Hyperadrenergic state following acute withdrawal from clonidine used at supratherapeutic doses (original) (raw)

Abstract

Abrupt cessation of clonidine treatment precipitates a physiological withdrawal syndrome, thought to be due to a hyperactive state of central autonomic and cognitive adrenergic neuronal systems dependent on presynaptic α2-adrenoceptors and/or imidazoline receptors. We hereby describe a 36-year-old male with history of end-stage renal disease, hypertension and medication non-compliance, who presented with severe hypertension and remarkable agitation. His daily clonidine intake was estimated to be 10 mg. The patient had abruptly discontinued his clonidine five days prior to admission. The following indices of adrenergic activity were measured in plasma (normal control values in parentheses): noradrenaline (NA) 8.59 nmol/l (1.32–4.56 nmol/l), adrenaline (Adr) 1.86 nmol/l (0.83–4.20 nmol/l), total 3-methoxy-4-hydroxyphenylglycol (MHPG) 152.2 nmol/l (45.1–111.5 nmol/l), and free MHPG 33.0 nmol/l (12.2–31.4 nmol/l). Plasma clonidine level was 3.53 ng/ml (15.9 nmol/l) with the usual therapeutic level being <2.0 ng/ml (8.9 nmol/l). Initially, the patient received sedatives and was started on clonidine for the first 24 hours only, after which time period prazosin was started, with good response of his blood pressure and reversal of his mental status changes. At that point, the plasma values of indices of adrenergic activity had decreased compared with their corresponding initial values by the following percentages: NA 60.6%, Adr 22.6%, total MHPG 42.2% and free MHPG 11.5%. Plasma clonidine level had decreased now by 43.6% to an absolute value of 1.99 ng/ml (8.85 nmol/l). We emphasize that physicians should be aware of clonidine's abuse potential and caution should be taken, as well as the appropriate route chosen, when prescribing clonidine in patients who show features of poor compliance to medications and especially in patients with psychoses, suicide potential or personality disorders.

