Spinal Cord Injuries — Dose Response to the Norepinephrine Precursor Droxidopa in Hypotensive Individuals With Spinal Cord Injury
Citation(s)
Arterial hypertension Report of a WHO expert committee. World Health Organ Tech Rep Ser. 1978;(628):7-56. No abstract available.
Barber DB, Rogers SJ, Fredrickson MD, Able AC Midodrine hydrochloride and the treatment of orthostatic hypotension in tetraplegia: two cases and a review of the literature. Spinal Cord. 2000 Feb;38(2):109-11. doi: 10.1038/sj.sc.3100959.
Barrett-Connor E, Palinkas LA Low blood pressure and depression in older men: a population based study. BMJ. 1994 Feb 12;308(6926):446-9. doi: 10.1136/bmj.308.6926.446.
Claydon VE, Krassioukov AV Orthostatic hypotension and autonomic pathways after spinal cord injury. J Neurotrauma. 2006 Dec;23(12):1713-25. doi: 10.1089/neu.2006.23.1713.
Claydon VE, Steeves JD, Krassioukov A Orthostatic hypotension following spinal cord injury: understanding clinical pathophysiology. Spinal Cord. 2006 Jun;44(6):341-51. doi: 10.1038/sj.sc.3101855. Epub 2005 Nov 22.
Clayton KS, Chubon RA Factors associated with the quality of life of long-term spinal cord injured persons. Arch Phys Med Rehabil. 1994 Jun;75(6):633-8. doi: 10.1016/0003-9993(94)90184-8.
Courtois FJ, Charvier KF, Leriche A, Vezina JG, Cote M, Belanger M Blood pressure changes during sexual stimulation, ejaculation and midodrine treatment in men with spinal cord injury. BJU Int. 2008 Feb;101(3):331-7. doi: 10.1111/j.1464-410X.2007.07254.x. Epub 2007 Oct 8.
Dolinak D, Balraj E Autonomic dysreflexia and sudden death in people with traumatic spinal cord injury. Am J Forensic Med Pathol. 2007 Jun;28(2):95-8. doi: 10.1097/PAF.0b013e3180600f99.
Duschek S, Hadjamu M, Schandry R Dissociation between cortical activation and cognitive performance under pharmacological blood pressure elevation in chronic hypotension. Biol Psychol. 2007 Jul;75(3):277-85. doi: 10.1016/j.biopsycho.2007.03.007. Epub 2007 Apr 5.
Duschek S, Hadjamu M, Schandry R Enhancement of cerebral blood flow and cognitive performance following pharmacological blood pressure elevation in chronic hypotension. Psychophysiology. 2007 Jan;44(1):145-53. doi: 10.1111/j.1469-8986.2006.00472.x.
Duschek S, Matthias E, Schandry R Essential hypotension is accompanied by deficits in attention and working memory. Behav Med. 2005 Winter;30(4):149-58. doi: 10.3200/BMED.30.4.149-160.
Duschek S, Schandry R Cognitive performance and cerebral blood flow in essential hypotension. Psychophysiology. 2004 Nov;41(6):905-13. doi: 10.1111/j.1469-8986.2004.00249.x.
Eker A, Yigitoglu PH, Ipekdal HI, Tosun A Acute Onset of Intracerebral Hemorrhage due to Autonomic Dysreflexia. J Korean Neurosurg Soc. 2014 May;55(5):277-9. doi: 10.3340/jkns.2014.55.5.277. Epub 2014 May 31.
Ekland MB, Krassioukov AV, McBride KE, Elliott SL Incidence of autonomic dysreflexia and silent autonomic dysreflexia in men with spinal cord injury undergoing sperm retrieval: implications for clinical practice. J Spinal Cord Med. 2008;31(1):33-9. doi: 10.1080/10790268.2008.11753978.
Freeman R, Landsberg L, Young J The treatment of neurogenic orthostatic hypotension with 3,4-DL-threo-dihydroxyphenylserine: a randomized, placebo-controlled, crossover trial. Neurology. 1999 Dec 10;53(9):2151-7. doi: 10.1212/wnl.53.9.2151.
