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Potentially life-threatening emergency
Alpha-2 adrenoceptor agonist poisoning
Other Resources UpToDate PubMed
Potentially life-threatening emergency

Alpha-2 adrenoceptor agonist poisoning

Contributors: E. Mason Jackson MD, Paritosh Prasad MD, Gerald F. O'Malley DO
Other Resources UpToDate PubMed

Synopsis

Emergent Care / Stabilization:
  • Aggressive airway control and ventilatory support should be initiated for patients unable to protect their airway or experiencing profound hypoxemia or hypercapnia.
  • Patients exhibiting an opioid toxidrome should be administered naloxone 0.4-2 mg via the quickest route feasible.
  • Early recognition of hemodynamic instability and correction with intravenous (IV) fluids and/or vasopressors should be initiated.
  • Call Poison Control Centers at 800-222-1222.
Diagnosis Overview:
Alpha-2 adrenergic receptor agonists (alpha-2 agonists) are antihypertensive medications with sympatholytic properties beneficial in attention deficit hyperactivity disorder (ADHD); they are also used as decongestants. These sympathomimetic agents selectively stimulate alpha adrenergic receptors. Most drugs in this category also agonize imidazoline receptors, adding to their efficacy.

Alpha-2 agonist overdose poses a significant threat to adults and children. Small doses, even a single pill, can cause severe illness and death in toddlers and young children. Patients suffering from toxicity from centrally acting alpha-2 agonists frequently require intensive care unit (ICU)-level care. Approximately 5% of pediatric ED visits for ingestions are due to alpha agonists, and given the current state of the opioid epidemic and drug contamination, pediatric exposure may be higher. Reports of less than 1 oz of tetrahydrozoline in a pediatric patient causing hypotension and bradycardia requiring treatment have been documented. 

Examples of alpha-2 agonists:
  • Dexmedetomidine (Precedex)
  • Oxymetazoline (Afrin)
  • Tetrahydrozoline (Visine)
  • Clonidine (Catapres)
  • Tizanidine (Zanaflex)
  • Xylazine (veterinary sedative and street drug adulterant)
  • Medetomidine (veterinary sedative and street drug adulterant)
  • Guanfacine (Intuniv)
  • Brimonidine (Alphagan P)
Signs / symptoms of toxicity:
  • Pupillary constriction (miosis)
  • Hypotension
  • Bradycardia
  • Altered mental status / excessive somnolence
  • Apnea / respiratory failure
Pathophysiology:
By stimulating alpha-2 receptors in the central nervous system (CNS), resultant inhibition of the nucleus tractus solitarius leads to decreased norepinephrine release, leading to decreased heart rate and blood pressure in addition to a decreasing level of arousal. The agonism of imidazoline receptors is hypothesized to stimulate the locus coeruleus to release GABA, causing further sedation. In addition, imidazoline-receptor-3 regulates insulin secretion from the pancreas, and glycemic irregularities can occur. Nitric oxide (NO) is also released, further propagating hypotension. In withdrawal or abrupt cessation of drug therapy, patients may exhibit elevated sympathetic tone, often referred to as rebound hypertension.

Codes

ICD10CM:
T44.4X1A – Poisoning by predominantly alpha-adrenoreceptor agonists, accidental (unintentional), initial encounter

SNOMEDCT:
291299006 – Alpha-adrenoceptor agonist poisoning

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Diagnostic Pearls

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Differential Diagnosis & Pitfalls

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Therapy

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Drug Reaction Data

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References

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Last Reviewed:09/06/2023
Last Updated:05/27/2024
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Potentially life-threatening emergency
Alpha-2 adrenoceptor agonist poisoning
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A medical illustration showing key findings of Alpha-2 adrenoceptor agonist poisoning
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