Current pharmacological treatment of pulmonary arterial hypertension

Current Clinical Pharmacology

Volumn 3, Issue 1, 2008, Pages 11-19

  Steiropoulos, Paschalis ^a   Trakada, Georgia ^a   Bouros, Demosthenes ^a  

^a DEMOCRITUS UNIVERSITY OF THRACE   (Greece)

Author keywords

Endothelin receptor antagonist; Phosphodiesterase 5 inhibitor; Prostacyclin analogues; Pulmonary arterial hypertension; Treatment

Indexed keywords

AMBRISENTAN; ARGININE; BERAPROST; BOSENTAN; BRAIN NATRIURETIC PEPTIDE; CALCIUM CHANNEL BLOCKING AGENT; DICHLOROACETIC ACID; DIGITALIS; DILTIAZEM; DIURETIC AGENT; ELASTASE INHIBITOR; ENDOTHELIN RECEPTOR ANTAGONIST; ILOPROST; IMATINIB; INFLUENZA VACCINE; M 249314; NIFEDIPINE; NITROUS OXIDE; PHOSPHODIESTERASE V INHIBITOR; PLACEBO; PROSTACYCLIN; PROSTAGLANDIN DERIVATIVE; SILDENAFIL; SIMVASTATIN; SITAXSENTAN; UNCLASSIFIED DRUG; UNINDEXED DRUG; UNIPROST; VASOACTIVE INTESTINAL POLYPEPTIDE; WARFARIN; ZD 0892;

ABSENCE OF SIDE EFFECTS; ANEMIA; BONE PAIN; BRADYCARDIA; CLINICAL TRIAL; COMBINATION CHEMOTHERAPY; CONNECTIVE TISSUE DISEASE; CONTINUOUS INFUSION; COUGHING; DIARRHEA; DIZZINESS; DRUG ABSORPTION; DRUG COST; DRUG DOSE INCREASE; DRUG DOSE REDUCTION; DRUG DOSE TITRATION; DRUG EFFICACY; DRUG HALF LIFE; DRUG MEGADOSE; DRUG OVERDOSE; DRUG SAFETY; DRUG TOLERABILITY; DYSPNEA; EDEMA; ENDOTHELIAL DYSFUNCTION; ERYTHEMA; EXERCISE TOLERANCE; FLUSHING; HEADACHE; HEART CATHETERIZATION; HEART FAILURE; HEART HEMODYNAMICS; HEART INDEX; HEART RIGHT VENTRICLE FAILURE; HEARTBURN; HUMAN; HYPOTENSION; HYPOXEMIA; LIVER TOXICITY; LOW DRUG DOSE; LUNG ARTERY PRESSURE; LUNG CAPILLARY PRESSURE; LUNG VASCULAR RESISTANCE; MEAN ARTERIAL PRESSURE; MONOTHERAPY; MYALGIA; NAUSEA; NONHUMAN; NOSE CONGESTION; OXYGEN SATURATION; PATHOGENESIS; PERIPHERAL EDEMA; PRIORITY JOURNAL; PULMONARY HYPERTENSION; RESPIRATORY TRACT INFECTION; REVIEW; SCLERODERMA; SIDE EFFECT; SODIUM RESTRICTION; SYNCOPE; TACHYCARDIA; THROMBOSIS; VASOCONSTRICTION; VASODILATATION; WALKING SPEED;

DIURETICS; EPOPROSTENOL; HUMANS; HYPERTENSION, PULMONARY; ILOPROST; NITRIC OXIDE; PIPERAZINES; PURINES; SULFONAMIDES; SULFONES;

EID: 38949195787     PISSN: 15748847     EISSN: None     Source Type: Journal    
DOI: 10.2174/157488408783329887     Document Type: Review

References (99)

