Clonidine toxicity

2D molecular structure of Clonidine


  • Class: Imidazolines
  • α-2, imidazoline, and opioid receptor agonist
    • α2-agonism leads to activation of inhibitory neurons in the nucleus tractus solitarius causing decreased norepinephrine release, precipitating decreased sympathetic outflow
    • Agonism of imidazoline receptors in the brain can cause unconsciousness, hypotension, and bradycardia
  • Clonidine is used therapeutically for hypertension, opioid abuse, PTSD, and tobacco withdrawal; criminally, it has been used for drug-facilitated sexual assault

Clinical Features

  • Note that initial presentation may stem from non-specific peripheral alpha1 agonism, and produce hypertension and reflex tachycardia - will transition to bradycardia and hypotension when central effects take over
  • Cardiac (alpha2)
    • Bradycardia
    • Hypotension
  • Neuro
    • CNS depression (most common)
    • Lethargy (may progress to apnea)
    • Miotic pupils
    • Respiratory depression
  • Respiratory
    • Hypoventilation
    • Hypoxia
    • Cheynes-Stokes respiration
    • Periodic apnea
  • Hypothermia
  • Can mimic opioid overdose
    • obtundation, miosis, respiratory depression, and hypothermia
  • Can mimic digoxin, Beta-blocker, or CCB toxicity with hypotension and bradycardia
  • Withdrawal from clonidine presents with tachycardia, hypertension, tremors, and agitation

Differential Diagnosis

Toxidrome Chart

Finding Cholinergic Anticholinergic Sympathomimetic Sympatholytic^ Sedative/Hypnotic
Example Organophosphates TCAs Cocaine Clonidine ETOH
Temp Nl Nl / ↑ Nl / ↑ Nl / ↓ Nl / ↓
RR Variable Nl / ↓ Variable Nl / ↓ Nl / ↓
HR Variable ↑ (sig) Nl / ↓ Nl / ↓
BP Nl / ↓ Nl / ↓
LOC Nl / Lethargic Nl, agitated, psychotic, comatose Nl, agitated, psychotic Nl, Lethargic, or Comatose Nl, Lethargic, or Comatose
Pupils Variable Mydriatic Mydriatic Nl / Miotic
Motor Fasciculations, Flacid Paralysis  Nl Nl / Agitated Nl
Skin Sweating (sig) Hot, dry Sweating Dry
Lungs Bronchospasm / rhinorrhea Nl Nl Nl
Bowel Sounds Hyperactive (SLUDGE) ↓ / Absent Nl / ↓ Nl / ↓
^Consider Sympatholytic when looking at Sedative OD or someone who doesn't respond to Narcan
Withdrawal from substances have the opposite effect


  • Diagnosis is largely based on history and clinical picture; there is no readily available serum test
  • Serial ECGs
  • Continuous cardiac monitoring
  • Clonidine itself does not cause electrolyte derangements


  • Respiratory/neuro depression
    • Naloxone
      • High dose may be required (up to 10mg)[1]
      • Not always effective
      • May require infusion, typically 2/3 effective treatment dose per hour
  • Bradycardia
  • Hypotension
    • IVF
    • Vasopressors if not responsive to fluids



  1. Naloxone reversal of clonidine toxicity: dose, dose, dose. Donna L Seger, et al. Clin Toxicol (Phila). 2018.

See Also

Toxicology (Main)