Organophosphate and Carbamate Insecticides

Organophosphate and Carbamate Insecticides

• Pesticides are chemicals used to kill unwanted pests (plants and animals).
• Pesticide types include:
  • Insecticides
  • Rodenticides
  • Fungicides
  • Herbicides
• Organophosphorus compounds are used as liquids or powders.
• They are absorbed by ingestion, inhalation, or skin contact.
• Organophosphates and carbamates are widely used globally.
• They are linked to approximately 3 million cases of human poisoning and cause around 40,000 deaths annually.

Insecticide Action

• Organophosphates and carbamates inhibit cholinesterases.
• This leads to acetylcholine accumulation at nerve endings (both central and peripheral).
• This accumulation affects neuromuscular junctions and can cause both muscarinic and nicotinic symptoms.
• Carbamates typically cause shorter-lived inhibition compared to organophosphates. The carbamate enzyme complex readily dissociates.

Cholinergic Receptors

• Two main receptor types exist and are blocked by atropine.
• Muscarinic Receptors: Located in smooth muscles and glands, and block by atropine.
• Nicotinic Receptors: Located in ganglia and neuromuscular junctions ; in sympathetic ganglia they stimulate post-ganglion neurons. High levels block transmission of impulses from pre to post neurons.
• Both receptors are found in high concentration in the brain.

Toxicity

• Binding of organophosphates/carbamates to the active site of acetylcholinesterase (AChE) inhibits AChE and leads to an increase of acetylcholine.
• This increase causes symptoms relating to both muscarinic and nicotinic stimulation.
• High levels of acetylcholine in the post ganglionic muscarinic synapses can lead to parasympathetic symptoms (SLUDGE: Salivation, Lacrimation, Urination, Defecation, Gastrointestinal upset, Emesis).
• In addition, high nicotine levels can cause generalized weakness, involuntary muscle contractions, and potentially respiratory problems.
• Organophosphates can cross the blood-brain barrier, causing severe symptoms such as seizures, respiratory depression, and central nervous system (CNS) depression.

Causes and Symptoms

• Acute poisoning occurs from self-ingestion, accidental ingestion of contaminated food, accidental ingestion of liquids by children, or skin contact.
• At the most basic level, symptoms could manifest as mild CNS effects, such as anxiety and sleep disturbances up to and including moderate symptoms like twitches, involuntary muscle contractions, paralysis (often impacting respiratory muscles) and generalized weakness, to severe CNS effects such as loss of consciousness, flaccid paralysis affecting the arms and legs and respiratory arrest.

Factors Determining Poisoning Severity

• The rate of enzyme phosphorylation
• The rate of enzyme hydrolysis
• The aging process of phosphorylated enzyme complex which leads to the loss of an alkyl side chain and irreversible inactivation of the enzyme

Paraquat

• Paraquat (a bipyridyl compound) is a widely used herbicide.
• It's primarily used in agricultural settings.
• Ingesting paraquat is highly toxic and can potentially lead to acute respiratory distress syndrome (ARDS).
• There are currently no specific antidotes, but fuller's earth or activated charcoal can be effective if administered quickly. Death is possible up to 30 days after ingestion.
• Paraquat poisoning has four stages: Stage 1 (1–5 days): Local corrosive action causes symptoms such as hemoptysis, ulceration of mucous membranes, nausea, diarrhea, and oliguria Stage 2 (2–8 days): Liver, kidney, and cardiac damage are the key features, accompanied by jaundice, fever, tachycardia, myocarditis, respiratory distress, cyanosis, and elevated levels of BUN and bilirubin. Stage 3 (3–14 days): Pulmonary fibrosis is the main characteristic. Key symptoms include cough, dyspnea, tachypnea, edema, pleural effusion, atelectasis, low arterial oxygen tension, and respiratory failure.

Diagnosis and Management

• Diagnosing organophosphate/carbamate poisoning from exposure history can be challenging.
• Gastrointestinal symptoms, along with fever and high white blood cell counts, may falsely lead to a gastroenteritis diagnosis.
• Reduced cholinesterase activity confirms the poisoning diagnosis.
  • In severe cases, less than 10% normal cholinesterase activity is observed .
• Management includes removing contaminated clothing and washing exposed skin.
• Gastric lavage, blood tests for AChE activity, and supplemental oxygen/respiratory support may be necessary.
• Atropine is often used as the primary treatment to combat muscarinic symptoms.
• Diazepam is used to relieve anxiety.
• Oximes, such as pralidoxime (2-PAM), can reactivate AChE, thus combating the poisoning.
• In paraquat poisoning, basic life support is critical. This includes preventing further absorption or exposure and decontamination, support of bodily functions and fluid/electrolyte replacement.

Late Complications

• Cranial nerve and brainstem lesions can occur within 1 to 4 days post-exposure.
• Peripheral neuropathy can potentially develop due to axonal degeneration 2 to 3 weeks after exposure.
• Exposure can result in chronic problems like insomnia, inability to concentrate, and depression.

This quiz explores the mechanisms and impacts of organophosphate and carbamate insecticides, including their effects on cholinesterase activity in the body. Learn about the various types of pesticides and their global usage, as well as health implications linked to their use. Test your knowledge on insecticide action and cholinergic receptors.