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Organophosphates

Organophosphates. Baby July M. Cuambot Aldrine Jay Espinosa. Nerve Agents/ Pesticides. Acetylcholinesterase and OP. Organophosphate. Moat common OP pesticides used in self-poisoning in Sri Lanka.

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Organophosphates

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  1. Organophosphates Baby July M. Cuambot Aldrine Jay Espinosa Nerve Agents/ Pesticides

  2. Acetylcholinesterase and OP Organophosphate

  3. 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

  4. Malathion An Organophosphate

  5. ChlorpyrifosDimethoateFenthion 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

  6. Complicates Assessment of the Evidence OPs are different • Differing Toxicity • Different Kinetics • Different Clinical Syndromes • Different Response to Antidotes • ? Need Different Treatment Responses

  7. Decontamination • Don’t confuse creating mess with efficacy • Decisions based on risk/benefit analysis

  8. 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

  9. 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)

  10. 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

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

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

  13. 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

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

  15. 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

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

  17. 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

  18. 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

  19. 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

  20. 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

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

  22. 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

  23. 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

  24. 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

  25. 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

  26. 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

  27. 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

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

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

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