Pharmaka mit Wirkung auf das kardiovaskuläre System

B. Kaiser

doi:10.1055/s-0037-1619500

Hämostaseologie, Table of Contents

Hamostaseologie 2001; 21(01): 17-21
DOI: 10.1055/s-0037-1619500

Original article

Schattauer GmbH

Pharmaka mit Wirkung auf das kardiovaskuläre System

Drugs for the treatment of cardiovascular disorders

B. Kaiser

¹Friedrich-Schiller-Universität Jena, Zentrum für Vaskuläre Biologie und Medizin Erfurt, Arbeitsgruppe Experimentelle Angiologie (Leiter: Univ.-Prof. Dr. med. E. Glusa)

› Author Affiliations

Abstract

Zusammenfassung

Neben ihren Wirkungen auf das Herz-Kreislauf-System beeinflussen kardiovaskuläre Pharmaka zahlreiche andere Strukturen des menschlichen Organismus, was sowohl in erwünschten als auch unerwünschten Nebenwirkungen, unter anderem auf die Hämostase, resultieren kann. So können, aufgrund der Interaktionen des Renin-Angiotensin-Systems mit dem Kallikrein-Kinin- und dem Fibrinolysesystem, Inhibitoren des Angiotensin-Converting-Enzyms (ACE) bzw. Angiotensin-II-Rezeptor-Antagonisten profibrinolytische und antithrombotische Effekte hervorrufen. Unter den Pharmaka, die zur Therapie der koronaren Herzkrankheit eingesetzt werden, sind vor allem vasoaktive Substanzen wie Nitroverbindungen von Interesse, da sie die Plättchenaggregation hemmen. Die zur Senkung des Lipidspiegels verwendeten HMG-CoA-Reduktase-Inhibitoren oder Statine haben antithrombotische Eigenschaften, die auf spezifischen, nicht mit der Lipidsenkung verbundenen Wirkungsmechanismen beruhen. Hinsichtlich unerwünschter Nebenwirkungen kardiovaskulärer Pharmaka auf die Hämostase ist nur wenig bekannt. Bei Anwendung von ACE-Inhibitoren und vasoaktiven Substanzen wurden vereinzelt Blutungen, insbesondere im Bereich des Magen-Darm-Traktes, beobachtet. Einige Diuretika und β-Blocker können den Fettstoffwechsel mit Auftreten einer Hyperlipidämie beeinflussen.

Summary

Besides their action on the cardiovascular system cardiovascular drugs may cause both desired and undesired effects on various other structures of the organism. Because of the interaction between the renin-angiotensin system with the kallikrein-kinin and the fibrinolytic system angiotensin-converting enzyme (ACE) inhibitors as well as angiotensin II-receptor antagonists can induce profibrinolytic and antithrombotic effects. Amongst the drugs used for the therapy of coronary artery disease especially vasoactive compounds such as organic nitrates are known to inhibit platelet reactions. Independent of their lipid-lowering action HMG-CoA-reductase inhibitors or statins exert antithrombotic effects which are based on specific mechanisms of action. Only little information is available on undesired side effects of cardiovascular drugs on the hemostatic system. There are some reports on bleeding complications especially in the gastrointestinal tract after administration of ACE inhibitors and vasoactive compounds. Some diuretics and β-blockers may cause hyperlipidemia.

