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CNS Drugs

, Volume 31, Issue 11, pp 975–989 | Cite as

Pharmacotherapy of Cardiovascular Autonomic Dysfunction in Parkinson Disease

  • Cyndya A. Shibao
  • Horacio KaufmannEmail author
Review Article

Abstract

Cardiovascular autonomic dysfunctions, including neurogenic orthostatic hypotension, supine hypertension and post-prandial hypotension, are relatively common in patients with Parkinson disease. Recent evidence suggests that early autonomic impairment such as cardiac autonomic denervation and even neurogenic orthostatic hypotension occur prior to the appearance of the typical motor deficits associated with the disease. When neurogenic orthostatic hypotension develops, patients with Parkinson disease have an increased risk of mortality, falls, and trauma-related to falls. Neurogenic orthostatic hypotension reduces quality of life and contributes to cognitive decline and physical deconditioning. The co-existence of supine hypertension complicates the treatment of neurogenic orthostatic hypotension because it involves the use of drugs with opposing effects. Furthermore, treatment of neurogenic orthostatic hypotension is challenging because of few therapeutic options; in the past 20 years, the US Food and Drug Administration approved only two drugs for the treatment of this condition. Small, open-label or randomized studies using acute doses of different pharmacologic probes suggest benefit of other drugs as well, which could be used in individual patients under close monitoring. This review describes the pathophysiology of neurogenic orthostatic hypotension and supine hypertension in Parkinson disease. We discuss the mode of action and therapeutic efficacy of different pharmacologic agents used in the treatment of patients with cardiovascular autonomic failure.

Notes

Acknowledgements

C.A.S. was supported by a Doris Duke Foundation Career Development Award. C.A.S. and H.K. received grant support from the Office of Orphan Products Development, Food and Drug Administration, Grant #FD-R-04778-01-A3.

Compliance with Ethical Standards

Funding

The authors did not receive funding for the preparation and writing of the present manuscript.

Conflict of interest

CA.S. has received research a grant from the Doris Duke Foundation. C.A.S. and H.K. received grant support from the Office of Orphan Products Development, Food and Drug Administration, Grant #FD-R-04778-01-A3. C.A.S. has received speaker honorarium from Lundbeck Pharmaceuticals. C.A.S. and H.K. received consulting honoraria from Lundbeck and Theravance Biopharma. C.A.S is a member of the Board for the American Autonomic Society.

