NERVE AGENTS & PRETREAMENT

1. U.S. ARMY MEDICAL RESEARCH INSTITUTE OF CHEMICAL DEFENSE MEDICAL MANAGEMENT OF CHEMICAL CASUALTIES NERVE AGENTS&PRETREAMENT

2. DEFINITION • A substance that causes biological effects by inhibiting acetylcholinesterase • Acetylcholine accumulates • Effects are due to excess acetylcholine

3. EXAMPLES • Carbamates • Physostigmine (Antilirium) • Neostigmine (Prostigmine) • Pyridostigmine (Mestinon) • Sevin (insecticide) • Organophosphates • Malathion • Diazinon • “Nerve Agents”

4. NERVE AGENTS • GA (Tabun) • GB (Sarin) • GD (Soman) • GF • VX

5. O CH3 CH3 CH2 O P N CH3 CN GA

6. O CH3 O CH P CH3 CH3 F GB

7. O CH3 CH3 P O CH C CH3 F CH3 CH3 GD

8. VX O CH(CH3)2 CH3 N CH2 S CH2 P CH(CH3)2 CH3 CH2 O

9. CONTINUED HISTORY • Germany, WW II, nerve agent munitions • Used by Iraq • In stockpiles

10. TERRORIST USE • Matsumoto, 1994 • 7 deaths • Tokyo, 1995 • 12 deaths

11. PHYSICAL PROPERTIES • Clear, colorless liquids (when fresh), not “nerve gas” • Tasteless, most are odorless • Freeze/melt <0º C • Boil >150º C • Volatility GB>GD>GA>GF>VX • Penetrate skin, clothing

12. TOXICITY LCt50LD50 mg-min/m3 mg/70kg GA 400 1,000 GB 100 1,700 GD 70 50 GF 50 30 VX 10 10

13. CHOLINESTERASE • Blood • Acetyl (red cell, erythrocyte, “true”) • Butyryl (plasma, pseudo) • Tissue • Tissue acetylcholinesterase (at cholinergic receptor sites)

14. EXPOSURE INDICATORS • Inhibition of • Acetylcholinesterase (RBC) • most sensitive for nerve agent • Butyrylcholinesterase (plasma) • more sensitive for most insecticides

15. PHYSIOLOGY: NORMAL • Electrical impulse goes down nerve • Impulse causes release of neurotransmitter, acetylcholine • ACh stimulates receptor site on organ • Causes organ to act • ACh is destroyed by AChE • No more organ activity

16. Nerve Transmission: Nerve to Nerve ACh

17. Nerve Transmission: Nerve to Nerve ACh

18. Nerve Transmission: Nerve to Nerve ACh

19. Nerve Transmission: Nerve to Skeletal Muscle

20. Nerve Transmission: Nerve to Smooth Muscle

21. Nerve Transmission: Nerve to Exocrine Gland

22. Impulse Termination: The Role of AChE AChE ACh

23. Impulse Termination: The Role of AChE AChE ACh

24. PHYSIOLOGY: NERVE AGENT • Enzyme (AChE) is inhibited • Does not destroy ACh • Excess ACh continues to stimulate organ • Organ overstimulation

25. Exposure to Nerve Agent AChE ACh

26. AChE ACh Exposure to Nerve Agent

27. Effects on Striated (Skeletal) Muscle AChE ACh

28. Effects on Smooth and Cardiac Muscle AChE ACh

29. Effects on Exocrine Glands AChE ACh

30. ORGANS • Muscarinic • Smooth muscles • Exocrine glands • Cranial nerves (vagus) • Nicotinic • Skeletal muscles • Pre-ganglionic nerves • Both • CNS

31. EFFECTS • Muscarinic • Smooth muscles • Airways - constrict • GI tract - constrict • Pupils - constrict • Glands • Eyes, nose, mouth, sweat, airways, GI • Heart, bradycardia (vagal)

32. NICOTINIC • Skeletal muscles • Fasciculations, twitching, fatigue, flaccid paralysis • Pre-ganglionic • Tachycardia, hypertension

33. ACh ACh ACh at Receptors Nicotinic Nicotinic Preganglionicsynapses in ANS Skeletal muscle ACh Muscarinic Muscarinic Synapses in CNS Smooth muscle Exocrine glands ACh

34. HEART RATE • Muscarinic (vagal) decreases • Nicotinic (ganglionic) increases • May be high, low, normal

35. CNS • Acutely, large exposure • Loss of consciousness • Seizures • Apnea • Death

36. CONTINUED CNS • Acutely, small exposure • Minor CNS effects • Slowness in thinking and decision making • Sleep disturbances • Poor concentration • Emotional problems • Other minor problems

37. CONTINUED CNS • Minor CNS effects • May last for 3 to 6 weeks • May follow any exposure • Not always present • Very slight, subtle

38. VAPOR • Small exposure • Eyes: Miosis; injection; dim, blurred vision; pain; maybe nausea, vomiting • Nose: Rhinorrhea • Mouth: Salivation • Airways: Shortness of breath

39. VAPOR - NOSE and MOUTH • Runny nose • Worse than cold or hay fever • Leaking faucet • Mouth • Excessive saliva • May run out corners

40. VAPOR - RESPIRATORY TRACT • Small exposure • Tight chest • Moderate exposure • Severe breathing difficulty • Gasping, irregular breathing • Compounded by excessive secretions

41. VAPOR - GASTROINTESTINAL • Exposure to a large but not lethal concentration may cause: • Nausea, vomiting • Pain in abdomen • Diarrhea, involuntary defecation or urination

42. VAPOR - CARDIAC • Heart rate • Increase or decrease • Blood pressure - increase • Not an indicator for care

43. CONTINUED VAPOR • Onset of effects: seconds to minutes • After removal from vapor • Effects do not worsen • May improve • No late-onset effects

44. CONTINUED VAPOR • Large exposure • Previously listed effects plus... • Loss of consciousness • Seizures • Apnea • Flaccid paralysis • Death

45. LIQUID ON SKIN • Small droplet: local effects • Sweating, fasciculations • Medium droplet: systemic effects • GI • Large droplet: CNS • Loss of consciousness, seizures, apnea, flaccid paralysis, death

46. CONTINUED LIQUID ON SKIN • Onset of effects • Small, medium drop • As long as 18 hours • Large, lethal drop • Usually <30 minutes

47. CONTINUED LIQUID ON SKIN • Onset time, penetration • Skin site • Temperature • Moisture

48. CONTINUED LIQUID ON SKIN • Effects may occur despite initial decontamination • Effects may worsen

49. MIOSIS • Almost always after vapor • After liquid on skin: • Small: no • Moderate: maybe • Severe: yes

50. MANAGEMENT • ABCs • Drugs • Decontamination • Supportive • Not necessarily in that order