Alpha-2 agonists


Agents such as clonidine act centrally and cause variable release of beta-endorphins and decrease release of norepinephrine.   Extremely large doses can cause initial sympathetic outflow of norepinephrine and cause hypertension (about 30 mins after overdose) followed by hypotension



  • Physical Exam: Opioid toxidrome due to release of opioid endorphins (pinpoint pupils, CNS depression, Respiratory Depression)
  • Laboratory abnormalities: None associated with overdose
  • ECG: Sinus bradycardia



  • IVF and high-dose naloxone
  • Naloxone may reverse the CNS and respiratory depression as well as hypotension.
  • Vasopressors such as norepinephrine/epinephrine are used if naloxone does not work.   


Quick dosing reference:  If hypotensive (do not treat isolated bradycardia):

  • Naloxone 10mg IVP followed by 5 mg/hr if there is no response:
  • Norepinephrine (0.01 to 3 mcg/kg/min – adjust rate per ICU protocol) and if no response:
  • Epinephrine (0.05 to 2 mcg/kg/min – adjust rate per ICU protocol)

*See also MICU/CCU drips for dosing recommendations that are not weight-based and may have lower limits depending on patient mass.