OrganophosphatesNerve Agents/ Pesticides
Baby July M. CuambotAldrine Jay Espinosa
Acetylcholinesterase and OP
Organophosphate
Moat common OP pesticides used in self-poisoning in Sri Lanka
Eddleston M et al Differences between organophosphorus insecticides in human self-poisoning: a prospective cohort study. Lancet. 2005 Oct 22-28;366(9495):1452-9
Malathion
An Organophosphate
Chlorpyrifos Dimethoate Fenthion
Number of cases 440 266 100
WHO Toxicity II II II
Formulation 40% EC 40% EC 50% EC
Chemistry Diethyl Dimethyl Dimethyl
Rat oral LD50 (mg/kg)
WHO 135 150 Not Given
OSHA 97 250 215-245
Eddleston M et al Differences between organophosphorus insecticides in human self-poisoning: a prospective cohort study. Lancet. 2005 Oct 22-28;366(9495):1452-9
OPs are different
• Differing Toxicity• Different Kinetics• Different Clinical Syndromes• Different Response to Antidotes• ? Need Different Treatment Responses
Complicates Assessment of the Evidence
Decontamination• Don’t confuse creating mess with efficacy
• Decisions based on risk/benefit analysis
Overview – Nerve Agents
• Tabun (GA)• 1936 - easiest to manufacture
• Sarin (GB)• 1938 - lethal through inhalation
• Soman (GD) • 1944 - fastest killing, lethal by inhalation
and skin contact
• VX • 1952 - lethal by inhalation and skin
contact
Overview – Pesticides
• Readily available for farm and home use
• Requires only an exterminator’s license
• Common lethal pesticides• TEPP (tetraethyl pyrophosphate)• Parathion• nicotine sulfate• DFP (diisopropyl-phosphorofluoridate)
Overview – Toxicity• Estimated LCt50s by inhalation• 400 mg-min/m3 for Tabun• 100 mg-min/m3 for Sarin• 50 mg-min/m3 for Soman• 10 mg-min/m3 for VX
• Percutaneous LD50s• 1000 mg• 1700 mg• 350 mg• and 6-10 mg, respectively
LD50 of VX Agent, 10 mg of liquid VX, enough to cover about two columns on the Lincoln Memorial on a penny.
Department of Defense image
Overview – Toxicity
• Full recovery likely after a single mild exposure
• Moderate to severe exposures require treatment for survival
• Repeated exposures are cumulative
Protective Equipment
• Semi-permeable, active carbon protective clothing
• Full-face respirator, appropriate filters• If unavailable: protective gowns,
masks, and gloves can minimize skin exposure
Detection
• Single and three-color detector papers are available to detect liquid nerve agent
• Area detectors / monitoring devices available through emergency management or military contacts
Decontamination
• Nerve agents hydrolyze rapidly in strongly alkaline or chlorinated solutions • Decontaminate victims,
equipment and material
Decontamination
• Dermal exposure:• Absorbing powders • talcum powder, Fullers earth
• Active neutralizing chemicals• chloramine solutions, 5% bleach
• Copious amounts of water can dilute and remove these agents
Decontamination
• Eyes exposure:• Flush well with water for 10-15 minutes
• Safely remove, contain victim clothing• Risk of secondary exposure for
healthcare providers
Signs and Symptoms
• Diagnosis is clinical• Confirmed by agent detection at
exposure scene
• Early signs depend on route of exposure
• Immediate symptoms following inhalation• Delayed as much as 18 hours
Signs and Symptoms
• Muscarinic effects are dominant first• Nicotinic effects follow
• Respiratory distress quickly predominates in moderate to severe exposures
• Ocular signs may come later in the progression of symptoms
• Decreased serum cholinesterase activity can confirm exposure to nerve agents
Signs and Symptoms
• Following a localized skin exposure• Meiosis, usually pinpoint and sometimes
unequal• Frontal headache• Nausea and vomiting• Weakness• Fasciculations or sweating at the
exposure site
Signs and Symptoms
• Severe dermal exposures• Eye pain on focusing and dimmed vision• Rhinorrhea, cough and wheezing• Chest tightness• Generalized muscular twitching or
convulsions• Paralysis• Loss of consciousness• Loss of bladder and bowel control
Signs and Symptoms
• Following a mild inhalation exposure• Meiosis and dimmed vision• Headache• Rhinorrhea• Salivation• Dyspnea and chest tightness
Signs and Symptoms
• Severe inhalation exposures• Chest pain, worsening pulmonary
symptoms• Gastrointestinal disturbances• Muscarinic signs, followed by nicotinic
signs• CNS disturbances• Ultimately: coma, areflexia, Cheyne-
Stokes respiration, convulsions, pulmonary edema, and respiratory and circulatory failure
Treatment• Basic first aid for victims• Assisted ventilation • General supportive measures• Anticholinergic / anticonvulsant agents• Atropine sulfate (antimuscarinic agent) • Titrate atropine until there is a decrease in
bronchial constriction and secretions• Diazepam (10mg IM initially)
MARK I Kit contains 600 mg of 2-pralidoxime chloride (the larger injector) and 2 mg of atropine
(the smaller one). Department of Defense image
Treatment
• Oximes (acetylcholinesterase reactivators)• Relieve the nicotinic symptoms• Pralidoxime chloride and others • Poor CNS penetration
• Pretreatment (prophylaxis)• Pyridostigmine, reversible
anticholinesterase agent, at 30 mg, 3 times daily
Long Term Medical Sequelae
• Full recovery can take up to 3 months • Increased susceptibility may persist up
to 3 months• Reported in animal studies• Persistent paralysis• Organophosphate induced delayed
neuropathy (OPIDN) • Axonal death with demyelination
Environmental Sequelae
• Tabun• Lasts 1-2 days (weather dependant)• Takes 20 times longer than water to
evaporate• Persists in water one day at 20°C, six
days at 5°C
• Sarin• Little persistence • Evaporates as fast as water or kerosene
Environmental Sequelae
• Soman • Lasts 1-2 days (weather dependant)• Takes 4 times longer than water to
evaporate• Thickeners can extend its persistence
• VX • Can persist for weeks to months,
particularly in temperatures near or below 0°C
• Evaporates 1,500 times slower than water
Summary
• Military grade G and V agents • Commercial pesticides• High potential for terrorist • Easily manufactured • Commercially available
• Inhibit tissue cholinesterases at synaptic sites
Summary
• Treatments include • Atropine (anticholinergic) • Diazepam (anticonvulsant)• Acetylcholinesterase reactivator
• High risk of exposure • Prophylactic treatment can be provided
with pyridostigmine