eMedicine Specialties > Emergency Medicine > Toxicology

Toxicity, Clonidine

Author: David Riley, MD, MS, RDMS, Assistant Clinical Professor of Medicine, Associate Ultrasound Program Director, Ultrasound Research Director, Attending Physician, Department of Emergency Medicine, Columbia University Medical Center-New York Presbyterian Hospital
Contributor Information and Disclosures

Updated: Mar 24, 2009

Introduction

Background

Clonidine is a central alpha-agonist that is used as an antihypertensive agent. Other reported clinical uses include treatment of opiate and alcohol withdrawal and control of atrial fibrillation with a rapid ventricular rate. It is also used as a pediatric preanesthetic, for pediatric postoperative pain management, treatment of migraine headaches, nicotine addiction, menopausal flushing, attention deficit disorder, Tourette syndrome, and pediatric panic and anxiety disorders.

At therapeutic doses (0.2-0.9 mg/d), clonidine is commonly associated with adverse effects such as dry mouth, sedation, dizziness, and constipation. While generally safe, at toxic doses, it can cause serious cardiopulmonary instability and central nervous system (CNS) depression in children and adults.

Clonidine is available in a weekly transdermal patch (Catapres TTS: 0.1 mg, 0.2 mg, or 0.3 mg/d, with each patch containing 2.5 mg, 5 mg, and 7.5 mg of clonidine, respectively) and in tablet form (Catapres: 0.1 mg, 0.2 mg, and 0.3 mg; Combipres includes 15 mg of chlorthalidone diuretic). An ophthalmic solution is occasionally used in the treatment of glaucoma.

Pathophysiology

Clonidine is an imidazole derivative and was first used as a nasal decongestant. Decongestants containing tetrahydrozoline, also an imidazole derivative, can result in signs and symptoms of clonidine poisoning when ingested, especially in children.

Clonidine acts primarily as a presynaptic CNS alpha2-agonist, stimulating receptors in the nucleus tractus solitarii of the medulla oblongata. This inhibits sympathetic outflow, which results primarily in a reduction of sympathetically mediated vasoconstriction, cardiac inotropy, and chronotropy.

Clonidine also has peripheral alpha1-agonist activity, which may produce transient vasoconstriction and hypertension early in overdose when peripheral drug levels may be transiently higher than levels in the CNS.

Clonidine is rapidly absorbed from the gastrointestinal tract and has excellent CNS penetration because of lipid solubility. Peak plasma concentrations are reached 3-5 hours after a single oral dose. Dermal application may take several days for steady state levels. No known pharmacologically active metabolites exist. Plasma half-life is 12-16 hours, with the antihypertensive effects occurring within 30-60 minutes of ingestion. Clonidine is excreted unchanged in the urine and metabolized by the liver.

Frequency

United States

In the 2007 Annual Report of the American Association of Poison Control Centers' Toxic Exposure Surveillance System (AAPCC TESS), 3499 single exposures to clonidine were reported. Of these, 2742 were unintentional toxicities, 637 were intentional, and 68 were reported as an adverse reaction.1

Mortality/Morbidity

Mortality is rare with a small number of reported deaths. Morbidity, in terms of cardiorespiratory and CNS dysfunction, generally tends to be more severe in young persons than in adults.

Of the 3499 reported toxic exposures to clonidine in 2007, 2235 were treated in a health care facility. Of this subset of patients, 763 had no significant outcome, 740 had minor effects, 841 had moderate morbidity, 765 had major morbidity, and 2 resulted in fatality.1

Age

Of the 3499 reported exposures to clonidine in 2007, a total of 1480 patients were younger than 6 years, 1147 were aged 6-19 years, and 782 were older than 19 years.1

Clinical

History

While elucidating the amount and timing of the clonidine ingestion is helpful, in practice, signs and symptoms guide therapy. Always suspect other co-ingestants and screen appropriately.

  • Children are particularly susceptible to toxic reaction from small doses (ie, normal adult therapeutic doses) of clonidine.
  • The Catapres TTS patch appears similar to a small Band-Aid or sticker, and a child could pull the patch off a sleeping caretaker.
    • Several case reports document patches detaching spontaneously from a sleeping parent in a bed shared with a child and subsequently adhering to the child with resultant toxicity.
    • In cases of possible clonidine toxicity involving children, always question family, friends, and emergency medical services (EMS) as to whether a child may have had access to clonidine.
  • Irritability

Physical

Symptoms develop rapidly (usually within 30-60 min) postingestion and may resemble an opioid overdose with miosis, bradycardia, respiratory depression, and coma. From a differential standpoint, comatose-appearing children with clonidine toxicity may awaken and be intermittently lucid when subjected to vigorous stimuli (eg, physical, verbal), whereas patients with opioid overdoses subjected to the same stimuli may awaken but are obtunded. Symptoms tend to be relatively more severe in pediatric patients. Toxic presentations also may include hypotension, hypertension, mydriasis, hypothermia, ileus, hypotonia, hyporeflexia, intermittent apnea, atrioventricular (AV) nodal heart block, and seizures.

