10: Pesticides

Pesticide

Any substance used intentionally to kill pests

Classes of anticholinesterases

Organophosphates and carbamates

Species susceptible to anticholinesterases

Anything with a nervous system

Source of OPs and carbamates

• Insecticides

• Chemical warfare agents: Sarin, Vx nerve agent

• Topicals

• Environmental/water contamination

Primary mechanism of OP and carbamate toxicity

Anti-acetylcholinesterase (AchE) activity

What happens with longer OP exposure

The OP-AchE bond becomes permanent, and the only way the body recovers is by generating new enzyme

How are carbamates different than OPs

They don’t form the same permanent bond with AchE

Chemical characteristics that make anticholinesterases so dangerous

They have been optimize to pass through the skin and BBB

Extremely potent type of anticholinesterase that is used in malicious poisonings

Aldicarb (tres pasitos)

Syndromes seen with anticholinesterase activity

Extreme parasympathomimetic and sympathomimetic activity due to prolonged Ach activity everywhere

Why were some OPs pulled off the market

They are associated with neuronal degeneration and delayed neuropathies

CS associated with nicotinic stimulation from anticholinesterases

Initial muscular excitation → fatigue → paralysis

• CNS: changed behavior

CS associated with muscarinic stimulation from anticholinesterases

• SLUD signs

• Modified cranial nerve activity

• Changed HR

• Apparent blindness

Dog specific CS associated with anticholinesterase activity

Lung edema

Cattle specific CS associated with anticholinesterase activity

Respiratory arrest

Sample that can be used antemortem to diagnose anticholinesterase toxicity

Serum

Best postmortem diagnostic for anticholinesterase toxicity

Test the brain, AchE inhibition can last for months

Specific treatment for anticholinesterase toxicity

Atropine

Downside of atropine for anticholinesterase toxicity

It has purely anti-muscarinic activity, does nothing for the nicotinic stimulation

Decontamination for anticholinesterase toxicity

• AC

• Remove/wash off substance with SOAP

How do we treat the nicotinic effects associated with anitcholinesterases

Symptomatic; if excitatory use benzodiazepines, if paralytic then support respiration

Drug that can be used to treat chronic OP exposure

2-PAM (pralidoxime/protopam) → promotes release of OP from AchE

Common sources of pyrethrins and pyrethroids

“Less toxic” household insecticides

Pyrethrins v pyrethroids

Pyrethrins are natural, pyrethroids are synthetic

Source of pyrethrins

Chrysanthemums

Species susceptible to pyrethrins/roids

More insect selective, less effective on mammals than anticholinesterases

Syndrome associated with pyrethrin/roid toxicity

Neurologic

Species that is HIGHLY susceptible to pyrethrins/roids

Aquatics and cats

Pyrethin/roid insecticide additive that increases the half life

Piperonyl butoxide

Type of kinetics exhibited by pyrethrins/roids

Flip flop kinetics

Explain flip flop kinetics of pyrethrins/roids

The chemical sequesters in fat tissues in much higher concentrations, and as the liver clears the chemicals in the blood the fat acts as a reservoir and releases the chemicals over days

Pyrethrin/roid mechanism of action

Slows the Na⁺ VGC and causes nerve depolarization

CS associated with pyrethrin/roid toxicity

• Ear twitching and muscle tremors

• CNS effects: hyperreactive and abnormal behavior

• Excess salivation from lack of swallowing

• Hyperesthesia

Treatment for pyrethrin/roid toxicity

Decontaminate, wash with soap, and control neuro with benzos

Difference between first and second generation anticoagulant rodenticides

Second generation has greater potency and longer half life

Anticoagulant rodenticide mechanism

Inhibits vitamin K epoxide reductase, preventing vit K recycling

Why does it take a couple days for anticoagulant rodenticides to cause bleeding

The body has stores of clotting factors

Types of drugs that increase the half life of anticoagulant rodenticides

Drugs that suppress liver enzymes

CS associated with anticoagulant rodenticide toxicity

• Epistaxis

• Melena

• Cavitary and articular bleeding

• Swollen paws

Clin path abnormalities associated with anticoagulant rodenticide toxicity

• Regen anemia

• Thrombocytopenia

• All clotting tests prolonged

Treatment for anticoagulant rodenticide toxicity

Vit K1 injection with oral vit K until the rodenticide is metabolized

Treatment that may be used for severe cases of anticoagulant rodenticide toxicity

Whole blood or plasma transfusion to provide clotting factors