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CPC Conclusion. Michael D. Schwartz, MD Centers for Disease Control/ ATSDR/Georgia Poison Center (Fellowship Sponsor: Oak Ridge Institute for Science & Education, Department of Energy). The ingestion was 100 x 100 mg (10 gm) Amantadine hydrochloride tablets.

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cpc conclusion

CPC Conclusion

Michael D. Schwartz, MD

Centers for Disease Control/

ATSDR/Georgia Poison Center

(Fellowship Sponsor: Oak Ridge Institute for Science & Education, Department of Energy)

the ingestion was 100 x 100 mg 10 gm amantadine hydrochloride tablets
The ingestion was 100 x 100 mg (10 gm) Amantadine hydrochloride tablets
  • Prescribed for Parkinsonian Sxs along with DPH
  • Stockpiled two months’ supply
  • 10 DPH tablets were missing
  • Subsequent comprehensive toxicology testing revealed no co-ingestants
amantadine hydrochloride
Amantadine hydrochloride
  • Dopamine agonist
    • Parkinsonism/EPS/Movement disorders
    • Inhibits Influenza virus uncoating
  • 90% absorbed from GI tract
  • 75 - 90% protein bound
  • Vd = 6 to 8 L/kg
  • Peak plasma levels in 4 hours
  • 15% acetylated in liver; 85% unchanged (renal)
  • T1/2 = 15 hours (even in moderate overdose)
amantadine toxicity
Amantadine Toxicity
  • Five reports detailing 1 gm to 3.5 gm ingestions
    • All ingestions (n=3) over 2.5 gm died
  • CNS Toxicity
    • Levels 1000 – 3400 ng/ml (Reference 100 – 1000)
    • Hallucinations, Psychosis, Delerium, Tremors
  • Cardiotoxicity (Levels >3000 ng/ml)
    • Ventricular arrhythmias, bradycardia, QT prolongation
    • Case reports (1 PVCs, 3 V-Tach/TdP)
    • Worsened by anticholinergic co-ingestion
amantadine is a tricyclic amine
Amantadine is a tricyclic amine

Amantadine

Amitriptyline

amantadine cardiotoxicity
Amantadine Cardiotoxicity
  • Fast Sodium Channel blockade
    • QRS widening
  • Block of Outward Repolarizing K+ Channels
    • Prolonged QT; Risk of Torsades
    • Intracellular shift K+ /channel blockade
amantadine cardiotoxicity treatment
Amantadine Cardiotoxicity: Treatment
  • Sodium bicarbonate or Hypertonic NaCl
  • Magnesium for Torsades
    • Chemical overdrive pacing is risky/fatal outcomes
  • Ventricular ectopy (PVCs) – Lidocaine
  • Hypotension: Direct-acting vasopressors (NE)
    • Epinephrine may worsen hypokalemia
    • Dopamine/isoproterenol worsen cardiotoxicity
      • Associated with all 3 fatalities in Case Reports
clinical course
Clinical course
  • Remained normotensive/NSR in ICU
  • Prolonged intubation
  • Developed ICU pneumonia
  • Progressed to ARDS; protracted recovery
  • Discharged on hospital day 30 to psych