The effects of chronic phosphodiesterase-5 inhibitor use on different organ systems

International Journal of Impotence Research

Volumn 19, Issue 2, 2007, Pages 139-148

  Schwarz, E R ^a,b   Kapur, V ^a   Rodriguez, J ^a   Rastogi, S ^a   Rosanio, S ^a  

^a CEDARS SINAI MEDICAL CENTER   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Erectile dysfunction; Heart disease; PDE 5 inhibitor; Side effects; Therapy

Indexed keywords

NITROPRUSSIDE SODIUM; PHOSPHODIESTERASE V; PHOSPHODIESTERASE V INHIBITOR; PLACEBO; PROSTACYCLIN; PROSTAGLANDIN INHIBITOR; SILDENAFIL; TADALAFIL; VARDENAFIL;

ARTERY RESISTANCE; BLOOD PRESSURE REGULATION; BLURRED VISION; CLINICAL TRIAL; CORONARY ARTERY BLOOD FLOW; DRUG APPROVAL; DRUG BIOAVAILABILITY; DRUG COST; DRUG EFFECT; DRUG EFFICACY; DRUG EXCRETION; DRUG INDUCED HEADACHE; DRUG MECHANISM; ERECTILE DYSFUNCTION; EYE; FOOD AND DRUG ADMINISTRATION; GASTROINTESTINAL TRACT; HEART FAILURE; HEART HEMODYNAMICS; HEART INDEX; HEART MUSCLE CONTRACTILITY; HUMAN; ISCHEMIC OPTIC NEUROPATHY; LONG TERM CARE; LUNG ARTERY PRESSURE; NONHUMAN; PRIORITY JOURNAL; PULMONARY HYPERTENSION; RECOMMENDED DRUG DOSE; RETINA ARTERY OCCLUSION; REVIEW; RISK BENEFIT ANALYSIS; SMOOTH MUSCLE RELAXATION; THROMBOCYTE; VASODILATATION; VISUAL IMPAIRMENT;

3',5'-CYCLIC-GMP PHOSPHODIESTERASE; AGE FACTORS; ANIMALS; BLOOD PLATELETS; CEREBROVASCULAR CIRCULATION; GASTROINTESTINAL TRACT; HEART; HUMANS; IMPOTENCE; LUNG; MALE; MYOCARDIAL ISCHEMIA; PHOSPHODIESTERASE INHIBITORS;

EID: 33847367689     PISSN: 09559930     EISSN: 14765489     Source Type: Journal    
DOI: 10.1038/sj.ijir.3901491     Document Type: Review

References (82)

