Organophosphates

1. Organophosphates Nerve Agents/ Pesticides

2. 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

3. 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)

4. 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

5. Overview – Toxicity • Full recovery likely after a single mild exposure • Moderate to severe exposures require treatment for survival • Repeated exposures are cumulative

6. Protective Equipment • Semi-permeable, active carbon protective clothing • Full-face respirator, appropriate filters • If unavailable: protective gowns, masks, and gloves can minimize skin exposure

7. 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

8. Decontamination • Nerve agents hydrolyze rapidly in strongly alkaline or chlorinated solutions • Decontaminate victims, equipment and material

9. 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

10. Decontamination • Eyes exposure: • Flush well with water for 10-15 minutes • Safely remove, contain victim clothing • Risk of secondary exposure for healthcare providers

11. 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

12. 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

13. 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

14. 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

15. Signs and Symptoms • Following a mild inhalation exposure • Meiosis and dimmed vision • Headache • Rhinorrhea • Salivation • Dyspnea and chest tightness

16. 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

17. 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

18. 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

19. 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

20. 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

21. 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

22. Summary • Military grade G and V agents • Commercial pesticides • High potential for terrorist • Easily manufactured • Commercially available • Inhibit tissue cholinesterases at synaptic sites

23. Summary • Treatments include • Atropine (anticholinergic) • Diazepam (anticonvulsant) • Acetylcholinesterase reactivator • High risk of exposure • Prophylactic treatment can be provided with pyridostigmine