Frewen J, Finucane C, Savva GM, Boyle G, Kenny RA Orthostatic hypotension is associated with lower cognitive performance in adults aged 50 plus with supine hypertension. J Gerontol A Biol Sci Med Sci. 2014 Jul;69(7):878-85. doi: 10.1093/gerona/glt171. Epub 2013 Nov 8.
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 Jan;62(1):117-22. doi: 10.1111/jgs.12592.
Fuhrer MJ, Rintala DH, Hart KA, Clearman R, Young ME Relationship of life satisfaction to impairment, disability, and handicap among persons with spinal cord injury living in the community. Arch Phys Med Rehabil. 1992 Jun;73(6):552-7.
Goldstein DS, Holmes C, Kaufmann H, Freeman R Clinical pharmacokinetics of the norepinephrine precursor L-threo-DOPS in primary chronic autonomic failure. Clin Auton Res. 2004 Dec;14(6):363-8. doi: 10.1007/s10286-004-0221-z.
GUTTMANN L, MUNRO AF, ROBINSON R, WALSH JJ EFFECT OF TILTING ON THE CARDIOVASCULAR RESPONSES AND PLASMA CATECHOLAMINE LEVELS IN SPINAL MAN. Paraplegia. 1963 May;1:4-18. doi: 10.1038/sc.1963.2. No abstract available.
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 Apr 15;30(5):646-54. doi: 10.1002/mds.26086. Epub 2014 Dec 9.
Hildrum B, Mykletun A, Holmen J, Dahl AA Effect of anxiety and depression on blood pressure: 11-year longitudinal population study. Br J Psychiatry. 2008 Aug;193(2):108-13. doi: 10.1192/bjp.bp.107.045013.
Illman A, Stiller K, Williams M The prevalence of orthostatic hypotension during physiotherapy treatment in patients with an acute spinal cord injury. Spinal Cord. 2000 Dec;38(12):741-7. doi: 10.1038/sj.sc.3101089.
Isaacson S, Vernino S, Ziemann A, Rowse GJ, Kalu U, White WB Long-term safety of droxidopa in patients with symptomatic neurogenic orthostatic hypotension. J Am Soc Hypertens. 2016 Oct;10(10):755-762. doi: 10.1016/j.jash.2016.07.010. Epub 2016 Aug 4.
Isaacson SH, Skettini J Neurogenic orthostatic hypotension in Parkinson's disease: evaluation, management, and emerging role of droxidopa. Vasc Health Risk Manag. 2014 Apr 3;10:169-76. doi: 10.2147/VHRM.S53983. eCollection 2014.
Jorm AF Association of hypotension with positive and negative affect and depressive symptoms in the elderly. Br J Psychiatry. 2001 Jun;178:553-5. doi: 10.1192/bjp.178.6.553.
Kannel WB, Wolf PA, Verter J, McNamara PM Epidemiologic assessment of the role of blood pressure in stroke. The Framingham study. JAMA. 1970 Oct 12;214(2):301-10. No abstract available.
Kaufmann H L-dihydroxyphenylserine (Droxidopa): a new therapy for neurogenic orthostatic hypotension: the US experience. Clin Auton Res. 2008 Mar;18 Suppl 1:19-24. doi: 10.1007/s10286-007-1002-2. Epub 2008 Mar 27.
Keating GM Droxidopa: a review of its use in symptomatic neurogenic orthostatic hypotension. Drugs. 2015 Feb;75(2):197-206. doi: 10.1007/s40265-014-0342-1.
Kim BS, Bae JN, Cho MJ Depressive symptoms in elderly adults with hypotension: different associations with positive and negative affect. J Affect Disord. 2010 Dec;127(1-3):359-64. doi: 10.1016/j.jad.2010.06.024.
Krassioukov A Autonomic dysreflexia: current evidence related to unstable arterial blood pressure control among athletes with spinal cord injury. Clin J Sport Med. 2012 Jan;22(1):39-45. doi: 10.1097/JSM.0b013e3182420699.