Schlüsselwörter

Kardiovaskuläre Pharmaka - Fibrinolyse - Plättchen - Thrombose

Keywords

Cardiovascular drugs - fibrinolysis - platelets - thrombosis

Full Text

References

Literatur
1 Nordt TK, Bode C. Endothel und endogene Fibrinolyse. Z Kardiol 2000; 89: 219-26.
2 Allikmets K, Parik T, Viigimaa M. The reninangiotensin system in essential hypertension: associations with cardiovascular risk. Blood Press 1999; 8: 70-8.
3 Gensini GF, Comeglio M, Colella A. Classical risk factors and emerging elements in the risk profile for coronary artery disease. Eur Heart J 1998; 19 (Suppl A) A53-A61.
4 Brown NJ, Vaughan DE. Prothrombotic effects of angiotensin. Adv Intern Med 2000; 45: 419-29.
5 Vaughan DR. The renin-angiotensin system and fibrinolysis. Am J Cardiol 1997; 79: 12-6.
6 Vaughan DE. Fibrinolytic balance, the reninangiotensin system and atherosclerotic disease. Eur Heart J 1998; 19 (Suppl G) G9-G12.
7 Brown NJ, Agirbasli MA, Williams GH, Litchfield WR, Vaughan DE. Effect of activation and inhibition of the renin-angiotensin system on plasma PAI-1. Hypertension 1998; 32: 965-71.
8 Vaughan DE. Endothelial function, fibrinolysis, and angiotensin-converting enzyme inhibition. Clin Cardiol. 1997 20. (Suppl 2): II-34-II-37.
9 Ridker PM, Vaughan DE. Potential antithrombotic and fibrinolytic properties of the angiotensin converting enzyme inhibitors. J Thromb Thrombolysis 1995; 1: 251-7.
10 Vaughan DE, Rouleau JL, Ridker PM, Arnold JM, Menapace FJ, Pfeffer MA. Effects of ramipril on plasma fibrinolytic balance in patients with acute anterior myocardial infarction. HEART study investigators. Circulation 1997; 96: 442-7.
11 Moriyama Y, Ogawa H, Oshima S, Takazoe K, Honda Y, Hirashima O, Arai H, Sakamoto T, Sumida H, Suefuji H, Kaikita K, Yasue H. Captopril reduced plasminogen activator inhibitor activity in patients with acute myocardial infarction. Jpn Circ J 1997; 61: 308-14.
12 Buczko W, Matys T, Kucharewicz I, Chabielska E. The role of endothelium in antithrombotic effect of the renin-angiotensin system blockade. J Physiol Pharmacol 1999; 50: 499-507.
13 Vanhoutte PM. Endothelial dysfunction and inhibition of converting enzyme. Eur Heart J 1998; 19 (Suppl J) J7-J15.
14 Napoleone E, Di Santo A, Camera M, Tremoli E, Lorenzet R. Angiotensin-converting enzyme inhibitors downregulate tissue factor synthesis in monocytes. Circ Res 2000; 86: 139-43.
15 Soejima H, Ogawa H, Yasue H, Kaikita K, Takazoe K, Nishiyama K, Misumi K, Miyamoto S, Yoshimura M, Kugiyama K, Nakamura S, Tsuji I. Angiotensin-converting enzyme inhibition reduces monocyte chemoattractant protein-1 and tissue factor levels in patients with myocardial infarction. J Am Coll Cardiol 1999; 34: 983-8.
16 Soejima H, Ogawa H, Yasue H, Suefuji H, Kaikita K, Tsuji I, Kumeda K, Aoyama N. Effects of enalapril on tissue factor in patients with uncomplicated acute myocardial infarction. Am J Cardiol 1996; 78: 336-40. 164-76.
17 Zurbano MJ, Anguera I, Heras M, Roig E, Lozano M, Sanz G, Escolar G. Captopril administration reduces thrombus formation and surface expression of platelet glycoprotein IIb/IIIa in early postmyocardial infarction stage. Arterioscler Thromb Vasc Biol 1999; 19: 1791-5.
18 Abrams J. Beneficial actions of nitrates in cardiovascular disease. Am J Cardiol 1996; 77: 31C-37C.
19 Abrams J. Mechanisms of action of the organic nitrates in the treatment of myocardial ischemia. Am J Cardiol 1992; 70: 30B-42B.
