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
• Inhibits cholinesterase reversibly
• In high dose can induce cholinergic crisis
– LD50-rats
• Cholinesterase
– What is it?
50-90 mg/kg oral - 2000 mg/kg dermal
Action of Acetylcholine & Cholinesterase
Cholinesterase Inhibiting Pesticides
• Organophosphates
– Irreversibly inhibit
cholinesterase
– Longer lasting
toxicity
– Detectible ChE
inhibition
Normal Electrical Nerve
Impulse Transmission
- acetylcholine
- cholinesterase
- acetate
- choline
- organophosphate
- 2-PAM
muscle
nerve cell
Symptoms of Toxicity
Toxicity of Cholinesterase Inhibitors
Organophosphates / Carbamates
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Miosis
Diaphoresis
Salivation
Lacrimation
Urination
Defecation
Gastroenteric cramping
Emessis
Miosis
Toxicity of Cholinesterase
Inhibitor Overexposure
Cholinergic-Nicotinic
• Fasciculations
• Weakness
• Voluntary muscle paralysis
• Hypertension
(nicotinic presynaptic effects)
• Diaphoresis
(nicotinic presynaptic effects)
Toxicity of Cholinesterase
Inhibitor Overexposure
Central Nervous System Symptoms
• Headache
• Confusion
• Dizziness
• Seizures
• Depression of Respiratory Drive
Toxicity of Cholinesterase
Inhibitor Overexposure
Death from cholinesterase inhibitors is due to
respiratory failure:
• Increased secretions
• Increased bronchial smooth muscle
constriction
• Respiratory muscle paralysis
• Decreased respiratory drive
Diagnosis & Long Term Effect
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
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
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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