  • With significant ingestions, patients usually present with bradycardia.
  • Associated hypotension may be severe and last up to 24 hours.
  • Hypertension is less common and usually more transient.
  • Hypothermia has been reported but is usually mild.
  • Patients may present with CNS depression, which may range from mild drowsiness (common) to coma.
  • Baseline mental status usually returns within 24-48 hours of ingestion.
  • Hyporeflexia may develop.
  • Seizures may occur.
  • Dysrhythmias may occur and include AV nodal block, Wenckebach, and tachycardia.
  • Pulmonary
    • Respiratory depression is common, especially in children, and may require endotracheal intubation.
    • Respiratory failure usually occurs within 1-2 hours of ingestion.
    • Ataxic breathing may be observed.
    • Patient may experience periods of apnea.
  • Pallor and cool extremities have been reported.

More on Toxicity, Clonidine

Overview: Toxicity, Clonidine
Differential Diagnoses & Workup: Toxicity, Clonidine
Treatment & Medication: Toxicity, Clonidine
Follow-up: Toxicity, Clonidine
References
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References

  1. Bronstein AC, Spyker DA, Cantilena LR Jr, Green JL, Rumack BH, Heard SE. 2007 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 25th Annual Report. Clin Toxicol (Phila). Dec 2008;46(10):927-1057. [Medline].

  2. Hegenbarth MA, American Academy of Pediatrics Committee on Drugs. Preparing for pediatric emergencies: drugs to consider. Pediatrics. Feb 2008;121(2):433-43. [Medline].

  3. American Academy of Pediatrics. American Academy of Pediatrics Committee on Drugs: Naloxone dosage and route of administration for infants and children: addendum to emergency drug doses for infants and children. Pediatrics. Sep 1990;86(3):484-5. [Medline].

  4. Anderson RJ, Hart GR, Crumpler CP, et al. Clonidine overdose: report of six cases and review of the literature. Ann Emerg Med. Feb 1981;10(2):107-12. [Medline].

  5. Domino LE, Domino SE, Stockstill MS. Relationship between plasma concentrations of clonidine and mean arterial pressure during an accidental clonidine overdose. Br J Clin Pharmacol. Jan 1986;21(1):71-4. [Medline].

  6. Fiser DH, Moss MM, Walker W. Critical care for clonidine poisoning in toddlers. Crit Care Med. Oct 1990;18(10):1124-8. [Medline].

  7. Glassman AH, Stetner F, Walsh BT, et al. Heavy smokers, smoking cessation, and clonidine. Results of a double- blind, randomized trial. JAMA. May 20 1988;259(19):2863-6. [Medline].

  8. Gold MS, Pottash AC, Sweeney DR, et al. Opiate withdrawal using clonidine. A safe, effective, and rapid nonopiate treatment. JAMA. Jan 25 1980;243(4):343-6. [Medline].

  9. Gulec S, Aydin Y, Uzuner K. Effects of clonidine pre-treatment on bupivacaine and ropivacaine cardiotoxicity in rats. Eur J Anaesthesiol. Mar 2004;21(3):205-9. [Medline].

  10. Killian CA, Roberge RJ, Krenzelok EP, et al. "Cloniderm" toxicity: another manifestation of clonidine overdose. Pediatr Emerg Care. Oct 1997;13(5):340-1. [Medline].

  11. Lowenthal DT, Matzek KM, MacGregor TR. Clinical pharmacokinetics of clonidine. Clin Pharmacokinet. May 1988;14(5):287-310. [Medline].

  12. Mikawa K, Maekawa N, Nishina K, et al. Efficacy of oral clonidine premedication in children. Anesthesiology. Nov 1993;79(5):926-31. [Medline].

  13. Moiseev VM, Edel' IuP. [Development of forensic medical expertise in Kharkov during the years of Soviet rule]. Sud Med Ekspert. Jan-Mar 1989;32(1):54-5. [Medline].

  14. Nichols MH, King WD, James LP. Clonidine poisoning in Jefferson County, Alabama. Ann Emerg Med. Apr 1997;29(4):511-7. [Medline].

  15. Prisant LM, Elliott WJ. Drug delivery systems for treatment of systemic hypertension. Clin Pharmacokinet. 2003;42(11):931-40. [Medline].

  16. Roberge RJ, Kimball ET, Rossi J, et al. Clonidine and sleep apnea syndrome interaction: antagonism with yohimbine. J Emerg Med. Sep-Oct 1998;16(5):727-30. [Medline].

