Toxins of Terrorism and Mass Aggression
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Transcript of Toxins of Terrorism and Mass Aggression
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Toxins of Terrorism and Mass Aggression
Rama B. Rao, MDNYUMC/Bellevue Hospital Center
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Non-Traditional Weapons
5th Century B.C. use of pitch and sulfur in wars between Athens and Sparta
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19th Century Hong Kong
1857 Arsenic laced bread sold to British patrons to induce terror at the E Sing Bakery
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Toxin Classes
• Chemical Warfare
• Biologicals• Nuclear Agent• Others
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Classification of Chemical Agents
• Blistering agents or vesicants
• Pulmonary or choking agents
• Cellular asphyxiants or blood agents
• Nerve Agents• Incapacitants
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Blistering Agents/
Vesicants• Lewisite• Phosgene oxime• Mustards of
– Sulfur– Nitrogen
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Blistering Agents
• Irritation to: – Mucus Membranes– Skin– Occasionally deeper
tissues• Onset minutes to hours• Care supportive• Decontamination• BAL?
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Pulmonary/ Choking Agents
• Phosgene• Chlorine• Oxides of Nitrogen
• Impaired gas exchange
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Pulmonary/Choking Agents
• Onset can be delayed• Pulmonary edema
• Treatment supportive• Role of LT
antagonists for phosgene uncertain
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Blood Agents: Arsine (AsH3)
• Fishy/garlic odor• Onset 2-24 hours• Oxidant stressor• Topical: frostbite• Intravascular hemolysis
and its complications• Limited decontamination• Treatment Supportive
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Cellular Asphyxiants
• Cyanide• Cyanogen chloride
• Mitochondrial toxins• Rapidly fatal• Antidote kit
Zyklon B, WWII Auschwitz
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Cyanide Antidote Kit
Cyanide
Methemoglobin
Cyanomethemoglobin
Sodium Thiosulfate
Cyt a-a3
Mitochondria
SodiumThiocyanate
Hemoglobin
Nitrites
Rhodanese
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Nerve Agents
• Sarin• Cyclohexy Sarin• Soman• Tabun• VX• Organophosphate
insecticides
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Normal Cholinergic FunctionNormal Cholinergic Function
Target Organ
Neuron
++++++++++------------------ +++++++
Target Event
ACh
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Cholinesterase Function
_
N-CH2-CH2-O-C-CH3
H3C
H3C O-
+
H3C
N+-HO
H3C-N-CH2-CH2-OH
H3C
H3C
Choline
+
CholinesteraseCholinesteraseHO-C-CH3
O
Acetic Acid
ACh
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Normal Cholinesterase Normal Cholinesterase FunctionFunction
Target Organ
Neuron
ACh
Termination of Event
++++++++++------------------ -----
Choline
Acetic acid
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Cholinesterase Poisoning
_
RO-P=OR’O- N+-HO
Poisoned Poisoned CholinesteraseCholinesterase
ON-CH2-CH2-O-C-CH3
H3C
H3C O-
+
H3CACh
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Cholinesterase Poisoning
Target Organ
Neuron
ACh
Repeated Stimulation
----+++------------- +++--------+++
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Cholinergic Agents: Muscarinic Effects
• Salivation• Small Pupils • Lacrimation• Urination• Defacation• GI• Emesis
• Bradycardia• Bronchorrhea• Bronchospasm
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Atropine:Muscarinic Blocker
AChM Target Organ
Neuron
ACh
----+++-------------------------+++
Atropine
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CNS
Parasympathetic Ganglia Sympathetic
Excess AChM
Excess AChN
Catecholamines
BradycardiaBronchospasmBronchorrhea
TachycardiaHTNMydriasis
Hypoxia
AUTONOMIC NERVOUS SYSTEM
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CNS
Parasympathetic Ganglia Sympathetic
AChM
AChN
Catecholamines
BradycardiaBronchospasmBronchorrhea
TachycardiaHTN
Neuromuscular Junction
SOMATIC NERVOUS SYSTEM
AChN
NERVOUS SYSTEM
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Excess Acetylcholine: NMJ: Nicotinic
Skeletal Muscle:AChN
Neuron
ACh
Contraction
----+++------------- +++--------+++
ContractionContraction
FASCICULATIONS
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Excess Acetylcholine: NMJ: Nicotinic
Skeletal Muscle:AChN
Neuron
ACh
----+++++++++++++++++++++++
FLACCID PARALYSIS
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_
RO-P=OR’O-
Pralidoxime Pralidoxime binds binds
cholinesterasecholinesterase
O
2-PAM
_
RO-P=OR’O-
O
2-PAM
Reactivates Reactivates cholinesterasecholinesterase
Pralidoxime, 2-PAM
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Nerve Agents
• Atropine for muscarinic toxicity
• Oximes for nicotinic toxicity– Pralidoxime– Obidoxime
• Aggressive decontamination
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Protective Equipment• Decontamination
– Shower– Bed
• Fluid collection• Gown• Mask
– Full face– PAPR– SCBA
• GLOVES– Rubber– Nitrile rubber– Neoprene rubber– Butyl rubber– Vitron
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Crowd Control Agents
• Lacrimators
• Superfentanyl
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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
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Resources
• www.bt.cdc.gov/AgentlistChem.asp• chemdef.apgea.army.mil/textbook/
contents.asp• www-cgsc.army.mil/carl/resources/csi/
Heller/HELLER.asp