CPC Conclusion
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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)
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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. - PowerPoint PPT Presentation
Transcript of CPC Conclusion
CPC Conclusion
Michael D. Schwartz, MDCenters 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
• 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
• 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
• 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 Amitriptyline
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
• 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
Serum Quantitative Amantadine and DPH Levels
Hours Post-ingestion
+6 +16 +24
Amantadine
(#100)
29,000 ng/ml
(100-1000)
7,000 ng/ml 920 ng/ml
Diphen-hydramine
(#10)
5,900 ng/ml
(100-1000)
1,200 ng/ml 99 ng/ml
Clinical course
• Remained normotensive/NSR in ICU
• Prolonged intubation
• Developed ICU pneumonia
• Progressed to ARDS; protracted recovery
• Discharged on hospital day 30 to psych