20 Diodati JG, Cannon 3rd RO, Hussain N, Quyyumi AA. Inhibitory effect of nitroglycerin and sodium nitroprusside on platelet activation across the coronary circulation in stable angina pectoris. Am J Cardiol 1995; 75: 443-8.
21 Lacoste LL, Theroux P, Lidon RM, Colucci R, Lam JY. Antithrombotic properties of transdermal nitroglycerin in stable angina pectoris. Am J Cardiol 1994; 73: 1058-62.
22 Chirkov YY, Naujalis JI, Sage RE, Horowitz JD. Antiplatelet effects of nitroglycerin in healthy subjects and in patients with stable angina pectoris. J Cardiovasc Pharmacol 1993; 21: 384-9.
23 Loscalzo J. Antiplatelet and antithrombotic effects of organic nitrates. Am J Cardiol 1992; 70: 18B-22B.
24 Diodati J, Theroux P, Latour JG, Lacoste L, Lam JY, Waters D. Effects of nitroglycerin at therapeutic doses on platelet aggregation in unstable angina pectoris and acute myocardial infarction. Am J Cardiol 1990; 66: 683-8.
25 Hjemdahl P, Larsson PT, Wallen NH. Effects of stress and beta-blockade on platelet function. Circulation 1991; 84 (Suppl. 06) VI44-VI61.
26 Winther K, Willich SN. Beta 1-blockade and acute coronary ischemia. Possible role of platelets. Circulation 1991; 84 (Suppl. 06) VI68-VI71.
27 Schachter M. Do calcium antagonists affect platelets?. Eur Heart J 1987; 8 (Suppl K) 75-82.
28 Tschöpe D, Homberg M, Rösen P, Gries FA. Reduced platelet thromboxane formation after long-term administration of a dihydropyridine calcium channel blocker: a prospective, double-blind, placebo-controlled study with nitrendipine in borderline hypertensive patients with IDDM-type diabetes mellitus. Diabetes Res 1992; 19: 125-31.
29 Fujinishi A, Takahara K, Ohba C, Nakashima Y, Kuroiwa A. Effects of nisoldipine on cytosolic calcium, platelet aggregation, and coagulation/fibrinolysis in patients with coronary artery disease. Angiology 1997; 48: 515-21.
30 Dhein S, Salameh A, Berkels R, Klaus W. Dual mode of action of dihydropyridine calcium antagonist: a role for nitric oxide. Drugs 1999; 58: 397-404.
31 Chou TC, Li CY, Yen MH, Ding YA. Antiplatelet effect of amlodipine: a possible mechanism through a nitric oxide-mediated process. Biochem Pharmacol 1999; 58: 1657-63.
32 Bassenge E, Mulsch A. Anti-ischemic actions of molsidomine by venous and large coronary dilatation in combination with antiplatelet effects. J Cardiovasc Pharmacol 1989; 14 (Suppl. 11) S23-S28.
33 Wallen NH, Held C, Rehnqvist N, Hjemdahl P. Platelet aggregability in vivo is attenuated by verapamil but not by metoprolol in patients with stable angina pectoris. Am J Cardiol 1995; 75: 1-6.
34 Knight CJ, Panesar M, Wilson DJ, Chronos NA, Patel D, Fox K, Goodall AH. Different effects of calcium antagonists, nitrates, and beta-blockers on platelet function. Possible importance for the treatment of unstable angina. Circulation 1997; 95: 125-32.
35 Bellosta S, Ferri N, Bernini F, Paoletti R, Corsini A. Non-lipid-related effects of statins. Ann Med 2000; 32: 164-76.
36 Weissberg P. Mechanisms modifying atherosclerotic disease – from lipids to vascular biology. Atherosclerosis 1999; 147 (Suppl. 01) S3-S10.
37 Dangas G, Smith DA, Unger AH, Shao JH, Meraj P, Fier C, Cohen AM, Fallon JT, Badimon JJ, Ambrose JA. Pravastatin: An antithrombotic effect independent of the cholesterol-lowering effect. Thromb Haemost 2000; 83: 688-92.
38 Davignon J, Laaksonen R. Low-density lipoprotein-independent effects of statins. Curr Opin Lipidol 1999; 10: 543-59.
39 Rosenson RS, Tangney CC. Antiatherothrombotic properties of statins: implications for cardiovascular event reduction. J Am Med Assoc 1998; 279: 1643-50.
