A. Introduction
[Figure] "Peripheral Nervous System Neurotransmitters"

1. Acetylcholinesterase inhibition with resultant cholinergic poisoning
2. Most common in USA, are parathion and malathion, insecticides and antiparasitic agents
3. Nerve gases (sarin and others) have similar mechanism of action
4. Blocks central as well as peripheral muscarinic and nicotinic acetylcholinesterase
5. An acute illnees with mild-moderate severity has been reported after pesticide exposure at schools: respiratory and gastrointestinal symptoms, headache, blurred vision [2]

B. Agents [3]

1. Extremely Toxic - Nerve Gas [4]
   1. Used in warfare and terrorism
   2. Sarin
   3. Tabun
   4. Soman
   5. VX
   6. TEPP
   7. OMPA
2. Highly Toxic
   1. Parathion (insecticide)
   2. Phosdin
   3. Demeton
   4. Disulfoton
   5. Schradan
3. Moderately Toxic
   1. Coumaphos
   2. Diazinon
   3. Dichlorvos
4. Mildly Toxic
   1. Dimethoate
   2. Malathion (insecticide, antiparasitic)
   3. Chlorthion

C. Symptoms

1. Due primarily to acetylcholine excess
2. Hyperglycemia, nonketotic; amylase increase from pancreatitis
3. Muscarinic Acetylcholine Receptor Mediated
   1. Pupils: miosis (constriction)
   2. Lungs: bronchospasm, bronchorrhea, pulmonary edema
   3. Skin: diaphoresis (sweat glands)
   4. Cardiovascular: hypotension, bradycardia
   5. Gastrointestingal: nausea, vomiting, diarrhea
   6. Salivary glands: salivation
   7. Lacrimal glands: tearing
   8. Bladder: urinary incontinence
4. Nicotinic Acetylcholine Receptor Mediated
   1. Muscle manifestations
   2. Fasciculations
   3. Muscle weakness
   4. Cramps
   5. Respiratory (diaphragm) paralysis
5. Central Nervous System (CNS)
   1. Headache
   2. Anxiety
   3. Slurred speech
   4. Delirium
   5. Seizures (convulsions)
   6. Coma
6. Death
7. Mnemonic: "BLUSH" Brachycardia, Lacrimation, Urination, Salivation, Hypotension
8. Different organophosphorus agents have distinct severity and risk of death [5]

D. Treatment of Adults [3,4]

1. Oxygen
   1. Should be given in all cases except in Paraquat poisoning
   2. Oxygen should be given before atropine except in Paraquat poisoning
2. Atropine
   1. Mainly effective at muscarinic sites
   2. 2mg iv q15 minutes until anti-cholinergic effects occur (dry mouth, dilated pupils)
   3. Usually 40mg per day total is given
   4. Continue for at least 24 hours; will not reverse muscle weakness (including meiosis)
3. Pralidoxime (Protopam®) [5]
   1. Reactivates cholinesterase
   2. Counteracts weakness, muscle fasciculations and respiratory decrease
   3. Give initial 2gm IV dose over 30-40 minutes
   4. After bolus, high dose infusion 1gm/hr IV x 48 hours is superior to 1gm q4 hours dosing [5]
   5. More effective in chlorpyrifos poisoning than in fenthion or dimethoate poisoning [6]
4. Diazepam (Valium®)
   1. Effective against seizures
   2. 5-10mg IV q10-20 minutes, titrate to effect (maximum 30mg in 8 hours)
   3. May repeat in 24 hours as required
5. Tropicamide: 1-2 drops 0.5% solution to eye; may repeat in 5 minutes
6. Hemoperfusion for severe overdoses
7. Decontamination of skin and clothing
8. Pyridostigmine (Mestinon®)
   1. Preatreatment for possible exposure
   2. Enhances effectiveness of atropine and pralidoxime against some nerve gas agents

E. Dosages for Treatment of Pediatric Cases [4]

1. Oxygen as above
2. Atropine 0.02mg/kg IV 2-5 minutes, to effect; 0.1mg maximum dose
3. Pralidoxime 15-25mg/kg IV
4. Diazepam 0.05-0.3mg IV over 2-3 minutes q15-30 minutes, to effect (maximum 10mg)
5. Tropicamide: dose not established

References

1. Kales SN and Christiani DC. 2004. NEJM. 350(8):800
2. Alarcon WA, Calvert GM, Blondell JM, et al. 2005. JAMA. 294(4):455
3. Organophosphate Poisoning. 1995. Med Let. 37(948):43
4. Lee EC. 2003. JAMA. 290(5):659
5. Pavar KS, Bhoite RR, Pillay CP, et al. 2006. Lancet. 368(9553):2136
6. Eddleston M, Eyer P, Worek F, et al. 2005. Lancet. 366(9495):1452