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Toxins of Terrorism and Mass Aggression. Rama B. Rao, MD NYUMC/Bellevue Hospital Center. Non-Traditional Weapons. 5th Century B.C. use of pitch and sulfur in wars between Athens and Sparta. 19th Century Hong Kong.
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Toxins of Terrorism and Mass Aggression Rama B. Rao, MD NYUMC/Bellevue Hospital Center
Non-Traditional Weapons 5th Century B.C. use of pitch and sulfur in wars between Athens and Sparta
19th Century Hong Kong 1857 Arsenic laced bread sold to British patrons to induce terror at the E Sing Bakery
Toxin Classes • Chemical Warfare • Biologicals • Nuclear Agent • Others
Classification of Chemical Agents • Blistering agents or vesicants • Pulmonary or choking agents • Cellular asphyxiants or blood agents • Nerve Agents • Incapacitants
Blistering Agents/ Vesicants • Lewisite • Phosgene oxime • Mustards of • Sulfur • Nitrogen
Blistering Agents • Irritation to: • Mucus Membranes • Skin • Occasionally deeper tissues • Onset minutes to hours • Care supportive • Decontamination • BAL?
Pulmonary/ Choking Agents • Phosgene • Chlorine • Oxides of Nitrogen • Impaired gas exchange
Pulmonary/Choking Agents • Onset can be delayed • Pulmonary edema • Treatment supportive • Role of LT antagonists for phosgene uncertain
Blood Agents: Arsine (AsH3) • Fishy/garlic odor • Onset 2-24 hours • Oxidant stressor • Topical: frostbite • Intravascular hemolysis and its complications • Limited decontamination • Treatment Supportive
Cellular Asphyxiants • Cyanide • Cyanogen chloride • Mitochondrial toxins • Rapidly fatal • Antidote kit Zyklon B, WWII Auschwitz
Cyanide Antidote Kit Hemoglobin Nitrites Methemoglobin Cyt a-a3 Mitochondria Cyanide Cyanomethemoglobin Sodium Thiosulfate Sodium Thiocyanate Rhodanese
Nerve Agents • Sarin • Cyclohexy Sarin • Soman • Tabun • VX • Organophosphate insecticides
Normal Cholinergic Function Neuron ACh ++++++++++ ------------------ +++++++ Target Organ Target Event
Cholinesterase Function Choline ACh H3C H3C H3C H3C-N-CH2-CH2-OH + N-CH2-CH2-O-C-CH3 H3C O- H3C N+-HO _ + Cholinesterase O HO-C-CH3 Acetic Acid
Normal Cholinesterase Function Neuron ACh Choline Acetic acid ++++++++++ ------------------ ----- Target Organ Termination of Event
Cholinesterase Poisoning ACh H3C H3C O + N-CH2-CH2-O-C-CH3 H3C RO-P=OR’ O- O- N+-HO _ Poisoned Cholinesterase
Cholinesterase Poisoning Neuron ACh ----+++------------- +++--------+++ Target Organ Repeated Stimulation
Cholinergic Agents: Muscarinic Effects • Bradycardia • Bronchorrhea • Bronchospasm • Salivation • Small Pupils • Lacrimation • Urination • Defacation • GI • Emesis
Atropine:Muscarinic Blocker Neuron ACh Atropine ----+++-------------------------+++ AChM Target Organ
AUTONOMIC NERVOUS SYSTEM Excess AChN Parasympathetic Ganglia Sympathetic Excess AChM Catecholamines CNS Bradycardia Bronchospasm Bronchorrhea Tachycardia HTN Mydriasis Hypoxia
NERVOUS SYSTEM AChN Parasympathetic Ganglia Sympathetic AChM Catecholamines CNS Bradycardia Bronchospasm Bronchorrhea Tachycardia HTN SOMATIC NERVOUS SYSTEM AChN Neuromuscular Junction
Excess Acetylcholine: NMJ: Nicotinic Neuron ACh ----+++------------- +++--------+++ Skeletal Muscle:AChN Contraction Contraction Contraction FASCICULATIONS
Excess Acetylcholine: NMJ: Nicotinic Neuron ACh ----+++++++++++++++++++++++ Skeletal Muscle:AChN FLACCID PARALYSIS
Pralidoxime, 2-PAM O 2-PAM RO-P=OR’ O O- 2-PAM RO-P=OR’ O- _ _ Pralidoxime binds cholinesterase Reactivates cholinesterase
Nerve Agents • Atropine for muscarinic toxicity • Oximes for nicotinic toxicity • Pralidoxime • Obidoxime • Aggressive decontamination
Decontamination Shower Bed Fluid collection Gown Mask Full face PAPR SCBA GLOVES Rubber Nitrile rubber Neoprene rubber Butyl rubber Vitron Protective Equipment
Crowd Control Agents • Lacrimators • Superfentanyl
Toxins of Mass Aggression • Identify agent or classify clinical effects • Decontamination • Live saving maneuvers • Be prepared for the undiagnosed exposure • Personal protection • Handling secondary fears
Resources • www.bt.cdc.gov/AgentlistChem.asp • chemdef.apgea.army.mil/textbook/contents.asp • www-cgsc.army.mil/carl/resources/csi/Heller/HELLER.asp