Lehmann KG, Lane JG, Piepmeier JM, Batsford WP Cardiovascular abnormalities accompanying acute spinal cord injury in humans: incidence, time course and severity. J Am Coll Cardiol. 1987 Jul;10(1):46-52. doi: 10.1016/s0735-1097(87)80158-4.
Lindholm L, Lanke J, Bengtsson B, Ejlertsson G, Thulin T, Schersten B Both high and low blood pressures risk indicators of death in middle-aged males. Isotonic regression of blood pressure on age applied to data from a 13-year prospective study. Acta Med Scand. 1985;218(5):473-80. doi: 10.1111/j.0954-6820.1985.tb08876.x.
Lopes P, Figoni S Current literature on orthostatic hypotension and training in SCI patients. Am Correct Ther J. 1982 Mar-Apr;36(2):56-9. No abstract available.
Mathias CJ L-dihydroxyphenylserine (Droxidopa) in the treatment of orthostatic hypotension: the European experience. Clin Auton Res. 2008 Mar;18 Suppl 1:25-9. doi: 10.1007/s10286-007-1005-z. Epub 2008 Mar 27.
MEADOR CK THE ART AND SCIENCE OF NONDISEASE. N Engl J Med. 1965 Jan 14;272:92-5. doi: 10.1056/NEJM196501142720208. No abstract available.
Mukand J, Karlin L, Barrs K, Lublin P Midodrine for the management of orthostatic hypotension in patients with spinal cord injury: A case report. Arch Phys Med Rehabil. 2001 May;82(5):694-6. doi: 10.1053/apmr.2001.22350.
Munakata M, Kameyama J, Kanazawa M, Nunokawa T, Moriai N, Yoshinaga K Circadian blood pressure rhythm in patients with higher and lower spinal cord injury: simultaneous evaluation of autonomic nervous activity and physical activity. J Hypertens. 1997 Dec;15(12 Pt 2):1745-9. doi: 10.1097/00004872-199715120-00083.
Nieshoff EC, Birk TJ, Birk CA, Hinderer SR, Yavuzer G Double-blinded, placebo-controlled trial of midodrine for exercise performance enhancement in tetraplegia: a pilot study. J Spinal Cord Med. 2004;27(3):219-25. doi: 10.1080/10790268.2004.11753752.
Pemberton J Does constitutional hypotension exist? BMJ. 1989 Mar 11;298(6674):660-2. doi: 10.1136/bmj.298.6674.660. No abstract available.
Phillips AA, Ainslie PN, Warburton DE, Krassioukov AV Cerebral Blood Flow Responses to Autonomic Dysreflexia in Humans with Spinal Cord Injury. J Neurotrauma. 2016 Feb 1;33(3):315-8. doi: 10.1089/neu.2015.3871. Epub 2016 Jan 7.
Phillips AA, Krassioukov AV, Ainslie PN, Warburton DE Perturbed and spontaneous regional cerebral blood flow responses to changes in blood pressure after high-level spinal cord injury: the effect of midodrine. J Appl Physiol (1985). 2014 Mar 15;116(6):645-53. doi: 10.1152/japplphysiol.01090.2013. Epub 2014 Jan 16.
Phillips AA, Warburton DE, Ainslie PN, Krassioukov AV Regional neurovascular coupling and cognitive performance in those with low blood pressure secondary to high-level spinal cord injury: improved by alpha-1 agonist midodrine hydrochloride. J Cereb Blood Flow Metab. 2014 May;34(5):794-801. doi: 10.1038/jcbfm.2014.3. Epub 2014 Jan 29.
Provitera V, Nolano M, Pagano A Acetylcholinesterase inhibition and orthostatic hypotension. Clin Auton Res. 2006 Apr;16(2):136. doi: 10.1007/s10286-006-0336-5. No abstract available.
Robbins JM, Korda H, Shapiro MF Treatment for a nondisease: the case of low blood pressure. Soc Sci Med. 1982;16(1):27-33. doi: 10.1016/0277-9536(82)90420-8.
Rosengren A, Tibblin G, Wilhelmsen L Low systolic blood pressure and self perceived wellbeing in middle aged men. BMJ. 1993 Jan 23;306(6872):243-6. doi: 10.1136/bmj.306.6872.243.