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References

  1. Goldberg A, Wilkinson P, Rafftery E. The overshoot phenomenon on withdrawal of clonidine therapy.Postgrad Med J 1976;52: 128–134.
    Google Scholar
  2. Weber M. Discontinuation syndrome following cessation of treatment with clonidine and other antihypertensive agents.J Cardiovasc Pharmacol 1980;20(suppl. 1):573–589.
    Google Scholar
  3. Vernon C, Sakub A. Fatal rebound hypertension after abrupt withdrawal of clonidine and popranolol.Br J Clin Pract 1979;33:112–121.
    Google Scholar
  4. Peters R, Hamilton B, Hamilton J, Kuzbida G, Pavlis R. Cardiac arrhythmias after abrupt clonidine withdrawal.Clin Pharmacol Ther 1983;34:435–439.
    Google Scholar
  5. Tollefson G. Hyperadrenergic hypomania consequent to the abrupt cessation of clonidine.J Clin Psychopharmacol 1981;1:93–95.
    Google Scholar
  6. Dillon J. Self-injurious behavior associated with clonidine with-drawal in a child with Tourette's disorder.J Child Neurol 1990;5: 308–310.
    Google Scholar
  7. Hökfelt B, Hedeland H, Dymling J-F. Studies on catecholamines. renin and aldosterone following Catapresan (2-(2,6-dichlor-phenylamine)-2-imidazoline hydrochloride) in hypertensive patients.Eur J Pharmacol 1970;10:389–397.
    Google Scholar
  8. Reid JL, Wing LMH, Dargie HJ, Hamilton CA, Davies DS, Dollery CT. Clonidine withdrawal in hypertension Changes in blood-pressure and plasma and urinary noradrenaline.Lancet 1977;i:1171–1174.
    Google Scholar
  9. DaPrada M, Zurcher G. Simultaneous radioenzymatic determination of plasma and tissue adrenaline, noradrenaline and dopamine within the femtomole range.Life Sci 1976;19:1161–1174.
    Google Scholar
  10. Gordon E, Oliver J, Black K, Kopir I. Simultaneous assay by mass fragmentography of vanillylmandelic acid, homovanillic acid and 3-methoxy-4-hydroxyphenethylene glycol in cerebrospinal fluid and urine.Biochem Med 1974;11:32–40.
    Google Scholar
  11. Arendts D, Stähle H, Struck O. A newly developed precise and sensitive radioimmunoassay of clonidine.Arzneim Forsch 1979;29:532–538.
    Google Scholar
  12. Hogan M, Wallin J, Chu L-C. Plasma clonidine concentration and pharmacologic effect.Clin Pharmacol Ther 1981;12:729–734.
    Google Scholar
  13. Kopin I, Blombery P, Ebert M et al. Disposition and metabolism of MHPG-CD3 in humans: plasma MHPG as the principal pathway of norepinephrine metabolism and as an important determinant of CSF levels of MHPG.Adv Biochem Psychopharmacol 1984;39: 57–68.
    Google Scholar
  14. McGrath B, Ledingham J, Benedict C. Catecholamies in peripheral venous plasma in patients on chronic hemodialysis.Clin Sci Med 1987;55:89–96.
    Google Scholar
  15. Elias A, Vaziri N, Maksy M. Plasma norepinephrine epinephrine and dopamine levels in end-stage renal disease. Effect of hemodialysis.Arch Intern Med 1985;145:1013–1035.
    Google Scholar
  16. Timmermans P, van Zwieten P. α2-adrenoceptors: classification, localisation mechanisms and target for drugs.J Med Chem 1982;25:1389–1400.
    Google Scholar
  17. Hamilton CA. The role of imidazoline receptors in blood pressure regulation.Pharmacol Ther 1992;54:231–148.
    Google Scholar
  18. Bricca G, Dontenwill M, Molines A, Feldman J, Belcourt A, Bousquet P. Evidence for the existence of a homogeneous population of imidazoline receptors in the human brainstem.Eur J Pharmacol 1988;150:401–402.
    Google Scholar
  19. Molderings GJ, Moura D, Fink K, Bönisch H, Göthert M. Binding of [3H]clonidine to l1-imidazoline sites in bovine adrenal medullary membranes.Naunyn-Schmiedeberg's Arch Pharmacol 1993;348: 70–76.
    Google Scholar
  20. Reis DJ, Regunathan S, Meeley MP. Imidazole receptors and clonidine-displacing substance in relationship to control of blood pressure, neuroprotection, and adrenomedullary secretion.Am J Hypertens 1992;5:51S-57S.
    Google Scholar
  21. Li G, Regunathan S, Barrow CJ, Eshraghi J, Cooper R, Reis DJ. Agmatine, an endogenous clonidine-displacing substance in the brain.Science 1994;263:966–969.
    Google Scholar
  22. Reid J, Campbell B, Hamilton C. Withdrawal reactions following cessation of central alpha-adrenergic receptor agonists.Hypertension 1984;6:11-71–11-75.
    Google Scholar
  23. Fornai F, Blandizzi C, del Tacca M. Central α2-adrenoceptors regulate central and peripheral functions.Pharmacol Res 1990;22:541–554.
    Google Scholar
  24. Rupp H, Jacob R. Excess catecholamine and the metabolic syndrome: should central imidazoline receptors be a therapeutic target?Med Hypothesis 1995;44:217–225.
    Google Scholar
  25. Campbell B, Reid J. Regimen for the control of blood pressure and symptoms during clonidine withdrawal.Int J Clin Pharmacol Res 1985;5:215–222.
    Google Scholar
  26. Rosenthal T, Rabinowitz B, Boichis H, Elazar E, Brauner A, Neufeld H. Use of labetalol in hypertensive patients during discontinuation of clonidine therapy.Eur J Clin Pharmacol 1981;20:239–240.
    Google Scholar
  27. Weigel J, Schlund J, Derlet R. Clonidine overdose and opiate withdrawal [letter].Ann Emerg Med 1988;17:387.
    Google Scholar
  28. Conway T, Balson A. Concomitant abuse of clonidine and heroin.South Med J 1993;86:954–956.
    Google Scholar
  29. Schaut J, Schnoll S. Four cases of clonidine abuse.Am J Psychiat 1983;140:1627–1635.
    Google Scholar
  30. Burris JF. The USA experience with the clonidine transdermal therapeutic system.Clin Autonom Res 1993;3:391–396.
    Google Scholar
  31. Shaw JE. Pharmacokinetics of nitroglycerin and clonidine delivered by the transdermal route.Am Heart J 1984;108:217–223.
    Google Scholar
  32. Metz S, Klein C, Morton N. Rebound hypertension after discontinuation of transdermal clonidine therapy.Am J Med 1987;82:17–19.
    Google Scholar

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Author notes

  1. N. J. Sarlis MD PhD
    Present address: NIDDK, National Institute of Health, Bldg 10/Rm 9N222, 10 Center Drive, 20892, Bethesda, MD, USA

Authors and Affiliations

  1. Department of Internal Medicine, University of Utah Health Sciences Center, 84132, Salt Lake City, UT, USA
    N. J. Sarlis MD PhD, O. Caticha MD, C. Kablitz MD & F. S. Shihab MD
  2. Department of Internal Medicine, LDS Hospital, 84143, Salt Lake City, UT, USA
    J. L. Anderson MD

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  1. N. J. Sarlis MD PhD
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  2. O. Caticha MD
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  3. J. L. Anderson MD
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  4. C. Kablitz MD
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  5. F. S. Shihab MD
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Sarlis, N.J., Caticha, O., Anderson, J.L. et al. Hyperadrenergic state following acute withdrawal from clonidine used at supratherapeutic doses.Clinical Autonomic Research 6, 115–117 (1996). https://doi.org/10.1007/BF02291233

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