1. Mechanism and Symptoms of Toxicity, and Diagnosis of Cholinesterase Inhibitors Pesticide Health Effects Medical Education Database (PHEMED) 2010

2. Mechanism of Toxicity

3. Toxicity of Pesticides Cholinergic Inhibitors Pesticides: –Lannate - Methomyl (29% active, 71% inert) N-methyl carbamate Inhibits cholinesterase reversibly In high dose can induce cholinergic crisis –LD50-rats 50-90 mg/kg oral - 2000 mg/kg dermal Cholinesterase –What is it?

4. Action of Acetylcholine & Cholinesterase

5. Cholinesterase Inhibiting Pesticides Organophosphates –Irreversibly inhibit cholinesterase –Longer lasting toxicity –Detectible ChE inhibition

6. - acetylcholine - cholinesterase - acetate - choline - organophosphate - 2-PAM nerve cell muscle Normal Electrical Nerve Impulse Transmission

7. Symptoms of Toxicity

8. Toxicity of Cholinesterase Inhibitors Organophosphates / Carbamates Miosis Diaphoresis Salivation Lacrimation Urination Defecation Gastroenteric cramping Emessis

9. Miosis

10. Toxicity of Cholinesterase Inhibitor Overexposure Cholinergic-Nicotinic Fasciculations Weakness Voluntary muscle paralysis Hypertension (nicotinic presynaptic effects) Diaphoresis (nicotinic presynaptic effects)

11. Toxicity of Cholinesterase Inhibitor Overexposure Central Nervous System Symptoms Headache Confusion Dizziness Seizures Depression of Respiratory Drive

12. Death from cholinesterase inhibitors is due to respiratory failure: Increased secretions Increased bronchial smooth muscle constriction Respiratory muscle paralysis Decreased respiratory drive Toxicity of Cholinesterase Inhibitor Overexposure

13. Diagnosis & Long Term Effect

14. Diagnosis of ChE Inhibitors Testing cholinesterases Two kinds. RBC and Plasma (or serum) Different pesticides inhibit the two differently The absolute value is less valuable than the relative amount of depression against baseline Baselines are rarely available so recheck after a few weeks. Recovery: –RBC at the rate of RBC replacement –Plasma- faster at about 1.2 % per day

15. Differential Diagnosis: Acute Syndromes Headache, nausea, vomiting –Viral syndrome –Food poisoning –Cholinesterase inhibitor poisoning Acral Parasthesias –Hypocalcemia –Pyrethroid pesticides Hypermetabolism –Hyperthyroidism –Pentachlorphenol toxicity Alcohol antabuse reaction –Bis-di-thiocarbamate exposure

16. Differential Diagnosis: Chronic Problems Peripheral Neuropathy –Diabetes –Organophosphate Induced Delayed Peripheral Neuropathy –Lead Arsenate Lymphoma –Consider Pesticide Exposure Lung Cancer-Skin Cancer –Arsenic Male Sterility –Mumps –Past DBCP Exposure (a nematocide)