1. Simonneau G, Galie N, Rubin LJ, et al. Clinical classification of pulmonary hypertension. J Am Coll Cardiol 2004; 43: 5S-12S.
2. Gaine SP, Rubin LJ. Primary pulmonary hypertension. Lancet 1998; 352: 719-725.
3. Abenhaim L, Moride Y, Brenot F, et al. Appetite-suppressant drugs and the risk of primary pulmonary hypertension. International Primary Pulmonary Hypertension Study Grorp. N Engl J Med 1996; 335: 609-616.
4. Speich R, Jenni R, Opravil M, Pfab M, Russi EW. Primary pulmonary hypertension in HIV infection. Chest 1991;, 100: 1268-1271.
5. Budhiraja R, Hassoun PM. Portopulmonary hypertension: a tale of two circulations. Chest 2003; 123: 562-576.
6. McGoon M, Gutterman D, Steen V, et al. Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest 2004; 126: 14S-34S.
7. D'Alonzo GE, Barst RJ, Ayres SM, et al. Survival in patients with primary pulmonary hypertension. Results from a national prospective registry. Ann Intern Med 1991; 115: 343-349.
8. Koh ET, Lee P, Gladman DD, Abu-Shakra M. Pulmonary hypertension in systemic sclerosis: an analysis of 17 patients. Br J Rheumatol 1996; 35: 989-993.
9. Kawut SM, Taichman DB, Archer-Chicko CL, Palevsky HI, Kimmel SE. Hemodynamics and survival in patients with pulmonary arterial hypertension related to systemic sclerosis. Chest 2003; 123: 344-350.
10. Barst RJ. Medical therapy of pulmonary hypertension. An overview of treatment and goals. Clin Chest Med 2001; 22: 509-515, ix.
11. Mehta S. Drug therapy for pulmonary arterial hypertension: what's on the menu today? Chest 2003; 124: 2045-2049.
12. Wood P. Pulmonary hypertension with special reference to the vasoconstrictive factor. Br Heart J 1958; 20: 557-570.
13. Yuan JX, Aldinger AM, Juhaszova M, et al. Dysfunctional voltage-gated K+ channels in pulmonary artery smooth muscle cells of patients with primary pulmonary hypertension. Circulation 1998; 98: 1400-1406.
14. Budhiraja R, Tuder RM, Hassoun PM. Endothelial dysfunction in pulmonary hypertension. Circulation 2004; 109: 159-165.
15. Petkov V, Mosgoeller W, Ziesche P, et al. Vasoactive intestinal peptide as a new drug for treatment of primary pulmonary hypertension. J Clin Invest 2003; 111: 1339-1346.
16. Pietra GG, Capron F, Stewart S, et al. Pathologic assessment of vasculopathies in pulmonary hypertension. J Am Coll Cardiol 2004; 43: 25S-32S.
17. Humbert M, Morrell NW, Archer SL, et al. Cellular and molecular pathobiology of pulmonary arterial hypertension. J Am Coll Cardiol 2004; 43: 13S-24S.
18. Cowan KN, Heilbut A, Humpl T, Lam C, Ito S, Rabinovitch M. Complete reversal of fatal pulmonary hypertension in rats by a serine elastase inhibitor. Nat Med 2000; 6: 698-702.
19. Du L, Sullivan CC, Chu D, et al. Signaling molecules in nonfamilial pulmonary hypertension. N Engl J Med 2003; 348: 500-509.
20. Dorfmuller P, Perros F, Balabanian K, Humbert M. Inflammation in pulmonary arterial hypertension. Eur Respir J 2003; 22: 358-363.
21. Eddahibi S, Humbert M, Fadel E, et al. Serotonin transporter over-expression is responsible for pulmonary artery smooth muscle hyperplasia in primary pulmonary hypertension. J Clin Invest 2001; 108: 1141-1150.
22. Friedman R, Mears JG, Barst RJ. Continuous infusion of prostacyclin normalizes plasma markers of endothelial cell injury and platelet aggregation in primary pulmonary hypertension. Circulation 1997; 96: 2782-2784.
23. Eisenberg PR, Lucore C, Kaufman L, Sobel BE, Jaffe AS, Rich S. Fibrinopeptide A levels indicative of pulmonary vascular thrombosis in patients with primary pulmonary hypertension. Circulation 1990; 82: 841-847.