References

  1. 1.
    Ascherio A, Schwarzschild MA. The epidemiology of Parkinson’s disease: risk factors and prevention. Lancet Neurol. 2016;15(12):1257–72.PubMedCrossRefGoogle Scholar
  2. 2.
    Wright Willis A, Evanoff BA, Lian M, Criswell SR, Racette BA. Geographic and ethnic variation in Parkinson disease: a population-based study of US Medicare beneficiaries. Neuroepidemiology. 2010;34(3):143–51.PubMedPubMedCentralCrossRefGoogle Scholar
  3. 3.
    Fearnley JM, Lees AJ. Ageing and Parkinson’s disease: substantia nigra regional selectivity. Brain. 1991;114(Pt 5):2283–301.PubMedCrossRefGoogle Scholar
  4. 4.
    de la Fuente-Fernandez R, Schulzer M, Kuramoto L, Cragg J, Ramachandiran N, Au WL, et al. Age-specific progression of nigrostriatal dysfunction in Parkinson’s disease. Ann Neurol. 2011;69(5):803–10.PubMedCrossRefGoogle Scholar
  5. 5.
    Braak H, Del Tredici K. Invited article: nervous system pathology in sporadic Parkinson disease. Neurology. 2008;70(20):1916–25.PubMedCrossRefGoogle Scholar
  6. 6.
    Braak H, Del Tredici K, Rub U, de Vos RA, Jansen Steur EN, Braak E. Staging of brain pathology related to sporadic Parkinson’s disease. Neurobiol Aging. 2003;24(2):197–211.PubMedCrossRefGoogle Scholar
  7. 7.
    Boeve BF, Silber MH, Saper CB, Ferman TJ, Dickson DW, Parisi JE, et al. Pathophysiology of REM sleep behaviour disorder and relevance to neurodegenerative disease. Brain. 2007;130(Pt 11):2770–88.PubMedCrossRefGoogle Scholar
  8. 8.
    Postuma RB, Gagnon JF, Pelletier A, Montplaisir J. Prodromal autonomic symptoms and signs in Parkinson’s disease and dementia with Lewy bodies. Mov Disord. 2013;28(5):597–604.PubMedCrossRefGoogle Scholar
  9. 9.
    Kaufmann H, Norcliffe-Kaufmann L, Palma JA, Biaggioni I, Low PA, Singer W, et al. Natural history of pure autonomic failure: a United States prospective cohort. Ann Neurol. 2017;81(2):287–97.PubMedPubMedCentralCrossRefGoogle Scholar
  10. 10.
    Velseboer DC, de Haan RJ, Wieling W, Goldstein DS, de Bie RM. Prevalence of orthostatic hypotension in Parkinson’s disease: a systematic review and meta-analysis. Parkinsonism Relat Disord. 2011;17(10):724–9.PubMedPubMedCentralCrossRefGoogle Scholar
  11. 11.
    Gibbons CH, Schmidt P, Biaggioni I, Frazier-Mills C, Freeman R, Isaacson S, et al. The recommendations of a consensus panel for the screening, diagnosis, and treatment of neurogenic orthostatic hypotension and associated supine hypertension. J Neurol. 2017;64(8):1567–82.CrossRefGoogle Scholar
  12. 12.
    Palma JA, Gomez-Esteban JC, Norcliffe-Kaufmann L, Martinez J, Tijero B, Berganzo K, et al. Orthostatic hypotension in Parkinson disease: how much you fall or how low you go? Mov Disord. 2015;30(5):639–45.PubMedPubMedCentralCrossRefGoogle Scholar
  13. 13.
    Ha AD, Brown CH, York MK, Jankovic J. The prevalence of symptomatic orthostatic hypotension in patients with Parkinson’s disease and atypical parkinsonism. Parkinsonism Relat Disord. 2011;17(8):625–8.PubMedCrossRefGoogle Scholar
  14. 14.
    Hely MA, Morris JG, Reid WG, Trafficante R. Sydney Multicenter Study of Parkinson’s disease: non-l-dopa-responsive problems dominate at 15 years. Mov Disord. 2005;20(2):190–9.PubMedCrossRefGoogle Scholar
  15. 15.
    Xin W, Lin Z, Mi S. Orthostatic hypotension and mortality risk: a meta-analysis of cohort studies. Heart. 2014;100(5):406–13.PubMedCrossRefGoogle Scholar
