Effect of Intrathecal Clonidine in Hypertensive Subjects With Poorly Controlled Blood Pressure

Summary

The purpose of this study is to determine the acute efficacy of intrathecal clonidine to reduce blood pressure in hypertensive subjects with poor blood pressure control and describe its effects on cardiovascular function.

Timeline

Start

2011-02

Primary completion

2012-07

Completion

2012-07

Publications

• Background Onesti G, Schwartz AB, Kim KE, Swartz C, Brest AN. Pharmacodynamic effects of a new antihypertensive drug, Catapres (ST-155). Circulation. 1969 Feb;39(2):219-28. doi: 10.1161/01.cir.39.2.219. No abstract available.
• Background Davies DS, Wing AM, Reid JL, Neill DM, Tippett P, Dollery CT. Pharmacokinetics and concentration-effect relationships of intervenous and oral clonidine. Clin Pharmacol Ther. 1977 May;21(5):593-601. doi: 10.1002/cpt1977215593.
• Background Frisk-Holmberg M, Paalzow L, Wibell L. Relationship between the cardiovascular effects and steady-state kinetics of clonidine in hypertension. Demonstration of a therapeutic window in man. Eur J Clin Pharmacol. 1984;26(3):309-13. doi: 10.1007/BF00548760.
• Background Reid JL, Wing LM, Mathias CJ, Frankel HL, Neill E. The central hypotensive effect of clonidine. Studies in tetraplegic subjects. Clin Pharmacol Ther. 1977 Apr;21(4):375-81. doi: 10.1002/cpt1977214375.
• Background Brown MJ, Struthers AD, di Silvio L. Peripheral alpha 2 adrenoceptor stimulation contributes to the sympatholytic effect of guanfacine in humans. J Cardiovasc Pharmacol. 1985;7 Suppl 6:S159-61. doi: 10.1097/00005344-198500076-00027.
• Background Guthrie GP Jr, Kotchen TA. Effects of prazosin and clonidine on sympathetic and baroreflex function in patients with essential hypertension. J Clin Pharmacol. 1983 Aug-Sep;23(8-9):348-54. doi: 10.1002/j.1552-4604.1983.tb02747.x.
• Background Mohanty PK, Sowers JR, McNamara C, Thames MD. Reflex vasoconstrictor responses to cardiopulmonary baroreceptor unloading, head-up tilt, and cold pressor testing in elderly mild-to-moderate hypertensives: effect of clonidine. J Cardiovasc Pharmacol. 1987;10 Suppl 12:S135-7.
• Background Muzi M, Goff DR, Kampine JP, Roerig DL, Ebert TJ. Clonidine reduces sympathetic activity but maintains baroreflex responses in normotensive humans. Anesthesiology. 1992 Nov;77(5):864-71. doi: 10.1097/00000542-199211000-00005.
• Background Houston MC. Treatment of hypertensive emergencies and urgencies with oral clonidine loading and titration. A review. Arch Intern Med. 1986 Mar;146(3):586-9.
• Background Masotti G, Scarti L, Poggesi L, Bisi G, Gallini C, Neri Serneri GG. Changes in cardiac function after effective treatment of hypertensive emergencies with i.v. clonidine. Eur Heart J. 1984 Dec;5(12):1036-42. doi: 10.1093/oxfordjournals.eurheartj.a061605.
• Background Niarchos AP. Evaluation of intravenous clonidine in hypertensive emergencies. J Clin Pharmacol. 1978 Apr;18(4):220-8. doi: 10.1002/j.1552-4604.1978.tb01596.x.
• Background Magorien RD, Hermiller JB, Unverferth DV, Leier CV. Regional hemodynamic effects of clonidine in congestive heart failure. J Cardiovasc Pharmacol. 1985 Jan-Feb;7(1):91-6. doi: 10.1097/00005344-198501000-00015.
