Los nitratos orgánicos, en sus diferentes presentaciones, han constituido uno de los pilares para el tratamiento de las enfermedades cardiovasculares durante más de 100 años. Los nitratos son donadores de óxido nítrico; por tanto, su efecto primordial es el de la relajación del músculo liso endotelial. Producen dilatación venosa y arterial, por lo que reducen la precarga y la poscarga. Sus principales indicaciones son el tratamiento sintomático de la angina de esfuerzo estable, el síndrome coronario agudo, y la insuficiencia cardíaca aguda y crónica. Asimismo, añadidos a la terapia convencional en pacientes afroamericanos con insuficiencia cardíaca crónica, en asociación con la hidralazina, producen una reducción de la mortalidad. Su papel actual en pacientes de otras razas aún se desconoce.
La principal limitación de esta terapia es el desarrollo de tolerancia, que conduce a la atenuación de los efectos farmacológicos antiisquémicos, antianginosos y hemodinámicos con la utilización continuada. En la práctica clínica, lo más conveniente para reducir al mínimo la tolerancia es utilizar la menor dosis necesaria y dejar un intervalo libre de nitratos, para permitir la recuperación del endotelio.
Palabras clave
Nitratos
Angina estable
Síndrome coronario agudo
Insuficiencia cardíaca
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Bibliografía
[1.]
Nitroglycerin. Encyclopædia Britannica. 2005, de Encyclopædia Britannica Premium Service [accedido 29 Ag 2005). Disponible en: http://www.britannica.com/eb/article-9055952.
[2.]
W.B. Fye.
T. Lauder Brunton and amyl nitrite: a Victorian vasodilator.
Circulation, (1986), 74 pp. 222-229
[3.]
W. Murrel.
Nitroglycerin as a remedy for angina pectoris.
Lancet, (1879), I pp. 80-81
[4.]
J. Abrams.
Mechanisms of action of the organic nitrates in the treatment of myocardial ischemia.
Am J Cardiol, (1992), 70 pp. B30-B42
[5.]
J.L. Dinerman, D.L. Lawson, J.L. Mehta.
Interactions between nitroglycerin and endothelium in vascular smooth muscle relaxation.
Am J Physiol, (1991), 260 pp. H698-H701
[6.]
E. Bassenge, J. Zanzinger.
Nitrates in different vascular beds, nitrate tolerance, and interactions with endothelial function.
Am J Cardiol, (1992), 70 pp. B23-B29
[8.]
B.I. Jugdutt.
Nitrates in instable angina and acute myocardial infarction.
Nitrate therapy and nitrate tolerante, Karger, pp. 111-167
[9.]
Y.Y. Chirkov, L.P. Chirkova, J.D. Horowitz.
Nitroglycerin tolerance at the platelet level in patients with angina pectoris.
Am J Cardiol, (1997), 80 pp. 128-131
[10.]
B.I. Jugdutt, J.W. Warnica.
Tolerance with low dose intravenous nitroglycerin therapy in acute myocardial infarction.
Am J Cardiol, (1989), 64 pp. 581-587
[11.]
D. Zimrin, N. Reichek, K.T. Bogin, G. Aurigemma, P. Douglas, B. Berko, et al.
Antianginal effects of intravenous nitroglycerin over 24 hours.
Circulation, (1988), 77 pp. 1376-1384
[12.]
U. Elkayam, A. Mehra, A. Shotan, E. Ostrzega.
Nitrate resistance and tolerance: potential limitations in the treatment of congestive heart failure.
Am J Cardiol, (1992), 70 pp. B98-B104
[13.]
B. Fink, M. Schwemmer, N. Fink, E. Bassenge.
Tolerance to nitrates with enhanced radical formation suppressed by carvedilol.
J Cardiovasc Pharmacol, (1999), 34 pp. 800-805
[14.]
G. Berkenboom, D. Fontaine, P. Unger, S. Baldassarre, N. Preumont.
Absence of nitrate tolerance after long-term treatment with ramipril: an endothelium-dependent mechanism.
J Cardiocasc Pharmacol, (1999), 34 pp. 547-553
[15.]
