Organophosphates

Organophosphates is a topic covered in the Washington Manual of Medical Therapeutics.

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General Principles

Epidemiology

  • OPs are commonly used as pesticides and insecticides. Some also have medical indications (e.g., malathion in lice shampoo).
  • In the developing world, OP and other pesticide poisonings represent the most common cause of overdose deaths.1
  • OPs are also potent chemical terrorism and warfare agents (“nerve gas” agents) (e.g., sarin in the Tokyo subway attack or in Syria, tabun in the Iraq–Iran War).2
  • Although self-inflicted OP poisoning with suicidal intent occurs, exposure is primarily occupational or accidental.3 Because absorption occurs through skin and airways, the handling of OPs requires appropriate protective gear.

Pathophysiology

  • Inhibition of AChE leads to accumulation of ACh at nicotinic and muscarinic receptors, resulting in excessive cholinergic stimulation.
  • The severity of symptoms varies depending on the route of exposure (dermal, inhalation, oral, parenteral), dose, lipid solubility of OP, type of OP, and enzyme affinity.4
  • Initially, most OPs bind AChE reversibly. Some OPs, however, become permanently bound over time, a phenomenon known as “aging.” If aging occurs, the only way to overcome the inhibitory effect is for the body to synthesize new enzyme.
  • OPs are hepatically metabolized. Some OPs become active toxins after liver metabolism and thus can have delayed effects (e.g., parathion).5

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General Principles

Epidemiology

  • OPs are commonly used as pesticides and insecticides. Some also have medical indications (e.g., malathion in lice shampoo).
  • In the developing world, OP and other pesticide poisonings represent the most common cause of overdose deaths.1
  • OPs are also potent chemical terrorism and warfare agents (“nerve gas” agents) (e.g., sarin in the Tokyo subway attack or in Syria, tabun in the Iraq–Iran War).2
  • Although self-inflicted OP poisoning with suicidal intent occurs, exposure is primarily occupational or accidental.3 Because absorption occurs through skin and airways, the handling of OPs requires appropriate protective gear.

Pathophysiology

  • Inhibition of AChE leads to accumulation of ACh at nicotinic and muscarinic receptors, resulting in excessive cholinergic stimulation.
  • The severity of symptoms varies depending on the route of exposure (dermal, inhalation, oral, parenteral), dose, lipid solubility of OP, type of OP, and enzyme affinity.4
  • Initially, most OPs bind AChE reversibly. Some OPs, however, become permanently bound over time, a phenomenon known as “aging.” If aging occurs, the only way to overcome the inhibitory effect is for the body to synthesize new enzyme.
  • OPs are hepatically metabolized. Some OPs become active toxins after liver metabolism and thus can have delayed effects (e.g., parathion).5

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