1. Beavo JA. Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms. Physiol Rev 1995; 75: 725-748.
2. Reffelmann T, Kloner RA. Therapeutic potential of phosphodiesterase 5 inhibition for cardiovascular disease. Circulation 2003; 108: 239-244.
3. Wallis RM, Corbin JD, Francis SH, Ellis P. Tissue distribution of phosphodiesterase families and the effect 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: 3C-12C.
4. Senzaki H, Smith CJ, Juang GJ, Isoda T, Mayer SP, Ohler A et al. Cardiac phosphodiesterase 5 (cGMP-specific) modulates adrenergic signaling in vivo, and is down-regulated in heart failure. FASEB J 2001; 15: 1718-1726.
5. Gresser U, Gleiter CH. Erectile dysfunction: comparison of efficacy and side effects of the PDE-5i sildenafil, vardenafil and tadalafil: review of the literature. Eur J Med Res 2002; 7: 435-446.
6. Corbin JD, Francis SH, Webb DJ. Phosphodiesterase Type 5 as a pharmacological target in erectile dysfunction. Urology 2002; 60: 4-11.
7. Mikhail GW, Prasad SK, Li W, Rogers P, Chester AH, Bayne S et al. Clinical and haemodynamic effects of sildenafil in pulmonary hypertension: acute and mid-term effects. Eur Heart J 2004; 25: 431-436.
8. Jackson G, Benjamin N, Jackson N, Allen MJ. Effects of sildenafil citrate on human hemodynamics. Am J Cardiol 1999; 83: 13C-20C.
9. Traverse JH, Chen YJ, Du R, Bache RJ. Cyclic nucleotide phosphodiesterase type 5 activity limits blood flow to hypoperfused myocardium during exercise. Circulation 2000; 102: 2997-3002.
10. Ludmer P, Selwyn A, Shook TL, Wayne RR, Mudge GH, Alexander RW et al. Paradoxical vasoconstriction induced by acetylcholine in atherosclerotic coronary arteries. N Eng J Med 1986; 315: 1046-1051.
11. Bossaller C, Habib GB, Yamamoto H, Williams C, Wells S, Henry PD. Impaired muscarinic endothelium-dependent relaxation and cyclic guanosine-5′-monophosphate formation in atherosclerotic human coronary artery and rabbit aorta. J Clin Invest 1987; 79: 170-182.
12. Chester AH, O'Neil GS, Moncada S, Tadjkarimi S, Yacoub MH. Low basal and stimulated release of nitric oxide in atherosclerotic epicardial coronary arteries. Lancet 1990; 336: 897-900.
13. Nabel EG, Selwyn AP, Ganz P. Large coronary arteries in humans are responsive to changing blood flow: an endothelium-dependent mechanism that fails in patients with atherosclerosis. J Am Coll Cardiol 1990; 16: 349-356.
14. Kaiser FE, Viosca SP, Morley JE, Moordian AD, Davis SS, Korenman SG. Impotence and aging: clinical and hormonal factors. J Amer Geriatr Soc 1988; 36: 511-519.
15. Seftel AD, Sun P, Swindle R. The prevalence of hypertension, hyperlipidemia, diabetes mellitus and depression in men with erectile dysfunction. J Urol 2004; 171: 2341-2345.
16. Shabsigh R, Fishman IJ, Schum C, Dunn JK. Cigarette smoking and other vascular risk factors in vasculogenic impotence. Urology 1991; 38: 227-232.
17. Derby CA, Mohr BA, Goldstein I, Feldman HA, Johannes CB, Mckinlay JB. Modifiable risk factors and erectile dysfunction: can lifestyle changes modify risk? Urology 2000; 56: 302-306.
18. Billups KL, Bank AJ, Padma-Nathan H, Katz S, Williams R. Erectile dysfunction is a marker for cardiovascular disease: Results of the minority health institute expert advisory panel. J Sex Med 2005; 2: 40-52.
19. Burnett AL. Role of nitric oxide in the physiology of erection. Biol Reprod 1995; 52: 485.
20. Andersson KE, Wagner G. Physiology of penile erection. Physiol Rev 1995; 75: 191-236.
21. Medina P, Segarra G, Vila JM, Domenech C, Martinez-Leon JB, Lluch S. Effects of sildenafil on human penile blood vessels. Urology 2000; 56: 539-543.
22. Ballard SA, Gingell CJ, Tang K, Turner LA, Price ME, Naylor MA. Effects of sildenafil on the relaxation of human corpus cavernosum tissue in vitro and on the activities of cyclic nucleotide phosphodiesterase isozymes. J Urol 1998; 159: 2164-2171.
23. Wallis RM, Corbin JD, Francis SH, Ellis P. 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: 3C-12C.
