Antihistamine toxicity

Non-sedating agents

• Cetirizine, desloratadine, fexofenadine, levocetirizine, loratidine
• Mild CNS depression in overdose +- anticholinergic effects
• Associated with QT prolongation
• QT prolongation is reported but rare
• Children: 1-3 tabs warrants home observation. Refer to hospital for drowsiness or anticholinergic symptoms

Non-sedating agents

• Toxic mechanism
  • Mildly lipophilic and less able to cross BBB
  • Selective, competitive reversible inhibitors of peripheral H1 receptors
  • Lower affinity for central H1, M1, alpha-1 and 5HT receptors than sedating agents
  • Selectivity may be lost in overdose
  • QT prolongation is due to cardiac K channel blockade
• Toxicokinetics
  • Well absorbed, peak effects at 1-3 hours and Vd 1.5L/kg
  • Hepatic metabolism is minor and elimination half-life ranges from 8-24 hours

Non-sedating agents

• Mild sedation, nausea, ataxia and mild anticholinergic symptoms
• Symptoms within 4-6 hours and resolve by 12-24 hours
• Monitor for 12 hours if symptomatic in case of QT prolongation
• If QT prolongation occurs, correct hypoxia/hypoK/hypoMg/hypoCa
• If HR <100, could overdrive pace chemically/electrically to 100-120
• Decontamination
  • AC not indicated
• Enhanced elimination n/a
• Physostigmine for severe anticholinergic delirium not controlled with benzodiazepines
  • 0.5-1mg as slow IV push over 5 minutes q10min
  • May need to repeat at 1-4 hours due to short half-life

Non-sedating agents

• Disposition
  • Symptomatic patients get 12-lead ECG every 4 hours until improvement
  • Fit for discharge once ambulating, eating, drinking, urinating and well
• Pitfall
  • Failure to recognise potential for prolonged QT

Sedating agents

• Chlorpheniramine, cyproheptadine, dexchlorpheniramine, dimenhydrinate, diphenhydramine, doxylamine (Restavit), pheniramine, promethazine (Phenergan)
• Dose-dependent sedation and anticholinergic effects
• Cardiovascular toxicity with massive OD
• All agents lower seizure threshold but this is infrequent
• Massive OD can cause QT prolongation, widened QRS and hypotension

Sedating agents

• Toxic mechanism
  • Competitive H1 antagonists with cross-antagonism of M1, alpha-1, 5HT
  • Cardiac sodium and K channel blockade in large OD
• Toxicokinetics
  • Well absorbed, peak levels at 2-3 hours
  • Lipid soluble and cross BBB
  • Metabolised in the liver
  • Half-lives 6-18 hours

Sedating agents

• Supportive care
• Serial ECG’s q6h
• Monitor for 6 hours if symptomatic
• Manage anticholinergic delirium with benzos +- physostigmine 0.5-1mg over 5 minutes q10min until desired effect
• Manage seizures with benzos
• Hypotension responds to fluids +- alpha agonists
• If QRS prolongation occurs complicated by ventricular dysrhythmias, intubate, hyperventilate and treat as per TCA

Sedating agents

• Decontamination
  • AC not indicated as sedation occurs early and good supportive care is adequate
• Enhanced elimination n/a
• Physostigmine if required
• Disposition
  • If asymptomatic and normal ECG at 6 hours, discharge in daylight
• Pitfalls
  • Failure to recognise anticholinergic delirium due to sedative effects
  • Failure to detect and relieve urinary retention

Last Updated on October 14, 2020 by Andrew Crofton