A. Introduction
[Figure] "Peripheral Nervous System Neurotransmitters"
- Acetylcholinesterase inhibition with resultant cholinergic poisoning
- Most common in USA, are parathion and malathion, insecticides and antiparasitic agents
- Nerve gases (sarin and others) have similar mechanism of action
- Blocks central as well as peripheral muscarinic and nicotinic acetylcholinesterase
- 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]
- Extremely Toxic - Nerve Gas [4]
- Used in warfare and terrorism
- Sarin
- Tabun
- Soman
- VX
- TEPP
- OMPA
- Highly Toxic
- Parathion (insecticide)
- Phosdin
- Demeton
- Disulfoton
- Schradan
- Moderately Toxic
- Coumaphos
- Diazinon
- Dichlorvos
- Mildly Toxic
- Dimethoate
- Malathion (insecticide, antiparasitic)
- Chlorthion
C. Symptoms
- Due primarily to acetylcholine excess
- Hyperglycemia, nonketotic; amylase increase from pancreatitis
- Muscarinic Acetylcholine Receptor Mediated
- Pupils: miosis (constriction)
- Lungs: bronchospasm, bronchorrhea, pulmonary edema
- Skin: diaphoresis (sweat glands)
- Cardiovascular: hypotension, bradycardia
- Gastrointestingal: nausea, vomiting, diarrhea
- Salivary glands: salivation
- Lacrimal glands: tearing
- Bladder: urinary incontinence
- Nicotinic Acetylcholine Receptor Mediated
- Muscle manifestations
- Fasciculations
- Muscle weakness
- Cramps
- Respiratory (diaphragm) paralysis
- Central Nervous System (CNS)
- Headache
- Anxiety
- Slurred speech
- Delirium
- Seizures (convulsions)
- Coma
- Death
- Mnemonic: "BLUSH" Brachycardia, Lacrimation, Urination, Salivation, Hypotension
- Different organophosphorus agents have distinct severity and risk of death [5]
D. Treatment of Adults [3,4]
- Oxygen
- Should be given in all cases except in Paraquat poisoning
- Oxygen should be given before atropine except in Paraquat poisoning
- Atropine
- Mainly effective at muscarinic sites
- 2mg iv q15 minutes until anti-cholinergic effects occur (dry mouth, dilated pupils)
- Usually 40mg per day total is given
- Continue for at least 24 hours; will not reverse muscle weakness (including meiosis)
- Pralidoxime (Protopam®) [5]
- Reactivates cholinesterase
- Counteracts weakness, muscle fasciculations and respiratory decrease
- Give initial 2gm IV dose over 30-40 minutes
- After bolus, high dose infusion 1gm/hr IV x 48 hours is superior to 1gm q4 hours dosing [5]
- More effective in chlorpyrifos poisoning than in fenthion or dimethoate poisoning [6]
- Diazepam (Valium®)
- Effective against seizures
- 5-10mg IV q10-20 minutes, titrate to effect (maximum 30mg in 8 hours)
- May repeat in 24 hours as required
- Tropicamide: 1-2 drops 0.5% solution to eye; may repeat in 5 minutes
- Hemoperfusion for severe overdoses
- Decontamination of skin and clothing
- Pyridostigmine (Mestinon®)
- Preatreatment for possible exposure
- Enhances effectiveness of atropine and pralidoxime against some nerve gas agents
E. Dosages for Treatment of Pediatric Cases [4]
- Oxygen as above
- Atropine 0.02mg/kg IV 2-5 minutes, to effect; 0.1mg maximum dose
- Pralidoxime 15-25mg/kg IV
- Diazepam 0.05-0.3mg IV over 2-3 minutes q15-30 minutes, to effect (maximum 10mg)
- Tropicamide: dose not established
References
- Kales SN and Christiani DC. 2004. NEJM. 350(8):800

- Alarcon WA, Calvert GM, Blondell JM, et al. 2005. JAMA. 294(4):455

- Organophosphate Poisoning. 1995. Med Let. 37(948):43
- Lee EC. 2003. JAMA. 290(5):659

- Pavar KS, Bhoite RR, Pillay CP, et al. 2006. Lancet. 368(9553):2136

- Eddleston M, Eyer P, Worek F, et al. 2005. Lancet. 366(9495):1452