24. Christman BW, McPherson CD, Newman JH, et al. An imbalance between the excretion of thromboxane and prostacyclin metabolites in pulmonary hypertension. N Engl J Med 1992; 327: 70-75.
25. Lane KB, Machado RD, Pauciulo, MW, et al. Heterozygous germline mutations in BMPR2, encoding a TGF-beta receptor, cause familial primary pulmonary hypertension. The International PPH Consortium. Nat Genet 2000; 26: 81-84.
26. Deng Z, Morse JH, Slager SL, et al. Familial primary pulmonary hypertension (gene PPH1) is caused by mutations in the bone morphogenetic protein receptor-II gene. Am J Hum Genet 2000; 67: 737-744.
27. Thomson JR, Trembath RC. Primary pulmonary hypertension: the pressure rises for a gene. J Clin Pathol 2000; 53: 899-903.
28. Tsukada T, Yokoyama K, Arai T, et al. Evidence of association of the ecNOS gene polymorphism with plasma NO metabolite levels in humans. Biochem Biophys Res Commun 1998; 245: 190-193.
29. Pearson DL, Dawling S, Walsh WF, et al. Neonatal pulmonary hypertension-urea-cycle intermediates, nitric oxide production, and carbamoyl-phosphate synthetase function. N Engl J Med 2001; 344: 1832-1838.
30. Galie N, Torbicki A, Barst R, et al. Guidelines on diagnosis and treatment of pulmonary arterial hypertension. The Task Force on Diagnosis and Treatment of Pulmonary Arterial Hypertension of the European Society of Cardiology. Eur Heart J 2004; 25: 2243-2278.
31. Archer SL, Michelakis ED. An evidence-based approach to the management of pulmonary arterial hypertension. Curr Opin Cardiol 2006; 21: 385-392.
32. Rich S, Kaufmann E, Levy PS. The effect of high doses of calcium-channel blockers on survival in primary pulmonary hypertension. N Engl J Med 1992; 327: 76-81.
33. Tuder RM, Cool CD, Geraci MW, et al. Prostacyclin synthase expression is decreased in lungs from patients with severe pulmonary hypertension. Am J Respir Crit Care Med 1999; 159: 1925-1932.
34. Barst RJ, Rubin LJ, Long WA, et al. A comparison of continuous intravenous epoprostenol (prostacyclin) with conventional therapy for primary pulmonary hypertension. The Primary Pulmonary Hypertension Study Group. N Engl J Med 1996; 334: 296-302.
35. Badesch DB, Tapson VF, McGoon MD, et al. Continuous intravenous epoprostenol for pulmonary hypertension due to the scleroderma spectrum of disease. A randomized, controlled trial. Ann Intern Med 2000; 132: 425-434.
36. McLaughlin VV, Shillington A, Rich S. Survival in primary pulmonary hypertension: the impact of epoprostenol therapy. Circulation 2002; 106: 1477-1482.
37. Sitbon O, Humbert M, Nunes H, et al. Long-term intravenous epoprostenol infusion in primary pulmonary hypertension: prognostic factors and survival. J Am Coll Cardiol 2002; 40: 780-788.
38. Barst RJ, Rubin LJ, McGoon MD, Caldwell EJ, Long WA, Levy PS. Survival in primary pulmonary hypertension with long-term continuous intravenous prostacyclin. Ann Intern Med 1994; 121: 409-415.
39. Shapiro SM, Oudiz RJ, Cao T, et al. Primary pulmonary hypertension: improved long-term effects and survival with continuous intravenous epoprostenol infusion. J Am Coll Cardiol 1997; 30: 343-349.
40. McLaughlin VV, Genthner DE, Panella MM, Rich S. Reduction in pulmonary vascular resistance with long-term epoprostenol (prostacyclin) therapy in primary pulmonary hypertension. N Engl J Med 1998; 338: 273-277.
41. Rich S, McLaughlin VV. The effects of chronic prostacyclin therapy on cardiac output and symptoms in primary pulmonary hypertension. J Am Coll Cardiol 1999; 34: 1184-1187.
