Carbamate Insecticide Toxicity - Causes, Symptoms, Diagnosis, and Treatment

Introduction:

Regarding structure and mechanism, carbamates are an insecticide class related to organophosphate (OP) insecticides. Acetylcholinesterase is carbamylated by carbamates, which are N-methyl carbamates generated from a carbamic acid, in neuronal synapses and neuromuscular junctions. While carbamates bind to acetylcholinesterase reversibly, they share a similar mode of action with the irreversible phosphorylation of acetylcholinesterase by organophosphates. Therefore, carbamates have a toxicological presentation comparable to OP toxicity, with a typical toxicity period of fewer than 24 hours. Aldicarb, Carbofuran, Carbaryl, Ethinenocarb, Fenobucarb, Oxamyl, Methomyl, Pirimicarb, Propoxur, and Trimethacarb are examples of substances that frequently cause harmful exposure.

What Are the Causes of Carbamate Toxicity?

Dermal, inhalational, and gastrointestinal (GI) exposures to carbamates can all result in toxic exposures. The type of pesticide used and the exposure dose affect how serious the symptoms appear. The most frequent causes of carbamate toxicity are deliberate oral consumption or occupational dermal exposure. Large outbreaks caused by contaminated food and crops have been documented in poor nations. According to the pharmacology of the different carbamates used, cutaneous exposure may cause symptoms to appear quickly. After working in recently insecticide-sprayed or insecticide-fogged regions, exposure can occur through mixed cutaneous and inhalational exposures. Children have been getting sick from playing on a sports field following pesticide spraying.

What Happens in Carbamate Toxicity?

Carbamates work by blocking AChE (acetylcholinesterase). This is accomplished through the carbamylation of a serine hydroxyl residue in the enzyme's active site, which cleaves the carbamate molecule, which is processed by the enzyme as if it were ACh. ACh accumulates at CNS synapses, neuromuscular junctions, and parasympathetic effector sites when AChE is inhibited. The carbamylated enzyme undergoes spontaneous hydrolysis, which results in the restoration of AChE activity. Systemic toxicity may result from consumption, inhalation, or skin contamination, and propoxur has been associated with severe neonatal toxicity by transplacental transfer. Although acute toxicity from carbamate insecticides can be severe and fatal, it is often less severe than acute toxicity from OP insecticides due to the group's members' varying toxicity levels.

What Happens After Getting Exposed to Carbamate Insecticides?

Exposure can be acute or chronic, and the skin, lungs, eyes, mucous membranes, GI system, and lungs can absorb it. Dermal absorption seems minimal, although it increases when the skin is damaged or exposed to highly poisonous carbamates. Patients may experience symptoms within five minutes of severe exposure. The toxicity of the provided carbamate and the exposure dose influence when symptoms may appear. Carbamates that are highly lipophilic will swiftly redistribute into fat storage from the extracellular fluid and initially have less severe clinical consequences.

90 percent of carbamates are renally eliminated within a few days after being hydrolyzed, hydroxylated, and conjugated in the liver. However, data on the penetration of carbamates into the CNS and cerebrospinal fluid are contradictory. Adults typically exhibit less CNS damage, but CNS depression is frequently the main symptom in childhood exposures. Notably, the carbamate-cholinesterase bond hydrolyzes spontaneously within hours and does not experience the ‘aging’ that occurs during the phosphorylation of organophosphates to acetylcholinesterase.

What Are the Signs and Symptoms of Carbamate Toxicity?

The signs and symptoms of carbamate toxicity are

• Fatigue.

• Weakened muscles.

• Lightheadedness.

• Sweating.

• Slurred speech.

• Jerking muscles.

• Blurred vision.

• Lack of coordination.

• Nausea and vomiting.

• Diarrhea.

• Stomach pain.

• Salivation.

Severe symptoms include

• Coma.

• Seizures.

• Hypotonicity - Abnormally low muscle tone.

• Hypertension.

• Cardio or respiratory depression.

How Is Carbamate Toxicity Diagnosed?