• Background Zochowski RJ, Lada W. Intravenous clonidine treatment in acute myocardial infarction (with comparison to a nitroglycerin-treated and control group). J Cardiovasc Pharmacol. 1986;8 Suppl 3:S41-5.
• Background Wallace AW, Galindez D, Salahieh A, Layug EL, Lazo EA, Haratonik KA, Boisvert DM, Kardatzke D. Effect of clonidine on cardiovascular morbidity and mortality after noncardiac surgery. Anesthesiology. 2004 Aug;101(2):284-93. doi: 10.1097/00000542-200408000-00007.
• Background Byrd BF 3rd, Collins HW, Primm RK. Risk factors for severe bradycardia during oral clonidine therapy for hypertension. Arch Intern Med. 1988 Mar;148(3):729-33.
• Background Kibler LE, Gazes PC. Effect of clonidine on atrioventricular conduction. JAMA. 1977 Oct 31;238(18):1930-2.
• Background Toussaint C, Cave D, Saoudi N, Moore N, Letac B. Electrophysiological effects of intravenous clonidine on sinus node function and conduction in man. J Cardiovasc Pharmacol. 1984 Jan-Feb;6(1):56-60.
• Background Clementy J, Castagne D, Wicker P, Dallocchio M, Bricaud H. Study of the electrophysiologic properties of clonidine administered intravenously. J Cardiovasc Pharmacol. 1986;8 Suppl 3:S24-9. doi: 10.1097/00005344-198608003-00007.
• Background Rupp H, Maisch B, Brilla CG. Drug withdrawal and rebound hypertension: differential action of the central antihypertensive drugs moxonidine and clonidine. Cardiovasc Drugs Ther. 1996 Jun;10 Suppl 1:251-62. doi: 10.1007/BF00120495.
• Background Fuxe K, Tinner B, Bjelke B, Agnati LF, Verhofstad A, Steinbusch HG, Goldstein M, Hersh L, Kalia M. Monoaminergic and Peptidergic Innervation of the Intermedio-Lateral Horn of the Spinal Cord. Eur J Neurosci. 1990;2(5):451-460. doi: 10.1111/j.1460-9568.1990.tb00436.x.
• Background Fuxe K, Tinner B, Bjelke B, Agnati LF, Verhofstad A, Steinbusch HG, Goldstein M, Kalia M. Monoaminergic and Peptidergic Innervation of the Intermedio-Lateral Horn of the Spinal Cord. Eur J Neurosci. 1990;2(5):430-450. doi: 10.1111/j.1460-9568.1990.tb00435.x.
• Background Unnerstall JR, Kopajtic TA, Kuhar MJ. Distribution of alpha 2 agonist binding sites in the rat and human central nervous system: analysis of some functional, anatomic correlates of the pharmacologic effects of clonidine and related adrenergic agents. Brain Res. 1984 Mar;319(1):69-101. doi: 10.1016/0165-0173(84)90030-4.
• Background Guyenet PG, Cabot JB. Inhibition of sympathetic preganglionic neurons by catecholamines and clonidine: mediation by an alpha-adrenergic receptor. J Neurosci. 1981 Aug;1(8):908-17. doi: 10.1523/JNEUROSCI.01-08-00908.1981.
• Background Stevens CW, Yaksh TL. Time course characteristics of tolerance development to continuously infused antinociceptive agents in rat spinal cord. J Pharmacol Exp Ther. 1989 Oct;251(1):216-23.
• Background Eisenach JC, Tong CY. Site of hemodynamic effects of intrathecal alpha 2-adrenergic agonists. Anesthesiology. 1991 Apr;74(4):766-71. doi: 10.1097/00000542-199104000-00021.
• Background De Kock M. Site of hemodynamic effects of alpha 2-adrenergic agonists. Anesthesiology. 1991 Oct;75(4):715-6. doi: 10.1097/00000542-199110000-00046. No abstract available.
• Background Eisenach JC, Hood DD, Curry R. Intrathecal, but not intravenous, clonidine reduces experimental thermal or capsaicin-induced pain and hyperalgesia in normal volunteers. Anesth Analg. 1998 Sep;87(3):591-6. doi: 10.1097/00000539-199809000-00018.
