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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.

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CPC Conclusion

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  1. 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)

  2. 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

  3. 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)

  4. 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

  5. Amantadine is a tricyclic amine Amantadine Amitriptyline

  6. Amantadine Cardiotoxicity • Fast Sodium Channel blockade • QRS widening • Block of Outward Repolarizing K+ Channels • Prolonged QT; Risk of Torsades • Intracellular shift K+ /channel blockade

  7. 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

  8. Serum QuantitativeAmantadine and DPH Levels

  9. Clinical course • Remained normotensive/NSR in ICU • Prolonged intubation • Developed ICU pneumonia • Progressed to ARDS; protracted recovery • Discharged on hospital day 30 to psych

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