24. Hyland R, Roe EG, Jones BC, Smith DA. Identification of the cytochrome P450 enzymes involved in the N-demethylation of sildenafil. Br J Clin Pharmacol 2001; 51: 239-248.
25. Muirhead GJ, Faulkner S, Harness JA, Taubel J. The effects of steady-state erythromycin and azithromycin on the pharmacokinetics of sildenafil in healthy volunteers. Br J Clin Pharmacol 2002; 53: 37S-43S.
26. Wilner K, Laboy L, LeBel M. The effects of cimetidine and antacid on the pharmacokinetic profile of sildenafil citrate in healthy male volunteers. Br J Clin Pharmacol 2002; 53: 31S-36S.
27. Hellstrom W, Gittelman M, Karlin G, Segerson T, Thibonnier M, Taylor T et al. Vardenafil for treatment of men with erectile dysfunction: efficacy and safety in a randomized double blind placebo controlled trial. J Androl 2002; 23: 763-771.
28. Brock G, McMahon CG, Chen KK, Costigan T, Shen W, Watkins V et al. Efficacy and safety of tadalafil in the treatment of erectile dysfunction: results of an integrated analysis. J Urol 2002; 168: 1332-1336.
29. Padma-Nathan H, Stecher VJ, Sweeny YM, Orazem J, Tseng LJ, Deriesthal H. Minimal time to successful intercourse after sildenafil citrate. Urology 2003; 62: 400-403.
30. Sénz de Tejada I, Anglin G, Knight JR, Emmick JT. Effects of tadalafil on erectile dysfunction in men with diabetes. Diabetes Care 2002; 25: 2159-2164.
31. Behrend L, Vibe-Petersen J, Perrild H. Sildenafil in the treatment of erectile dysfunction in men with diabetes: demand, efficacy and patient satisfaction. Int J Impot Res 2005; 17: 264-269.
32. Goldstein I, Lue TF, Padma-Nathan H, Rosen RC, Steers WD, Wicker PA, for the Sildenafil Study Group. Oral sildenafil in the treatment of erectile dysfunction. N Engl J Med 1998; 338: 1397-1404.
33. Steidle C, Feldman R, Lettieri J, Agarwal V, Segerson T. Pharmacokinetics of vardenafil (a new selective PDE5 inhibitor) in the elderly and subgroup data on efficacy and safety in elderly patients with erectile dysfunction. Annual American Geriatrics Society Meeting, May 9-13, 2001.
34. Conti CR, Pepine CJ, Sweeney M. Efficacy and safety of sildenafil citrate in the treatment of erectile dysfunction in patients with ischemic heart disease. Am J Cardiol 1999; 83: 29C-34C.
35. Zapol WM, Rimar S, Grillis N, Marletta M, Bosken CH. Nitric oxide and the lung. Am J Respir Crit Care Med 1994; 149: 1375-1380.
36. Sanchez LS, de la Monte SM, Filippov G, Jones RC, Zapol WM, Bloch KD. Cyclic-GMP-binding, cyclic-GMP-specific phosphodiesterase (PDE5) gene expression is regulated during rat pulmonary development. Pediatr Res 1998; 43: 163-168.
37. Guazzi M, Tumminello G, Di Marco F, Fiorentini C, Guazzi MD. The effects of phosphodiesterase-5 inhibition with sildenafil on pulmonary hemodynamics and diffusion capacity, exercise ventilatory efficiency, and oxygen uptake kinetics in chronic heart failure. J Am Coll Cardiol 2004; 44: 2339-2348.
38. Lepore JJ, Maroo A, Pereira NL, Ginns LC, Dec GW, Zapol WM et al. Effect of sildenafil on the acute pulmonary vasodilator response to inhaled nitric oxide in adults with primary pulmonary hypertension. Am J Cardiol 2002; 90: 677-680.
39. Michelakis E, Tymchak W, Lien D, Webster L, Hashimoto K, Archer S. Oral sildenafil is an effective and specific pulmonary vasodilator in patients with pulmonary arterial hypertension: comparison with inhaled nitric oxide. Circulation 2002; 105: 2398-2403.
40. Palmieri EA, Affuso F, Fazio S, Lembo D. Tadalafil in primary pulmonary arterial hypertension. Ann Intern Med 2004; 141: 743-744.
41. Ghofrani HA, Schermuly RT, Rose F, Wiedemann R, Kohstall MG, Kreckel A et al. Sildenafil for long-term treatment of nonoperable chronic thromboembolic pulmonary hypertension. Am J Respir Crit Care Med 2003; 167: 1139-1141.
42. Humbert M, Sitbon O, Simonneau G. Treatment of pulmonary arterial hypertension. N Engl J Med 2004; 351: 1425-1436.