  16. 16.
    Pathak A, Lapeyre-Mestre M, Montastruc JL, Senard JM. Heat-related morbidity in patients with orthostatic hypotension and primary autonomic failure. Mov Disord. 2005;20(9):1213–9.PubMedCrossRefGoogle Scholar
  17. 17.
    Stolze H, Klebe S, Zechlin C, Baecker C, Friege L, Deuschl G. Falls in frequent neurological diseases–prevalence, risk factors and aetiology. J Neurol. 2004;251(1):79–84.PubMedCrossRefGoogle Scholar
  18. 18.
    Woodford H, Walker R. Emergency hospital admissions in idiopathic Parkinson’s disease. Mov Disord. 2005;20(9):1104–8.PubMedCrossRefGoogle Scholar
  19. 19.
    Low V, Ben-Shlomo Y, Coward E, Fletcher S, Walker R, Clarke CE. Measuring the burden and mortality of hospitalisation in Parkinson’s disease: a cross-sectional analysis of the English Hospital Episodes Statistics database 2009–2013. Parkinsonism Relat Disord. 2015;21(5):449–54.PubMedCrossRefGoogle Scholar
  20. 20.
    Allen NE, Schwarzel AK, Canning CG. Recurrent falls in Parkinson’s disease: a systematic review. Parkinsons Dis. 2013;2013:906274.PubMedPubMedCentralGoogle Scholar
  21. 21.
    Francois C, Biaggioni I, Shibao C, Ogbonnaya A, Shih HC, Farrelly E, et al. Fall-related healthcare use and costs in neurogenic orthostatic hypotension with Parkinson’s disease. J Med Econ. 2017;20(5):525–32.PubMedCrossRefGoogle Scholar
  22. 22.
    Schrag A, Hovris A, Morley D, Quinn N, Jahanshahi M. Caregiver-burden in parkinson’s disease is closely associated with psychiatric symptoms, falls, and disability. Parkinsonism Relat Disord. 2006;12(1):35–41.PubMedCrossRefGoogle Scholar
  23. 23.
    Magerkurth C, Schnitzer R, Braune S. Symptoms of autonomic failure in Parkinson’s disease: prevalence and impact on daily life. Clin Auton Res. 2005;15(2):76–82.PubMedCrossRefGoogle Scholar
  24. 24.
    Pilleri M, Facchini S, Gasparoli E, Biundo R, Bernardi L, Marchetti M, et al. Cognitive and MRI correlates of orthostatic hypotension in Parkinson’s disease. J Neurol. 2013;260(1):253–9.PubMedCrossRefGoogle Scholar
  25. 25.
    Allcock LM, Kenny RA, Mosimann UP, Tordoff S, Wesnes KA, Hildreth AJ, et al. Orthostatic hypotension in Parkinson’s disease: association with cognitive decline? Int J Geriatr Psychiatry. 2006;21(8):778–83.PubMedCrossRefGoogle Scholar
  26. 26.
    Frewen J, Savva GM, Boyle G, Finucane C, Kenny RA. Cognitive performance in orthostatic hypotension: findings from a nationally representative sample. J Am Geriatr Soc. 2014;62(1):117–22.PubMedCrossRefGoogle Scholar
  27. 27.
    Mehrabian S, Duron E, Labouree F, Rollot F, Bune A, Traykov L, et al. Relationship between orthostatic hypotension and cognitive impairment in the elderly. J Neurol Sci. 2010;299(1–2):45–8.PubMedCrossRefGoogle Scholar
  28. 28.
    Poda R, Guaraldi P, Solieri L, Calandra-Buonaura G, Marano G, Gallassi R, et al. Standing worsens cognitive functions in patients with neurogenic orthostatic hypotension. Neurol Sci. 2012;33(2):469–73.PubMedCrossRefGoogle Scholar
  29. 29.
    Centi J, Freeman R, Gibbons CH, Neargarder S, Canova AO, Cronin-Golomb A. Effects of orthostatic hypotension on cognition in Parkinson disease. Neurology. 2017;88(1):17–24.PubMedCrossRefGoogle Scholar
  30. 30.
    Li ST, Dendi R, Holmes C, Goldstein DS. Progressive loss of cardiac sympathetic innervation in Parkinson’s disease. Ann Neurol. 2002;52(2):220–3.PubMedCrossRefGoogle Scholar