• Background Kooner JS, Birch R, Frankel HL, Peart WS, Mathias CJ. Hemodynamic and neurohormonal effects of clonidine in patients with preganglionic and postganglionic sympathetic lesions. Evidence for a central sympatholytic action. Circulation. 1991 Jul;84(1):75-83. doi: 10.1161/01.cir.84.1.75.
• Background Castro MI, Eisenach JC. Pharmacokinetics and dynamics of intravenous, intrathecal, and epidural clonidine in sheep. Anesthesiology. 1989 Sep;71(3):418-25. doi: 10.1097/00000542-198909000-00018.
• Background Eisenach JC, Lysak SZ, Viscomi CM. Epidural clonidine analgesia following surgery: phase I. Anesthesiology. 1989 Nov;71(5):640-6. doi: 10.1097/00000542-198911000-00003.
• Background Mendez R, Eisenach JC, Kashtan K. Epidural clonidine analgesia after cesarean section. Anesthesiology. 1990 Nov;73(5):848-52. doi: 10.1097/00000542-199011000-00009.
• Background Huntoon M, Eisenach JC, Boese P. Epidural clonidine after cesarean section. Appropriate dose and effect of prior local anesthetic. Anesthesiology. 1992 Feb;76(2):187-93. doi: 10.1097/00000542-199202000-00005.
• Background Eisenach JC, D'Angelo R, Taylor C, Hood DD. An isobolographic study of epidural clonidine and fentanyl after cesarean section. Anesth Analg. 1994 Aug;79(2):285-90. doi: 10.1213/00000539-199408000-00014.
• Background Chiari A, Lorber C, Eisenach JC, Wildling E, Krenn C, Zavrsky A, Kainz C, Germann P, Klimscha W. Analgesic and hemodynamic effects of intrathecal clonidine as the sole analgesic agent during first stage of labor: a dose-response study. Anesthesiology. 1999 Aug;91(2):388-96. doi: 10.1097/00000542-199908000-00012.
• Background D'Angelo R, Evans E, Dean LA, Gaver R, Eisenach JC. Spinal clonidine prolongs labor analgesia from spinal sufentanil and bupivacaine. Anesth Analg. 1999 Mar;88(3):573-6. doi: 10.1097/00000539-199903000-00020.
• Background Rauck RL, Eisenach JC, Jackson K, Young LD, Southern J. Epidural clonidine treatment for refractory reflex sympathetic dystrophy. Anesthesiology. 1993 Dec;79(6):1163-9; discussion 27A.
• Background Eisenach JC, Rauck RL, Buzzanell C, Lysak SZ. Epidural clonidine analgesia for intractable cancer pain: phase I. Anesthesiology. 1989 Nov;71(5):647-52. doi: 10.1097/00000542-198911000-00004.
• Background Eisenach JC, DuPen S, Dubois M, Miguel R, Allin D; Epidural Clonidine Study Group. Epidural clonidine analgesia for intractable cancer pain. The Epidural Clonidine Study Group. Pain. 1995 Jun;61(3):391-399. doi: 10.1016/0304-3959(94)00209-W.
• Background Eisenach J, Detweiler D, Hood D. Hemodynamic and analgesic actions of epidurally administered clonidine. Anesthesiology. 1993 Feb;78(2):277-87. doi: 10.1097/00000542-199302000-00011.
• Background Eisenach JC, Hood DD, Tuttle R, Shafer S, Smith T, Tong C. Computer-controlled epidural infusion to targeted cerebrospinal fluid concentrations in humans. Clonidine. Anesthesiology. 1995 Jul;83(1):33-47. doi: 10.1097/00000542-199507000-00005.
• Background Hood DD, Mallak KA, Eisenach JC, Tong C. Interaction between intrathecal neostigmine and epidural clonidine in human volunteers. Anesthesiology. 1996 Aug;85(2):315-25. doi: 10.1097/00000542-199608000-00013.
