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Mechanism and Symptoms of Toxicity, and Diagnosis of Cholinesterase Inhibitors

Mechanism and Symptoms of Toxicity, and Diagnosis of Cholinesterase Inhibitors. Pesticide Health Effects Medical Education Database (PHEMED) 2010. Mechanism of Toxicity. Toxicity of Pesticides Cholinergic Inhibitors. Pesticides: Lannate - Methomyl (29% active, 71% inert) N-methyl carbamate

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Mechanism and Symptoms of Toxicity, and Diagnosis of Cholinesterase Inhibitors

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

  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)

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