  31. 31.
    Mitsui J, Saito Y, Momose T, Shimizu J, Arai N, Shibahara J, et al. Pathology of the sympathetic nervous system corresponding to the decreased cardiac uptake in 123I-metaiodobenzylguanidine (MIBG) scintigraphy in a patient with Parkinson disease. J Neurol Sci. 2006;243(1–2):101–4.PubMedCrossRefGoogle Scholar
  32. 32.
    Braune S, Reinhardt M, Schnitzer R, Riedel A, Lucking CH. Cardiac uptake of [123I]MIBG separates Parkinson’s disease from multiple system atrophy. Neurology. 1999;53(5):1020–5.PubMedCrossRefGoogle Scholar
  33. 33.
    Kaufmann H, Goldstein DS. Autonomic dysfunction in Parkinson disease. Handb Clin Neurol. 2013;117:259–78.PubMedCrossRefGoogle Scholar
  34. 34.
    Orimo S, Uchihara T, Nakamura A, Mori F, Kakita A, Wakabayashi K, et al. Axonal alpha-synuclein aggregates herald centripetal degeneration of cardiac sympathetic nerve in Parkinson’s disease. Brain. 2008;131(Pt 3):642–50.PubMedCrossRefGoogle Scholar
  35. 35.
    Palma JA, Kaufmann H. Autonomic disorders predicting Parkinson’s disease. Parkinsonism Relat Disord. 2014;20(Suppl 1):S94–8.PubMedPubMedCentralCrossRefGoogle Scholar
  36. 36.
    Braune S. The role of cardiac metaiodobenzylguanidine uptake in the differential diagnosis of parkinsonian syndromes. Clin Auton Res. 2001;11(6):351–5.PubMedCrossRefGoogle Scholar
  37. 37.
    Diedrich A, Biaggioni I. Segmental orthostatic fluid shifts. Clin Auton Res. 2004;14(3):146–7.PubMedCrossRefGoogle Scholar
  38. 38.
    Novak V, Novak P, Spies JM, Low PA. Autoregulation of cerebral blood flow in orthostatic hypotension. Stroke. 1998;29(1):104–11.PubMedCrossRefGoogle Scholar
  39. 39.
    Bird ST, Delaney JA, Brophy JM, Etminan M, Skeldon SC, Hartzema AG. Tamsulosin treatment for benign prostatic hyperplasia and risk of severe hypotension in men aged 40–85 years in the United States: risk window analyses using between and within patient methodology. BMJ. 2013;05(347):f6320.CrossRefGoogle Scholar
  40. 40.
    Podoleanu C, Maggi R, Brignole M, Croci F, Incze A, Solano A, et al. Lower limb and abdominal compression bandages prevent progressive orthostatic hypotension in elderly persons: a randomized single-blind controlled study. J Am Coll Cardiol. 2006;48(7):1425–32.PubMedCrossRefGoogle Scholar
  41. 41.
    Smit AA, Wieling W, Fujimura J, Denq JC, Opfer-Gehrking TL, Akarriou M, et al. Use of lower abdominal compression to combat orthostatic hypotension in patients with autonomic dysfunction. Clin Auton Res. 2004;14(3):167–75.PubMedCrossRefGoogle Scholar
  42. 42.
    Jordan J, Shannon JR, Grogan E, Biaggioni I, Robertson D. A potent pressor response elicited by drinking water. Lancet. 1999;353(9154):723.PubMedCrossRefGoogle Scholar
  43. 43.
    Jordan J. Effect of water drinking on sympathetic nervous activity and blood pressure. Curr Hypertens Rep. 2005;7(1):17–20.PubMedCrossRefGoogle Scholar
  44. 44.
    Ten Harkel AD, Baisch F, Karenmaker JM. Increased orthostatic blood pressure variability after prolonged head-down tilt. Acta Physiol Scand. 1992;1992(144):89–99.Google Scholar
  45. 45.
    van Lieshout JJ, Ten Harkel AD, Wieling W. Fludrocortisone and sleeping in the head-up position limit the postural decrease in cardiac output in autonomic failure. Clin Auton Res. 2000;10(1):35–42.PubMedCrossRefGoogle Scholar