42. Gomberg-Maitland M, Tapson VF, Benza RL, et al. Transition from intravenous epoprostenol to intravenous treprostinil in pulmonary-hypertension. Am J Respir Crit Care Med 2005; 172: 1586-1589.
43. Simonneau G, Barst RJ, Galie N, et al. Continuous subcutaneous infusion of treprostinil, a prostacyclin analogue, in patients with pulmonary arterial hypertension: a double-blind, randomized, placebo-controlled trial. Am J Respir Crit Care Med 2002; 165: 800-804.
44. Gessler T, Schmehl T, Hoeper MM, et al. Ultrasonic versus jet nebulization of iloprost in severe pulmonary hypertension. Eur Respir J 2001; 17: 14-19.
45. Olschewski H, Ghofrani HA, Schmehl T, et al. Inhaled iloprost to treat severe pulmonary hypertension. An uncontrolled trial. German PPH Study Group. Ann Intern Med 2000; 132: 435-443.
46. Hoeper MM, Schwarze M, Ehlerding S, et al. Long-term treatment of primary pulmonary hypertension with aerosolized iloprost, a prostacyclin analogue. N Engl J Med 2000; 342: 1866-1870.
47. Olschewski H, Simonneau G, Galie N, et al. Inhaled iloprost for severe pulmonary hypertension. N Engl J Med 2002; 347: 322-329.
48. Okano Y, Yoshioka T, Shimouchi A, Satoh T, Kunieda T. Orally active prostacyclin analogue in primary pulmonary hypertension. Lancet 1997; 349: 1365.
49. Galie N, Manes A, Branzi A. The new clinical trials on pharmacological treatment in pulmonary arterial hypertension. Eur Respir J 2002; 20: 1037-1049.
50. Galie N, Humbert M, Vachiery JL, et al. Effects of beraprost sodium, an oral prostacyclin analogue, in patients with pulmonary arterial hypertension: a randomized, double-blind, placebo-controlled trial. J Am Coll Cardiol 2002; 39: 1496-1502.
51. Barst RJ, McGoon M, McLaughlin V, et al. Beraprost therapy for pulmonary arterial hyportension. J Am Coll Cardiol 2003; 41: 2119-2125.
52. Kim H, Yung GL, Marsh JJ, et al. Endothelin mediates pulmonary vascular remodelling in a canine model of chronic embolic pulmonary Hypertension. Eur Respir J 2000; 15: 640-648.
53. Yamane K. Endothelin and collagen vascular disease. a review with special reference to Raynaud's phenomenon and systemic sclerosis. Intern Med 1994; 33:579-582.
54. Giaid A, Yanagisawa M, Langleben D, et al. Expression of endothelin-1 in the lungs of patients with pulmonary hypertension. N Engl J Med 1993; 328: 1732-1739.
55. Rubens C, Ewert R, Halank M, et al. Big endothelin-1 and endothelin-1 plasma levels are correlated with the severity of primary pulmonary hypertension. Chest 2001; 120: 1562-1569.
56. Benigni A, Remuzzi G. Endothelin antagonists. Lancet 1999; 353: 133-138.
57. Channick RN, Simenneau G, Sitbon O, et al. Effects of the dual endothelin-receptor antagonist bosentan in patients with pulmonary hypertension: a randomised placebo-controlled study. Lancet 2001; 358: 1119-1123.
58. Rubin LJ, Badesch DB, Barst RJ, et al. Bosentan therapy for pulmonary arterial hypertension. N Engl J Med 2002; 346: 896-903.
59. Provencher S, Sitbon O, Humbert M, Cabrol S, Jais X, Simonneau G. Long term outcome with first-line bosentan therapy in idiopathic pulmonary arterial hypertension. Eur Heart J 2006; 27: 589-595:
60. Barst RJ, Langleben D, Frost A, et al. Sitaxsentan therapy for pulmonary arterial hypertension. Am J Respir Crit Care Med 2004; 169:441-447.
61. Braner DA, Fineman JR, Chang R, Soifer SJ. M&B 22948, a cGMP phosphodiesterase inhibitor, is a pulmonary vasodilator in lambs. Am J Physiol 1993; 264: H252-258.
