Clonidine

Written By Brandon Ho

Pathophysiology

Clonidine is an alpha-2 agonist that is used to treat hypertension, ADHD, and spasticity in pediatric patients. Other common medications in the same class include guanfacine, dexmetomidine, and oxymetazoline. Clonidine comes in PO and transdermal patch formulations. Clonidine has rapid GI absorption reaching peak concentrations in 3-5 hours. Patches can have delayed and prolonged presentations.

  •  Clonidine stimulates alpha-2 receptors in the CNS causing:

    • Decrease sympathetic outflow

    • Increase GABA release

    • Endogenous opioid release

  • Clonidine stimulates alpha-2 receptors in the peripheral vasculature causing vasoconstriction and initial hypertension then a hypotensive phase

Presentation

Toxidrome: AMS, miosis, respiratory depression, bradycardia, and hypotension

  • Neurologic: AMS, lethargy, coma, hypotonia, hyporeflexia, seizures

  • Ophthalmic: Miosis

  • Respiratory: Respiratory depression, periodic apnea, Cheyne-stokes respiration

  • Cardiovascular: Early transient hypertension secondary to peripheral vasoconstriction followed by hypotension and bradycardia. Rare cases of AV block and sinus arrest. 

  • Metabolic: Hypothermia, pallor

Diagnosis

Consult Poison Control: 1800-222-1222

What type of product was ingested (immediate vs. sustained release)?

Any presence of synergistic co-ingestants (other antihypertensives, sedatives)? 

  1. Workup: Blood gas, POC glucose, CMP, acetaminophen level, salicylate level, ethanol level, UDS, EKG

  2. Consider head CT if focal neurologic findings or persistent alterations in mental status

Management

  • Respiratory depression: Supplemental oxygen as needed. Intubate if concerns about patient’s ability to adequately breathe on their own or if pulmonary aspiration poses a significant risk

    Transient, early hypertension: Avoid use of antihypertensive therapy as initial hypertension can be followed by significant hypotension. Only rarely indicated when there are signs of hypertensive emergency.

    Bradycardia: Atropine may be used bradycardia but it has a short-lived effect so repeat doses may be required. Transcutaneous pacing can be used for refractory bradycardia

    Hypotension: IV crystalloid bolus. Vasopressors are indicated for fluid-refractory hypotension

  • Activated charcoal (1 g/kg; max 50 g): Only indicated if patient presents with one hour of ingestion as clonidine is rapidly absorbed within the first 30 min to 1 hour.

    Whole Bowel Irrigation (Polyethylene glycol 500 ml/hr): Only indicated if a transdermal patch was ingested. Continue until patch has passed in the stool

  • 0.1 mg/kg; max single dose 2 mg repeated every 1-2 minutes up to 10 mg total dose. If concerned for significant decompensation, just start with the max 10 mg dose.

    Counteracts endogenous opioid release. Clonidine ingestions typically require higher doses compared to treatment for opioid intoxications. The half-life of naloxone is shorter than that of clonidine, and additional doses of naloxone may be required. A naloxone drip may be indicated in cases of ingestion of long-acting formulations.

Disposition:

  • All symptomatic patients regardless of response to naloxone require admission for monitoring.

  • Asymptomatic patients who ingest a transdermal patch should be admitted and closely monitored as symptoms may not present until 24 hours.

  • Asymptomatic patients 6 hours post-ingestion of immediate release oral formulations may be discharged home with close follow-up

References

  1.  Manzon L, Nappe TM, DelMaestro C, et al. Clonidine Toxicity. [Updated 2020 Jun 30]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK459374/

  2. Wedin GP, Richardson SL, Wallace GH. Clonidine Poisoning in Children. Am J Dis Child. 1990;144(8):853–854. doi:10.1001/archpedi.1990.02150320015011 

Brandon Ho
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