  46. 46.
    Puvi-Rajasingham S, Mathias CJ. Effect of meal size on post-prandial blood pressure and on postural hypotension in primary autonomic failure. Clin Auton Res. 1996;6(2):111–4.PubMedCrossRefGoogle Scholar
  47. 47.
    Mathias CJ. Postprandial hypotension. Pathophysiological mechanisms and clinical implications in different disorders. Hypertension. 1991;18(5):694–704.PubMedCrossRefGoogle Scholar
  48. 48.
    Visvanathan R, Chen R, Garcia M, Horowitz M, Chapman I. The effects of drinks made from simple sugars on blood pressure in healthy older people. Br J Nutr. 2005;93(5):575–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Onrot J, Goldberg MR, Biaggioni I, Hollister AS, Kincaid D, Robertson D. Hemodynamic and humoral effects of caffeine in human autonomic failure. NEnglJMed. 1985;1985(313):549–54.CrossRefGoogle Scholar
  50. 50.
    Chaudhuri KR, Ellis C, Love-Jones S, Thomaides T, Clift S, Mathias CJ, et al. Postprandial hypotension and parkinsonian state in Parkinson’s disease. Mov Disord. 1997;12(6):877–84.PubMedCrossRefGoogle Scholar
  51. 51.
    Kaufmann H, Norcliffe-Kaufmann L, Palma JA. Droxidopa in neurogenic orthostatic hypotension. Expert Rev Cardiovasc Ther. 2015;13(8):875–91.PubMedPubMedCentralCrossRefGoogle Scholar
  52. 52.
    Biaggioni I, Freeman R, Mathias CJ, Low P, Hewitt LA, Kaufmann H, et al. Randomized withdrawal study of patients with symptomatic neurogenic orthostatic hypotension responsive to droxidopa. Hypertension. 2015;65(1):101–7.PubMedCrossRefGoogle Scholar
  53. 53.
    Hauser RA, Isaacson S, Lisk JP, Hewitt LA, Rowse G. Droxidopa for the short-term treatment of symptomatic neurogenic orthostatic hypotension in Parkinson’s disease (nOH306B). Mov Disord. 2015;30(5):646–54.PubMedCrossRefGoogle Scholar
  54. 54.
    Chatrchyan S, Khachatryan V, Sirunyan AM, Tumasyan A, Adam W, Bergauer T, et al. Measurement of inclusive W and Z boson production cross sections in pp collisions at sqrt[s] = 8 TeV. Phys Rev Lett. 2014;112(19):191802.PubMedCrossRefGoogle Scholar
  55. 55.
    Kaufmann H, Freeman R, Biaggioni I, Low P, Pedder S, Hewitt LA, et al. Droxidopa for neurogenic orthostatic hypotension: a randomized, placebo-controlled, phase 3 trial. Neurology. 2014;83(4):328–35.PubMedPubMedCentralCrossRefGoogle Scholar
  56. 56.
    Biaggioni I, Arthur Hewitt L, Rowse GJ, Kaufmann H. Integrated analysis of droxidopa trials for neurogenic orthostatic hypotension. BMC Neurol. 2017;17(1):90.PubMedPubMedCentralCrossRefGoogle Scholar
  57. 57.
    Hauser RA, Heritier S, Rowse GJ, Hewitt LA, Isaacson SH. Droxidopa and reduced falls in a trial of parkinson disease patients with neurogenic orthostatic hypotension. Clin Neuropharmacol. 2016;39(5):220–6.PubMedPubMedCentralCrossRefGoogle Scholar
  58. 58.
    Goldberg MR, Hollister AS, Robertson D. Influence of yohimbine on blood pressure, autonomic reflexes and plasma catecholamines in humans. Hypertension. 1983;1983(5):772–8.CrossRefGoogle Scholar
  59. 59.
    Onrot J, Goldberg MR, Biaggioni I, Wiley R, Hollister AS, Robertson D. Oral yohimbine in human autonomic failure. Neurology. 1987;1987(37):215–20.CrossRefGoogle Scholar
  60. 60.
    Jordan J, Shannon JR, Biaggioni I, Norman R, Black BK, Robertson D. Contrasting actions of pressor agents in severe autonomic failure. Am J Med. 1998;105(2):116–24.PubMedCrossRefGoogle Scholar
