Diazinon — Poison Information

1. Overview & Classification

• Use: Agricultural and household insecticide; also used in animal care (flea-dip products)
• Status: Phased out from household use in the United States in 2000 due to neurotoxicity, particularly to the developing brains of children — but still widely used in many other countries
• WHO Classification: Moderately hazardous (Class II)
• Formulations: Aerosols, dusts adsorbed to inert particulate material, liquid concentrates

2. Mechanism of Toxicity

1. Irreversible inhibition of acetylcholinesterase (AChE) — via phosphorylation of the serine hydroxyl group at the active site of the AChE catalytic triad (Ser-Glu-His)
2. This prevents the breakdown of acetylcholine (ACh) at synapses
3. ACh accumulates at:
   • Muscarinic receptors (parasympathetic/autonomic)
   • Nicotinic receptors (neuromuscular junction, autonomic ganglia)
   • CNS synapses
4. "Aging": Over 24–48 hours, irreversible dealkylation of AChE occurs, forming a phosphoryl-oxyanion-serine bond completely resistant to pharmacological hydrolysis — this is why early treatment is critical

3. Routes of Exposure

• Inhalation (spray/aerosol)
• Transdermal (skin contact)
• Transconjunctival (eye contact)
• Gastrointestinal (ingestion)
• Mucous membrane contact

4. Clinical Features (Cholinergic Toxidrome)

Muscarinic Effects (SLUDGE / DUMBELS)

Nicotinic Effects

• Muscle fasciculations
• Weakness → paralysis
• Tachycardia (can counteract bradycardia)
• Hypertension

CNS Effects

• Anxiety, restlessness
• Seizures
• Coma
• Respiratory depression

5. Delayed Syndromes

A. Intermediate Syndrome (24–96 hours post-exposure)

• Paralysis of proximal limb muscles, neck flexors, cranial nerves, and respiratory muscles
• Caused by excessive nicotinic receptor stimulation
• May result from redistribution of lipophilic organophosphate from adipose tissue or inadequate oxime therapy
• Respiratory muscle paralysis can be fatal

B. Organophosphate-Induced Delayed Neuropathy (OPIDN) — 1–3 weeks post-exposure

• Weakness of extremities, ataxia, eventually paralysis
• Peripheral neuropathy from phosphorylation of neuropathy target esterase (NTE)
• Respiratory muscles NOT affected

C. Extrapyramidal Syndrome (rare)

• Parkinson-like symptoms appearing days after cholinergic crisis resolution
• Responds to antiparkinsonian agents

6. Laboratory Findings

7. Management

Decontamination

• Remove clothing, wash skin thoroughly with soap and water
• Eye irrigation if ocular exposure
• Activated charcoal for recent ingestion (if airway protected)

Antidotes

1. Atropine (Muscarinic Antagonist) — PRIORITY

• Blocks muscarinic receptors; does NOT reverse nicotinic effects
• Dose: 2–4 mg IV in adults (children: 0.02–0.05 mg/kg); repeat every 5–10 minutes
• Endpoint: Drying of secretions, heart rate normalization — not pupil dilation
• Massive doses may be required (hundreds of mg in severe cases)

2. Pralidoxime (2-PAM) — Oxime / AChE Reactivator

• Reactivates AChE before "aging" occurs — must be given early
• Reverses both muscarinic AND nicotinic effects
• Dose: 1–2 g IV over 15–30 minutes; infusion at 200–500 mg/hr
• Ineffective after aging is complete (>24–48 hours)

3. Benzodiazepines

• For seizure control (diazepam preferred)

Supportive Care

• Airway management — intubation often required (use succinylcholine cautiously — prolonged paralysis due to pseudocholinesterase inhibition; prefer rocuronium)
• Mechanical ventilation for respiratory failure
• ICU monitoring

8. Prognosis

• Most deaths from organophosphate poisoning are due to respiratory failure (bronchospasm + bronchorrhea + respiratory muscle paralysis)
• Globally, organophosphate poisoning results most commonly from deliberate self-poisoning
• More than 150,000 pesticide poisoning deaths occur worldwide each year, with insecticides (including organophosphates) accounting for the majority

9. Special Populations

• Children: Particularly vulnerable — developing nervous systems are more sensitive; diazinon was specifically removed from household use in the US due to neurotoxicity in children
• Occupational exposure: Agricultural workers and pet groomers (flea-dip products) are at risk of chronic low-level exposure