43. Michelakis ED, Tymchak W, Noga M, Webster L, Wu XC, Lien D et al. Long-term treatment with oral sildenafil is safe and improves functional capacity and hemodynamics in patients with pulmonary arterial hypertension. Circulation 2003; 108: 2066-2069.
44. Corbin J, Rannels S, Neal D, Chang P, Grimes K, Beasley A et al. Sildenafil citrate does not affect cardiac contractility in human or dog heart. Curr Med Res Opin 2003; 19: 747-752.
45. Herrmann HC, Chang G, Klugherz BD, Mahoney PD. Hemodynamic effects of sildenafil in men with severe coronary artery disease. New Engl J Med 2000; 342: 1662-1666.
46. Barry AB, Vojtech M, Tricia M, Patricia F, David AK. Sildenafil Inhibits-adrenergic-stimulated cardiac contractility in humans. Circulation 2005; 112: 2642-2649.
47. Mahmud A, Hennessy M, Feely J. Effect of sildenafil on blood pressure and arterial wave reflection in treated hypertensive men. J Hum Hypertens 2001; 15: 707-713.
48. Emmick JT, Stuewe SR, Mitchell M. Overview of the cardiovascular effects of tadalafil. Eur Heart J 2002; 4: H32-H37.
49. Pomara G, Morelli G, Pomara S, Taddei S, Ghiadoni L, Dinelli N et al. Cardiovascular parameter changes in patients with erectile dysfunction using PDE-5i: a study with sildenafil and vardenafil. J Androl 2004; 25: 625-629.
50. Bocchi EA, Guimaraes G, Mocelin A, Bacal F, Bellotti G, Ramires JF. Sildenafil effects on exercise, neurohormonal activation, and erectile dysfunction in congestive heart failure: a double-blind, placebo-controlled, randomized study followed by a prospective treatment for erectile dysfunction. Circulation 2002; 106: 1097-1103.
51. Webster L, Michelakis E, Davis T, Archer S. Use of sildenafil for safe improvement of erectile function and quality of life in men with New York Heart Association classes II and III congestive heart failure. Arch Intern Med 2004; 164: 514-520.
52. Katz SD. Potential role of type 5 phosphodiesterase inhibition in the treatment of congestive heart failure. Congest Heart Failure 2003; 9: 9-15.
53. Milan DP, Stuart DK. Phosphodiesterase 5 inhibition in chronic heart failure and pulmonary hypertension. Am J Cardiol 2005; 96: 47M-51M.
54. Dunkern TR, Hatzelmann A. The effect of sildenafil on human platelet secretory function is controlled by a complex interplay between phosphodiesterases 2, 3 and 5. Cellular Signalling 2005; 17: 331-339.
55. Cheitlin M, Hutter Jr AM, Brindis RG, Ganz P, Kaul S, Russell Jr RO et al. ACC/AHA expert consensus document. Use of sildenafil (Viagra) in patients with cardiovascular disease. American College of Cardiology/American Heart Association. J Am Coll Cardiol 1999; 33: 273-282.
56. Araujo PV, Clemente CM, da Graca JR, Rola FH, de Oliveira RB, dos Santos AA et al. Inhibitory effect of sildenafil on rat duodenal contractility in vitro: putative cGMP involvement. Clin Exp Pharmacol Physiol 2005; 32: 191-195.
57. Zhang X, Tack J, Janssens J, Sifrim DA. Effect of sildenafil, a phosphodiesterase-5i, on oesophageal peristalsis and lower oesophageal sphincter function in cats. Neurogastroenterol Motil 2001; 13: 325-331.
58. Sarnelli G, Sifrim D, Janssens J, Tack J. Influence of sildenafil on gastric sensorimotor function in humans. Am J Physiol Gastrointest Liver Physiol 2004; 287: G988-G992.
59. Jones OM, Brading AF, McC Mortensen NJ. Phosphodiesterase inhibitors cause relaxation of the internal anal sphincter in vitro. Dis Colon Rectum 2002; 45: 530-536.
60. Rastogi S, Rodriguez JJ, Kapur V, Schwarz ER. Why do patients with heart failure suffer with erectile dysfunction? A critical review and suggestions on how to approach this problem. Int J Impot Res 2005; 17: S25-S36.
61. Ahn GJ, Yu JY, Choi SM, Kang KK, Ahn BO, Kwon JW et al. Chronic administration of phosphodiesterase 5i improves erectile and endothelial function in a rat model of diabetes. Int J Androl 2005; 28: 260-266.
62. Gori T, Sicuro S, Dragoni S, Donati G, Forconi S, Parker JD. Sildenafil prevents endothelial dysfunction induced by ischemia and reperfusion via opening of adenosine triphosphate-sensitive potassium channels: a human in vivo study. Circulation 2005; 111: 721-723.