V. Elkayam, J.V. Johnson, A. Shutan, S. Bokhari, A. Soldky, M. Canetti, et al.
Double-blind, placebo-controlled study to evaluate the effects of organic nitrates in patients with heart failure treated with IECA.
Circulation, (1999), 99 pp. 2652-2657
[16.]
M. Sarr, I. Lobysheva, A.S. Diallo, J.C. Stoclet, V.B. Schini-Kerth, B. Muller.
Formation of releasable NO stores by S-nitrosoglutathione in arteries exhibiting tolerance to glyceryl-trinitrate.
Eur J Pharmacol, (2005), 513 pp. 119-123
[17.]
M.M. Bassan, D. Weiler-Ravell, O. Shalev.
Comparison of the antianginal effectiveness of nifedipine, verapamil, and isosorbide dinitrate in patients receiving propranolol: a double-blind study.
Circulation, (1983), 68 pp. 568-575
[18.]
F. Akhras, G. Jackson.
Efficacy of nifedipine and isosorbide mononitrate in combination with atenolol in stable angina.
Lancet, (1991), 338 pp. 1036-1039
[19.]
P.A. Heidenreich, K.M. McDonald, T. Hastie, B. Fadel, V. Hagan, B.K. Lee, et al.
Meta-analysis of trials comparing beta-blockers, calcium antagonists, and nitrates for stable angina.
JAMA, (1999), 281 pp. 1927-1936
[20.]
R.J. Wainwright, J.P. Foran, S.F. Padaria, F. Akhras, G. Jackson, A.R. Clark.
The long-term safety and tolerability of transdermal glyceryl trinitrate, when used with a patch-free interval in patients with stable angina.
Br J Clin Pract, (1993), 47 pp. 178-182
[21.]
R.J. Gibbons, J. Abrams, K. Chatterjee, J. Daley, P.C. Deedwania, J.S. Douglas, et al.
ACC/AHA 2002 guideline update for the management of patients with chronic stable angina-summary article: a report of the American College of Cardiology/American Heart Association Task Force on practice guidelines (Committee on the Management of Patients With Chronic Stable Angina).
J Am Coll Cardiol, (2003), 41 pp. 159-168
[23.]
X. Bosch, E. López de Sá, J. López Sendón, J. Aboal, F. Miranda-Guardiola, A. Bethencourt, et al.
Perfil clínico, pronóstico y variabilidad en el tratamiento del síndrome coronario agudo sin elevación del segmento ST. Datos del registro PEPA.
Rev Esp Cardiol, (2003), 56 pp. 346-353
[24.]
K.D.R. Kaplan, M. Parker, J. Przybylek, J.R. Teagarden, M. Lesch.
Intravenous nitroglycerin for the treatment of angina at rest unresponsive to standard nitrate therapy.
Am J Cardiol, (1983), 51 pp. 694-698
[25.]
N. DePace, I.M. Herling, M.N. Kotler, A.H. Hakki, S.R. Spielman, B.L. Segal.
Intravenous nitroglycerin for rest angina. Potential pathophysiologic mechanisms of action.
Arch Intern Med, (1982), 142 pp. 1806-1809
[26.]
J.R. Mikolich, N.B. Nicoloff, P.H. Robinson, R.B. Logue.
Relief of refractory angina with continuous intravenous infusion of nitroglycerin.
Chest, (1980), 77 pp. 375-379
[27.]
G. Curfman, J.A. Heinsimr, E.C. Lozner, H.L. Fung.
Intravenous nitroglycerin in the treatment of spontaneous angina pectoris: a prospective randomized trial.
Circulation, (1983), 67 pp. 276-282
[28.]
M. Dellborg, G. Gustafsson, K. Swedberg.
Buccal versus intravenous nitroglycerin in unstable angina pectoris.
Eur J Clin Pharmacol, (1991), 41 pp. 5-9
[29.]
J. Figueras, R. Lidon, J. Cortadellas.
Rebound myocardial ischaemia following abrupt interruption of intravenous nitroglycerin infusion in patients with unstable angina at rest.
Eur Heart J, (1991), 12 pp. 405-411
[30.]
E. Braunwald, E.M. Antman, J.W. Beasley, R.M. Califf, M.D. Cheitlin, J.S. Hochman, et al.
ACC/AHA guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction-2002: summary article: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee on the Management of Patients With Unstable Angina).