Ross AJ, Stewart JM Prospects for droxidopa in neurogenic orthostatic hypotension. Hypertension. 2015 Jan;65(1):34-5. doi: 10.1161/HYPERTENSIONAHA.114.04204. Epub 2014 Oct 27. No abstract available.
Rutan GH, Hermanson B, Bild DE, Kittner SJ, LaBaw F, Tell GS Orthostatic hypotension in older adults. The Cardiovascular Health Study. CHS Collaborative Research Group. Hypertension. 1992 Jun;19(6 Pt 1):508-19. doi: 10.1161/01.hyp.19.6.508.
Schatz IJ Orthostatic hypotension predicts mortality. Lessons from the Honolulu Heart Program. Clin Auton Res. 2002 Aug;12(4):223-4. doi: 10.1007/s10286-002-0047-5. No abstract available.
Senard JM, Arias A, Berlan M, Tran MA, Rascol A, Montastruc JL Pharmacological evidence of alpha 1- and alpha 2-adrenergic supersensitivity in orthostatic hypotension due to spinal cord injury: a case report. Eur J Clin Pharmacol. 1991;41(6):593-6. doi: 10.1007/BF00314991.
Shapiro MF, Korda H, Robbins J Diagnosis and treatment of low blood pressure in a Canadian community. Can Med Assoc J. 1982 Apr 15;126(8):918-20.
Strassheim V, Newton JL, Tan MP, Frith J Droxidopa for orthostatic hypotension: a systematic review and meta-analysis. J Hypertens. 2016 Oct;34(10):1933-41. doi: 10.1097/HJH.0000000000001043.
Stroup-Benham CA, Markides KS, Black SA, Goodwin JS Relationship between low blood pressure and depressive symptomatology in older people. J Am Geriatr Soc. 2000 Mar;48(3):250-5. doi: 10.1111/j.1532-5415.2000.tb02642.x.
Teasell RW, Arnold JM, Krassioukov A, Delaney GA Cardiovascular consequences of loss of supraspinal control of the sympathetic nervous system after spinal cord injury. Arch Phys Med Rehabil. 2000 Apr;81(4):506-16. doi: 10.1053/mr.2000.3848.
Vijayan J, Sharma VK Neurogenic orthostatic hypotension - management update and role of droxidopa. Ther Clin Risk Manag. 2015 Jun 8;11:915-23. doi: 10.2147/TCRM.S68439. eCollection 2015.
Wan D, Krassioukov AV Life-threatening outcomes associated with autonomic dysreflexia: a clinical review. J Spinal Cord Med. 2014 Jan;37(1):2-10. doi: 10.1179/2045772313Y.0000000098. Epub 2013 Nov 26.
Wecht JM, Bauman WA Decentralized cardiovascular autonomic control and cognitive deficits in persons with spinal cord injury. J Spinal Cord Med. 2013 Mar;36(2):74-81. doi: 10.1179/2045772312Y.0000000056.
Wecht JM, Radulovic M, Rosado-Rivera D, Zhang RL, LaFountaine MF, Bauman WA Orthostatic effects of midodrine versus L-NAME on cerebral blood flow and the renin-angiotensin-aldosterone system in tetraplegia. Arch Phys Med Rehabil. 2011 Nov;92(11):1789-95. doi: 10.1016/j.apmr.2011.03.022. Epub 2011 Jul 16.
Wecht JM, Rosado-Rivera D, Handrakis JP, Radulovic M, Bauman WA Effects of midodrine hydrochloride on blood pressure and cerebral blood flow during orthostasis in persons with chronic tetraplegia. Arch Phys Med Rehabil. 2010 Sep;91(9):1429-35. doi: 10.1016/j.apmr.2010.06.017.
Wecht JM, Rosado-Rivera D, Weir JP, Ivan A, Yen C, Bauman WA Hemodynamic effects of L-threo-3,4-dihydroxyphenylserine (Droxidopa) in hypotensive individuals with spinal cord injury. Arch Phys Med Rehabil. 2013 Oct;94(10):2006-12. doi: 10.1016/j.apmr.2013.03.028. Epub 2013 Apr 18.