  17. Roberge RJ, Krenzelok EP, Mrvos R. Transdermal drug delivery system exposure outcomes. J Emerg Med. Feb 2000;18(2):147-51. [Medline].

  18. Roberge RJ, McGuire SP, Krenzelok EP. Yohimbine as an antidote for clonidine overdose. Am J Emerg Med. Nov 1996;14(7):678-80. [Medline].

  19. Roth A, Kaluski E, Felner S, et al. Clonidine for patients with rapid atrial fibrillation. Ann Intern Med. Mar 1 1992;116(5):388-90. [Medline].

  20. Sanklecha M, Jog A, Raghavan K. Clonidine casualty. Indian J Pediatr. Jul-Aug 1993;60(4):611-2. [Medline].

  21. Spies CD, Dubisz N, Neumann T, et al. Therapy of alcohol withdrawal syndrome in intensive care unit patients following trauma: results of a prospective, randomized trial. Crit Care Med. Mar 1996;24(3):414-22. [Medline].

  22. Stieger DS, Cantieni R, Frutiger A. Acute colonic pseudoobstruction (Ogilvie's syndrome) in two patients receiving high dose clonidine for delirium tremens. Intensive Care Med. Jul 1997;23(7):780-2. [Medline].

  23. Wasserberger J, Ordog GJ. Naloxone-induced hypertension in patients on clonidine. Ann Emerg Med. May 1988;17(5):557. [Medline].

  24. Williams PL, Krafcik JM, Potter BB, et al. Cardiac toxicity of clonidine. Chest. Dec 1977;72(6):784-5. [Medline].

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Further Reading

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Keywords

clonidine poisoning, clonidine overdose, clonidine toxicity, hypertension medication, antihypertensive, withdrawal treatment, antihypertensive agent, opiate withdrawal, alcohol withdrawal, control of atrial fibrillation, pediatric preanesthetic, pediatric postoperative pain management

migraine headaches, nicotine addiction, menopausal flushing, attention deficit disorder, Tourette syndrome, pediatric panic and anxiety disorders, glaucoma,Catapres TTS patch, mydriasis, hypothermia, ileus, hypotonia, hyporeflexia, intermittent apnea, atrioventricular nodal heart block, AV nodal heart block, respiratory failure, ataxic breathing, apnea, seizures

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Contributor Information and Disclosures

Author

David Riley, MD, MS, RDMS, Assistant Clinical Professor of Medicine, Associate Ultrasound Program Director, Ultrasound Research Director, Attending Physician, Department of Emergency Medicine, Columbia University Medical Center-New York Presbyterian Hospital
David Riley, MD, MS, RDMS is a member of the following medical societies: American Academy of Emergency Medicine, American College of Emergency Physicians, American Institute of Ultrasound in Medicine, American Society of Echocardiography, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Medical Editor

Edward A Michelson, MD, Program Director, Associate Professor, Department of Emergency Medicine, University Hospital Health Systems in Cleveland
Edward A Michelson, MD is a member of the following medical societies: American College of Emergency Physicians, National Association of EMS Physicians, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Pharmacy Editor

John T VanDeVoort, PharmD, Regional Director of Pharmacy, Sacred Heart & St. Joseph's Hospitals
John T VanDeVoort, PharmD is a member of the following medical societies: American Society of Health-System Pharmacists
Disclosure: Nothing to disclose.

Managing Editor

John G Benitez, MD, MPH, FACMT, FACPM, FAAEM, Associate Professor, Department of Medicine, Clinical Pharmacology Division, Vanderbilt University; Managing Director, Tennessee Poison Center
John G Benitez, MD, MPH, FACMT, FACPM, FAAEM is a member of the following medical societies: American Academy of Emergency Medicine, American College of Medical Toxicology, American College of Preventive Medicine, Society for Academic Emergency Medicine, Undersea and Hyperbaric Medical Society, and Wilderness Medical Society
Disclosure: Nothing to disclose.

CME Editor

John D Halamka, MD, MS, Associate Professor of Medicine, Harvard Medical School, Beth Israel Deaconess Medical Center; Chief Information Officer, CareGroup Healthcare System and Harvard Medical School; Attending Physician, Division of Emergency Medicine, Beth Israel Deaconess Medical Center
John D Halamka, MD, MS is a member of the following medical societies: American College of Emergency Physicians, American Medical Informatics Association, Phi Beta Kappa, and Society for Academic Emergency Medicine
Disclosure: Nothing to disclose.

Chief Editor

Asim Tarabar, MD, Assistant Professor, Director, Medical Toxicology, Department of Emergency Medicine, Yale University School of Medicine; Consulting Staff, Department of Emergency Medicine, Yale-New Haven Hospital
Disclosure: Nothing to disclose.

 
 
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