Circulation, (2002), 106 pp. 1893-1900
[31.]
M.E. Bertrand, M.L. Simoons, K.A. Fox, L.C. Wallentin, C.W. Hamm, E. McFadden, et al.
Management of acute coronary syndromes in patients presenting without persistent ST-segment elevation.
Eur Heart J, (2002), 23 pp. 1809-1840
[32.]
A.D. Levison, J.L. Velianou, S. Yusuf.
Nitrates.
Clinical trials in cardiovascular disease: a companion to Braunwald's heart disease, W.B. Saunders Company, pp. 131-144
[33.]
W.D. Bussmann, D. Passek, W. Seidel, M. Kaltenbach.
Reduction of CK and CK-MB indexes of infarct size by intravenous nitroglycerin.
Circulation, (1981), 63 pp. 615-622
[34.]
Y.I. Kim, J.F. Williams Jr.
Large dose sublingual nitroglycerin in acute myocardial infarction: relief of chest pain and reduction of Q wave evolution.
Am J Cardiol, (1982), 49 pp. 842-848
[35.]
B.I. Jugdutt.
Nitrates in myocardial infarction.
Cardiovasc Drugs Ther, (1994), 8 pp. 635-646
[36.]
S. Yusuf, R. Collins, S. MacMahon, R. Peto.
Effect of intravenous nitrates on mortality in acute myocardial infarction: an overview of the randomised trials.
Lancet, (1988), 1 pp. 1088-1092
[37.]
ISIS-4 investigators.
ISIS-4: a randomised factorial trial assessing early oral captopril, oral mononitrate, and intravenous magnesium sulphate in 58,050 patients with suspected acute myocardial infarction. ISIS-4 (Fourth International Study of Infarct Survival) Collaborative Group.
Lancet, (1995), 345 pp. 669-685
[38.]
H.S. Mellen, H.S. Goldberg, H.F. Friedman.
Therapeutic effects of pentaerythritol tetranitrate in the immediate postmyocardial-infarction period.
N Engl J Med, (1967), 276 pp. 319-322
[39.]
D.J. Newell.
Pentaerythritol tetranitrate (sustained action) in acute myocardial infarction.
Br Heart J, (1970), 32 pp. 16-20
[40.]
A. Oscharoff.
Pentaerythritol tetranitrate, as adjunct therapy in the immediate postinfarction period.
Angiology, (1964), 15 pp. 505-514
[41.]
T.J. Ryan, M. Schnee.
Pentaerythritol tetranitrate in acute myocardial infarction (abstract).
Circulation, (1965), 32 pp. II105
[42.]
GISSI-3 investigators.
GISSI-3: effects of lisinopril and transdermal glyceryl trinitrate singly and together on 6-week mortality and ventricular function after acute myocardial infarction. Gruppo Italiano per lo Studio della Sopravvivenza nell’infarto Miocardico.
Lancet, (1994), 343 pp. 1115-1122
[43.]
ESPRIM investigators.
The ESPRIM trial: short-term treatment of acute myocardial infarction with molsidomine. European Study of Prevention of Infarct with Molsidomine (ESPRIM) Group.
Lancet, (1994), 344 pp. 91-97
[44.]
F. Van de Werf, D. Ardissino, A. Betriu, D.V. Cokkinos, E. Falk, K.A. Fox, et al.
Management of acute myocardial infarction in patients presenting with ST-segment elevation. The Task Force on the Management of Acute Myocardial Infarction of the European Society of Cardiology.
Eur Heart J, (2003), 24 pp. 28-66
[45.]
E.M. Antman, D.T. Anbe, P.W. Armstrong, E.R. Bates, L.A. Green, M. Hand, et al.
ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction-executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Writing Committee to Revise the 1999 Guidelines for the Management of Patients With Acute Myocardial Infarction).
Circulation, (2004), 110 pp. 588-636
[46.]
G. Cotter, E. Metzkor, E. Kaluski, Z. Faigenberg, R. Miller, A. Simovitz, et al.
Randomised trial of high-dose isosorbide dinitrate plus low-dose furosemide versus high-dose furosemide plus lowdose isosorbide dinitrate in severe pulmonary oedema.