40 Maron DJ, Fazio S, Linton MF. Current perspectives on statins. Circulation 2000; 101: 207-13.
41 Wheeler DC. Are there potential non-lipid-lowering uses of statins?. Drugs 1998; 56: 517-22.
42 Szczeklik A, Musial J, Undas A, Gajewski P, Gora P, Swadzba J, Jankowski M. Inhibition of thrombin generation by simvastatin and lack of additive effects of aspirin in patients with marked hypercholesterolemia. J Am Coll Cardiol 1999; 33: 1286-93.
43 Fenton II JW, Shen GX. Statins as cellular antithrombotics. Haemostasis 1999; 29: 166-9.
44 Fenton II JW, Shen GX, Minnear FL, Brezniak DV, Walenga JW, Bognacki JJ, Ofosu FA. Statins induce hypothrombotic state?. Clin Appl Thrombosis/Hemostasis 2000; 6: 18-21.
45 Laufs U, Gertz K, Huang P, Nickenig G, Bohm M, Dirnagl U, Endres M. Atorvastatin upregulates type III nitric oxide synthase in thrombocytes, decreases platelet activation, and protects from cerebral ischemia in normocholesterolemic mice. Stroke 2000; 31: 2442-9.
46 Indolfi C, Cioppa A, Stabile E, Di Lorenzo E, Esposito G, Pisani A, Leccia A, Cavuto L, Stingone AM, Chieffo A, Capozzolo C, Chiariello M. Effects of hydroxymethylglutaryl coenzyme A reductase inhibitor simvastatin on smooth muscle cell proliferation in vitro and neointimal formation in vivo after vascular injury. J Am Coll Cardiol 2000; 35: 214-21.
47 Pahor M, Guralnik JM, Furberg CD, Carbonin P, Havlik R. Risk of gastrointestinal haemorrhage with calcium antagonists in hypertensive persons over 67 years old. Lancet 1996; 347: 1061-5.
48 Suissa S, Bourgault C, Barkun A, Sheehy O, Ernst P. Antihypertensive drugs and the risk of gastrointestinal bleeding. Am J Med 1998; 105: 230-5.
49 Kaplan RC, Heckbert SR, Koepsell TD, Rosendaal FR, Psaty BM. Use of calcium channel blockers and risk of hospitalized gastrointestianl tract bleeding. Arch Intern Med 2000; 160: 1849-55.
50 Bevan JS, Oza AM, Burke CW, Adams CB. Pituitary apoplexy following isosorbide administration. J Neurol Neurosurg Psychiatr 1987; 50: 636-7.
51 Bayer I, Kyzer S, Creter D, Lewinski UH. Rectal bleeding induced by dipyridamole. Dis Colon Rectum 1986; 29: 123-5.
52 Ring T, Knudsen F, Kristensen SD, Larsen CE. Nitroglycerin prolongs the bleeding time in healthy males. Thromb Res 1983; 29: 553-9.
53 Magnusson B, Rodjer S. Alprenolol-induced thrombocytopenia. Acta Med Scand 1980; 207: 231-3.
54 Hannedouche T, Godin M, Fries D, Fillastre JP. Acute renal thrombosis induced by angiotensin-converting enzyme inhibitors in patients with renovascular hypertension. Nephron 1991; 57: 230-1.
55 Trifiletti A, Barbara N, Scamardi R, Bagnato L, Pizzoleo MA, Nevoso A, Lasco A, Pedulla M, Frisina N. Effects of medium-term antihypertensive therapy on haemostatic parameters in patients with essential hypertension. Haemostasis 1997; 27: 35-8.
56 Keohane SG, Edmunds M, Holton J, Swales JD. Minoxidil, hypercoagulability and thromboembolic disease of the lung. Postgrad Med J 1996; 72: 229-30.
57 Day JL, Metcalfe J, Simpson CH. Adrenergic mechanisms in control of plasma lipid concentration. Br Med J 1982; 284: 1145-8.
58 Abshagen U. (Ed.). Handbook of Experimental Pharmacology, Vol. 76: Clinical Pharmacology of Antianginal Drugs. Berlin, Heidelberg, New York: Springer-Verlag; 1985
59 Greger RF, Knauf H, Mutschler E. (Eds.). Handbook of Experimental Pharmacology, Vol. 117: Diuretics. Berlin, Heidelberg, New York: Springer-Verlag; 1995
60 Ganten D, Mulrow PJ. (Eds.). Handbook of Experimental Pharmacology, Vol. 93: Pharmacology of Antihypertensive Therapeutics. Berlin, Heidelberg, New York: Springer-Verlag; 1990