Clonidine toxicity

2D molecular structure of Clonidine

Background

• Class: Imidazolines
  • Clonidine
  • Guanfacine
  • Oxymetazoline(Afrin)
  • Tetrahydrolozine (Visine)
  • Naphazoline (Naphcon)
  • Apraclonidine
• 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

Evaluation

• 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

Management

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

See Also

Toxicology (Main)