Wecht JM, Weir JP, Galea M, Martinez S, Bauman WA Prevalence of abnormal systemic hemodynamics in veterans with and without spinal cord injury. Arch Phys Med Rehabil. 2015 Jun;96(6):1071-9. doi: 10.1016/j.apmr.2015.01.018. Epub 2015 Feb 4.
Wecht JM, Weir JP, Krothe AH, Spungen AM, Bauman WA Normalization of supine blood pressure after nitric oxide synthase inhibition in persons with tetraplegia. J Spinal Cord Med. 2007;30(1):5-9. doi: 10.1080/10790268.2007.11753907.
Wecht JM, Weir JP, Martinez S, Eraifej M, Bauman WA Orthostatic hypotension and orthostatic hypertension in American veterans. Clin Auton Res. 2016 Feb;26(1):49-58. doi: 10.1007/s10286-015-0328-4. Epub 2015 Dec 22.
Wecht JM, Weir JP, Radulovic M, Bauman WA Effects of midodrine and L-NAME on systemic and cerebral hemodynamics during cognitive activation in spinal cord injury and intact controls. Physiol Rep. 2016 Feb;4(3):e12683. doi: 10.14814/phy2.12683.
Wecht JM, Zhu C, Weir JP, Yen C, Renzi C, Galea M A prospective report on the prevalence of heart rate and blood pressure abnormalities in veterans with spinal cord injuries. J Spinal Cord Med. 2013 Sep;36(5):454-62. doi: 10.1179/2045772313Y.0000000109.
Weisz N, Schandry R, Jacobs AM, Mialet JP, Duschek S Early contingent negative variation of the EEG and attentional flexibility are reduced in hypotension. Int J Psychophysiol. 2002 Sep;45(3):253-60. doi: 10.1016/s0167-8760(02)00032-6.
Wessely S, Nickson J, Cox B Symptoms of low blood pressure: a population study. BMJ. 1990 Aug 18-25;301(6748):362-5. doi: 10.1136/bmj.301.6748.362.
Wu JS, Yang YC, Lu FH, Wu CH, Chang CJ Population-based study on the prevalence and correlates of orthostatic hypotension/hypertension and orthostatic dizziness. Hypertens Res. 2008 May;31(5):897-904. doi: 10.1291/hypres.31.897.
Yap PL, Niti M, Yap KB, Ng TP Orthostatic hypotension, hypotension and cognitive status: early comorbid markers of primary dementia? Dement Geriatr Cogn Disord. 2008;26(3):239-46. doi: 10.1159/000160955. Epub 2008 Oct 8.
Yokomizo Y, Goubara A, Tanaka K, Yokoyama O [A case of cerebellar hemorrhage secondary to autonomic dysreflexia (AD) in a patient with cervical spinal cord injury]. Hinyokika Kiyo. 2010 Nov;56(11):659-61. Japanese.
Zhao J, Wecht JM, Zhang Y, Wen X, Zeman R, Bauman WA, Cardozo C iNOS expression in rat aorta is increased after spinal cord transection: a possible cause of orthostatic hypotension in man. Neurosci Lett. 2007 Mar 30;415(3):210-4. doi: 10.1016/j.neulet.2007.01.025. Epub 2007 Jan 14.
Zhu C, Galea M, Livote E, Signor D, Wecht JM A retrospective chart review of heart rate and blood pressure abnormalities in veterans with spinal cord injury. J Spinal Cord Med. 2013 Sep;36(5):463-75. doi: 10.1179/2045772313Y.0000000145.
Dose Response to the Norepinephrine Precursor Droxidopa in Hypotensive Individuals With Spinal Cord Injury
Interventional studies are often prospective and are specifically tailored to evaluate direct impacts of treatment or preventive measures on disease.
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Clinical trials are conducted in a series of steps, called phases - each phase is designed to answer a separate research question.
Phase 1: Researchers test a new drug or treatment in a small group of people for the first time to evaluate its safety, determine a safe dosage range, and identify side effects.
Phase 2: The drug or treatment is given to a larger group of people to see if it is effective and to further evaluate its safety.
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