• Background De Kock M, Eisenach J, Tong C, Schmitz AL, Scholtes JL. Analgesic doses of intrathecal but not intravenous clonidine increase acetylcholine in cerebrospinal fluid in humans. Anesth Analg. 1997 Apr;84(4):800-3. doi: 10.1097/00000539-199704000-00019.
• Background Eisenach JC, Hood DD, Curry R. Relative potency of epidural to intrathecal clonidine differs between acute thermal pain and capsaicin-induced allodynia. Pain. 2000 Jan;84(1):57-64. doi: 10.1016/S0304-3959(99)00181-5.
• Background Eisenach JC, De Kock M, Klimscha W. alpha(2)-adrenergic agonists for regional anesthesia. A clinical review of clonidine (1984-1995). Anesthesiology. 1996 Sep;85(3):655-74. doi: 10.1097/00000542-199609000-00026. No abstract available.
• Background Baker A, Klimscha W, Eisenach JC, Li XH, Wildling E, Menth-Chiari WA, Chiari AI. Intrathecal clonidine for postoperative analgesia in elderly patients: the influence of baricity on hemodynamic and analgesic effects. Anesth Analg. 2004 Jul;99(1):128-134. doi: 10.1213/01.ANE.0000114549.17864.36.
• Background Nishikawa T, Kimura T, Taguchi N, Dohi S. Oral clonidine preanesthetic medication augments the pressor responses to intravenous ephedrine in awake or anesthetized patients. Anesthesiology. 1991 Apr;74(4):705-10. doi: 10.1097/00000542-199104000-00014.
• Background Wing LM, Reid JL, Davies DS, Neill EA, Tippett P, Dollery CT. Pharmacokinetic and concentration-effect relationships of clonidine in essential hypertension. Eur J Clin Pharmacol. 1977 Dec 28;12(6):463-9. doi: 10.1007/BF00561067.
• Background Abdelhammed AI, Smith RD, Levy P, Smits GJ, Ferrario CM. Noninvasive hemodynamic profiles in hypertensive subjects. Am J Hypertens. 2005 Feb;18(2 Pt 2):51S-59S. doi: 10.1016/j.amjhyper.2004.11.043.
• Background Ferrario CM. New approaches to hypertension management: always reasonable but now necessary. Am J Hypertens. 2005 Feb;18(2 Pt 2):23S-25S. doi: 10.1016/j.amjhyper.2004.11.042. No abstract available.
• Background Adji A, O'Rourke MF. Determination of central aortic systolic and pulse pressure from the radial artery pressure waveform. Blood Press Monit. 2004 Jun;9(3):115-21. doi: 10.1097/01.mbp.0000132426.32886.e0.
• Background Lemogoum D, Flores G, Van den Abeele W, Ciarka A, Leeman M, Degaute JP, van de Borne P, Van Bortel L. Validity of pulse pressure and augmentation index as surrogate measures of arterial stiffness during beta-adrenergic stimulation. J Hypertens. 2004 Mar;22(3):511-7. doi: 10.1097/00004872-200403000-00013.
• Background al'Absi M, Devereux RB, Lewis CE, Kitzman DW, Rao DC, Hopkins P, Markovitz J, Arnett DK. Blood pressure responses to acute stress and left ventricular mass (The Hypertension Genetic Epidemiology Network Study). Am J Cardiol. 2002 Mar 1;89(5):536-40. doi: 10.1016/s0002-9149(01)02305-0.
• Background Hood DD, Eisenach JC, Tong C, Tommasi E, Yaksh TL. Cardiorespiratory and spinal cord blood flow effects of intrathecal neostigmine methylsulfate, clonidine, and their combination in sheep. Anesthesiology. 1995 Feb;82(2):428-35. doi: 10.1097/00000542-199502000-00013.
• Background Yaksh TL, Rathbun M, Jage J, Mirzai T, Grafe M, Hiles RA. Pharmacology and toxicology of chronically infused epidural clonidine.HCl in dogs. Fundam Appl Toxicol. 1994 Oct;23(3):319-35. doi: 10.1006/faat.1994.1112.

Drugs

Indications