Post on 22-Feb-2016
description
Toxins of Terrorism and Mass Aggression
Rama B. Rao, MDNYUMC/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
Cyanide
Methemoglobin
Cyanomethemoglobin
Sodium Thiosulfate
Cyt a-a3
Mitochondria
SodiumThiocyanate
Hemoglobin
Nitrites
Rhodanese
Nerve Agents
• Sarin• Cyclohexy Sarin• Soman• Tabun• VX• Organophosphate
insecticides
Normal Cholinergic FunctionNormal Cholinergic Function
Target Organ
Neuron
++++++++++------------------ +++++++
Target Event
ACh
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
Normal Cholinesterase Normal Cholinesterase FunctionFunction
Target Organ
Neuron
ACh
Termination of Event
++++++++++------------------ -----
Choline
Acetic acid
Cholinesterase Poisoning
_
RO-P=OR’O- N+-HO
Poisoned Poisoned CholinesteraseCholinesterase
ON-CH2-CH2-O-C-CH3
H3C
H3C O-
+
H3CACh
Cholinesterase Poisoning
Target Organ
Neuron
ACh
Repeated Stimulation
----+++------------- +++--------+++
Cholinergic Agents: Muscarinic Effects
• Salivation• Small Pupils • Lacrimation• Urination• Defacation• GI• Emesis
• Bradycardia• Bronchorrhea• Bronchospasm
Atropine:Muscarinic Blocker
AChM Target Organ
Neuron
ACh
----+++-------------------------+++
Atropine
CNS
Parasympathetic Ganglia Sympathetic
Excess AChM
Excess AChN
Catecholamines
BradycardiaBronchospasmBronchorrhea
TachycardiaHTNMydriasis
Hypoxia
AUTONOMIC NERVOUS SYSTEM
CNS
Parasympathetic Ganglia Sympathetic
AChM
AChN
Catecholamines
BradycardiaBronchospasmBronchorrhea
TachycardiaHTN
Neuromuscular Junction
SOMATIC NERVOUS SYSTEM
AChN
NERVOUS SYSTEM
Excess Acetylcholine: NMJ: Nicotinic
Skeletal Muscle:AChN
Neuron
ACh
Contraction
----+++------------- +++--------+++
ContractionContraction
FASCICULATIONS
Excess Acetylcholine: NMJ: Nicotinic
Skeletal Muscle:AChN
Neuron
ACh
----+++++++++++++++++++++++
FLACCID PARALYSIS
_
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
Nerve Agents
• Atropine for muscarinic toxicity
• Oximes for nicotinic toxicity– Pralidoxime– Obidoxime
• Aggressive decontamination
Protective Equipment• Decontamination
– Shower– Bed
• Fluid collection• Gown• Mask
– Full face– PAPR– SCBA
• GLOVES– Rubber– Nitrile rubber– Neoprene rubber– Butyl rubber– Vitron
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