Clonidine Toxicity: A Brief Review

Image Credit: Flickr Pranjal Mahna

Author: Matt Rosen, MSIV
Georgetown School of Medicine

This post was peer reviewed.
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Background:
Clonidine was once a popular antihypertensive agent, and while its use as a primary blood pressure agent has declined, it continues to have a role in hypertension management for some patients. Clonidine is also being used in other applications such as treatment of migraines, treatment of vasomotor symptoms associated with menopause or withdrawal, and in a number of pediatric applications such as pre-anesthesia, postoperative pain management, and panic/anxiety disorders.[1, 5]

Epidemiology:
In 2012 there were 5,047 single exposures to clonidine reported to poison control centers; 3,754 were unintentional, 1094 were intentional, and 125 were reports of an adverse reaction to a normal prescribed dose.[2] In 2007, out of the 2235 patients treated at a medical facility with clonidine ingestion, 841 had moderate morbidity, 765 had major morbidity, and there were two fatalities.[2]

MOA:
Acts centrally as a presynaptic alpha-2 receptor agonist which decreases sympathetic outflow, but in early toxic doses it may act as a peripheral alpha-1 receptor agonist leading to vasoconstriction and hypertension.[1]

Pharmacodynamics:
Peak plasma concentration in 3-5 hours (PO), and 2-3 days with transdermal patch.[5]

Side effects:

• Therapeutic doses (0.2-0.9 mg/day): dry mouth, sedation, dizziness, and constipation.
• Toxic doses: cardiorespiratory instability and CNS depression.[6] 

Overdose:

• Oral ingestion – symptoms within 1 hour, new findings are rare after 4 hours.[5]
  
• Symptoms may resemble opioid intoxication (miosis, bradycardia, respiratory depression, coma).
• May respond more readily than those with opioid intoxication.
• More severe in pediatric population, may necessitate intubation.
• Patients may also be hyper or hypotensive with mydriasis, ileus, hypotonia, AV block, or seizures.[6]

Management:

• ABC’s
• If hypotensive: give fluids.
• If patient continues to be hypotensive may require dopamine or epinephrine.
• If hypertensive
• Usually transient and requires no treatment. If necessary, consider nitroprusside.
• National Poison Control number (1-800-222-1222).
• Clonidine levels shouldn’t be drawn (no correlation with toxicity).
• BMP to evaluate for hypoglycemia, anion gap acidosis.
• Frequent blood glucose checks.
• EKG to evaluate for bradycardia or AV nodal blockade.
• Bradycardia --> atropine.[5]
• AV nodal blockade --> transcutaneous pacing.[5]
• Mental status
• Naloxone may improve mental status in adults and children, but response is inconsistent. Doses for naloxone are 0.1 mg/kg, up to 2 mg. If there is improvement with naloxone dose, a drip may be necessary.[4, 5]
• Theoretical reversal agent Yohimbine (central alpha-2 receptor antagonist) should be considered only in consultation with a medical toxicologist as the risk may exceed any benefit from administration, therefore it is rarely administered.[3] 

References:

1. Wang GS, Le Lait MC, Heard K. Unintentional pediatric exposures to central alpha-2 agonists reported to the National Poison Data System. J Pediatr. 2014;164(1):149. PMID: 24094880

2. Mowry JB, Spyker DA, Cantilena LR Jr, Bailey JE, Ford M. 2012 Annual Report of the American Association of Poison Control Centers' National Poison Data System (NPDS): 30th Annual Report. Clin Toxicol (Phila). Dec 2013;51(10):949-1229. PMID: 24359283

3. Roberge RJ, McGuire SP, Krenzelok EP. Yohimbine as an antidote for clonidine overdose. Am J Emerg Med. Nov 1996;14(7):678-80. PMID: 8906769

4. 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 PMID: 2388800

5. Wiley JF 2nd, Wiley CC, Torrey SB, Henretig FM. Clonidine poisoning in young children. J Pediatr. 1990;116(4):654. PMID: 1969468

6. Williams PL, Krafcik JM, Potter BB, et al. Cardiac toxicity of clonidine. Chest. Dec 1977;72(6):784-5. PMID: 923317