Clonidine Toxicity 

  • Author: David Riley, MD, MS, RDMS, RDCS; Chief Editor: Asim Tarabar, MD   more...
 
Updated: Nov 4, 2010
 

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.

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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.

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Epidemiology

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]

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Contributor Information and Disclosures
Author

David Riley, MD, MS, RDMS, RDCS  Assistant Clinical Professor of Medicine, Director of Emergency Ultrasonography and Ultrasound Research, Attending Physician, Department of Emergency Medicine, Columbia University Medical Center-New York Presbyterian Hospital

David Riley, MD, MS, RDMS, RDCS 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.

Specialty Editor Board

Edward A Michelson, MD  Associate Professor, Program Director, Department of Emergency Medicine, University Hospital Health Systems of 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.

John T VanDeVoort, PharmD  Regional Director of Pharmacy, Sacred Heart and 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.

John G Benitez, MD, MPH  Associate Professor, Department of Medicine, Medical Toxicology, Vanderbilt University Medical Center; Managing Director, Tennessee Poison Center

John G Benitez, MD, MPH is a member of the following medical societies: American Academy of Clinical Toxicology, 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.

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.

References

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  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].

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