  61. 61.
    Shibao C, Okamoto LE, Gamboa A, Yu C, Diedrich A, Raj SR, et al. Comparative efficacy of yohimbine against pyridostigmine for the treatment of orthostatic hypotension in autonomic failure. Hypertension. 2010;56(5):847–51.PubMedPubMedCentralCrossRefGoogle Scholar
  62. 62.
    Singer W, Opfer-Gehrking TL, McPhee BR, Hilz MJ, Bharucha AE, Low PA. Acetylcholinesterase inhibition: a novel approach in the treatment of neurogenic orthostatic hypotension. J Neurol Neurosurg Psychiatry. 2003;74(9):1294–8.PubMedPubMedCentralCrossRefGoogle Scholar
  63. 63.
    Singer W, Sandroni P, Opfer-Gehrking TL, Suarez GA, Klein CM, Hines S, et al. Pyridostigmine treatment trial in neurogenic orthostatic hypotension. Arch Neurol. 2006;63(4):513–8.PubMedCrossRefGoogle Scholar
  64. 64.
    Simpson D, Plosker GL. Atomoxetine: a review of its use in adults with attention deficit hyperactivity disorder. Drugs. 2004;64(2):205–22.PubMedCrossRefGoogle Scholar
  65. 65.
    Shibao C, Raj SR, Gamboa A, Diedrich A, Choi L, Black BK, et al. Norepinephrine transporter blockade with atomoxetine induces hypertension in patients with impaired autonomic function. Hypertension. 2007;50(1):47–53.PubMedCrossRefGoogle Scholar
  66. 66.
    Ramirez CE, Okamoto LE, Arnold AC, Gamboa A, Diedrich A, Choi L, et al. Efficacy of atomoxetine versus midodrine for the treatment of orthostatic hypotension in autonomic failure. Hypertension. 2014;64(6):1235–40.PubMedPubMedCentralCrossRefGoogle Scholar
  67. 67.
    Low PA, Gilden JL, Freeman R, Sheng KN, McElligott MA. Efficacy of midodrine vs placebo in neurogenic orthostatic hypotension. A randomized, double-blind multicenter study. Midodrine Study Group. Jama. 1997;277(13):1046–51.PubMedCrossRefGoogle Scholar
  68. 68.
    Wright RA, Kaufmann HC, Perera R, Opfer-Gehrking TL, McElligott MA, Sheng KN, et al. A double-blind, dose-response study of midodrine in neurogenic orthostatic hypotension. Neurology. 1998;51(1):120–4.PubMedCrossRefGoogle Scholar
  69. 69.
    Bevegard S, Castenfors J, Lindblad LE. Haemodynamic effects of dihydroergotamine in patients with postural hypotension. Acta Med Scand. 1974;1974(196):473–7.Google Scholar
  70. 70.
    Benowitz NL, Byrd R, Schambelan M, Rosenberg J, Roizen MF. Dihydroergotamine treatment for orthostatic hypotension from Vacor rodenticide. Ann Int Med. 1980;1980(92):387–8.CrossRefGoogle Scholar
  71. 71.
    Chobanian AV, Tifft CP, Faxon DP, Creager MLA, Sackel H. Treatment of orthostatic hypotension with ergotamine. Circulation. 1983;1983(67):602–9.CrossRefGoogle Scholar
  72. 72.
    Hoeldtke RD, Cavanaugh ST, Hughes JD, Polansky M. Treatment of orthostatic hypotension with dihydroergotamine and caffeine. Ann Int Med. 1986;1986(105):168–73.CrossRefGoogle Scholar
  73. 73.
    Biaggioni I, Zygmunt D, Haile V, Robertson D. Pressor effect of inhaled ergotamine in orthostatic hypotension. Am J Cardiol. 1990;1990(65):89–92.CrossRefGoogle Scholar
  74. 74.
    Arnold AC, Ramirez CE, Choi L, Okamoto LE, Gamboa A, Diedrich A, et al. Combination ergotamine and caffeine improves seated blood pressure and presyncopal symptoms in autonomic failure. Front Physiol. 2014;5:270.PubMedPubMedCentralCrossRefGoogle Scholar
  75. 75.
