OP and carbamates-1

Pesticide Overview

  • Organophosphates (OPs) and carbamates (CMs) are widely used as pesticides globally.

  • Employed in agriculture, industry, and veterinary medicine as parasiticides.

  • Both categories act by inhibiting the enzyme acetylcholinesterase (AChE), resulting in neurotoxic effects.

Learning Objectives

  • Understand characteristics of OPs and CMs.

  • Learn about toxicokinetics and mechanisms of action.

  • Recognize clinical signs and lesions from poisoning.

  • Familiarize with diagnostic and therapeutic protocols for pesticide poisoning.

Characteristics and Use

  • Toxicity: Many OPs and CMs are extremely toxic, with ~40 registered with the US EPA, responsible for ~50% of pesticide use.

  • Example: Malathion is the most common OP.

  • Vary in water and lipid solubility; often less persistent in the environment.

  • Originally used in residential areas until 2001 when banned by the EPA.

Organophosphates

  • Early OPs, like Parathion, replaced DDT in the 1940s.

  • Development of more toxic OPs occurred during WWII, leading to creation of nerve agents like Sarin and VX.

  • Some OPs are microencapsulated to extend their activity and reduce toxicity.

  • Chemical Composition: Derivatives of phosphoric or phosphonic acid, often containing 'phos' or 'phosphate' in their names.

Carbamates

  • Derived from carbamic acid, named commonly with 'carb.'

  • Examples: Carbaryl, Aldicarb, Bendiocarb, Carbofuran, and others.

  • First carbamate Physostigmine was isolated in the 1860s for glaucoma treatment.

  • Aldicarb mimics the structure of acetylcholine (ACh) and is the most toxic of the carbamates.

Toxicokinetics

  • Exposure can be oral, dermal, or inhalation; toxicity is dependent on how they are metabolized.

  • OPs can undergo activation or detoxification.

  • Phosphate (P=O) vs. Thiophosphate (P=S): Different modes of biological activity.

    • OPs act directly, while thiophosphates require liver activation to become toxic.

  • Delayed Effects: Include organophosphate-induced delayed polyneuropathy and other syndromes.

Mechanism of Action

  • OPs and CMs inhibit AChE, leading to ACh accumulation, which causes overstimulation of muscarinic and nicotinic receptors.

  • Binding Characteristics:

    • OPs bind irreversibly to AChE; the "ageing effect" can occur with prolonged binding.

    • CMs competitively bind and thus are reversible.

Clinical Signs

  • Onset of symptoms usually occurs within 15 minutes to 1 hour after exposure.

  • Local Effects: Eye irritation and respiratory distress.

  • Systemic Effects categorized into muscarinic, nicotinic, and central effects:

    • Muscarinic: Vomiting, SLUD symptoms, miosis.

    • Nicotinic: Muscle twitching, tremors, convulsions.

    • Central: Apprehension followed by depression and potential respiratory failure.

Diagnosis

  • Detection of OPs/CMs can be through direct analysis of body fluids or tissues.

  • The specific AChE activity level is essential for diagnosis; >70% inhibition is indicative of poisoning.

  • Clinical Approach: Involves history, clinical signs, and administering test doses like atropine.

Treatment Protocols

  • Decontamination: Wash off chemicals thoroughly; gastric lavage and activated charcoal may be used.

  • Antidotes:

    • Atropine is used to block muscarinic effects, dosed according to animal size.

    • Pralidoxime chloride (2-PAM) is given to reactivate inactivated AChE and relieve nicotinic symptoms but is not effective for CMs.

    • Use 2-PAM within 24 hours of OP exposure to be effective.

Case Presentations

  • Examples include treatment of puppies exposed to diazinon: clinical signs like hypersalivation and diarrhea occurred.

  • Another case involved suspicious increases in animal mortality potentially tied to carbamate poisoning, with investigations revealing foreign materials in the environment.

Toxicological Lesions

  • Few specific lesions exist, potentially including pulmonary edema or necrosis in muscle tissues.

  • Common findings include congested or edematous organs, particularly the lungs and brain.

References

  • Gupta, R. (ed): Veterinary Toxicology: Basic and Clinical Principles, 2018, Academic Press.

  • Plumlee, Konnie H. Clinical Veterinary Toxicology, 2004. Elsevier Science.

  • Blackwell’s Five-Minute Veterinary Consult, Small Animal Toxicology, 2011.

Conclusion

  • Understanding the mechanisms, effects, and treatment options for pesticide poisoning is crucial in veterinary medicine.