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