    Armstrong E, Mathias CJ. The effects of the somatostatin analogue, octreotide, on postural hypotension, before and after food ingestion, in primary autonomic failure. Clin Auton Res. 1991;1(2):135–40.PubMedCrossRefGoogle Scholar
  76. 76.
    Hoeldtke RD, O’Dorisio TM, Boden G. Treatment of autonomic neuropathy with a somatostatin analog SMS 201-995. Lancet. 1986;1986(2):602–5.CrossRefGoogle Scholar
  77. 77.
    Hoeldtke RD, Dworkin GE, Gaspar SR, Israel BC, Boden G. Effect of the somatostatin analogue SMS-201-995 on the adrenergic response to glucose ingestion in patients with post prandial hypotension. Am J Med. 1989;1989(86):673–7.CrossRefGoogle Scholar
  78. 78.
    Chobanian AV, Volicer L, Tifft CP, Gavras H, Liang CS, Faxon D. Mineralocorticoid-induced hypertension in patients with orthostatic hypotension. N Engl J Med. 1979;1979(301):68–73.CrossRefGoogle Scholar
  79. 79.
    Campbell IW, Ewing DJ, Clarke BF. 9-a-fluorohydrocortisone in the treatment of postural hypotension in diabetic autonomic neuropathy. Diabetes. 1975;1975(24):381–4.CrossRefGoogle Scholar
  80. 80.
    Hoehn MM. Levodopa-induced postural hypotension. Treatment with fludrocortisone. Arch Neurol. 1975;1975(32):50–1.CrossRefGoogle Scholar
  81. 81.
    Campbell IW, Ewing DJ, Clarke BF. Therapeutic experience with fludrocortisone in diabetic postural hypotension. Br Med J. 1976;1(6014):872–4.PubMedPubMedCentralCrossRefGoogle Scholar
  82. 82.
    Hussain RM, McIntosh SJ, Lawson J, Kenny RA. Fludrocortisone in the treatment of hypotensive disorders in the elderly. Heart. 1996;76(6):507–9.PubMedPubMedCentralCrossRefGoogle Scholar
  83. 83.
    Pathak A, Raoul V, Montastruc JL, Senard JM. Adverse drug reactions related to drugs used in orthostatic hypotension: a prospective and systematic pharmacovigilance study in France. Eur J Clin Pharmacol. 2005;61(5–6):471–4.PubMedCrossRefGoogle Scholar
  84. 84.
    Maule S, Tredici M, Dematteis A, Matteoda C, Chiandussi L. Postprandial hypotension treated with acarbose in a patient with type 1 diabetes mellitus. Clin Auton Res. 2004;14(6):405–7.PubMedCrossRefGoogle Scholar
  85. 85.
    Lyons TJ, McLoughlin JC, Shaw C, Buchanan KD. Effect of acarbose on biochemical responses and clinical symptoms in dumping syndrome. Digestion. 1985;31(2–3):89–96.PubMedCrossRefGoogle Scholar
  86. 86.
    Shibao C, Gamboa A, Diedrich A, Dossett C, Choi L, Farley G, et al. Acarbose, an alpha-glucosidase inhibitor, attenuates postprandial hypotension in autonomic failure. Hypertension. 2007;50(1):54–61.PubMedCrossRefGoogle Scholar
  87. 87.
    Biaggioni I, Robertson RM. Hypertension in orthostatic hypotension and autonomic dysfunction. Cardiol Clin. 2002;20(2):291–301.PubMedCrossRefGoogle Scholar
  88. 88.
    Arnold AC, Biaggioni I. Management approaches to hypertension in autonomic failure. Curr Opin Nephrol Hypertens. 2012;21(5):481–5.PubMedPubMedCentralCrossRefGoogle Scholar
  89. 89.
    Vagaonescu TD, Saadia D, Tuhrim S, Phillips RA, Kaufmann H. Hypertensive cardiovascular damage in patients with primary autonomic failure. Lancet. 2000;355(9205):725–6.PubMedCrossRefGoogle Scholar
  90. 90.
    Garland EM, Gamboa A, Okamoto L, Raj SR, Black BK, Davis TL, et al. Renal impairment of pure autonomic failure. Hypertension. 2009;54(5):1057–61.PubMedPubMedCentralCrossRefGoogle Scholar
  91. 91.
    Shannon JR, Jordan J, Diedrich A, Pohar B, Black BK, Robertson D, et al. Sympathetically mediated hypertension in autonomic failure. Circulation. 2000;101(23):2710–5.PubMedCrossRefGoogle Scholar