Lancet, (1998), 351 pp. 389-393
[47.]
M.S. Nieminen, M. Bohm, M.R. Cowie, H. Drexler, G.S. Filippatos, G. Jondeau.
Executive summary of the guidelines on the diagnosis and treatment of acute heart failure: the Task Force on Acute Heart Failure of the European Society of Cardiology.
Eur Heart J, (2005), 26 pp. 384-416
[48.]
U. Elkayam, J.V. Johnson, A. Shotan, S. Bokhari, A. Solodky, M. Canetti, et al.
Double-blind, placebo-controlled study to evaluate the effect of organic nitrates in patients with chronic heart failure treated with angiotensin-converting enzyme inhibition.
Circulation, (1999), 99 pp. 2652-2657
[49.]
B.I. Jugdutt, M.I. Khan.
Effect of prolonged nitrate therapy on left ventricular remodeling after canine acute myocardial infarction.
Circulation, (1994), 89 pp. 2297-2307
[50.]
M. Anguita Sánchez.
Investigadores del Registro BADAPIC. Características clínicas, tratamiento y morbimortalidad a corto plazo de pacientes con insuficiencia cardíaca controlados en consultas específicas de insuficiencia cardíaca. Resultados del Registro BADAPIC.
Rev Esp Cardiol, (2004), 57 pp. 1159-1169
[51.]
M. Komajda, F. Follath, K. Swedberg, J. Cleland, J.C. Aguilar, A. Cohen-Solal, et al.
The EuroHeart Failure Survey programme-a survey on the quality of care among patients with heart failure in Europe. Part 2: treatment.
Eur Heart J, (2003), 24 pp. 464-474
[52.]
J.N. Cohn, D.G. Archibald, S. Ziesche, J.A. Franciosa, W.E. Harston, F.E. Tristani, et al.
Effect of vasodilator therapy on mortality in chronic congestive heart failure. Results of a Veterans Administration Cooperative Study.
N Engl J Med, (1986), 314 pp. 1547-1552
[53.]
J.N. Cohn, G. Johnson, S. Ziesche, F. Cobb, G. Francis, F. Tristani, et al.
A comparison of enalapril with hydralazine-isosorbide dinitrate in the treatment of chronic congestive heart failure.
N Engl J Med, (1991), 325 pp. 303-310
[54.]
A.L. Taylor, S. Ziesche, C. Yancy, P. Carson, R D’Agostino Jr, K. Ferdinand, et al.
Combination of isosorbide dinitrate and hydralazine in blacks with heart failure.
N Engl J Med, (2004), 351 pp. 2049-2057
[55.]
J.N. Cohn, D.G. Archibald, G.S. Francis, S. Ziesche, J.A. Franciosa, W.E. Harston, et al.
Veterans Administration Cooperative Study on Vasodilator Therapy of Heart Failure: influence of prerandomization variables on the reduction of mortality by treatment with hydralazine and isosorbide dinitrate.
Circulation, (1987), 75 pp. IV49-54
[56.]
C.W. Yancy.
Heart failure in African Americans: a cardiovascular engima.
J Card Fail, (2000), 6 pp. 183-186
[57.]
L. Kalinowski, I. Dobrucki, T. Malinski.
Race-specific differences in endothelial function: predisposition of African Americans to vascular disease.
Circulation, (2004), 109 pp. 2511-2517
[58.]
D.J. Dries, C.W. Yancy, M.A. Strong, M.H. Drazner.
Racial response to angiotensin-converting enzyme therapy in systolic heart failure.
Congest Heart Fail, (2004), 10 pp. 30-33
[59.]
K. Swedberg, J. Cleland, H. Dargie, H. Drexler, F. Follath, M. Komajda, et al.
Guidelines for the diagnosis and treatment of chronic heart failure: executive summary (update 2005): The Task Force for the Diagnosis and Treatment of Chronic Heart Failure of the European Society of Cardiology.
Eur Heart J, (2005), 26 pp. 1115-1140
[60.]
M.D. Cheitlin, A.M. Hutter Jr, R.G. Brindis, P. Ganz, S. Kaul, R.O. Russell Jr, 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 pp. 273-282
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