Treat the patient immediately if there are clear clinical signs of acute N-methyl carbamate toxicity and a history of carbamate exposure. It is necessary to acquire blood to measure plasma pseudocholinesterase and RBC AchE. It is unlikely that blood cholinesterase activity would be observed to be decreased until a significant amount of N-methyl carbamate has been absorbed and a blood sample is taken within an hour or two. Because enzyme reactivation happens both in vitro and in vivo, it is still necessary to employ a quick test for enzyme activity to identify an effect even under the conditions mentioned.

Urine testing for specific metabolites from several N-methyl carbamates, including

• Alpha-naphthol from carbaryl.

• Isopropoxyphenol from propoxur.

• Carbofuran phenol from carbofuran.

• Aldicarb sulfone, sulfoxide, and nitrile from aldicarb can be used to confirm absorption.

When accessible, these detailed analyses can help pinpoint the offending party and track the disposal of carbamates.

How Is Carbamate Toxicity Treated?

The following modalities are used to treat carbamate toxicity.

• Decontamination - Decontamination must happen as quickly as feasible because of the continuing cutaneous absorption of carbamate insecticides. The patients should be stripped of all clothing, and their skin should be cleaned three times: once with water, once with soap, and once again with water. In GI ingestions, vomiting, and diarrhea may lead to cutaneous absorption in healthcare professionals. GI decontamination may be an option in cases of significant, life-threatening ingestions.

  • If the patient has not experienced episodes of emesis.

  • If the ingestion took place within an hour.

  • If the patient is guarding their airway.

  • Nasogastric lavage may be used in this situation. In addition, patients may have seizures, respiratory paralysis, and coma in cases of severe toxicity. If these characteristics are present, airway protection should be performed before GI decontaminating.

• Respiratory Management - The primary cause of death following hazardous exposure to AChE inhibitors (carbamate) is respiratory failure and hypoxia. This is multifactorial due to bronchorrhea, muscle weakness that may lead to flaccid paralysis, and CNS respiratory drive depression. Following decontamination, the focus of the initial patient evaluation should be on ensuring adequate breathing and oxygenation. Atropine can reduce increased respiratory secretions by competitively inhibiting the overexcitation of muscarinic receptors. Patients with trouble controlling their respiratory secretions, comatose or extremely depressed mental condition, or considerable skeletal muscle weakness should have early endotracheal intubation.

  • Atropine - Atropine reduces symptoms of lacrimation, salivation, miosis, emesis, diarrhea, diaphoresis, urine incontinence, bronchospasm, and excessive respiratory secretions by competitively antagonizing the elevated acetylcholine levels at muscarinic receptors. Atropine should be provided starting at doses of 1 to 3 milligrams intravenously (IV) for adults or 0.05 mg/kg IV for children with a minimum dose of 0.1 milligrams. The dose should be raised every five minutes if the preceding amount does not respond sufficiently. A steady infusion of Atropine, typically 10 % to 20 % of the bolus dose each hour, is used to maintain the therapy response once a stable dose of Atropine has been reached. Following Atropine administration, patients must be monitored for any potential respiratory failure necessitating mechanical ventilation.

  • Oxime - To stop the ‘aging’ process caused by OPs' irreversible binding to AChE, pralidoxime (2-PAM) is frequently given to patients with OP toxicity at the earliest possible presentation stage. Within 24 to 48 hours, carbamates will spontaneously separate from AChE and regain function.

  • Benzodiazepines - Following carbamate toxicity, intubated patients who experience convulsions and agitation are treated with benzodiazepines.

• Disposition - Due to temporary cholinesterase inhibition and swift restoration of AChE enzymatic activity, carbamates often have a less severe clinical course than OP toxicity. The majority of patients will fully recover in 24 hours. Low levels of consciousness can lead to high mortality in patients. Patients who first exhibit little symptoms and do not require Atropine can be safely discharged after being observed. Patients who require Atropine should be admitted to a monitored setting for continuous monitoring of their respiratory function. Moderate toxicity will require 24 hours of observation.

Conclusion:

The consequences of carbamate toxicity depend on how much is consumed. Full recovery is anticipated for moderate instances, but severe cases may necessitate a lengthy hospital stay and ventilation.