62. McMahon TJ, Ignarro LJ, Kadowitz PJ. Influence of Zaprinast on vascular tone and vasodilator responses in the cat pulmonary vascular bed. J Appl Physiol 1993; 74: 1704-1711.
63. Clarke WR, Uezono S, Chambers A, Doepfner P. The type III phosphodiesterase inhibitor milrinone and type V PDE inhibitor dipyridamole individually and synergistically reduce elevated pulmonary vascular resistanct. Pulm Pharmacol 1994; 7: 81-89.
64. Cohen AH, Hanson K, Morris K, et al Inhibition of cyclic 3′-5′- guanisine monophosphate-specific phosphodiesterase selectively vasodilates the pulmonary circulation in chronically hypoxic rats. J Clin Invest 1996; 97: 172-179.
65. Thusu KG, Morin FC, 3rd, Russell JA, Steinhom RH. The cGMP phosphodiesterase inhibitor zaprinast enhances the effect of nitric oxide. Am J Respïr Crit Care Med 1995; 152: 1605-1610.
66. Ziegler JW, Ivy DD, Wiggins JW, Kinsella JP, Clarke WR, Abman SH. Effects of dipyridamole and inhaled nitric oxide in pediatric patients with pulmonary hypertension, Am J Respir Crit Care Med 998; 158: 1388-1395.
67. Ziegler JW, Ivy DD, Fox JJ, Kinsella JP, Clarke WR, Abman SH. Dipyridamole potentiates pulmonary vasodilation induced by acetylcholine and nitric oxide in the ovine fetus. Am J Respir Crit Care Med 1998; 157: 1104-1110.
68. Zhao L, Mason, NA, Morrell NW, et al. Sildenafil inhibits hypoxia-indueed pulmonary hypertension. Circulation 2001; 104: 424-428.
69. 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.
70. Lepore JJ, Maroo A, Pereira NL, 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.
71. Wilkens H, Guth A, Konig J, et al. Effect of inhaled iloprost plus oral sildenafil in patients with primary pulmonary hypertension. Circulation 2001; 104: 1218-1222.
72. Ghofrani HA, Wiedemann R, Rose F, et al. Combination therapy with oral sildenafil and inhaled iloprost for severe pulmonary hypertension. Ann Intern Med 2002; 136: 515-522.
73. Galie N, Ghofrani HA, Torbicki A, et al. Sildenafil citrate therapy for pulmonary arterial hypertension. N Engl J Med 2005; 353: 2148-2157.
74. Wilkins MR, Paul GA, Strange JW, et al. Sildenafil versus Endothelin Receptor Antagonist for Pulmonary Hypertension (SERAPH) study. Am J Respir Crit Care Med 2005; 171: 1292-1297.
75. Sastry BK, Narasimhan C, Reddy NK, et al. A study of clinical efficacy of sildenafil in patients with primary pulmonary hypertension. Indian Heart J 2002; 54: 410-414.
76. Ghofrani HA, Schermuly RT, Rose F, et al. Sildenafil for long-term treatment of nonoperable chronic thromboembolic pulmonary hypertension. Am J Respir Crit Care Med 2003; 167: 1139-1141.
77. Ghofrani HA, Rose F, Schermuly RT, et al. Oral sildenafil as long-term adjunct therapy to inhaled iloprost in severe pulmonary arterial hypertension. J Am Coll Cardiol 2003; 42: 158-164.
78. Gomberg-Maitland M, McLaughlin V, Gulati M, Rich S. Efficacy and safety of sildenafil added to treprostinil in pulmonary hypertension. Am J Cardiol 2005; 96: 1334-1336.
79. Das S, Kumar KN. Nitric oxide: its identity and role in blood pressure control. Life Sci 1995; 57: 1547-1556.
80. Pepke-Zaba J, Higenbottam TW, Dinh-Xuan AT, Stone D, Wallwork J. Inhaled nitric oxide as a cause of selective pulmonary vasodilatation in pulmonary hypertension. Lancet 1991; 338: 1173-1174.
81. Ivy DD, Griebel JL, Kinsella JP, Abman SH. Acute hemodynamic effects of pulsed delivery of low flow nasal nitric oxide in children with pulmonary hypertension. J Pediatr 1998; 133: 453-456.