  92. 92.
    Ibrahim MM, Tarazi RC, Dustan HP, Bravo EL. Idiopathic orthostatic hypotension: circulatory dynamics in chronic autonomic insufficiency. Am J Cardiol. 1974;1974(34):288–94.CrossRefGoogle Scholar
  93. 93.
    Biaggioni I, Garcia F, Inagami T, Haile V. Hyporeninemic normoaldosteronism in severe autonomic failure. J Clin Endocrinol Metab. 1993;1993(76):580–6.Google Scholar
  94. 94.
    Gamboa A, Shibao C, Diedrich A, Paranjape SY, Farley G, Christman B, et al. Excessive nitric oxide function and blood pressure regulation in patients with autonomic failure. Hypertension. 2008;51(6):1531–6.PubMedPubMedCentralCrossRefGoogle Scholar
  95. 95.
    Arnold AC, Okamoto LE, Gamboa A, Shibao C, Raj SR, Robertson D, et al. Angiotensin II, independent of plasma renin activity, contributes to the hypertension of autonomic failure. Hypertension. 2013;61(3):701–6.PubMedCrossRefGoogle Scholar
  96. 96.
    Arnold AC, Okamoto LE, Gamboa A, Black BK, Raj SR, Elijovich F, et al. Mineralocorticoid receptor activation contributes to the supine hypertension of autonomic failure. Hypertension. 2016;67(2):424–9.PubMedGoogle Scholar
  97. 97.
    Okamoto LE, Gamboa A, Shibao C, Black BK, Diedrich A, Raj SR, et al. Nocturnal blood pressure dipping in the hypertension of autonomic failure. Hypertension. 2009;53(2):363–9.PubMedCrossRefGoogle Scholar
  98. 98.
    Okamoto LE, Celedonio JE, Gamboa A, Shibao CA, Raj SR, Diedrich A, et al. Abstract 022: Blood pressure-lowering effect of local passive heat in autonomic failure patients with supine hypertension. Hypertension. 2016;68(Suppl 1):A022-A.Google Scholar
  99. 99.
    Jordan J, Shannon JR, Pohar B, Paranjape SY, Robertson D, Robertson RM, et al. Contrasting effects of vasodilators on blood pressure and sodium balance in the hypertension of autonomic failure. J Am Soc Nephrol. 1999;10(1):35–42.PubMedGoogle Scholar
  100. 100.
    Pahor M, Guralnik JM, Corti MC, Foley DJ, Carbonin P, Havlik RJ. Long-term survival and use of antihypertensive medications in older persons. J Am Geriatr Soc. 1995;43(11):1191–7.PubMedCrossRefGoogle Scholar
  101. 101.
    Okamoto LE, Gamboa A, Shibao CA, Arnold AC, Choi L, Black BK, et al. Nebivolol, but not metoprolol, lowers blood pressure in nitric oxide-sensitive human hypertension. Hypertension. 2014;64(6):1241–7.PubMedPubMedCentralCrossRefGoogle Scholar
  102. 102.
    Moriwaki H, Uno H, Nagakane Y, Hayashida K, Miyashita K, Naritomi H. Losartan, an angiotensin II (AT1) receptor antagonist, preserves cerebral blood flow in hypertensive patients with a history of stroke. J Hum Hypertens. 2004;18(10):693–9.PubMedCrossRefGoogle Scholar
  103. 103.
    Kario K, Ishikawa J, Hoshide S, Matsui Y, Morinari M, Eguchi K, et al. Diabetic brain damage in hypertension: role of renin-angiotensin system. Hypertension. 2005;45(5):887–93.PubMedCrossRefGoogle Scholar

Copyright information

© Springer International Publishing AG 2017

Authors and Affiliations

  1. 1.Division of Clinical Pharmacology, Department of Medicine, Vanderbilt Autonomic Dysfunction CenterVanderbilt University Medical CenterNashvilleUSA
  2. 2.Department of NeurologyNYU Langone Medical Center, Dysautonomia CenterNew YorkUSA

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