 2, 2004; 43(11): 2150 - 2151. [Full Text] [PDF]

				R. F. DeBusk Sexual Activity in Patients With Angina JAMA, December 17, 2003; 290(23): 3129 - 3132. [Full Text] [PDF]

				R. A. Kloner, A. M. Hutter, J. T. Emmick, M. I. Mitchell, J. Denne, and G. Jackson Time course of the interaction between tadalafil and nitrates J. Am. Coll. Cardiol., November 19, 2003; 42(10): 1855 - 1860. [Abstract] [Full Text] [PDF]

				J.T. Emmick, S.R. Stuewe, and M. Mitchell Overview of the cardiovascular effects of tadalafil Eur. Heart J. Suppl., December 1, 2002; 4(suppl_H): H32 - H47. [Abstract] [PDF]

				U. Ikeda, Y. Maeda, K. Yamamoto, and K. Shimada C-Reactive protein augments inducible nitric oxide synthase expression in cytokine-stimulated cardiac myocytes Cardiovasc Res, October 1, 2002; 56(1): 86 - 92. [Abstract] [Full Text] [PDF]

				G. Jackson Cardiovascular safety in erectile dysfunction treatment The British Journal of Diabetes & Vascular Disease, July 1, 2002; 2(4): 301 - 304. [Abstract] [PDF]

				K. Y. Yoo, H. S. Kim, J.-D. Moon, and J. Lee Sildenafil (Viagra(R)) Augments Sodium Nitroprusside-Induced But Not Nitroglycerin-Induced Hypotension in Dogs Anesth. Analg., June 1, 2002; 94(6): 1505 - 1509. [Abstract] [Full Text] [PDF]

				A. M. Arruda-Olson, D. W. Mahoney, A. Nehra, M. Leckel, and P. A. Pellikka Cardiovascular Effects of Sildenafil During Exercise in Men With Known or Probable Coronary Artery Disease: A Randomized Crossover Trial JAMA, February 13, 2002; 287(6): 719 - 725. [Abstract] [Full Text] [PDF]

				L. J. Ignarro, C. Napoli, and J. Loscalzo Nitric Oxide Donors and Cardiovascular Agents Modulating the Bioactivity of Nitric Oxide: An Overview Circ. Res., January 11, 2002; 90(1): 21 - 28. [Abstract] [Full Text] [PDF]

				J. D. Parker and T. Gori Tolerance to the Organic Nitrates: New Ideas, New Mechanisms, Continued Mystery Circulation, November 6, 2001; 104(19): 2263 - 2265. [Full Text] [PDF]

				M. Swissa, T. Ohara, M.-H. Lee, S. Kaul, P. K. Shah, H. Hayashi, P.-S. Chen, and H. S. Karagueuzian Sildenafil-nitric oxide donor combination promotes ventricular tachyarrhythmias in the swine right ventricle Am J Physiol Heart Circ Physiol, May 1, 2002; 282(5): H1787 - H1792. [Abstract] [Full Text] [PDF]