82. Channick RN, Newhart JW, Johnson FW, et al. Pulsed delivery of inhaled nitric oxide to patients with primary pulmonary hypertension: an ambulatory delivery system and initial clinical tests. Chest 1996; 109: 1545-1549.
83. Mehta S, Stewart DJ, Langleben D, Levy RD. Short-term pulmonary vasodilation with L-arginine in pulmonary hypertension. Circulation 1995; 92: 1539-1545.
84. Surdacki A, Zmudka K, Bieron K, Kostka-Trabka E, Dubiel JS, Gryglewski RJ. Lack of beneficial effects of L-arginine infusion in primary pulmonary hypertension. Wien Klin Wochenschr 1994; 106: 521-526.
85. Nagaya N, Uematsu M, Oya H, et al. Short-term oral administration of L-arginine improves hemodynamics and exercise capacity in patients with precapillary pulmonary hypertension. Am J Respir Crit Care Med 2001, 163: 887-891.
86. Nishimura T, Vaszar LT, Faul JL, et al. Simvastatin rescues rats from fatal pulmonary hypertension by inducing apoptosis of neointimal smooth muscle cells. Circulation 2003; 108: 1640-1645.
87. Kao PN. Simvastatin treatment of pulmonary hypertension: an observational case series. Chest 2005; 127: 1446-1452.
88. Iwabuchi S, Ono S, Tanita. T, Koike K, Fujimura S. Vasoactive intestinal peptide causes nitric oxide-dependent pulmonary vasodilation in isolated rat lung. Respiration 1997; 64: 54-58.
89. Soderman C, Eriksson LS, Juhlin-Dannfelt A, Lundberg JM, Broman L, Holmgren A. Effect of vasoactive intestinal polypeptide (VIP) on pulmonary ventilation-perfusion relationships and central haemodynamics in healthy subjects. Clin Physiol 1993; 13: 677-685.
90. Gunaydin S, Imai Y, Takanashi Y, et al. The effects of vasoactive intestinal peptide on monocrotaline induced pulmonary hypertensive rabbits following cardiopulmonary bypass: a comparative study with isoproteronol and nitroglycerine. Cardiovasc Surg 2002; 10: 138-145.
91. Cox CP, Linden J, Said SI. VIP elevates platelet cyclic AMP (cAMP) levels and inhibits in vitro platelet activation induced by platelet-activating factor (PAF). Peptides 1984; 5: 325-328.
92. Maruno K, Absood A, Said SI. VIP inhibits basal and histamine-stimulated proliferation of human airway smooth muscle cells. Am J Physiol 1995; 268: L1047-1051.
93. Klinger JR, Thaker S, Houtchens J, Preston IR, Hill NS, Farber HW. Pulmonary bemodynamic responses to brain natriuretic peptide and sildenafil in patients with pulmonary arterial hypertension. Chest 2006; 129: 417-425.
94. Archer SL, Peterson D, Nelson DP, et al. Oxygen radicals and antioxidant enzymes alter pulmonary vascular reactivity in the rat lung. J Appl Physiol 1989; 66: 102-111.
95. Ghofrani HA, Seeger W, Grimminger F. Imatinib for the treatment of pulmonary arterial hypertension. N Engl J Med 2005; 353: 1412-1413.
96. Schermuly RT, Dony E, Ghofrani HA, et al. Reversal of experimental pulmonary hypertension by PDGF inhibition. J Clin Invest 2005; 115: 2811-2821.
97. McMurtry MS, Bonnet S, Wu X, et al. Dichloroacetate prevents and reverses pulmonary hypertension by inducing pulmonary artery smooth muscle cell apoptosis. Circ Res 2004; 95: 830-840.
98. Michelakis ED, McMurtry MS, Wu XC, et al. Dichloroacetate, a metabolic modulator, prevents and reverses chronic hypoxic pulmonary hypertension in rats: role of increased expression and activity of voltage-gated potassium channels. Circulation 2002; 105: 244-250.
99. McMurtry MS, Archer SL, Altieri DC, et al. Gette therapy targeting survivin selectively induces pulmonary vascular apoptosis and reverses pulmonary arterial hypertension. J Clin Invest 2005; 115: 1479-1491.