Pesticides Poisoning: Organophosphates & Carbamates

Pesticides Poisoning (Organophosphates & Carbamates)

• Learning Objectives: Students should know the circumstances of poisoning, toxicokinetics, mechanism of toxicity, clinical picture, treatment, comparison with carbamate poisoning, and pearls/pitfalls in cases.

Circumstances of Poisoning

• Accidental: Exposure during insecticide use (manufacturing and spraying), contaminated drinking water or food, combined use with cocaine for prolonged effects.
• Suicidal: Common, easily accessible, known for rapid death.
• Homicidal: Rare, identified by a distinct garlic odor.

Toxicokinetics of Organophosphates (OPCs)

• Absorption: Rapid absorption through various routes (respiratory, gastrointestinal, conjunctival, dermal, mucous membranes), faster through respiratory passages. Increased absorption in broken skin or dermatitis, high environmental temperatures.
• Distribution: Distributed throughout the body, crossing the blood-brain barrier; highly lipid-soluble, stored in fat tissue. This storage can result in persistent toxicity lasting several days.
• Metabolism: Primarily metabolized in the liver by cytochrome P-450 system.
• Excretion: Through urine and stool.

Mechanism of OPC Toxicity

• Cholinesterase Inhibition: Acetylcholine is normally rapidly hydrolyzed by cholinesterase. Organophosphates inhibit this enzyme, causing acetylcholine accumulation. This initially stimulates and is followed by depression of impulse transmission at postganglionic parasympathetic nerve endings (muscarinic), autonomic ganglia, and neuromuscular junctions (nicotinic), and the central nervous system (CNS).

Mechanism of Toxicity (Autonomic Nervous System)

• Diagram showing the effects of OPCs on the parasympathetic and sympathetic nervous systems. The effects include but are not limited to:
  • Hollow organs: Salivation, Lacrimation, Urination, Vomiting, Diarrhea, Nausea and Colic,
  • Miosis: Blurred vision,
  • Bradycardia and Hypotension: Slow heart rate and low blood pressure,
  • Bronchospasm, wheezing and cyanosis,
  • Increased secretions (sweating and salivation).
  • Sympathetic: Hypertension, Tachycardia (increased heart rate), Mydriasis (pupil dilation).

Clinical Picture of OPC Poisoning

• Muscarinic Effects (DUMBELLS): Classic cholinergic syndrome. Symptoms include diarrhea, nausea, vomiting, colic, urination, defecation, miosis, blurred vision, bradycardia, hypotension, bronchospasm, wheezing, cyanosis, and increased secretions (sweating, salivation, lacrimation).
• Nicotinic Effects: Prolonged QT interval (torsade de pointes), diaphoresis (sweating), hypertension, tachycardia, skeletal muscle fasciculations, weakness, paralysis, and respiratory arrest.
• CNS Effects: Initial stimulation (anxiety, insomnia, confusion, ataxia, coma), followed by seizures (more prevalent in children), and respiratory and circulatory depression.

Cause of Death

• Respiratory failure primarily due to bronchospasm, bronchorrhea, respiratory muscle failure, or respiratory center inhibition; Arrhythmias

Treatment of OPC Poisoning

• I) Emergency & Supportive Measures: Priority is airway and breathing management, frequent secretions suctioning, respiratory support, and intubation if necessary. Manage ventricular arrhythmias, control fluid loss and other manifestations (IV diazepam, phenobarbital for status epilepticus). Administer IV fluids for fluid loss in secretions.
• II) Decontamination: Avoid direct contact with contaminated skin or clothes. Observe asymptomatic patients for 8-12 hours. Profuse vomiting and diarrhea, gastric lava, activated charcoal (recent ingestion).
• Dermal Contamaination: Protective clothing, careful removal of clothes and shoes, wash patient's skin carefully, and remove hair, then use ethyl alcohol and water to prevent further absorption. Shave greasy hair, and wash all crevices, ears, genitalia, hair, and under nails.
• Eye decontamination: Rinse affected area with copious water or saline for at least 15 minutes. Seek ophthalmologist consultation.
• III) Enhancement of elimination: No role described.

Treatment of OPC Poisoning: Antidotal Therapy (IV)

• Physiological Antidotes (Atropine): Competitive antagonist of acetylcholine at muscarinic and CNS receptors, reversing muscarinic effects. Not effective against nicotinic effects but required for muscarinic symptoms. Lasts ≥ 24 hours and administered only after patient is well oxygenated (otherwise arrhythmia risk). Potential adverse effects with high dose (tachycardia, flushed skin, mydriasis, urinary retention, hallucinations).
• Physiological Antidotes (Oximes): Reactivate cholinesterase enzyme, detoxify organophosphates, anticholinergic effect, most effective on nicotinic receptors/less effective for muscarinic.; Used for suspected or confirmed OPC poisoning or significant NM weakness or need for high atropine dosage. Treat with Obidoxime (toxogonin), administered intravenously (1 ampule (250mg) in 100ml of saline solution over 15-30 minutes). Careful dosage and administration to avoid adverse effects (transient dizziness, blurred vision, sudden cardiac, resp. arrest).

Carbamate Poisoning

• Carbamate insecticides are acetylcholinesterase inhibitors. Their toxic effects are short-lived (minutes to 48 hours), and the effect of the carbamate-cholinesterase binding is reversible. Similar to organophosphates but manifestations are less severe and of shorter duration, and less penetrant of the BBB (leading to less CNS symptoms).
• Treatment: Oximes are not indicated as the action of carbamates is reversible unless it is mixed organophosphate carbamate poisoning or the diagnosis of organophosphate/carbamate poisoning is unclear.

Pearls and Pitfalls

• Prognosis: Prompt diagnosis and treatment of organophosphate insecticide poisoning typically yields a good outcome. However, untreated individuals may die within 24 hours due to respiratory failure, if unsuccessful treatment means death within 10 days.
• Observation: Maintain patient observation (12-24 hours) for delayed symptom onset, especially in individuals exposed to fat-soluble agents.
• Return to work: Avoid returning individuals to work (especially farmers) where CHE levels are <75% of normal.
• Intubation: If intubation is needed, avoid succinylcholine and mivacurium as they may prolong paralysis due to metabolism by pseudocholinesterase.