63. Rosano GM, Aversa A, Vitale C, Fabbri A, Fini M, Spera G. Chronic treatment with tadalafil improves endothelial function in men with increased cardiovascular risk. Eur Urol 2005; 47: 214-220.
64. Dishy V, Harris PA, Pierce R, Prasad HC, Sofowora G, Bonar HL et al. Sildenafil does not improve nitric oxide-mediated endothelium-dependent vascular responses in smokers. Br J Clin Pharmacol 2004; 57: 209-212.
65. Vlachopoulos C, Tsekoura D, Alexopoulos N, Panagiotakos D, Aznaouridis K, Stefanadis C. Type 5 phosphodiesterase inhibition by sildenafil abrogates acute smoking-induced endothelial dysfunction. Am J Hypertens 2004; 17: 1040-1044.
66. Katz SD, Balidemaj K, Homma S, Wu H, Wang J, Maybaum S. Acute type 5 phosphodiesterase inhibition with sildenafil enhances flow-mediated vasodilation in patients with chronic heart failure. J Am Coll Cardiol 2000; 36: 845-851.
67. Laties A, Sharlip I. Ocular safety in patients using sildenafil citrate therapy for erectile dysfunction. J Sex Med 2006; 3: 12-27.
68. Cunningham AV, Smith KH. Anterior ischemic optic neuropathy associated with Viagra. J Neuroophthalmol 2001; 21: 22-25.
69. Donahue SP, Taylor RJ. Pupil-sparing third nerve palsy associated with sildenafil citrate (Viagra). Am J Ophthalmol 1998; 126: 476-477.
70. Gorkin L, Hvidsten K, SObel RE, Siegel R. Sildenafil citrate use and the incidence of nonarteritic anterior ischemic optic neuropathy. Int J Clin Prac 2006; 60: 500-503.
71. Giordano D, De Stefano ME, Citro G, Modica A, Giorgi M. Expression of cGMP-binding cGMP-specific phosphodiesterase (PDE5) in mouse tissues and cell lines using an antibody against the enzyme amino-terminal domain. Biochim Biophys Acta 2001; 1539: 16-27.
72. Kruuse C, Rybalkin SD, Khurana TS, Jansen-Olesen I, Olesen J, Edvinsson L. The role of cGMP hydrolysing phosphodiesterases 1 and 5 in cerebral artery dilatation. Eur J Pharmacol 2001; 420: 55-65.
73. Arnavaz A, Aurich A, Weissenborn K, Hartmann U, Emrich HM, Schneider U. Effect of sildenafil (Viagra) on cerebral blood flow velocity: a pilot study. Psychiatry Res 2003; 122: 207-209.
74. Schermuly RT, Kreisselmeier KP, Hossein A, Hüseyin GY, Butrous G, Ermert L et al. Chronic sildenafil treatment inhibits monocrotaline-induced pulmonary hypertension in rats. Am J Respir Crit Care Med 2004; 169: 39-45.
75. Fisher PW, Salloum F, Das A, Hyder H, Kukreja RC. Phosphodiesterase-5 inhibition with sildenafil attenuates cardiomyocyte apoptosis and left ventricular dysfunction in a chronic model of doxorubicin cardiotoxicity. Circulation 2005; 111: 1601-1610.
76. Takimoto E, Champion HC, Li M, Belardi D, Ren S, Rodriguez ER et al. Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. Nat Med 2005; 11: 214-222.
77. Ferrini MG, Kovanecz I, Nolazco G, Rajfer J, Gonzalez-Cadavid NF. Effects of long-term vardenafil treatment on the development of fibrotic plaques in a rat model of Peyronie's disease. Br J Urol 2006; 97: 625-633.
78. Stiebellehner L, Petkov V, Vonbank K, Funk G, Schenk P, Ziesche R et al. Long-term treatment with oral sildenafil in addition to continuous IV epoprostenol in patients with pulmonary arterial hypertension. Chest 2003; 123: 1293-1295.
79. Barreto AC, Franchi SM, Castro S, Lopes AA. One-year follow-up of the effects of sildenafil on pulmonary arterial hypertension and veno-occlusive disease. Braz J Med Biol Res 2005; 38: 185-195.
80. Knoderer CA, Ebenroth ES, Brown JW. Chronic outpatient sildenafil therapy for pulmonary hypertension in a child after cardiac surgery. Pediatr Cardiol 2005; 26: 859-861.
81. Preston IR, Klinger JR, Houtches J, Nelson D, Farber HW, Hill NS. Acute and chronic effects of sildenafil in patients with pulmonary arterial hypertension. Resp Med 2005; 99: 1501-1510.
82. Kloner RA, Mitchell M, Emmick JT. Cardiovascular effects of tadalafil. Am J Cardiol 2003; 92(9A): 37M-46M.